Symposium BM4 : Materials and Manufacturing of Biointerface Devices and Stretchable Electronics

Wearable sensor technologies play a significant role in realizing personalized medicine through continuously monitoring an individual’s health state. To this end, human sweat is an excellent candidate for non-invasive monitoring as it contains physiologically rich information. In this talk, I will present our recent advancement on fully-integrated perspiration analysis system that can simultaneously measure sweat metabolites, electrolytes and heavy metals, as well as the skin temperature to calibrate the sensors' response. Our work bridges the technological gap in wearable biosensors by merging plastic-based sensors that interface with the skin, and silicon integrated circuits consolidated on a flexible circuit board for complex signal processing. This wearable system is used to measure the detailed sweat profile of human subjects engaged in prolonged physical activities, and infer real-time assessment of physiological state of the subjects.

Wearable electrochemical sensors have attracted tremendous attention and are experiencing rapid growth in recent years. Non-invasive wearable sensors solve the potential issue in invasive sensors which may cause infection and painful feeling in the sensing area. Stretchable property also provides a comfortable wearable healthcare monitoring to users which is essential for the next generation of wearable sensors. Sweat, one of the most suitable biological fluids for non-invasive monitoring, contains multiple chemical elements relevant to abundant message about people’s health condition. Since the plasma ammonia is the main source of ammonia in human perspiration, the level of ammonium salt concentration in sweat is directly related to ammonia in plasma which is an excellent indicator of body health, for example, liver problem. In this work, a new type of non-invasive and stretchable potentiometric sweat sensor is developed by using all-solid-state ion-selective electrodes (ISEs) coupled with poly(dimethylsiloxane) (PDMS). The novel fabrication employs screen printing for both working and reference electrodes, incorporating graphene as ion-to-electron transducer with ammonium-selective membrane as the top layer. The advantages of PDMS-based substrate include simple fabrication with high flexibility of design and components. Stretchable PDMS-based substrate provides comfortability and ensures intimate contact with skin. Our stretchable electrochemical ammonium sensor also has the capability of maintaining its function under the intricate stress of bending and stretching on body while users perform daily activities. The tensile test results of our sensors showed stable potentiometric performance with negligible effect by mechanical deformation. Due to the unique nanostructure of graphene, the resulting potentiometric sensor displays a wide range of EMF response from 10^-6 M to 1 M with high stability and sensitivity. Furthermore, the hydrophobic graphene layer contributes an excellent chemical sensing reversibility by preventing aqueous layer formation between the ISEs and conductive electrode surface. Such new stretchable electrochemical PDMS-based sweat sensor architecture will provide a revolutionary shift from hospital-centric healthcare monitoring to daily wearable-based personal healthcare management.

The touch panel was developed decades ago and has become a popular input device in daily life. Because human-computer interaction is becoming more important, the next generation of touch panels require stretchability and bio-compatibility to allow integration with the human body. However, because most touch panels were developed based on stiff, brittle electrodes, electronic touch panels face difficulties to achieve such requirements. In this paper, for the first time, we demonstrate an ionic touch panel based on polyacrylamide hydrogel containing LiCl ions. The panel is soft and stretchable and thus, can sustain a large deformation. The panel can freely transmit light information through it because the hydrogel is transparent, with 99 % transmittance for visible light. A 1-dimensional touch strip was investigated to reveal the basic mechanism of sensing, and a 2-dimensional touch panel was developed to demonstrate its functionalities. The ionic touch panel was operated under high deformation with more than 1000% areal strain without sacrificing its functionalities. Furthermore, an epidermal touch panel on the skin was developed to demonstrate the mechanical and optical invisibility of the ionic touch panel through writing a word, playing piano, and playing a game.

Wearable biosensors using sweat based detection is a propeller for technological leap towards lancet-free health monitoring. Non-faradaic electrochemical sensors, which are label-free, cost-effective and are low-power applications, are desirable in the development of wearable biosensors. Nanomaterials such as Zinc oxide (ZnO) can be used to build non-faradaic electrochemical biosensors for enhanced sensitivity and specificity. The surface states of ZnO can be leveraged for immobilizing various linker molecules for ultra-specific detection of biomolecules. Also, the electrochemical modulation of ZnO due to linker binding can be optimized to achieve amplified sensor response. However, sweat based detection has unresolved challenges such as, stability of sensor element in human sweat pH range of pH 4.5 to pH 7 and multiple biomarker detection. In order to address the challenges related to stability, we studied the interactions of Room Temperature Ionic Liquid (RTIL) and ZnO thin film and its effective utilization for leveraging the stability of bio-immunoassay for sweat based detection. RTILs are being studied widely due to their desirable properties such as low volatility, wide electrochemical window and high thermal and chemical stability. We have used RTIL 1-Butyl-3-methylimidazolium tetrafluoroborate, which has been previously utilized for the detection of breast cancer gene and prostate specific antigen. We have used thiol based molecule Dithiobis succinimidyl propionate (DSP) for binding to zinc terminations of pulsed laser deposited ZnO thin film. In order to understand the RTIL interface between ZnO surface, linker and antibody , surface analysis was applied after performing Fourier Transform Infrared measurements on the layered structure of RTIL, DSP and Interleukin-6 (IL-6) antibody arranged in three different combinations on ZO surface. The optimized combination was recognized after identifying and correlating the absorption energy of different binding interactions on ZnO surface to the respective wavelengths. This analysis was also done for time-based stability study, where the same functionalized substrates were measured using FTIR for five weeks. We also performed electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV) measurements on the optimized stack to capture the electrochemical interactions. The capacitive component due to electrical double layer of RTIL and attached bio-immunoassay and resistive component due to charge transfer between DSP linker molecule and ZnO thin film was observed using Zview (Scribner Associates, Inc) software after fitting the data to equivalent circuit diagram. Hysteresis for time based variation in the sensor performance was compared by CV. Further, the optimized stack was used to detect the cytokine Interleukin-6 (IL-6) in sweat in range of 2 pg/mL to 20 pg/mL. It is capable of sensitively detecting 2 pg/mL IL-6 in synthetic sweat and shows stable performance over 5 week period.

This seminar introduces three recent progresses that can extend the application of self-powered flexible inorganic electronics. The first part will introduce self-powered flexible piezoelectric energy harvesting technology. Energy harvesting technologies converting external sources (such as vibration and bio-mechanical energy) into electrical energy is recently a highly demanding issue. The high performance flexible thin film nanogenerator was fabricated by transferring the perovskite thin film from bulk substrates for self-powered biomedical devices such as pacemaker and brain stimulation. The second part will introduce flexible electronics including large scale integration (LSI) and high density memory. Flexible memory is an essential part of electronics for data processing, storage, and radio frequency (RF) communication. To fabricate flexible large scale integration and fully functional memory, we integrated flexible single crystal silicon transistors with 0.18 CMOS process and memristor devices. The third part will discuss the flexible GaN/GaAs LED for implantable biomedical applications. Inorganic III-V light emitting diodes (LEDs) have superior characteristics, such as long-term stability, high efficiency, and strong brightness. Our flexible GaN/GaAs thin film LED enable the dramatic extension of not only consumer electronic applications but also the biomedical devices such as biosensor or optogenetics. Finally, we will discuss laser material interaction for flexible and nanomaterial applications. Laser technology is extremely important for future flexible electronics since it can adopt high temperature process on plastics, which is essential for high performance electronics, due to ultra-short pulse duration. (e.g. LTPS process over 1000 °C) We will explore our new exciting results of this field from both material and device perspective.

Related References (from Keon’s group as corresponding authors)
[1] Nano Letters 11, 5438, 2011. [2] Nano Letters 10, 4939, 2010. [3] Nano Letters 12, 4810, 2012. [4] Nano Letters 14, 7031, 2014. [5] Adv. Mater, 26, 2514, 2014. [6] Adv. Mater. 26, 4880, 2014. [7] Adv. Mater, 26, 7480, 2014. [8] Adv. Mater. 24, 2999, 2012. [9] Adv. Mater. 27, 3982, 2015. [10] Adv. Mater. 27, 2866, 2015. [11] Adv. Mater. 10.1002/adma201602339. [12] Energy Environ. Sci. 8, 2677, 2015. [13] Energy Environ. Sci., 7, 4035, 2014. [14] ACS Nano 7, 11016, 2013. [14] ACS Nano 9, 4120, 2015. [15] ACS Nano, 10, 3435, 2016. [16] ACS Nano 7, 4545, 2013. [17] ACS Nano 7, 2651, 2013. [18] ACS Nano 8, 9492, 2014. [19] ACS Nano 8, 7671, 2014. [20] ACS Nano, 9, 6587, 2015. [21] Adv. Energy Mater. 3, 1539, 2013. [22] Adv. Energy Mater. 5, 1500051, 2015. [23] Adv. Func. Mater. 24, 2620, 2014. [24] Adv. Energy Mater. 6, 1600237, 2016. [25] Adv. Func. Mater. 24, 6914, 2014. [26] Adv. Func. Mater. 10.1002/adfm.201601296. [27] Nano Energy, 1, 145, 2012
[28] Nano Energy, 14, 111, 2015. [29] IEDM, 19.3, 1, 2015

This paper describes a new class of thin-film mechanical sensor based on metallic nanoislands on graphene. These films are formed by exploiting the characteristic of graphene known as wetting transparency. That is, a thin film formed by an evaporated flux of metal atoms impinging on a graphene surface will adopt a morphology that is largely determined (at nominal thicknesses below approximately 20 nm) by the identity and surface energy of the material supporting the graphene. This control permits the formation of several technologically useful morphologies, among them are disconnected highly crystalline nanoislands that are separated from each other by gaps smaller than 10 nm. The electrical current through these films can be modulated by mechanical strain, which through mechanisms ranging from quantum tunneling at low applied strains to fracture of the graphene at higher strains can exhibit gauge factors over 1000. This sensitivity permits detection of strains ≤0.001%. This talk will describe our efforts to understand the mechanism of formation of these nanoisland-graphene sensors using atomistic dynamics simulations, and the detailed mechanism by which strain modulates the electrical resistance over a large dynamic range, from 0.001% to 10% strain. These sensors can be used to detect the pulse pressure waveform in the radial artery and contractions of stem-cell derived human cardiomyocytes. In another application, strips of these sensors can be bonded to gloves and used to detect the letters of American Sign Language.

Recent spotlight on wearable electronics generates huge attention on resilient electrodes as stretchable rubber-type electronics. And especially silver nanowire (AgNW)-based composites have been effectively utilized to achieve reliable stretchability as well as qualified conductivity for the stretchable conductor applications. Here we introduce a novel 3D printing technology with capability of electrical property control depending on extruder nozzle’s shape difference, which enables us to print electrically conductive and dielectric parts with the same composition of AgNW in rubber composite. Additionally, the computational simulation for the optimization of 3D conductor depending on highly anisotropic filler’s alignment and distribution has been investigated. The extrusion of rubber composite has been analyzed theoretically by consideration of fluid-mechanical behavior of AgNW fillers in the rubber composites. Computational simulation is also matched well with the experimental result, where AgNWs’ aligned behavior with a round nozzle, and AgNWs’ random distribution with a flat nozzle. Composites with aligned and randomly distributed AgNWs show dielectric and 3D conductive characteristic respectively. Finally, the epitaxially printed stretchable sensors using silicone rubber composite with same concentration of AgNWs have been demonstrated. The fabricated stretchable wireless sensor shows a reliable response to the mechanical strain change by linear change in resonant frequency.

The lack of stretchable semiconductors has limited the development of stretchable and wearable electronics. All the existing approaches typically sacrifices charge-transport mobility. Here, we present a concept based on nanoconfinement effect of polymers to significantly improve the stretchability of polymer semiconductors, without affecting its charge transport mobility. Our fabricated semiconducting film can be stretched up to 100% strain without affecting its mobility, through which a record-high mobility of 1.32 cm²/Vs has been achieved at 100% strain. Consequently, our fabricated fully stretchable transistor device also has very high stretchability in both directions to the charge transport channel, again measured at a record high mobility value of 0.55 cm²/Vs at 100% strain. We proceed to demonstrate this transistor device as a finger-wearable driver circuit for a LED. Furthermore, this versatile methodology was extended to four other semiconducting conjugated polymers with significant improvement in stretchabilility, which brings the mobilities of three resulting films over 1 cm²/Vs at 100% strain. Because of high versatility on different semiconducting polymers, our nanoconfinement concept could be utilized to impart high stretchability onto any molecular-engineered high-performance conjugated polymers that are developed in the future.

Innovative methods to produce transparent and flexible electrodes are highly demanded in modern optoelectronic and bioelectronic applications, but available solutions suffer from drawbacks such as excessive compliance, prohibitive costs and difficult processability. We propose a simple and highly compatible strategy to produce hierarchically-structured composites of functionalized graphene in polymeric matrices that exhibit high transparency, electron conductivity, and flexibility [1]. Our approach relies on the magnetically-directed assembly of colloidal particles in a fluid that is later converted into a solid composite [2,3]. To this end, we functionalized graphene sheets with protein-assisted attachment of superparamagnetic nanoparticles, to magnetically assemble them directly within matrices undergoing sol-gel transitions. By applying rotating magnetic fields or using specific magnetic virtual moulds, both orientation and local distribution of graphene flakes can be controlled within the composite’s microstructure. Such unique architectural control was confirmed with optical imaging and X-ray scattering techniques. Interestingly, the use of magnetic virtual moulds of predefined meshes allows us to assemble graphene flakes into two independent percolating networks. This results in a significant reduction of the percolation threshold from 1.2 vol% to 0.6 vol% only and enables a combination of optical transparency, electrical conductivity, and flexibility that is not accessible in homogeneously dispersed materials. Indeed, with such optimization of the microstructure, gelatine films of hundreds of micrometer in thickness with 90% transparency and 0.01 S.cm^-1 electrical conductivity could be produced. The resulting composites may open new possibilities on the quest of biocompatible transparent electrodes and stretchable optoelectronic sensors: strain resolutions as small as 0.005 % were demonstrated for double percolated composite films under unidirectional compression.
[1] H. Le Ferrand, S. Bolisetty, A.F. Demirörs, R. Libanori, A.R. Studart, R. Mezzenga, Magnetic assembly of transparent and conducting graphene-based functional composites, Nature Communications. (2016)
[2] R.M. Erb, R. Libanori, N. Rothfuchs, A.R. Studart, Composites Reinforced in Three Dimensions by Using Low Magnetic Fields, Science. 335 (2012)
[3] A.F. Demirörs, P.P. Pillai, B. Kowalczyk, B.A Grzybowski, Colloidal assembly directed by virtual magnetic moulds., Nature. 503 (2013)

Optical stimulation is an alternative to electrical stimulation that promises more selective activation of neurons populations.
We designed and validated a soft opto-cuff, a device that allows for optical stimulation of a peripheral nerve in freely moving mice. The nerve interface is composed of a soft implantable nerve cuff and a tethered ultra-compliant optic fiber further connected to a headstage fixed on the skull.
The opto-cuff is prepared with a 100kPa silicone membrane wrapped around the nerve and coated with a metallic light reflective film to minimize optical losses in the surrounding tissue. The implant was typically 2.5mm long and adjusted to the mouse sciatic nerve diameter.
We demonstrate the soft opto-cuff enables epineural optical modulation of the mouse sciatic nerve without disrupting the animal behavior. We found the compliant cuffs to be well tolerated by the animals and suitable for chronic experiments.
The soft opto-cuff technology offers exciting opportunities to study sensory pathways such as pain.

Implanted electrodes provide one of the most important neurotechniques by allowing for acquisition of individual neuron electrical activities in the living brain. However, their recording stability and efficacy in both the short and long term pose limitations on their scientific and clinical applications. Conventional brain probes suffer from substantial recording condition changes in time scales as short as hours due to the micro-movements of the implanted electrodes relative to the brain tissue. Over a period of weeks to months, their recording performance often deteriorates due to sustained foreign body reactions. Here we show that ultra-flexible, subcellular sized brain probe architecture, the nano-electronic thread (NET), forms reliable, glial scar free neural-probe interface, as verified by chronic neural recordings and tissue-probe interface characterizations. We observed that the electrode impedance, the noise level, the single-unit recording yield, and the signal amplitude remain stable during long-term implantation. We demonstrate that individual units can be reliably detected and tracked for months. In vivo two-photon imaging and postmortem histological analysis revealed seamless, subcellular integration of NET probes with the local cellular and vasculature networks. Significantly, we observed fully recovered capillaries with intact blood brain barrier, and complete absence of chronic neuronal degradation and glial scar. The unprecedented chronic reliability and stability is expected to fundamentally advance both basic and applied neuroscience, as well as lead to substantial improvement in brain-machine interface that can be applied to neuroprosthetics. Further, the subcellular dimension probes provide new opportunities for high density electrical recording by overcoming current physical limitations.

In order to develop system-level understanding and control of the highly complex brain activities, extensive efforts have been made to integrate multiple functionalities in neural probes, including simultaneous optical stimulation, drug delivery and high-capacity electrical recording. However, most of demonstrated multimodal neural devices involve highly specialized, high cost fabrication processes and often compromise on overall performance. Here, we present a novel multimodal neural probe platform realised by applying ultra-thin nanoelectronic coating (NEC) on the surface of conventional devices such as optical fibers and micro-pipettes. We fabricated the NEC devices by planar photolithography techniques using a substrate-less and multi-layer design to achieve a total thickness below 1µm and multiple individually addressed electrodes. Guided by an analytic model and taking advantage of surface tension, we attach the NEC device onto and wrap them around the surface of these conventional devices. We demonstrated in mouse model optical stimulation and controlled drug infusion with concurrent electrical recording using the resulted multimodal probes. We also demonstrated great functional versatility enabled by different application-specific electrode patterns on the NEC devices. This study provides a low-cost, versatile and efficient approach to multimodal neural probes that can be useful in both fundamental and applied neuroscience.

Significant advances have been made in the last two decades in interfacing electronic devices with the nervous system. Organic electronic materials in particular have emerged as ideal materials for interfacing with neurological systems due to their flexibility, biocompatibility and moreover their electronic and ionic conductivity. The ability to conduct ions confers a significant advantage over other electronic materials as organic electronics can in essence communicate in the native language of neurons via ionic currents. To that end, significant research efforts are being pursued to develop minimally invasive, implantable organic electronic devices integrating recording, stimulating, and drug delivery features.

Here we demonstrate multimodal probes with the ability to record and stimulate neurons using low impedance PEDOT:PSS coated electrodes. Furthermore, we show that such devices can also incorporate organic electronic ion pumps for electrophoretic delivery of neurotransmitters with high spatial and temporal resolution. By using a novel vertical ion pump design with a fluidic reservoir along the length of the probe, the voltage needed to pump ions is reduced by more than 10 fold compared to previously reported ion pump platforms. The efficacy of the ion pumps is demonstrated in an epileptic neural network by delivering GABA to stop epileptic behavior. Due to the probes unique biocompatibility and being equipped with high-fidelity organic electronic devices, we anticipate this work to be the starting point for new stimulation, recording and drug delivery paradigms in chronic neural implantation.

Neurological degenerative diseases and obsessive-compulsive disorders represent one of the major problems in the public’s health. The development of novel tools devoted to early diagnosis and treatment of these neurological diseases are an important and urgent medical need. In particular, deep brain stimulation (DBS) via implanted intracerebral electrodes that stimulate neurons at different frequencies, is a key technology in neuroprosthetic applications. However, although their adoption for therapeutic treatment is well established, the efficiency and biocompatibility of the probes are far from being ideal [1][2]. Organic bioelectronics [3] offers unprecedented opportunities for a novel design of neural electrodes, able to both record and stimulate neurons. Conductive polymers (CP) have emerged as ideal candidates for neurological electrodes, particularly suitable for being interfaced with the nervous tissue. Indeed π-conjugated polymers, besides being mechanically soft, are able to sustain mixed electronic/ionic transport, particularly suitable for interfacing the ionic current in cell membranes. CP-coating on metals [4] have been already proved to drastically decrease the impedance, required to ensure and maintain an efficient charge injection during stimulation and to improve signal to noise ratio. CP-coated microelectrodes have been further proved to lower the stimulation voltage threshold, resulting beneficial for electrode quality and tissue safety. In our work we have coated DBS microelectrodes made of W and Pt/Ir. We have performed PEDOT:PSS and PEDOT:PF₆ electropolymerization exploring different deposition conditions and achieving improved electrical and mechanical performances. The porous morphology of the film have been characterized and measured through Scanning Electron Microscopy (SEM). The electrical performances and stability have been studied using cyclic voltammetry (CV) in aqueous media (Ringer’s solution). Measurements of the temporal frequency-dependent complex impedance have been conducted via Electrochemical Impedance Spectroscopy on conducting polymer coated and bare DBS electrodes within a frequency window of 1.0-105 Hz, according with the range of most interesting neurological processes. In particular, via CP-coating we were able to minimize the magnitude impedance │Z │of the PEDOT-coated electrodes compared with the bare DBS electrodes, thus providing an optimal charge injection achieved with a lower voltage stimulation and more friendly tissue-electrode interface.


[1] J. Groothuis et al., 2014, Brain Stimulation, 7, 1-6.
[2] E. Leuthardt et al., 2006, Neurosurgery, 59, 1-16.
[3] M. Berggren, A. Richter-Dahlfors, 2007, Adv. Mater., 19, 3201-3213.
[1] D.Martin and G. Malliaras, 2016, ChemElectroChem, 3, 1-4.

Organic bioelectronics is an emerging field of science and technology that promise for novel system tools to record and regulate physiology and functions of biological systems in a highly automated fashion. Here, we report advances in combining organic electronic materials and devices to achieve integrated and distributed circuit systems applied to, implanted into and also manufactured in living systems, in vivo, that sense and deliver relevant biological signals aiming for autoregulation. The nature and characteristics of signalling in biology includes a vast array of ions and chemicals, frequency components ranging from 1 μHz to 10 kHz and a spatial resolution spanning from meters down to sub-micron scales. Our effort aims at establishing a signalling translation technology that bridges the biology-technology signalling gap by developing distributed chemical circuits that perform at the specifications of biological systems and the addressing protocols of traditional electronics. Our goal is to derive a technology for future prosthesis, medical therapy and plant biology applications that also take use of the electrolytic medium of the actual biological system as the communication network.

Organic electrochemical transistors (OECTs) are receiving a great deal of attention due to the ability to efficiently transduce biological signals. The working principle of OECTs relies on the modulation of the conductivity of the active material, which can be modified by electrochemical redox reactions in aqueous solution (doping/de-doping reactions). OECTs can either be operated in accumulation or depletion mode; operation in accumulation mode has the advantage of lowering the operational voltage. To date, only p-type OECTs, working in both depletion^[1] and accumulation mode^[2], have been reported.

We have developed an ambipolar OECT with balanced ambipolar charge transport characteristics. To realize the requirements for stable p- and n-type doping of the active material in aqueous solution, we have prepared conjugated polymers with high electron affinities and low ionisation potentials to allow for efficient doping of the semiconductor at relatively low voltages (vs Ag/AgCl). The electrochemical redox reactions of the polymers were analysed by spectroelectrochemical measurements as well as electric impedance spectroscopy where a capacitance per volume unit (C*) of 397 F/cm³ was measured demonstrating the potential of these materials for bioelectronic applications. Stability measurements were carried out in aqueous solution and a remarkably stable OECT, in operation for over two hours, was achieved without degradation of the active material.

Reference
1. Khodagholy, D. et al. High transconductance organic electrochemical transistors. Nat. Commun. 4, 2133 (2013).
2. Inal, S. et al. A High Transconductance Accumulation Mode Electrochemical Transistor. Adv. Mater. 26, 7450–7455 (2014).

Because of their electrochemical and mechanical properties, conjugated polymers have been identified as a possible bridge between the chemical signalling in our cells and electronic communication used in technology. Organic bioelectronic surfaces can be used to influence cell growth and behaviour by forming gradients and patterns of biomolecules and to induce detachment of cells. Recently, we have added organic ferroelectrics to our collection of organic electronic materials to be used together with biological systems. Ferroelectric materials display a stable polarization, for which the direction can be controlled by the application of an electric field. Once the material has been polarized the polarization is stable. We have shown that the ferroelectric polymer poly(vinylidene-trifluoroethylene) can be polarized through an aqueous electrolyte, offering the possibility to change the surface energy of the polymer while in contact with a biological sample. This makes the ferroelectric materials good candidates for selective adsorption of charged molecules and chemical patterning of surfaces.

A significant challenge in bioelectronics is an improved understanding of the biotic/abiotic interface. It has been postulated by Fromherz and co-workers that tuning of the gap (or cleft) between a cell and a transducer would allow increased signal transduction of electrical activity of the cell.^[1] As a fundamental structure of all biological membranes, lipid bilayers with are widely employed as a model system to investigate interactions between cells and their environment. Interfacing biomimetic lipid bilayers with materials is a much studied problem, and one which can benefit from introduction of novel functional materials, particularly to improve readout of the functionality of the biological systems. The conducting polymer PEDOT:PSS, in particular in its embodiment in the organic electrochemical transistor (OECT), has shown great potential in biosensing applications as it efficiently transduces ionic currents into electronic signals. Mixed ionic/ electronic conduction, along with an ideal biocompatible surface and soft tissue-like mechanical properties, have contributed to the successful use of this material for integration with biological components. We show, for the first time, the assembly of supported lipid bilayers (SLB) on both free-standing PEDOT:PSS films, and OECTs, by vesicle fusion.^[2] We further show fusion of blebbed (lipid and protein containing) vesicles from live cells and demonstrate membrane protein functionality. Characterization of lipid bilayers and embedded proteins was carried out using the OECT (electrically), QCM (quartz crystal microbalance) and also via optical techniques (FRAP (fluorescence recovery after photobleaching) and TIRF spectroscopy (total internal reflection fluorescence) thanks to the optical transparency of the conducting polymer films. This work not only shows potential for development of a platform to monitor cellular ion channel activity, but also contributes to our understanding of the interaction of transducers with the outermost surface of cells for future optimization of brain machine interfaces.


[1] P. Fromherz, Chemphyschem 2002, 3, 276.
[2] Zhang, Yi, Inal, Sahika, Hsia, chih-hyun, Ferro, Magali, Ferro, Marc, Daniel, Susan, in review. 2016.

Organic electrochemical transistors (OECTs) make use of hydrated conducting polymers which can change their conductivity by reversibly exchanging ions with an electrolyte. Because this working mechanism is favorable for a wide variety of sensing principles in aqueous media, OECTs have been intensively studied in applications such as environmental and physiological monitoring. While much emphasis has been placed on analyzing and maximizing the OECTs signal, a key factor determinant for the sensors performance has been mostly overlooked to date: noise. The major noise source in sensing devices is 1/f noise, which is dominant at low frequencies. Since the binding kinetics of many species of interest in biosensing (e.g. proteins) typically require timescales up to minutes, the 1/f noise becomes a key parameter limiting the performance of the sensor. Low-frequency noise has therefore been studied in depth for several transistor biosensors such as Si nanowires, liquid-gated graphene and single-walled carbon nanotube (SWCNT) transistors. We discuss here the low-frequency noise of OECTs based on the conducting polymer poly(3,4-ethylenedioxythiophene) doped with poly(styrene sulfonic acid) (PEDOT:PSS). We present the noise scaling behavior with gate voltage, channel dimensions and polymer thickness. We demonstrate that the noise in OECTs scales only inversely with the area of the channel rather than with its volume. These results suggest the use of large area PEDOT:PSS in order to maximize the signal-to-noise ratio (SNR) for biochemical and electrostatic sensing applications. We estimate the characteristic limit of detection (LOD) and SNR of an OECT in a typical ion-sensing measurement, as well as the magnitude of the noise. Comparison with literature shows that the magnitude of the noise in PEDOT:PSS- based OECTs is only slightly larger than that in SWCNTs and Si nanowires devices whereas it is similar to that observed in graphene transistors.

Heart disease comes to us without clinical manifestation from time to time. Currently used instruments for cardiac diagnosis such as electrocardiogram (ECG), echocardiogram (ECHO) are limited to temporary check. With the needs of the real-time continuous monitoring, wearable ECG sensors are implemented in these days, but still have difficulty in detecting presymptom of coronary disease or myocardial ischaemia. Several mechanocardiogram have been presented as a promising complementary analysis to ECG. Apex cardiogram (ACG) is a one of representative mechanocardiogram, which monitors the temporal volume of and pressure changes in the heart and through the ACG, hemodynamics of heart can be indirectly monitored. However, ACG had not been commercialized due to its inconvenience and high cost. This study suggests convenient and inexpensive patch type ACG sensor based on emerging electronic skin technology, having possibility of utilization in daily life. The sensor is composed of micro-sized conductive particles. Via rubbing process, the particles could have two-dimensional pattern. The confined conduction paths of particles are varied considerably by applied strain and it induces the sensor to have high sensitivity and accuracy at low strain. Additionally, the sensitivity and measureable strain range can be modulated by changing particle density with modulus of substrate. Through high sensitivity at low strain and large stretchability, the sensor can recognize small palpation at precordium and also bear large strain from body motions. Although further investigation is needed for practical use, the new sensor is a promising tool for mechanocardiac diagnosis, which has limitations with current equipment.

Flexible and stretchable electronics integrate functional electronic devices on plastic substrates and fill niches complementary to silicon electronics in applications where bending and stretching of devices are required or preferred. Strain sensing is one of the fundamental applications for flexible and stretchable electronics. Here we present our recent efforts to design novel device structure and employ eco-friendly bioplastics for electronic devices. Our devices with nano- and micro-materials and structures show high reproducibility and repeatability, and will enable potential applications in biomedical healthcare.
Nanomaterial-based resistive and capacitive strain sensors have attracted more and more attentions for their applications in artificial skins. Most of these devices provide persistent changes of signals upon human motions. Due to the complexity of materials and system integration, the reproducibility and repeatability are major concerns for further commercialization. For simplifying device design, we proposed a new concept, digital strain sensor, based on the insulating-to-conducting transition[1] of devices through mechanical switching. We fabricated devices with various sensitivities and detection limits by engineering device structures. Further demonstrations of our digital strain sensors were achieved for gesture control and heart-beat monitoring. For the simple design and durable materials, our devices can be reproducibly fabricated and maintain the performance after 10,000 times’ bending.
Biocompatible and biodegradable electronic devices are of interest in biomedical healthcare. Cellulose nanocrystal (CNC) materials, eco-friendly bioplastics, recently attract a great attention in flexible and stretchable electronics. In addition to the unique property of dissolving in water, CNC materials could be applied for future flexible electronics for high tensile strength, low density, low thermal expansion, and non-toxicity. Here we report the first demonstration of using PDMS stencils to pattern metal electrodes on CNC substrates. PDMS stencil lithography prevents the potential damage to the cellulose based flexible substrate, which conventional photolithography process will lead to, without compromising the resolution in patterning. Our strain sensors have high sensitivity with a gauge-factor of over 50 in strain testing, which is the highest among reported strain sensors fabricated on water-soluble substrates.
[1]Lai Y, Ye B, Lu C, Chen C, Jao M, Su W, Hung W, Lin T and Chen Y 2016 Extraordinarily Sensitive and Low-Voltage Operational Cloth-Based Electronic Skin for Wearable Sensing and Multifunctional Integration Uses : A Tactile-Induced Insulating-to-Conducting Transition Adv. Funct. Mater. 26 1286–95

Reproducing the human sense of touch with an artificial system is a very challenging task in particular because it involves the capability of fabricating, possibly with the same fabrication technology, different kinds of sensing devices on the same substrate. Moreover, they also have to be fabricated on highly flexible and compliant substrates, as artificial skin patches generally require to be transferred onto complex, possibly 3D, surfaces. Low Voltage Charge Modulated OTFTs (OCMFETs) represents a versatile tool for the realization of a wide range of sensing applications. The architecture is based on a floating gate organic transistor, capable to be operated at low voltages thanks to an ultra-thin, hybrid dielectric. The sensitivity of the device is obtained by anchoring in a part of the floating gate a sensing layer directly exposed to the measurement environment; this sensing layer can be chosen according to the specific external stimulus to be sensed.

In this work we will show that Low Voltage OCMFETs can be fabricated on ultrathin and highly compliant plastic substrates, with a nominal thickness around 1 µm, and employed for the realization of multimodal tactile transducers. In order to achieve sensitivity to pressure, a piezoelectric thin film, namely PVDF, is deposited on the sensing area of the device. In this way, when pressure is applied on the PVDF, the charges induced in the piezoelectric film lead to a variation of transistor threshold voltage and a current variation can be detected as a result of the applied pressure. We will demonstrate that such devices can detect very small pressure, below 300 Pa and can detect forces within a range from 0.01 up to 5 N. A detailed dynamic electromechanical characterization have been carried out, showing that such devices are able to detect dynamic stimuli at a frequency up to 500 Hz. Moreover, being PVDF also a pyroelectric material, temperature variations ranging from 10° up to 45 °C could be also detected. Interestingly, since the responses of the device to the two different physical stimuli are characterized by marked differences in sensitivity and response time, it is possible to employ the same device for the fabrication of multimodal tactile sensing systems. The highly flexibility of the developed structure, and the easiness of the employed process, make this solution very interesting for the fabrication of multimodal, highly compliant artificial skin.

We have developed an ultra-flexible and conformable, three-color, highly efficient polymer light-emitting diodes (PLEDs) and organic photo detectors (OPDs) to realize pulse oximetry. Optoelectronic devices are especially important in medical field since these devices can non-invasively detect bio singnals and other clinical information. Recently, organic light-emitting diodes (OLEDs) and OPDs were manufactured on glass or bulky (less than 1 mm) plastic substrates and then combined to form a transmission-mode pulse oximeter [1] and muscle contraction sensor [2]. In previous reports, organic LEDs and photovoltaics were fabricated on 1-µm-thick films, but were driven in nitrogen atmosphere [3, 4].
We report ultra-thin and high-performance PLEDs and OPDs with thin passivation layers. The total thickness of the PLEDs and OPDs, including the substrate and encapsulation layer, is only three micrometers. This value is one order of magnitude thinner than the epidermal layer of human skin. By integrating green and red PLEDs and OPDs, we fabricate an ultra-flexible reflective pulse oximeter.

Three-color PLEDs were manufactured on 1-µm-thick parylene films. The surface of the parylene substrate was planarized by 500-nm polyimide layer. For realizing these optical devices, indium-tin-oxide (ITO) was formed by sputter process. To reduce heat damage to the ultra-flexible substrate, the ITO was formed without substrate heating. Thanks to a reduction of the device thickness (3 µm) and placement of the active layer in the neutral strain position, our ultrathin PLESs and OPDs show the good mechanically flexibility. Our PLEDs wasn’t broken even when bent with a bending radius of 100 µm on the tip of a razor and crumpled.

By integrating ultra-flexible green and red PLEDs with an OPD, a flexible and conformable reflective pulse oximetry has been demonstrated. The pulse oximetry was laminated to skin using adhesive tape with a thickness of 6 mm. The total thickness was approximately 30 µm. In order to detect pulse waves and blood oxygen levels, the device was turned over and wrapped around a finger. While the driving voltage of the PLEDs was set at 5 V, the open-circuit voltage (V_oc) of the OPD was monitored to measure the absorption of green and red light in the blood to the pulse.

This work was supported by the Someya Bio-Harmonized ERATO grant.

[1] C. M. Lochner, Y. Khan,, A. Pierre, and A. C. Arias, Nature Commun. 5 5745 (2014).
[2] A. K. Bansal, S. Hou, O. Kulyk, E. M. Bowman, and I. D. W. Samuel, Adv. Mater. 27,
[3] M. S. White, et al., Nature Photonics 7 811–816 (2013).
[4] M. Kaltenbrunner, et al., Nature Commun. 3 770 (2012).

The availability of higher performance microprocessors, communication chips, and inertial sensors with ever smaller dimensions has driven the miniaturization of passive IC components as well as the development of high-throughput surface mount assembly technology. Currently, circuit boards using these components are assembled by mechanical pick and place operations. Further decreases in component size require mutual advances in pick-and-place machine dynamic, component mounting and placement on supply tapes, and micro-scale gripping. Fluidic assembly provides an alternative scalable route to placement of micro-scale objects; however, the requirement for complementary chemistry and/or shape-driven interaction establishes constraints on the process for assembling arbitrary patterns. For these reasons, a flexible process for high-throughput placement of components that overcomes the constraints of pick-and-place assembly is needed.
We present a hybrid manufacturing process for printed electronics, involving inkjet printing of thin-film conductors combined with template-free photo-anchoring of micro-components provided in a continuous flow. To enable template-free anchoring, it was necessary to build the hardware and software that enables real-time imaging of the flow of components over the substrate, image processing, and photopatterning via maskless projection. By this method, software-defined specifications can be used to specify the object placement locations, including for example, the relative positions of each object, dynamic reference points on the substrate (e.g., printed traces where the objects should be placed), selection rules (e.g., object size, orientation, color), and positional tolerances for anchoring. The rate and accuracy of the dynamic anchoring process are studied using polymer beads, and a model is developed to calculate the areal throughput versus the pattern design and image processing performance. Printing accuracies of three pixels (10 μm) on average are demonstrated for beads ranging from 5 to 90 μm. Last, we demonstrate the fabrication of flexible NFC sensing tags, by first inkjet printing Ag antennas on a flexible paper substrate, and subsequently photoanchoring micro-LEDs onto the antenna.

The development of stretchable electronics and optoelectronics poses fundamental challenges in developing new electronic materials that are mechanically compliant and solution processable. Thin-film field effect transistor (TFT) is a fundamental component behind modern electronic devices including displays, sensor arrays, microprocessers, and identification tags. We report the fabrication of transparent TFTs that behave like an elastomer film while retaining high electronic performance. The transistors are comprised of screen-printed silver nanowires-polyurethane acrylate composite as the gate, source, and drain electrodes, semiconducting single-walled carbon nanotube network channel, and a polyurethane-co-polyethylene oxide dielectric. All these materials are deformable like elastomers. The entire fabrication processes of the stretchable transistors, including the preparation of the source, drain and gate electrodes, semiconductor layer, dielectric layer, and substrate, are all carried out by solution-based techniques under ambient conditions.

Among the family of Organic Thin Film Transistors (OTFTs), the class of transistors made of electrochemically active polymers are currently of highly interest mainly because of their ability to interface ideally with aqueous environment , mimicking biological systems interfaces. Organic Electrochemical Transistors (OECTs) have been exploited with success as biosensors and transducers in a number of bio-applications, as logic elements and as electrodes for brain interface. With the aim to enhance the selectivity properties of the OECT towards specific bio-molecules, we manufactured a graphene electrode made on a plastic substrate, modified with nanoparticles and used as a gate electrode in an OECT device. As a first step we characterize the OECT response when equipped with the plastic graphene gate modified with different types of nanoparticles. Nanoparticles of Gold (Au) and Silver (Ag) were prepared using a dedicated protocol, with spherical and pyramidal shapes. Transfers characteristics were acquired with two physiological solutions at different molar concentrations. We found an obvious response of the OECT depending on the kind of electrolytes, and interestingly the OECT response depends on the shape of nanoparticle as well as the electrolyte concentration. The transfer curves show a plateaux at low gate voltages, in the range between ~0.2 and ~0.4 V, representing the fingerprint of nanoparticles on the gate surface. The gate voltage shift increases with the increasing of the dimension of nanoparticles. The plateaux of the drain current represents the range of the gate voltage that is not transferred to the electrolyte at the gate/electrolyte interface, representing therefore a special “blind space” where anchoring biomolecules to functionalized nanoparticles.

A major need and, at the same time, challenge in additive manufacturing is the ability to pattern materials over a wide range of physical properties. Existing printing techniques have severe limitations inherent to their physical mechanisms, such as narrow range of ink viscosities (e.g., inkjet printing), restrictive ink rheology (e.g. direct ink writing) or limited geometries (e.g., laser induced forward transfer LIFT). As a result, inks must be carefully engineered to match the narrow property range of existing printers. Here we present acoustophoretic printing, in which nonlinear acoustic forces are designed and employed to print drop on demand (DOD) wide range of materials. By controlling these forces, ejected droplet volume can be varied continuously by more than two orders of magnitude, from the nanoliter to microliter range. Specifically, we show that ink viscosities (µ) spanning more than five orders of magnitude (µ =0.5 – 25’000 mPas) can be printed by this method, ranging from food, polymer solutions, cell-laden inks, optical resins, and liquid metals. Such material versatility paves new way in the field of additive manufacturing of stretchable devices. As initial demonstration, we printed bulk eutectic Gallium Indium (eGaIn), patterning conductive lines in a contactless, drop-by-drop fashion. In such a way, simple electronics circuits could be manufactured on stretchable fabrics, without any modification of either the environment or the printed material.

Most electronic materials exhibit limited elasticity. Brittle films display fracture strains of less than about 5%. Ductile films plastically flow at strain larger than 5%. Here, we explore how to engineer reversible elasticity in thin film on plastic substrate using repeated cut patterns through the multilayer structure.

Inspired by the topography of stretchable film gold films on silicone that display dense distributions of Y-shaped cracks to favor out of-plane deformation, we cut Y-shaped motifs throughout the film(s). The motif is characterized by the length of the Y branch a, the distance between two motifs L, and the width of the cut w.

Using a 75µm thick polyimide foil, we prepared macroscopic dog-bone shaped structures with a range of designs: a/L varied from 0.5 to 0.8 and w from 0.7 to 1.5mm. We next recorded the tensile stress (strain) response of the structure to fracture and at 1mm/s strain rate. The structures were also modeled using Finite Element Modeling.

Upon stretching, the polyimide ligaments locally deflect out of plane around the openings, allowing the plastic foil to macroscopically stretch. The effective spring constant of the engineered polyimide can be reduced by two orders of magnitude compared to the plain foil using a/L = 0.8 and w = 1.1mm, nearly matching the spring constant of a silicone elastomer of equivalent thickness (75µm). Moreover, these Y-shaped patterns have no preferential direction of stretching.

Next we applied our design to ductile platinum film on polyimide (PI) foil and brittle ITO (Indium Tin Oxide) film on PET (Polyethylene Terephthalate) foil. We further optimized the Y motif dimensions against the resulting electrical conduction of the film. The conductor macroscopic geometry was 29mm in width, 45mm in length and 100nm in thickness.

The Pt/PI system displayed stable electrical conduction when stretched up to an engineered strain of up to 70%. Moreover, it withstood 100k stretch cycles to 10% applied strain without electromechanical fatigue. Similarly, the ITO/PET structure stretched up to a maximum 50% uniaxial strain, and withstood electrically and mechanically 10k stretch cycle to 10% applied strain.

The proposed design is versatile and compatible with thin-film processing. We anticipate the patterned motifs can be scaled down to offer a wider range of readily elastic electronic materials for applications in stretchable electronics and soft bioelectronics.

Developing inherently stretchable materials will enable significant advancement in stretchable electronics allowing for seamless transition of traditional device including transistors and optoelectronics into a stretchable platform. Polymer semiconductors are inherently soft materials due to the weak van der Waal intermolecular bonding allowing for flexible devices. However, these materials are not typically stretchable and when large strains are applied they either crack or plastically deform. Here, we study the use of repeated plastic deformation as a means of achieving stretchable films.

In this talk, we will discuss the critical aspects of polymer semiconductor material selection, morphology and interface properties that enable this simple but highly successful approach of achieving stretchable electronic films. We demonstrate that plastic deformation can include both extension and contraction of the film allowing for large repeated deformations of over 75%. During this process we thoroughly characterize the morphology and show that the films follow a well controlled repeated deformation pattern for over 100 stretching cycles. In addition, we show that one can employ high performance donor-acceptor polymer semiconductors that are typically brittle through proper polymer blending. This allows for films that can be stretched over 75% while maintaining charge mobility above 0.1 cm²/Vs throughout the stretching process when applied in a transistor configuration.

Electrical measurements from cells and synapses in large populations of animals would help reveal fundamental properties of the nervous system and neurological diseases. Small model organisms like worms, hydra, and larvae are ideal for these large-scale studies because they can be manipulated in parallel using microfabricated devices; however, current methods to measure electrical activity in these tiny animals requires low-throughput and invasive dissections. To overcome these limitations we present nano-SPEARs: suspended electrodes that are smaller than a single cell, integrated into a microfluidic device, and able to record electrical activity from intact small animals. Using this technology we have made the first extracellular recordings of body-wall muscle action potentials inside an intact roundworm, Caenorhabditis elegans. By reconfiguring the microfluidic chamber we can use the same technology to record electrical activity from the freshwater cnidarian Hydra littoralis, demonstrating that nano-SPEARs are suitable for multiple species. Furthermore, by recording electrophysiology without dissections, nano-SPEARs can accelerate studies that use small organisms to model human diseases. As an example, we use nano-SPEARs to establish the first electrophysiological phenotypes for C. elegans models for Amyotrophic Lateral Sclerosis (ALS) and Parkinson’s disease (PD), and show that the PD phenotype can be partially rescued with the drug clioquinol. Together these results demonstrate that nano-SPEARs provide the core technology for scalable electrophysiology microchips that will enable high-throughput in vivo studies of fundamental neurobiology and neurological diseases.

Silicon-based materials exhibit biocompatibility, biodegradability as well as a spectrum of important electrical, optical, thermal and mechanical properties, leading to their potential applications in biophysical or biomedical research. However, existing forms of silicon (Si) materials have been primarily focused on one-dimensional (1D) nanowires and two-dimensional (2D) membranes. Si with three-dimensional (3D) mesoscale features has been an emerging class of materials with potentially unique physical properties. Here, we incorporated new design elements in traditional synthetic methods to prepare various forms of 3D Si mesostructures and studied their functional biointerfaces with cellular components. In the first example, an anisotropic Si mesostructure, fabricated from atomic gold-enabled 3D lithography, displayed enhanced mesoscale interfacial interactions with extracellular matrix network. This topographically-enabled adhesive biointerface could be exploited for building tight junctions between bioelectronics devices and biological tissues. Another Si mesostructure with multi-scale structural and chemical heterogeneities, was adopted to establish a remotely-controlled lipid-supported bioelectric interface. We further adapted the bioelectric interface into the non-genetic optical modulation of single dorsal root ganglia neuron electrophysiology dynamics. Our results suggest that the dimensional extension of existing forms of Si could open up new opportunities in the research of biomaterials manufacturing and application.

Creating an interface between living cells and electronics, both for recording and stimulation, is of paramount importance for various applications such as brain-machine interfaces and neuroprosthetic devices. Current microelectrode array technologies, however, have certain drawbacks for recording applications. For instance, their intrinsic electronic noise and impedance are inversely proportional to the electrode size, making downsizing for large scale high density integration difficult and creating challenges for signal multiplexing. Furthermore, the recorded small voltages are highly susceptible to noise from the environment. As an alternative, field-effect transistors where the oxide and the metal gate are replaced by an electrode and an electrolyte, so-called solution-gated field-effect transistors (SGFETs), can overcome these issues since their performance mainly depends on the geometry of the transistor making downsizing possible and facilitating multiplexing. In addition, they provide an intrinsic signal amplification, reducing susceptibility to noise while maintaining a low fabrication complexity. To be suitable for in vivo applications, the transistor material has to allow for the fabrication of flexible devices, must be biocompatible and stable in the harsh biological environments and provide good electronic properties such as high carrier mobility and low intrinsic electronic noise. While many of these requirements are difficult to fulfill with common semiconductors, graphene is a very promising candidate for fulfilling all requirements simultaneously.
In this work, we present the fabrication of flexible graphene SGFETs on biocompatible polyimide substrates using chemical vapor deposition graphene. We investigate in detail their performance in electrolyte, including electronic noise, and compare them to graphene SGFETs prepared on rigid substrates¹. As a next step we show that flexible graphene transistors are able to record electrical activity from brain slices and cell cultures in vitro¹. Finally, we use flexible graphene SGFETs during in vivo experiments to record spontaneous slow oscillations, visually evoked responses and pre-epileptic activity in the visual cortex of anesthetized rats. We compare the signal-to-noise ratio of the graphene SGFETS to state of the art platinum electrodes and other competing technologies, demonstrating an excellent performance confirming the potential of graphene to be used in the new generation of electrically-functional neuroprosthetic devices.

1. Blaschke, B. M. et al. Flexible graphene transistors for recording cell action potentials. 2D Mater. 3, 25007 (2016)

In this work, graphene field effect transistors (GFETs) [1] and graphene microelectrode arrays (GMEAs) [2] are used for cellular interfacing. Combination of flexibility, transparency, biological stability and exceptional sensitivity of the graphene charge carriers to the adjacent environment makes the graphene-based devices perfect for interfacing them with neuronal cell cultures or brain tissue.
In vitro experiments have shown excellent recordings from HL-1 cells, embryonic heart tissue and cortical neurons [3]. While GMEAs are comparably easy in fabrication and usage, exhibit excellent signal-to-noise ratios (SNR) of the recordings (up to 50 for neuronal action potentials and over 100 for HL-1 action potentials). At the same time, GFETs are slightly noisier, but their performance is tunable, and therefore the usage can be more specific. The GFETs, fabricated on flexible polyimide-on-steel substrates exhibit extremely large transconductance values up to 11 mS/V [4]. Here the last development has to be done towards determining the device geometry (L/W, diameter) for the best signal-to-noise ratio.
Further, both GFETs and GMEAs are fabricated on a thin (10 μm) polyimide film for in vivo applications. The large scale fabrication technique [5] allows us to fabricate the devices on 4-inch wafers with high yield and minimal waste. Usage of a biodegradable materials will simplify the penetration of the probe in vivo.


[1] L. H. Hess, et al., Adv. Mater, vol. 23, no. 43, pp. 5045–9, 4968, 2011.
[2] D. Kuzum, et al., Nat. Commun., vol. 5, no. May, p. 5259, 2014.
[3] D. Kireev, et. al., “Graphene multi electrode arrays as a versatile tool for cellular measurements”, in preparation.
[4] D. Kireev, et. al., “Graphene field effect transistors for in vitro and ex vivo recordings”, submitted.
[5] D. Kireev, D. Sarik, T. Wu, X. Xie, B. Wolfrum, and A. Offenhäusser, Carbon, 2016, doi: 10.1016/j.carbon.2016.05.058

Stretchable electronics has received significant attention in recent years due to the prospects of new and exciting applications. Conformal, soft and stretchable electronic devices are especially attractive for medical applications where the matching of the mechanical properties of tissue is essential. To date a variety of applications have been developed, ranging from electronic skin, in vivo temperature sensors to multi electrode arrays (MEAs) for stimulation and recording. Although significant progress has been made in the development of soft and stretchable MEAs in recent years, there is still plenty of room for improvements. Specifically, there is a need for the development of inert and high performance stretchable conductors with long term stability. Further, these conductors should be patternable at high resolution to enable the fabrication of high density MEAs, which are essential in neural recording.
Here we address the above challenges by developing an inert high performance stretchable nanowire conductor. The composite shows excellent strain cycling stability as well as long term stability. Based on this novel composite, we develop a stretchable high density MEA with a conductor line width of 30 µm. The 50 µm large electrodes show excellent characteristics with an impedance of around 20 kΩ at 1 kHz.

In this talk, I will present the advantages and limitations of printed devices, and then discuss how to integrate the individual components together. There are two progressive printing approaches: simple systems (<100 transistors) are inkjet printed entirely from solution electronic inks, whereas more complex functions are met by printing interconnects between silicon ICs and printed passive components, to combine the advantages of flexible printed devices with the high performance of silicon chips. I will discuss the design rules we learned in the course of developing a fully printed sensor platform and the approaches to achieve designs that tolerate the variations in printed devices.
Specifically, sensors relying on direct-current (dc) amplitude modulated signals may suffer from drift and noise over long transmission distances across a large matrix. To overcome this limitation, we encoded dc stimuli into digital signals whose alternating current (ac) frequency varies with stimulation intensity. Printed organic ring oscillator circuits, consisting of odd numbers of repeating inverter stages based on complementary field effect transistors, were used to generate the ac modulation. These circuits were integrated in collaboration with the Zhenan Bao group at Stanford University into a power-efficient skin-inspired mechanoreceptor that transduces pressure into digital signals directly. As force is applied on the sensor, the output frequency ranges from between 0 – 130 Hz to mimic slow-adapting skin mechanoreceptors. This work has broad implications for designing integrated sensor feedback.

Stretchable thin-film transistors (TFTs) are the key components to realize stretchable electronic devices like displays and electronic skins. However, it has been a great challenge to fabricate intrinsically stretchable TFTs by low cost and scalable processes. Here, we report intrinsically stretchable TFTs and integrated logic gates, including inverter, NAND and NOR gates, fabricated through a mask-free, digital printing process. We have developed a high performance hybrid dielectric material that is both printable and highly stretchable. Semiconducting enriched carbon nanotubes and unsorted carbon nanotubes are used as stretchable channel material and stretchable electrodes, respectively. The TFTs and logic gates maintain excellent electrical performance while being stretched with strains higher than 60% for more than 1000 cycles. The success in fabricating fully printed all-carbon nanotube intrinsically stretchable TFTs and integrated logic gates represents a great advancement towards low cost and large area stretchable electronic systems.

Oppositely charged polyelectrolyte multilayers (PEMs) were built-up in a layer-by-layer assembly (LBL) on top of the active channel of an Organic Electrochemical Transistor (OECT) consisting of Poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS). The multilayered film serves herein as a model system to investigate the interaction of charged polymer species with PEDOT:PSS. The understanding of physical interactions and mechanism of charge transport modulation when sensing charged species upon direct contact with the transistor channel provides useful insights for novel biosensing applications such as polynucleotide sensing. As a proof of concept, viral RNA sensing is successfully demonstrated herein with the highly sensitive devices (down to 50 pg/ml). Moreover, LBL is demonstrated as a versatile electrode modification/coating tool to confer tailored surface features (i.e., film thickness, softness, surface charge) allowing thus for control over specific surface functionalities. Overall, LBL build-up on top of integrated electronic devices will open up new applications for coupling electronics with biology enabling thus novel multiplexed bioelectronic platforms toward drug-delivery, tissue engineering and medical diagnostics.

To improve the mechanical reliability of flexible electronics for ‘wearable’ applications in health and medical monitoring, new wearable electrical components must have soft curvilinear surfaces, stretchability and flexibility such that they can move with the body’s motion. It is critical to overcome rigid, brittle, and largely planar current electronics and sensors to develop more insightful investigations for human body monitoring. Therefore, stretchable, flexible electronics will fulfill the growing interest in long term wearable monitoring systems for personalized fitness, physical rehabilitation, entertainment/gaming/virtual reality devices, and continuous health monitoring for various parameters such as body movements, blood pressure, breathing and body temperature. Piezoresistive based sensors transduce the mechanical deformation to a resistance change upon induced stretching, bending, or pressing.
We demonstrate that mats of deposited CNTs on the SMP result in densified, self-similar nano to micro-scale featured wrinkles upon heat-induced shrinkage. These wrinkled CNT thin films can be transferred from the rigid SMP carrier film into soft materials similar to that of the human epidermis. Furthermore, these hierarchal self-similar wrinkled structures provide large amounts of strain relief during stretching. Wrinkled carbon nanotube-Ecoflex (wCE) strain sensors were able strain out to ~750% and remain conductive.
The strain-resistance responses showed two distinct regions: from 0-400% and 400-700% strain. In the first region from 0-400% strain, the gauge factor was 0.65 and the second region from strains 400%~700%, had a gauge factor of 48.The wCE sensor was attached on the respective joints for the elbow, knee, and finger. During joint bending, the wCE sensor stretched and flexed with the joint inducing an electromechanical response. The experiments highlight the potential use of wCE sensors as wearable devices for human motion detection.
In addition the pressure sensors could also be utilized for human physiological signal detection. We fabricate two layers of biaxially shrunk wrinkled CNT thin films and uniaxially shrunk wrinkled CNT thin films. Placing the uniaxially and biaxially aligned wrinkles face-to- face improves sensitivity by increasing contact surface area with pressure. Due to the increasing contact surface area, the resistance of the device is reduced showing a response to pressure. The sensitivity was calculated to be 22 kPa -1 , high enough to detect pulsatile blood flow on the wrist for health monitoring.
In conclusion, this is the first demonstration of fabricating stretchable strain and pressure sensors for wearable health monitoring applications using a shrinking fabrication platform. By using this platform, we were able to achieve wrinkled micro/nanostructures that provide strain relief for wearable applications. We have demonstrated that the devices can be used for human motion and human physiological sign detection.

Organic electrochemical transistor (OECT) is a novel type of sensing device for monitoring the extracellular signals of excitable cells. Our group has reported the use of OECT to study the electrophysiological activities of transepithelial cell line Calu-3 and cardiac cell line HL-1 [1, 2]. However those studies showed electrophysiological recording at the single channel, limiting the use of OECTs for cardiac pharmacological investigation. We previously reported the first study on a two-dimensional OECT array to map the cardiac action potential propagation in vitro in 2015 spring MRS meeting. In this present study, we have expanded our investigation to perform detailed characterizations of the OECT array and use the platform to study the pharmacological effects of several reagents on cardiac conduction properties.
The as-fabricated OECTs showed a response time of around 100 µs, which is fast enough for recording the electrophysiological signals of cardiac cells. The action potential propagation direction and velocity calculated from 16-channel OECT recording were consistent with the results from Fluo-4 AM calcium imaging analysis, further confirming the accuracy of OECT mapping. Long-term monitoring up to 42 days were conducted to show the biocompatibility of OECT platform. We then prepared primary rat cardiomyocytes as well as stem cell derived cardiomyocytes in the form of 2D cell monolayer and 3D microtissues for OECT recording. The microtissues, which have tissue-like structures that are more suitable for drug testing, were assembled by hanging-drop method and cultured on OECT, facilitated by a microfabricated PDMS stencil. For the first time, the real-time mapping of action potential conduction of 2D and 3D cardiac cells at normal state and drug treatment environment were studied in details by OECT platform. A representative result was that the application of chronotropic agent isoproterenol caused the change of propagation direction and the increase of velocity of 2D cultured cardiomyocyte, which is consistent with journal reviews [3, 4]. A combination of patch clamp stimulation with OECT recording was also demonstrated for quantitative analysis of conduction behavior. Our study verifies that OECT serves as a promising platform for in vitro drug testing and electrophysiological researches.

Acknowledgement: The authors thank the financial support from the Theme-based Research Scheme of Research Grants Council of Hong Kong SAR Government (Project Number: T13-706/11-2).
References
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Interfacing soft and hard electronics is a key challenge for flexible hybrid electronics. Bioelectronic interfaces require electrodes that are mechanically flexible and chemically inert as the conformal form factor allows pristine electrode contact to skin and tissue. The chemical properties and inertness prevents electrodes from reacting with biological fluids and living tissues. Typically a multi-substrate approach is employed, where soft and hard devices are fabricated or assembled on separate substrates, and bonded or interfaced using rigid connectors - this hinders the overall flexibility of the device, and is prone to interconnect issues. We have designed a system that uses a single substrate interfacing approach, where flexible sensors are directly printed on Kapton® polyimide substrates. Developing a process flow compatible with Flexible Printed Circuit Board assembly process, we demonstrated a wearable sensor patch composed of inkjet-printed gold electrocardiography (ECG) electrodes and a stencil-printed nickel oxide thermistor. The ECG electrodes provide 1mV_p-p ECG signal at 4.7 cm electrode spacing and the thermistor is highly sensitive at normal body temperatures with α values of approximately 5.84 % K^-1 and β values of 4400 K.

We will be presenting an ultra-thin electronic decal that can simultaneously collect, transmit and interrogate a bio-fluid. Our technology effectively integrated a thin-film organic electrochemical transistor (sensing component) with an ultrathin microbial nanocellulose wicking membrane (sample handling component). As far as we are aware, OECTs have not been integrated in thin, permeable membrane substrates for epidermal electronics. The design of the biocompatible decal allows for the physical isolation of the electronics from the human body while providing efficient bio-fluid delivery to the transistor via vertical wicking. High currents and ON-OFF ratios were achieved, with mg-L^-1 sensitivity.

Stretchable electronic devices,¹ are able to interface with irregular, soft or moving objects so that they can be plastered on human body to monitor muscle movement, temperature, or even pulses. They can also be used for brain activity monitoring which enables us to gain a better understanding of diseases. As a result, stretchable electronic has attracted considerable attention in both academia and industry due to its great commercial prospects and society’s benefit.

In recent years, we have seen the rise of research on organic bioelectronics devices based on the conducting polymer PEDOT:PSS,^{2, 3} where cells and tissues are demonstrated to directly interface with electronic devices via ionic signal communication. This technology has already been successfully used to in vivo recording the brain activities and monitoring the electrocardiographic signals. A stretchable organic bioelectronics devices could lead to a mechanical compliance device which will be a promising candidate for implantable electrodes towards future e-skin or e-health applications. In addition, to promote these devices towards real application, understanding their self-healing capability is another interest topic, since stretchable devices with self-healing repeatably can be of use in emerging fields such as soft robotics and biomimetic prostheses.

In this work, we realized stretchable organic electrochemical transistors based on the conducting polymer PEDOT:PSS. A transparent hydrogel was synthesized and used as the stretchable electrolyte. The highly stretchable hydrogel conforms to the deformation of the substrates while under strain. Our devices operate at low voltages and remain stable as well as the same performance under stretching. Moreover, the self-healing property of the PEDOT:PSS is investigated. Significantly, we observed water induced self-healing behavior of the PEDOT:PSS films on PDMS. Further studies show that rapid, stable, self-healing of highly conductive PEDOT:PSS films can be realized, without the requirement of any plasticizers.

References:
1. J. A. Rogers, T. Someya, Y. Huang, Science 2010, 327, 1603.
2. S. Zhang, P. Kumar, A. S. Nouas, L. Fontaine, H. Tang, F. Cicoira, APL Mater. 2015, 3, 014911.
3. S. Zhang, E. Hubis, C. Girard, P. Kumar, J. DeFranco, F. Cicoira, Journal of Materials Chemistry C 2016, 4, 1382-1385

Soft electronic devices that can be worn on or implanted into the body, such as sensors and displays, create new opportunities and uses for electronics that will fundamentally change the computer-human interaction. The development of stretchable electronic devices that are soft and conformable, however, has relied heavily on a single material – polydimethylsiloxane – as the elastomeric substrate. Although polydimethylsiloxane has a number of advantageous characteristics, its high gas permeability is detrimental to stretchable devices that use materials sensitive to oxygen and water vapor, such as organic semiconductors and oxidizable metals. Failing to protect these materials from atmosphere-induced decomposition leads to premature device failure; therefore, it is imperative to develop elastomers with gas barrier properties that enable stretchable electronics with practical lifetimes. In this presentation, we describe the reinvention of butyl rubber – a material with an intrinsically low gas permeability traditionally used in the innerliners of tires to maintain air pressure – for stretchable electronics. We present a new butyl rubber material that is smooth and optically transparent yet possesses the low gas permeability typical of butyl rubber. We discuss the advantages of using transparent butyl rubber as an encapsulating material for sensitive electronic materials and devices, as well as methods to modify the surface chemistry of transparent butyl rubber to enable its use in stretchable electronics. The merits of transparent butyl rubber presented here position this material as an important counterpart to polydimethylsiloxane that will enable future generation stretchable electronics.

In this talk, I will discuss our recent progress in stretchable material and device development. Specifically, I will discuss several material design rules for enable strechability in electronic materials and the fabrication of related devices.

Stretchable semiconductor has become a core element for next generation of wearable electronics and conferring intrinsic stretchability on electronic materials has been regarded as an ultimate strategy for ideal stretchable electronic materials and devices. Here, we present a new concept of molecular design to provide intrinsic stretchability to semiconducting polymer with maintaining excellent electrical property. The concept involves incorporating chemical moieties into backbone chains to promote dynamic non-covalent crosslinking of the conjugated polymers. Moreover, the non-covalent crosslinking moieties allow mechanically damaged polymer to repair/heal via a simple treatment. The stretchable and healable semiconducting polymer enabled us to fabricate highly stretchable and high performance organic transistors. This material design concept should open the way to future development of skin-inspired wearable electronics.

Touch sensing is a field that is rapidly advancing as driven by vast applications including human-machine interfacing, skin-like electronics, industrial automation, medical procedures, and security systems. Touch sensors, according to transducing mechanism, can be divided into the following major categories: capacitive, piezoelectric, resistive, and optical. All of these mechanisms rely on deformation of the sensing unit in response to interaction with an object. Such a deformation-dependence poses a challenge in touch detection when very weak interaction is involved. Another major limitation of aforementioned sensors is that they all require an external power supply to generate an electrical parameter for characterizing the output of the sensor; otherwise none of them can normally operate. This causes problems such as power consumption and structural complexity. Besides, fragility, stiffness, and high cost are also common concerns that impair widespread adoption of touch sensors in a large area.

Herein, we report a type of self-powered triboelectric sensor (TES). The polymer-based TES utilizes interface triboelectrification to generate a voltage signal in response to a physical contact without the reliance on an external power supply, completely resolving the issue of power consumption for a sensing unit. The TES shows an excellent pressure sensitivity of 44 mV/Pa (0.009% Pa-1) in low-pressure region. By integrating an array of sensor units together (16*16), the TES array can not only identify the occurrence of a touch but also distinguish the position, the trajectory, and the profile of the touching object. As the result of our shielding design, the cross-talk between adjacent units is greatly suppressed, as indicated by the obtained signal ratio of over 100. The polymer-based structure enables the TES to be area-scalable, rollable, transparent, and cost-effective. Upon integration of the sensing array with a signal-processing circuit and a software interface, a complete prototype system for real-time touch sensing is established. The system possesses widespread immediate applications, including human-electronics interface, automatic control, health care surveillance, remote operation, and security.

Soft materials including elastomers and hydrogels have enabled diverse modern technologies including tissue engineering, drug delivery, biomedical devices, microfluidics, optics, stretchable and bio-integrated electronics, and soft robotics. Whereas elastomers have unique characters such as stable in various environments, mechanically robust, and easy for micro-/nano-scale fabrications (e.g., soft lithography); hydrogels’ distinctive attributes include high water contents, permeable to various chemical and biological molecules, biocompatible and/or biodegradable. Since the merits of elastomers and hydrogels are complementary to each other, it is naturally desirable to integrate them into hybrid structures that can potentially transform their existing applications and enable new functions. In nature, mammalian skins laminate elastomer-like epidermis and hydrogel-like dermis into hybrids with robust interfaces (e.g., interfacial toughness over 100 Jm^-2) and functional microstructures (e.g., blood and lymphatic vessels et al). However, elastomers and hydrogels in most technological applications are used separately, and few existing hydrogel-elastomer hybrids suffer from limitations such as weak interfacial bonding, low robustness and difficulties in patterning microstructures.
Tough bonding of hydrogels to rigid solids (e.g., glass, ceramics and metals) have been recently achieved by covalently crosslinking the stretchy polymer networks of tough hydrogels on surfaces of the solids. However, this method is generally inapplicable in forming hydrogel-elastomer hybrids with robust interfaces and functional microstructures due to several challenges including weak and unreliable adhesion between elastomers and hydrogels and difficulties of introducing functional microstructures at the interfaces. Hence, a general method capable of fabricating hydrogel-elastomer hybrids with robust interfaces and functional microstructures is still a critical demand and central challenge in the field.
Inspired by the structures and functions of mammalian skins, we report a simple yet general method capable of assembling pre-shaped elastomers and hydrogels into hybrid structures with extremely robust interfaces (e.g., interfacial toughness over 1000 Jm^-2) and functional microstructures (e.g., micro-channels and circuit patterns). The method is generally applicable to various types of commonly-used elastomers and diverse tough hydrogels. We further explore a number of novel applications taking advantage of the robust and microstructured hydrogel-elastomer hybrids including anti-dehydration tough hydrogel with elastomeric coating, stretchable diffusive and reactive hydrogel-elastomer microfluidics, and stretchable hydrogel circuit board patterned on elastomer.

Paper-based skin-like devices are emerging as attractive light-weight, recyclable, and flexible sensors with simple fabrication. Paper-based skins are potentially capable of sensing touch, temperature, pressure and humidity, which broadens their application as human or humanoid interfaces. The fabrication processes generally include printing, deposition, or coating to create electrically conductive regions on the paper. In contrast, this work describes a fabrication process that embeds the conductive material within the paper to create piezoresistive composites for skin-like sensing. Further tuning of these substrates is possible with embossing, and the property of primary focus at this point is electrical conductivity.
The substrates consist of cellulose fibers with embedded nanoparticles of carbon black. This basic system permits the study of the effects of embossing on tuning the porosity and percolation threshold. Without embossing, fluffy paper has a high porosity of 90%. Embossing then permits reductions in porosity with significant increases in conductivity. To characterize conductivity over frequencies ranging from 10 Hz to 10 MHz, this project employs impedance spectroscopy. At low volume fractions of carbon black and high porosities, the composite paper behaves as an insulator. With embossing, the porosity decreased by a factor of three and increased the conductivity by a factor of 100.
Embossing permits tuning the bulk properties of a substrate, along with spatial patterning along the material. Interdigitated electrodes consist of patterned regions of high conductivity interspersed with un-embossed regions of high resistivity. These interdigitated electrodes serve as capacitive buttons. When a finger touches a button, it bridges the interdigitated electrodes to cause a measurable change in impedance. By monitoring the changes in impedance, a microcontroller-based system provides sensory feedback.
In addition to creating conductive traces, the material itself is piezoresistive. When the piezoresistive sheets filled with embedded conductive nano fillers are compressed elastically during use as sensors, there are measurable changes in resistivity. By compressing 5% piezoresistive sheets starting with force from 0N to 40N, the resistivity decreased from 40 m to 18 m. Repeated experiments show a small degree of hysteresis.
Overall, tuning the conductivity of paper-based substrates provides a method of creating paper for tactile sensors. These features have the potential to open opportunities for prosthetics and robotics, haptic feedback, and structural health monitoring on expansive surfaces of buildings and vehicles.

Cellular components in tissue engineering have been shown to improve integration of devices with the body. The encapsulation of neurons at the interface of bionic devices aims to improve contact between electrodes and the tissue being recorded or stimulated. Key considerations that effect the success of such an approach include the cell source, the capacity for growth and differentiation cues and the materials used for both the electrode coating and cell scaffold. These issues are discussed and multiple approaches presented using a layered approach of conductive polymers and hydrogels.

In recent years the organic bioelectronics community has dedicated increasing effort in developing electronic devices that can operate non-invasively in contact with and from within the human body. In this context, a few interesting examples of devices fabricated with edible materials have been proposed, such as edible power sources based on melanin, and organic thin film transistors obtained by vapour-phase deposition of semiconducting pigments. The target applications of this apparently exotic technology range from the pharmaceutical industry, e.g. gastrointestinal tissue stimulation, monitoring of patients adherence to medications and controlled drug delivery, to the food and beverage sector in which they would be conducive in ensuring quality monitoring and goods tracking. Because of the potential scale such applications, cost-effective and up-scalable fabrication techniques are of preference, along with the choice of the appropriate biocompatible materials.

The present work aims at demonstrating edible active electronic components. Specifically, it shows the realization of p-type and n-type organic thin film transistors through direct ink-jet printing of materials that are either biocompatible, nature derived or commonly used in the food industry. The transistor bottom-contacts and top-gate electrode consist of PEDOT:PSS, a very well known conducting polymer, also widely employed as a highly conformable neural electrode. Alternative conductive materials can be adopted, e.g. edible gold used for food decoration. Shellac, a biodegradable bug secreted resin, acts both as smoothing layer and dielectric. Among organic semiconductors, biocompatible or commercially available polymer semiconductors can be easily ink-jet printed on edible and transferrable substrates with performances compatible with the state-of-the-art. Preliminary evidence of biocompatibility is also provided for commercially available polymers, and the devices operation after transfer on pharmaceutical capsules and food specimens is reported.

The present work thus shows the all-printed realization of biocompatible p-type and n-type transistors on a transferrable and ingestible substrate. These devices are fabricated with an up-scalable and cost-effective technique, and they can be easily integrated on ingestible supports. For these reasons, this approach constitutes a further step towards the realization of a multifunctional platform for biosensors and bioactuators meant to operate within the gastrointestinal tract and on food.

Kim, Y. J., et al. (2013). Journal of Materials Chemistry B, 1(31), 3781-3788.
Fattahi, P., et al. (2014). Advanced Materials, 26(12), 1846-1885.
Irimia-Vladu, M., et al. (2013). Green Chemistry, 15(6), 1473-1476.
Bettinger, Christopher J. Trends in Biotechnology 33.10 (2015): 575-585.

Organic bioelectronics have been mainly oriented towards biomedical applications for controlling physiology, therapy, neural prosthetics and in vitro diagnostics. However the biological world extends beyond the animal kingdom. Plants are an essential part of our ecosystem and are vital to our survival. They are our primary source of food and oxygen and they play a very important role in the regulation of the climate and water. Recently we have demonstrated the first example of interface between organic bioelectronics and plants with the concept of Electronic Plants. Using the vascular system and organs of a plant we manufactured organic electronic devices and circuits in vivo, having the internal structure of the plant as integral part of the device. Here we present a new conjugated oligomer that can be delivered in the vascular tissue xylem of the plant and polymerize in vivo from stem to flower without application of external stimuli. The conducting wires exhibit long-range high conductivity and specific capacitance. In addition the oligomer can be delivered in the apoplast of the leaves through the veins opening pathways for new device concepts. Our findings pave the way for new technologies and tools based on the amalgamation of organic electronics and plants for regulation of plant physiology, energy harvesting from photosynthesis, and alternatives to genetic modification for plant optimization.

I will present the recent progresses and future prospects of ultra-soft, conductive gel electrodes and sheet-type flexible electronic sensor systems for bio-medical applications. Ultrasoft gel electrodes consist of highly-conductive nano-conductive materials including Ag-based nanowires and flakes, carbon nanowires and nanocomposites, and bio-compatible gels. The conductive gel composite shows conductivity greater than 10,000 S/cm, and can be stretched more than 100% without any damages in electrical and mechanical performances, so that it can spread over arbitrary curved surfaces even on the ultrasoft brain surface. With integrating the ultrafsoft gel electrodes, ultraflexible amplifier, Si-LSI platform consisting of wireless data-transmission module and analog-to-digital converter, Li-ion-based thin-film battery, and information engineering, here I would like to demonstrate the applications of wearable and implantable wireless sensors including 64-channel sheet-type electric potential monitoring systems. This wireless system with soft gel electrodes can measure biological signals less than 1 microvolt. Taking full advantages of this system, electrocorticogram (ECoG), signals from cerebral cortex have been wirelessly measured from rat’s brain for more than two months. Furthermore, electroencephalogram (EEG: Brain wave), signals from a forehead have successfully measured.

The concept of smart-textiles is witnessing a rapid development with recent advances in nanotechnology and materials engineering. Bearing in mind that the concept of textiles is much wider than clothes and garments, the potential is immense. While most current commercial applications rely on conventional hardware simply mounted onto fibres or fabrics, a new approach to e-textiles consisting in using functionalised textiles for several technologic applications has the potential to change the paradigm of wearable electronics completely.

Conducting fibres are an important component of any e-textile, nor only because they can be used as wiring for simple textile-based electronic component, but also because they can be used to build electronic devices directly on textile fibres. We have reported a new method to coat insulating textile fibres with monolayer graphene to make them conductive while preserving their appearance.[1] There are a number of factors that can greatly influence the sheet resistance achieved by graphene-coated textile fibres. In order to understand the influence of the topography of the fibres on the effectiveness of the graphene coating, an extensive study encompassing microscopy techniques like Atomic Force Microscopy and Scanning Thermal Microscopy, as well as Raman spectroscopy was performed.[2]

This method has proven to be a versatile tool to achieve flexible, transparent and conducting fibres of different materials, sizes and shapes. The first applications of electronic devices built on such fibres are demonstrated, opening up the way for the realisation of wearable devices on textiles.

[1] AIS Neves et al., Sci. Rep. 2015, 5, 09866
[2] AIS Neves et al. 2016 (in preparation)

Organic and polymeric based resistive devices [1] are receiving an increasing interest on one hand because they are in principle closer to the natural synaptic behavior of biological systems but also because of their biocompatibility, giving raise to potential bioelectronics applications. The present contribution is based on the original work carried out on polymeric memristor developing their interfacing with living biological systems [2].
In the present work, part of two multidisciplinary projects named Phychip and MaDEleNA, we report and discuss the growth of living beings (the slime mold “physarus Polycepharum ” and human immortalized HEK293T, tumor cells HeLa, and neuroblastoma cell line,SH-SY5Y) on memristive substrates (covered with PANI). In the case of Physarum to prove the biocompatibility of the polymer is sufficient to observe the networks created by the mold over the substrate. In unfavorable condition for its survival, the Physarum enters in the Sclerotic phase, a sleeping stage in which a strong brownish membrane enwrapped the living being protecting it from the outside.
The growth of Physarum polycephalum on PANI was characterized by the creation of networks with branches trying to reach the food sources, demonstrating a good biocompatibility. Moreover its growth results in the patterning of the polymer substrate, since once in contact with the non-conductive form of the polymer (blue form), it creates a doping effect, that result in a conductivity increment of the areas underneath the organism.
In this scenario, we provided new evidences in favor of PANI biocompatibility to several, not tested before, neuronal-like cell types [3].The cell line SH-SY5Y was selected as these cells can differentiate towards a neuron-like phenotype after treatment with retinoic acid (RA) and brain derived neurotrophic factor (BDNF), producing neurites and forming small complex networks. After 24 and 48 h from cell seeding, the growth of all cell lines was comparable with uncoated microscope glass slides used as controls. During the differentiation of SH-SY5Y cells, morphological changes occurred both in cells grown on PANI and controls: cells developed neurites that were physically attached to the surfaces, whose structure was assessed by immunofluorescence using an anti-beta tubulin antibody. The appearance of these protrusions suggests that PANI is compatible with neuronal growth and development.
In addition, patch-clamp recordings of the cells' bioelectrical activity confirmed the viability data obtained by the morpho-functional analysis reported above.

[1] Erokhin,V. Journal of applied physics 97.6 (2005): 064501.
[2] Tarabella, G. et al. Chemical Science 6.5 (2015): 2859-2868.
[3] Juarez-Hernandez L., at al Biophysical Chemistry 208, 2016 40-47

Wearable electronics for tomorrow will be soft and form a seamless connection between network connectivity, data visualization and human body. Printed devices, such as printed antenna and transmission line are accounted for the majority of the entire wireless printed electronics market. Since more and more successful realization of the stretchable conductor, an electromagnetic consideration of conductive elastomer and understanding the mechanism for the variation of transmission and radiation properties is important. These soft electromagnetic - sensitive devices can be easily mounted on clothing or directly attached onto skin, resulting in far more different to steady-state evaluation. In this work, we report biocompatible, highly conductive, highly stretchable and low cost printed silver- polydimethylsiloxane (Ag-PDMS) composite elastomer for wireless wearable communication applications. To investigate its potentials in wearable wireless communication applications, soft dipole antennas and transmission lines under various tensile and bended test were experimentally studied under RFID (860-960MHz) and Bluetooth (2.4GHz) ISM band. The result of experiments demonstrate that the printed Ag-PDMS conductive elastomer can be used for RF signal radiating, scattering and receiving, which represents some of the essential functionalities of RF signal processing in wearable wireless communication systems. Moreover, the reduction of attenuation is extremely sensitive to the skin depth, leading to the possibility of controlling the thickness by tuning the printing process. This work demonstrates a scalable approach to stretchable RF materials enabled low cost and biocompatible wearable wireless systems.

Ultra-flexible yet robust characteristic of materials has been desired in emerging soft systems such as electronic skins, clinical patches and actuators in soft robots. The flexibility is essential to minimize the gap, a major obstacle to collect signals or transfer matters in between the device and the biosurface. It can be easily achieved by reducing the flexural rigidity (D ~ Et³, where E is the elastic modulus and t is the thickness). However, because the flexibility and the robustness are mutually exclusive, a solid becomes drastically weakened as the flexural rigidity decreases. Therefore, the flexural rigidity is limited to such level that the soft systems can be physically manipulated, resulting in a nano-sized gap at the boundary. To overcome the constraints that occurred in linear systems, here we introduce new nonlinear framework that has both flexibility and robustness via multiplex lithography and dewetting-based molding process which enabled the fabrication of sophisticated and heterogeneous multiscale structures in minutes. The flexibility and the robustness of the proposed framework lie in nonlinear correlation by means of the hierarchical design covering from macroscale to nanoscale. Consequently, it reversibly adheres along the arbitrary curvature by deforming their shape simultaneously without any cracks or tear-offs. The optimized framework allows the structure to fit on the natural surfaces with assorted roughness (i.e. a human skin, a hair and a leaf), potentially providing a versatile strategy for zero-gap boundaries on complex biointerface. Furthermore, we used different materials at each layer, thereby combining various functions hierarchically. In this study, the layers made of the thermo-responsive hydrogel (PNIPAm) and the polyurethane acrylate were integrated in tandem to mimic perspiration systems by controlling the area fraction of pores. Although the PNIPAm features temperature-dependent volume transition (T_c ~ 32°C), the simple structure that are monolithically patterned with holes or lines does not show an automatic and spontaneous valve-like behavior because the volume change is symmetric, leading to no variation of pore fraction. Therefore, we patterned the PNIPAm hydrogel and suspended it onto the mechanically fixed supporting layer to achieve a nonlinear deformation of the hydrogel. Since the pattern size was designed as small (~50 μm), the structure showed fast response (< 1 s) in contrast to the slow response (> 1 min) of the bulk. This system is devised to reserve the sweat when the environment is cool and to evaporate more under opposite state, that is similar to the ways of homoeothermic animals. We expect the system can be applied not only to control the skin temperature, but also can enhance and regulate the thermoelectric generator which converts the body heat to electricity, by controlling the amount of latent heat of sweat extracting additional heat from the body.

Sputtered iridium oxide films (SIROF) are used mainly for neural stimulation electrodes when high charge injection capacities are desired. In contrast to activated iridium oxide films (AIROF) activation in vivo is not neaded as the iridium oxide is generated during the fabrication process. Though, SIROF electrodes have to be hydrated in vitro via cyclic voltammetry (CV) (with high scan rates and a high number of cycles) to clean the surface and increase the cathodical charge storage capacity (CSC_c). We already showed that hot steam sterilization at 134°C reduces the impedance and the CSC_c of the hydrated SIROF. It was also proved that pressure has almost no influence on the electrochemical performance.
Now we investigated the temperature dependency of hydrated SIROF subject to its electrochemical performance. Consequent we can determine which temperature we should use for sterilizing with hot steam in an autoclave.

Thin film electrodes based on Polyimide (PI) as substrate material were fabricated in a class 100 cleanroom using standard lithographic processes. The conduction pathways were made of platinum and the contact sites of SIROF. The openings for the contact sites were realized with reactive ion etching (RIE). The electrodes contained six contact sites with 80 µm in diameter and four with 100 µm respectively. To contact the electrodes electrically a zero insertion force layout and connector was used. We performed measurements on six devices with six contact sites of 80 µm diameter, i.e. 36 contact sites in total.
An electrochemical setup with a potentiostat, a Ag/AgCl-reference and a platinum counter electrode was used to perform electrochemical impedance spectroscopy (EIS) and CV of the above described working electrode. First the initial state of the electrodes was acquired and afterwards the electrodes were hydrated. Subsequently the hydrated state was recorded with EIS and CV. Next step was to temper the electrodes at 50°C, 70°C, 90°C, 105°C, 121°C and 134°C for 20 minutes and characterizing the tempered state, again with EIS and CV. Each electrode therefore underwent solely one temperature treatment.

The initial resistance of all electrodes was 5.8 kΩ at 1 kHz. After hydration the resistance at 1 kHz dropped to 4.7 kΩ. The tempering at 50°C further decreased the resistance to 4.4 kΩ. The other higher temperatures all led to an increase of the resistance up to 8 kΩ.

The tempering of the electrodes at 50°C might release some byproducts from the hydration causing a slight resistance drop. However, the impedances measured via EIS are increasing with increasing temperature. Hence, it is preferable to use lower temperature sterilization processes to achieve good performance of the electrodes, e.g. ethylene oxide (ETO).

The development of stretchable organic light-emitting devices (OLEDs) has been attracting increasing interest in recent years. Compared with conventional OLEDs based on rigid or nonelastic substrates, stretchable OLEDs are flexible and deformable and could be conformable to complex surface topology, which makes them play an important role in some emerging applications such as deformable displays and electronic skin. Although highly stretchable OLEDs have been demonstrated, their luminous efficiency and mechanical stability remain impractical for the purposes of real-life applications. This is due to significant challenges arising from the high strain-induced limitations on the structure design of the OLED, the materials used and the difficulty of controlling the stretch-release process. Here, we have developed stretchable OLEDs by a laser-programmable buckling process to overcome these obstacles. We used thermal evaporation to fabricate highly efficient and flexible OLEDs on thin polymer substrates and achieved stretchable OLEDs with controllable and periodic buckles by transferring the flexible OLEDs onto laser-patterned elastomeric substrates. The resulted highly stretchable OLEDs exhibited unprecedented efficiency and mechanical robustness. The strained OLED luminous efficiency - 70 cd A^-1 under 70% strain - is the largest to date and the OLED can accommodate 100% strain while exhibiting only small fluctuations in performance over 15,000 stretch-release cycles. This work paves the way towards fully stretchable OLEDs that can be used in wearable electronic devices.

Rapid prototyping, as well as actual manufacturing by 3D printing, is limited to certain material types. One key class of materials that has not been successfully 3D printed is those used for actuators especially in the area of microfluidics. Materials used for microfluidic actuators must have sufficient rigidity to hold the printed shape while having flexibility to allow for actuation to open and close valves for channel flow.
Triblock copolymers of the A-B-A type have recently been discovered by Lincoln Laboratory to be a new class of 3D printable materials. The triblock copolymers have an A block that is composed of polystyrene and a B block that can contain one of several vinyl-based polymers that include polybutadiene, hydrogenated polybutadiene, or isoprene. These A-B-A triblock copolymer combinations are all commercially available. We will also describe a new class of A-B-A triblock copolymers with improved microfluidic performance. We have demonstrated 3D printing of these triblock copolymers to 8 micrometer resolution and have printed a number of test structures in which the material remains flexible and clear, two properties that are critical to acting as microfluidic actuators.
A key application for actuators is a microfluidic device that allows for the manipulation of fluids within 5-10 mm channels and contains active components like pumps and valves. We have used these A-B-A triblock polymers to 3D print flexible actuators, initially using vinyl containing triblock polymers and eventually transitioning to the other triblock copolymers. We will present the polymer printing ink rheology and resulting actuation characteristics of the flexible actuators for the polymers investigated.

Two dimensional nanomaterials, including graphene, boron nitride and transition metal dichalcogenide monolayers, have been extensively used to fabricate electronic devices. However, the vast majority of previous work utilizes these 2D layered materials in their flat and planar geometry, which can limit their applications in wearable and foldable electronics, or interfacing with soft or biological materials. In this work, we use origami based approaches to self-fold graphene into 3D micro- and nanostructures. Briefly, the surface of graphene is selectively modified with responsive polymers and nanoparticles in order to introduce structural and chemical heterogeneity. The surface modified graphene is patterned into arrays with predefined shape, using photolithography or nanoimprint lithography. Once released from the substrate, the patterned graphene can form 3D structures via self-folding or by applying an external trigger. By programming the original graphene building blocks with different size and shapes, the resulting folded graphene can have various geometry including ellipsoid, box and gripper. We also explore the potential of using the folded graphene 3D structure as an atomically thin shell to encapsulate and communicate with cells, as well as fabrication of flexible electronic devices which can fold and unfold at the cellular level. We anticipate that these novel structures and devices could provide new capabilities in bioelectronics, bio-sensing and drug delivery.

In the upcoming internet of things (IoT) era, flexible and stretchable pressure sensors have recently attracted increasing interests in the electronic skin, display and human machine interaction. Especially, flexible and stretchable pressure sensors are essential in health care fields such as heartbeat, arterial waveform and pulse wave velocity because these signs show significant information about cardiovascular diseases. Many researchers have developed various flexible pressure sensor based on piezo-resistive, capacitive and optical types. However, these types of pressure sensors have drawback about operating power consumption. It is avoidable for these sensors to apply voltage during the operation, which will cause power consumption problems and increase the cost and weight of devices.
Herein, we demonstrate a self-powered, PZT based flexible and stretchable pressure sensor on ultra-thin polyethylene terephthalate (PET, 4.8um) substrate via inorganic laser lift off (ILLO) and thermal release tape transfer. After PZT thin film transferred to PET substrate, Au top electrode is deposited by RF sputtering. Because reducing the substrate thickness can decrease bending rigidity, we have used ultra-thin PET substrate that improving conformal contact of flexible sensor to arbitrary curved surface. Piezoelectric based flexible pressure sensors that convert mechanical deformation into electrical energy are not needed external power source, so these sensors can simplify the device packaging by removing heavy battery components.
The fabricated piezoelectric pressure sensor shows a sensitivity of ~0.38kPa^-1 in the below 0.7kPa range and a fast response time of 70ms .By attaching our pressure sensor on wrist, we detect a real-time radial artery pulse wave. Also, the pulse wave signal is transmitted to smart phone by microcontroller and wireless Bluetooth module. From the results, we demonstrate the self-powered pressure sensors have a great potential in fields from smart electronics to real-time health monitoring.

Conventional methods of fabricating electronics and bioelectronics require much energy and time, as high temperatures and high vacuum conditions are needed. For wearable and flexible applications, low-temperature procedures are crucial as flexible substrates usually experience rupture at temperatures of 200°C or higher. All solution-processed electronic devices using colloidal nanocrystals may offer a practical and cost-effective route for bioelectronic applications. Hereby we report all-nanocrystal and all-solution based techniques to realize wearable human body temperature sensors. The chemical, optical, and electrical properties of Ag nanocrystal thin films treated by various ligands were investigated. For temperature sensors, we investigate the fundamental charge transport of Ag nanocrystal thin films treated with various ligands by conducting temperature variable electrical measurements. Metallic and insulating transport behavior were observed for different ligand treatments, as a result of different interparticle distances from different ligand exchange materials. Nanocrystal thin films treated with Br- showed rapid sintering at room temperature and a very low resistivity of 7.016x10^-5 ohm.cm, comparable to the record one derived from nanocrystals. The low resistivity was attributed to the formation of nanowires from Br- ligand exchange. Br- treated nanocrystal thin films showed a positive tendency, having a thermal temperature coefficient of 1.772x10^-3/K, indicating metallic transport. On the contrary, nanocrystal thin films treated with organic ligands exhibited a negative temperature coefficient of -5.118x10^-3/K. By utilizing different properties originating from one material, and by an all-solution process, we realize nanocrystal based, wearable thin temperature sensors with an oxidation prevention layer. The temperature sensors worked on human skin with high precision, having an error of merely 0.04%. Environmental effects such as mechanical strain were successfully decoupled by integrating two temperature sensors treated by different ligand exchange materials. We emphasize that our strategy through an all-solution based low temperature ligand exchange process has the potential to achieve low-cost, highly functioning, biointerface devices and bioelectronics.

S-layer proteins of various lattice-forming types are the most abundant protein by mass on earth. They form the outermost cell crystalline component in a broad range of bacteria and archaea in nature. They are porous monomolecular layer with crystalline unit cell size in tens of nanometers. These monomer proteins are capable of forming self-assembled mono- or double layers. After isolate them from the cell surface or through recombinant protein production, they are able to form very ordered 2D crystal lattice on a variety of non-cellular surfaces, including hydrophobic, hydrophilic, non-conducting, semi-conducting and conducting surfaces. We studies S-layer SbpA protein, found in mesophilic organism Lysinibacillus sphaericus, which completely cover the cell surface with square lattice crystallinity. Wild type SbpA (wtSbpA) proteins have been studied extensively. The recombinant SbpA (rSbpA) can be genetically modified and expressed in E.coli in different truncated forms. Previous studies showed that rSbpA is capable of forming the ordered lattice structure on some surfaces. Using both the purified wt-SpbA and truncated rSbpA proteins, we reproduced the unique two-dimensional self-assembly pattern on silicon wafer and other solid surfaces of electronic devices interests. By surface modification and changing recrystallization buffer environment, we can promote or regulate the self-assembly of SbpA on substrates. This enables a potential means of creating complex functional nanostructure. Delicate control of the self-assembly processes of S-layer on surfaces also serves the prerequisite of building the supramolecular structure as bio-electronic platform through protein fusing and anchoring on surface. Scale-up production and understanding the detailed interaction of the S-layer interface will likely be useful for nanobiotechnology and synthetic biology.
* This presentation will also cover the recent discoveries in following papers:
[1] Pum et al. Nanotechnology 25 (2014) 312001
[2] Rothbauer et al. ACS Nano, 2013, 7 (9), pp 8020–8030

To enable electronics intimately wearable on curvilinear human bodies with various gesture and motion, it requires electronic devices to be breathable, foldable and elastic, as well as reliable and durable. To date, technologies based on in-plane or out-of-plane buckled thin films on compliant silicones or plastics, net-shaped integrated circuits, as well as organic stretchable conductors have all contributed to the development of flexible and stretchable electronics. Yet it is uncomfortable when elastic rubbers make an intimate contact with human skins for a long time. Also, the reliability and long-term durability of the stretchable electronics needs to be investigated. Without relying on elastic rubbers, this paper conducts a systematical investigation into three-dimensionally deformable textile-based flexible and stretchable electronics.

Currently, three primary kinds of textiles, i.e. woven, knits, and nonwoven, have been proposed and demonstrated as substrates of flexible and stretchable electronics with different characteristics for specific applications. This paper will describe the fabric substrates in terms of structures, materials, geometrical and mechanical properties. Textile-based flexible and stretchable electronics are created by 1) printing or depositing electric materials, including metal films, conducting polymers and carbon (or graphite) based conductive composites, on three primary textiles, i.e., woven, knitted and nonwovens; 2) weaving, knitting, stitching or embroidering conductive fibers (or threads), such as metal fibers and polymeric- conducting yarns, into fabric structures. The electro-mechanical behavior of the created textile-based electronics with applied mechanical strain will be further discussed, demonstrating its potential use for healthcare applications.

A liquid alloy allows large strain due to its liquid state in a stretchable and deformable system and thus, a resistive strain sensor made of liquid alloy can measure large strain of human motion. Liquid alloy-based strain sensors have been demonstrated with various designs for a better understanding of human motion dynamics and to improve the design of wearable robotics. So far, the sensors have a large size of several centimeters.
To expand the applicability of liquid alloy-based strain sensors, a high resolution patterning technique would enable a small size and high density of the strain sensor. This allows strain measurements in area-limited situations or directional strain measurement with high density arrays. A small-size, high-density stretchable strain sensor array can benefit many DOF (degree of freedom) dynamics measurements on, e.g., a shoulder, hand, foot, or neck.
For realizing a highly stretchable strain sensor, a novel soft, highly stretchable and sticky elastomer was used to encapsulate the liquid alloy. A quick and simple patterning technique for high density design has been developed. This combined our previously developed spray printing technique of the liquid alloy with a stretched elastomer substrate and encapsulation of it. The substrate could be stretched either one dimensionally or radially, depending on the design.
High resolution patterns that were radially stretched and uniformly shrunken on an elastomer substrate were successfully achieved with the stretch-shrink-printing technique. This technique enables large area fabrication with one step processing. High density patterns that have a low resistance and large stretchability were realized with the liquid alloy for a small and highly stretchable strain sensor. A high density array of small strain sensors was demonstrated in measuring strains in different directions of neck movements of the human body.

In human health monitoring, abnormalities in the breath rates and patterns can ascertain the condition of the human body, such as sleep, exercise, anaerobic threshold during athletes, etc. [1-5]. For illness detection, abnormalities in the rate and pattern of breath can reflect some specific illnesses, such as ovarian carcinoma, chronic obstructive pulmonary disease, flu, pneumonia, diagnosing sleep apnea, asthma, lung cancer, etc. [3-9]. Therefore, breath sensor plays a significant role in healthcare system and attracts more and more attention.
There has many researchers have investigated the human breath with various methods, however, these approaches need the high cost of the analyzing equipment, and are interfered with ambient air [1-5]. Moreover, the size is very cumbersome and rigid, thus inconvenient in use [1-5]. Hence, the needs of simple fabricated methods and low cost human breathing sensors with fast response, high sensitivity and stretchability are highly required.
In this work, a simple method employing the stretchable nitrile rubber films with copper foil as electrodes is proposed to investigate the human breath. To fabricate such simple sensor, it is only requiring two copper foils pasted (in plane) on the surface of nitrile rubber film. During breath, significant electric current change would occur between two electrodes on nitrile rubber film， because of the formation of a water layer from exhaled breath. This type of simple sensor shows fast response (within 1 second), high sensitivity (more than 100 times signal change when exhaled breath), and can be stretched by 100% with stable breath sensing property. These sensors can detect different persons’ breath, and can detect one person’s different conditions, such as sleep, exercise, illness, etc. Compared with already reported oxidized silicon and paper based breath sensors [1, 2], our sensor shows better signals and it is stretchable. Thus, considering the highly efficient, scalable and low-cost fabrication process, such nitrile rubber films based stretchable breath sensor is favorable to healthcare monitoring applications in the near future.

References
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Electrospun scaffolds of poly(glycerol sebacate)–poly(ε-caprolactone) (PGS–PCL) have been extensively used as scaffolds for engineered tissues due to their desirable mechanical properties as well as their tunable degradability. In this paper, we aimed at fabricating micro-fibrous scaffolds from a composite of PGS/PCL using a standard electrospinning approach and coated them with silver (Ag) using a novel RF sputtering method. The Ag coating decreases the pore size and increases the diameter of fibers which resulted in enhanced electrical properties. We further compared the electrical properties of the composite fibrous scaffolds with different thicknesses of the Ag coated scaffolds. The flexible and stretchable patches form an excellent conformal contact with surrounding tissues. In vitro studies confirmed the platform’s biocompatibility and biodegradability. Lastly, potential controlled release of Ag coating from the composite fibrous scaffolds could present interesting clinical applications.

Eutectic gallium-indium (eGaIn) has been investigated as a promising stretchable conductive material for soft devices with widely reported uses in many silicon based materials like PDMS.[1,2] However, fabrication methods for its inclusion in hydrogels have been limited due to unfavourable surface interactions.[3] In this presentation, we propose a novel method of printing eGaIn directly onto hydrogels through the use of a custom syringe tip allowing for the omnidirectional extrusion of the liquid metal into its own oxide skin. We report the advantages of this printing technique and the use of eGaIn in hydrogels by demonstrating its application as a practical method of actuating thermally responsive N-isopropyl acrylamide (NIPAM) based hydrogel materials via Joule heating. Finite element modelling with ANSYS was used to model the process and determine the optimal configuration to provide maximal uniform heating to a localized area. The 3D-printed structure was characterized by thermal imaging, impedance analysis, and actuation time over repeated cycles. Its successful application as a device component in soft robotics was then demonstrated through the 3D printing of a finger-like structure with a NIPAM “joint.”


[1] Boley J. W., White E. L., Chiu G. T.-C., and Kramer R. K. Adv. Funct. Mater. 2014, 24, 3501–3507, DOI 10.1002/adfm.201303220.
[2] Muth J. T., Vogt D. M., Truby R. L., Mengüç Y., Kolesky D. B., Wood R. J., and Lewis J. A. Adv. Mater. 2014, 26: 6307–6312, DOI:10.1002/adma.201400334
[3]Khan M. R., Trlica C., So J. H., Valeri M., and Dickey M. D. ACS Appl. Mater. Interfaces, 2014, 6, 22467 - 22473, DOI: 10.1021/am506496u

Throughout the central nervous system, neurons are assembled in highly specialized circuits. The role each neuronal type plays in these circuits can provide insight on how information is processed in the brain and on the pathology of diseased states. A common strategy to uncover the underlying mechanisms of these circuits involves interrogating individual neurons and monitoring the activity of the postsynaptic targets. The current technologies for stimulating neurons rely on stiff microscale electrodes or on genetic tools, such as optogenetics. Here, we present a novel, easily deliverable nanoscale semiconductor material that can be utilized as an alternative platform for the excitation of individual neurons. Because of its spectral properties, porous silicon exhibits rapid heating in response to visible light making it an ideal candidate material for the photothermal excitation of neurons. In this study, nanoporous silicon nanowires (SiNWs) were fabricated by depositing noble metal particles during vapor-liquid-solid (VLS) growth using a pressure perturbation method followed by post-synthesis metal assisted chemical etching. The resulting structures display porosity throughout the entire length of the nanowires. We believe that the rough and porous topography of these nanostructures, in combination with increased surface area, lead to enhanced interactions at the interface between the nanomaterial surface and excitable membranes. To explore the potential of porous SiNWs as neural modulators, we used the mouse retina as a model neuronal tissue. Our results demonstrate that porous SiNWs can initiate trains of action potentials in retinal ganglion cells in response to millisecond scale pulses of 473nm blue laser.

Electrophysiological sensors, or recording devices, have proven to be among the most useful tools for today’s modern medicine. however, some of these devices are highly dependable on gels that serve as the point of contact with the human skin; these tend to degrade over time, disabling the device. Therefore, hereby we report results on the implementation of large area bilayer graphene as a durable solution for long term electrophysiological sensing. The large area bilayer graphene has been synthesized using the hot filament chemical vapor deposition (HF-CVD) technique on copper substrates. The as synthesized material was later transfer to a more suitable substrate for electrophysiological measurements. Raman spectroscopy, alongside sheet resistance measurements, ensures the high quality of the material prior to its implementation. A graphene based sensor solution is suitable for human skin contact and electrical measurements by offering biocompatibility and low impedance performance. This sensor has reveal to outperform commercially available electrophysiological sensors by owing chemical stability, thus preserving its low impedance through several hours of measurements.

Heart diseases may exist without clinical manifestations, and symptomatic cases may be difficult to detect. Continuous heart monitoring in daily life is necessary for prophylaxis and early treatment of heart disease. Recently, electronic skin (e-skin) sensors have emerged as effective non-invasive transducers of human physiological signals in healthcare. Among these, wearable electrocardiogram (ECG) e-skin sensors have been recently developed for real-time monitoring. Although mechanical heart palpitations remain a fundamental part of the physical examinations of heart disease, wearable mechanocardiograms have been rarely investigated. A representative mechanocardiogram is the apexcardiogram (ACG), which detects the temporal volume and pressure changes in the heart. The ACG is a promising complementary analysis to ECG. We fabricated a stretchable e-skin ACG strain sensor from a composite of metal nanoparticles and an elastomer. The two-dimensional (2D) percolation of metal particles provides high sensitivity to small strains (e < 2%) during apex palpitation and also high stretchability (e > 30%) for large body motions. ACG contours recorded by the sensor were wirelessly transmitted to a mobile device. This simple innovative sensor provides precise hemodynamic information before and after exercise.
Although the complicated mechanical movement of the left ventricle cannot be directly monitored by current technologies, physical examination remains a valuable component of cardiac diagnosis. In addition to sensing volume and pressure changes in the left ventricle, the ACG is strongly correlated with the hemodynamic state of the heart, a crucial indicator of the heart condition that assists the detection of atrial fibrillation, valve diseases, anemia, and myocardial infarction. These diseases are not easily detected by ECG. However, since the 1970s, the ACG has lost popularity because it is inconvenient to operate and requires large space in a sound-proof room. Small-size, inexpensive ACG sensors are expected to facilitate pragmatic, continuous hemodynamic monitoring in cardiac diagnosis. Typical stretchable strain sensors have been fabricated using two main approaches: the structural approach, in which flexible sensors are mounted on a rubber or ultrathin polymer film, and the elastic composite approach, which embeds one-dimensional (1D) conductive fillers such as metal nanowires and carbon nanotubes. However, to detect apex beat, the sensor requires high strain resolution in a small strain region (e < ~2%), which is difficult to achieve in conventional stretchable sensors. To achieve both small strain sensitivity and high stretchability, we generated a two-dimensional (2D) percolation of metal nanoparticles through the surface of a polydimethylsiloxane (PDMS) rubber substrate using the dry rubbing process.

Demand for flexible and wearable electronics is on the rise due to its versatility, convenient interaction with human body and other rugged, curvilinear surfaces. However, the fabrication of flexible electronic devices typically requires cleanroom techniques which are expensive, require elevated temperatures and are energy inefficient. Polyurethane (PU) sponge has been explored in the field of wearable electronics as a pressure sensor due to its fracture design which allows for sensitive pressure detection. However techniques to make the sponge conductive often make use of expensive materials and techniques which increases the overall cost of the sensor. Furthermore, most of the fabricated sensor is restricted to exhibiting unique functionality thus limiting its use in multi sensor platform. To overcome the drawback, array of sensors have been fabricated in 2D planar structure with each sensor functionalized for a specific sensing capability. However, selectivity is major concern in 2D planar array sensors. Here in this work, we propose a multi sensor platform where sensors are stacked over one another (3D stacked) each offering a unique functionality. The technique involves the use of PU sponge and PVDF/graphene/ZnO composites for simultaneous detection of pressure,temperature and can also act as all photodetector (UV, VIS and IR). Pressure sensor was fabricated by making the sponge conductive by dipping it in different weight percentages of pencil lead dispersed in DI water through ultrasonication. Temperature sensor was fabricated by in-situ synthesized graphene PVDF film which also acted as a substrate for the 3D stacked sensor. Photodetector was fabricated by the use of graphene/ZnO/PVDF film wherein ZnO was grown hydrothermally over graphene/PVDF film. Silver paste and copper tape were used as contact pads. Pressure sensor was tested using both resistive and capacitive configurations with capacitive showing higher sensitivity. Photodetection was performed for UV, VIS and IR range for different intensities and the results revealed that the as fabricated sensor was sensitive to all UV, VIS and IR. Temperature sensing was performed over the body temperature range (35°C to 37°C) and also in the high temperature range (40°C to 100°C) wherein the device exhibited negative temperature of coefficient. The 3D stacked sensors were tested simultaneously for individual sensing and negligible effect on the performance of its counterparts was observed. The as fabricated sensor could further be scaled up for humidity and flow sensors. The 3D stacked sensor array platform with its multifunctionality is a step ahead in wearable electronics which can be integrated on human and can function as an e-skin for burn and acid victims, robotics and human machine interactions.

Microalgae are aquatic unicellular plant organisms known for its ability to produce high-value products such as biofuels, pharmaceuticals and recombinant proteins. Genetic modification of these organisms is considered the key technology to bring down the costs of such products. However, the small volume of individual cells (~0.5 pL) and the hard cell wall presents a major challenge for successful gene delivery, and the lack of genetic transformation tools is a major obstacle to the advancement of this technology.¹
In this paper, we report our development of an EOF based microinjection device that enables the use of electroosmotic flow (EOF) to inject fluid into individual Chlamydomonas reinhardtii cells.
A cell-capturing glass capillary pipette (CP) was designed to immobilize the mobile microalgal cell, and allow impalement by the sharp-tipped microinjection glass capillary pipette (IP). EOF was induced by applying a voltage bias between a Ag wire inserted into the IP and a AgCl wire immersed in the droplet of growth media containing the cells and the IP. A positive bias was applied to the Ag wire with respect to the AgCl wire to induce EOF and eject fluid from the IP. Under a high voltage bias (e.g. 5 V), a volume expansion of ~30% was observed indicating significant injection of the fluid into the cell.
The viability of the cells was confirmed after impalement (before applying a voltage bias), during EOF injection (under different voltage bias) and after injection, using dual fluorescent dye markers: fluorescein diacetate (FDA) which stains live cells green and propidium iodide (PI) which stains dead cells orange. The details of each procedures and the effect of the injection parameters on the microinjection efficiency will be discussed in our presentation.

Reference:
1. Gong, Y.; Hu, H.; Gao, Y.; Xu, X.; Gao, H., Microalgae as platforms for production of recombinant proteins and valuable compounds: progress and prospects. Journal of industrial microbiology & biotechnology 2011, 38 (12), 1879-1890.

Highly stretchable and conductive fibers have attracted considerable interests as promising candidates for various applications such as stretchable electronic circuits, wearable electronics, energy-harvesting devices, sensors, and electronic textiles. For such purposes, various stretchable conductive fibers have been intensively explored by attaching or incorporating conducting polymers, metal nanoparticles, and carbon-based materials in elastomeric fibers. However, the stretchable conductive fibers, generally, have limitations in achieving an excellent electrical conductivity and a wide range of strain, in which the electrical conductivity is preserved, at the same time. To ensure the high-performance superelastic conductive fibers, several outstanding features of nature can be effectively utilized. For insistence, inspired by spider silk in nature, which has exceptional mechanical properties based on its hierarchical structure in micro-scale and nanoscale, superelastic conductive fibers with high performances can be designed.
In this research, we describe a facile approach of fabricating high-performance superelastic conductive fibers by imitating the hierarchically structural features of spider silk. The superelastic conductive fibers were simply fabricated using the composites of metal nanoparticles and elastomeric fibers through chemical reduction process. The conductive fibers exhibited superb strain range, in which the conductivity was preserved, due to the spider silk-inspired hierarchical structures of the elastomeric fibers as well as an excellent electrical conductivity. The superelastic conductive fibers were successfully demonstrated for several applications such as superelastic electrical connectors, high-performance wearable heaters, smart gloves which could operate a robot hand by detecting hand motion of human.

Introduction: Sugar chains, also known as oligosaccharides, are biomolecules that widely exist in our body, and play important roles in life activities. As there are such oligosaccharides as Sialyl Lewis (SLeA and SLeX), known to exist specifically on cancer cell membrane [1], oligosaccharides could possibly be targeted for valuable-cell recognition. Our group previously reported the molecularly imprinted polymer-coated gate field effect transistor (MIP-gate FET) for specific lactate recognition, and noted the possible application of this sensor in various molecular recognitions [2]. In this research, we have improved the MIP interface for the FET biosensor and investigated the detection selectivity of MIP-gate FET for sugar chains, especially targeted 3’-Sialyl lactose and 6’-Sialyl lactose, that are similar in structure with Sialyl Lewis, by comparing with the electrical signals for various sugar chains such as paromomycin and kanamycin.

Experimental: Sugar chain-template MIP gel was synthesized on Au electrode by surface initiated-activator regenerated by electron transfer-atomic transfer radical polymerization (SI-ARGET-ATRP). 4-vinylphenylboronic acid was used as functional monomer to bind diol group in sugar chain, N-3-(dimethylamino)propylmethacrylamide was used to modify pH, and finally, ethyleneglycol dimethacrylate was used as a crosslinker. As a measurement, while target molecules (3’-SLac and 6’-SLac) were added to the MIP-gate FET system, the gate surface potential was measured in real-time manner by FET real-time monitoring system. N-channel junction type FET (K246, TOSHIBA) was used. pH was controlled to be 7.4 by phosphate buffered saline (PBS), assuming cellular environment.

Results and Discussions: First, we developed 3’-SLac-template MIP and 6’-SLac-template MIP interfaces on the FETs. Using these MIP-gate FETs, we confirmed that they could be sensed quantitatively from 10uM for each sample. Moreover, the functionalized sensors showed the selectivity to detect each target to some extent, where the signal from competent was suppressed by 40% at maximum. We also found that the selectivity of MIP interface differed depending on the templated sugar chains in the MIPs, although these sugars were similar in structures. Together with the further investigation of paromomycin and kanamycin template-MIPs, we consider that the characteristics of MIP are significantly affected by conformational structure of the sugar chain. From these results, we have obtained the strategy to design the MIP interface with selectivity on the FET biosensor, which can be applied widely in medical fields.

References
[1] A. Takada et al., Cancer Research 53 (1993) 354-361.
[2] S. Nishitani, T. Kajisa, and T. Sakata, MRS Fall Meeting (2015)

Charge-Limited Current (SCLC) spectroscopy is a standard tool used to study transport in different materials, structures and devices, including organic semiconductors, diodes, transistors and solar cells and, more recently, 2D materials. The SCLC spectroscopy allows obtaining microscopic information, such as the density of traps or states within the material. Instead of the traditional SCLC data analysis in terms of transport regimes, determined from the slopes of a log-log plot of the current-voltage curve, a novel analysis based on the normalized differential conductance (NDC) has recently been proposed and used to study the transport mechanisms in nanocomposites of chitosan with gold nanoparticles (AuNP). Natural and synthetic biopolymers are gaining attention due to their applications in biodegradable or bioresorbable electronic devices. Chitosan (CHI) is a natural polymer with excellent biocompatibility and non-toxicity properties, used in biomedical, food and pharmaceutical industries. Chitosan has already been used as matrix for electronic and optoelectronic applications, as photodiodes, dispersed liquid crustal systems and biosensors. Recently chitosan doped with silver has been proposed as a material suitable for biocompatible and flexible memories. Poly(vinyl alcohol) PVA is a highly polar water-soluble polymer with a large dielectric constant, extensively used as a biomaterial and also in photolithography (when combined with photosensitizers) and as a gate dielectric in organic transistors. Both materials present memory effects, which can be modulated by introducing nanoparticles. In this work, the SCLC spectroscopy technique with an analysis based on the NDC function is used to study the hysteresis effect observed in biopolymer-based nanocomposites of CHI/AuNP and PVA/AuNP, with applications in resistive memories. At high voltages, a depletion of charge is observed, as indicated by a NDC value close to 1, corresponding to the ohmic transport. The NDC exhibits an unexpected behavior during the descending ramp, when voltage approaches the zero. These facts and the loss of different features in the NDC curves indicate a drastic change in the transport mechanisms during the voltage cycle.

We present unique double-layer structures of gold ribbons (Au RBs) and silver nanowires (Ag NWs) embedded in flexible polymeric substrates. A thin layer of n-paraffin (eicosane, C₂₀H₄₂) is first prepared on silicon (Si) substrates by a spin-coating method. Then a prism-shaped elastomeric stamp is directly pressurized on the surface of n-paraffin layer to produce prism-shaped patterns of eicosane. By using bare Si surface exposed between two prism-shaped patterns of eicosane as reaction sites, galvanic displacement is carried out to deposit thin layers of gold. The prism-shaped patterns of eicosane is also used to guide silver nanowires during evaporation of their suspending solvent, so that they are selectively deposited on gold layers prepared between two prism-shaped patterns of eicosane due to surface energy difference and height contrast. Thermal treatment at 200 °C can remove n-paraffin and remain the double-layer structures of Au RBs and Ag NWs on silicon substrates. Finally, as a layer of poly(dimethyl siloxane) (PDMS) is cured on the samples and peeled off from the Si substrates, the embedded double-layer structures are successfully transferred to flexible PDMS substrates. Electrical properties of the samples are also characterized by measuring relative change in resistances (ΔR/R₀) of the devices under various types of deformations like bending and stretching. In addition, electrochemiluminescent (ECL) device which is driven by alternative current voltage was fabricated by using the double-layer electrode.

By investigating the geometry design, this talk exploits the strategy that making the fully printed device fabricated by the non-stretchable material Silver Nanoparticles (AgNPs) stretchable, following by the demonstration of two applications --- stretchable conductor and strain gauge. We had printed the AgNPs pattern onto the elastomer substrate and showed the stretchability of the device could be tuned by changing the radius of the serpentine structure. The device with smaller radius was more sensitive to the strain, resulting a high gauge factor of 10⁶, demonstrated as a stain gauge to detect the finger motion of human beings, while the device with larger radius was more stretchable (more than 25%), used as a stretchable conductor for driving the LED. The printed strategy and demonstrated application would have broad prospects in stretchable electronics.

In recent years, flexible and stretchable interconnection technologies have been received huge attentions. Several approaches were performed to develop stretchable interconnects using conductive polymer, graphene, and even embedded metal in elastomers. Even though each technology has their own advantages, the most critical factor for electronic device is conductivity. In terms of the conductivity, using metal interconnects may be a reasonable solution so far. When integrated on polymeric substrate, however, metal interconnects experienced buckling or delamination and could be severely damaged by cracks. Poor reliability of metal interconnects are originated from the different Poisson’s ratio or Young’s modulus between polymer and metal, which could produce mismatch strain during deformation.
Here, we developed high-reliable metal interconnects with excellent stretching capability by controlling the Poisson’s ratio of polymer substrate. To manipulate the Poisson’s ratio, we embedded auxetic materials in substrate and decreased the mismatch strain between metal and substrate. Auxetic materials are known to have negative Poisson’s ratio derived from their unique structure. In our experiment, we fabricated PDMS substrate with re-entrant auxetic Si rubber embedded. By embedding auxetic rubber, Poisson’s ratio of the PDMS substrate effectively decreased from 0.5 to 0.3. To prove the parameter matching strategy, horseshoe Cu interconnects were deposited on the modulated PDMS substrate and cyclic tensile test was proceeded with 5 % strain. We observed that Cu interconnects with modulated PDMS could endure up to 1,000 cycles while that with bare PDMS showed initial breakdown. From this result, we expect that design strategy of stretchable metal interconnects can be proposed for high-reliable metal based stretchable devices

Robots have traditionally thrived in tasks that require speed and precision. To achieve these qualities, robots for industrial automation, for example, have historically relied on rigid components, traditional “nuts-and-bolts” construction, high force/torque actuators, and variety of off-the-shelf sensors. Robots made from soft materials do not share these traits and components, motivating new solutions to sensing, actuation, and manufacturing. This talk will describe recent advances in robots composed predominantly of soft polymers and both passive and "smart" fluids resulting in liquid-elastomer composites. The absence of more traditional robot building blocks results in composites with characteristic modulus on the order of hundreds of kPa to tens of MPa. A fundamental challenge for these soft systems is how to recreate the functionality found in rigid robots using only soft or liquid phase materials. Capabilities such as variable compliance, motion and force sensing, and actuation are achieved through the creation of microchannels in elastomer matrices filled with conductive or smart fluids, bendable but inextensible strain-limiting materials, and high-pressure pneumatic or hydraulic channels. In addition to fluidic systems, we are developing multiple classes of electrically-stimulated soft and compliant actuators based on electrostatic forces. Manufacturing is an additional challenge. Given the nature of the constituent materials, we construct soft robots using a combination of molding, soft lithography, additive manufacturing (e.g., lamination and printing), and surface-tension driven patterning. Each of these techniques involves relatively inexpensive materials, minimal infrastructure, and minimal time relative to subtractive machining of hard materials, resulting in an added benefit of soft robotics: rapid and inexpensive prototyping enables a short design-manufacture-evaluate cycle and maximizes accessibility, democratizing these techniques and the resulting robots. Finally, combining soft actuation with rigid articulated mechanisms achieves the best features of both: back-drivability with precision and ease of modeling and control. This talk will conclude with an overview of the state of the art in soft components, morphologies, and applications including wearable devices (e.g., soft sensing suits), muscle-like actuators, soft robots for minimally-invasive surgical procedures, delicate manipulators for the deep sea, and robust robots capable of autonomous locomotion.

Recently, soft robots have been used to mimic the motions of biological systems through clever design of elastomeric balloons. Examples range from synthetic, heart-like pumps, to quadrupeds with natural gaits that balance and locomote using no sensing or feedback control. Here we present a new capability for soft robotic systems: simultaneous shape and color modulation. This is a step towards replicating the cephalopod’s ability to change its visual appearance and shape at once to achieve visual and textual camouflage. Our synthetic adaptation of this system is based on a hyperelastic light-emitting capacitor, or HLEC, that is fully embedded into an elastomeric actuator. The HLEC can actively emit light under extreme deformations of ~635% and ~480% areal and tensile strains, respectively, enabling it to function over the entire deformation spectrum required to replicate these natural movements. Here I will share two specific lines of inquiry related to achieving polychromatic displays and how various stretchable electrode materials perform for this application.

Soft robotics is a dynamic field that aims at combining advanced manufacturing techniques with electronic materials to achieve systems with mechanical agility (actuation) and localized sensing capabilities. In this work, we present the functional integration of soft pneumatic actuators with stretchable, thin-film resistive sensors capable of capturing the entire dynamic response of the system ranging from static inputs to dynamic inputs up to 150 Hz.

The sensor-actuator system is entirely processed with silicone elastomers and thin metal films. The soft actuators, composed of an inflatable elastomeric membrane, are pneumatically inflated with a positive pressure input. A sensor skin that hosts meanders of the stretchable metallization is laminated on top of the actuator membrane. The thin sensor membrane (20 μm thick in total) affects little the actuator performance. The sensor metallization is a biphasic (liquid-solid) film deposited during two physical vapor deposition phases of gold and gallium. This intrinsically stretchable metal film is capable of withstanding uniaxial strains in excess of 400%.

The patterned sensors are strain gauges, exhibiting resistance increase correlated to the inflation of the underlying actuator. During cyclic inflation at a constant actuation frequency, the response of the sensor increases with increased input pressure, due to the increased strain distribution across the inflated membrane. During cyclic inflation to a fixed maximum pressure, the response of the sensor decreases with increased actuation frequency, as the air flow rate is limited by inlet pneumatic tube diameter and length. The sensors demonstrated in this work exhibit negligible hysteresis (< 5%, independent of strain rate) and rapid response times (< 1 ms). Additionally, the gauge factor of the metallization, approximately 1 depending on the deposition parameters, is independent of the strain rate from 0.018 mm/s to 18 mm/s.

We demonstrate the integration of an entirely elastic actuator-sensor system. This will facilitate the implementation of closed loop control of the actuator amplitude over a wide range of frequencies owing to the large dynamic range of sensors. This type of sensors can also be applied to other compliant systems, opening the door to soft robots with closed loop control.

Endoscopes provide visualization of gastrointestinal tracts and simple therapeutic functions such as tissue resection and biopsy for diagnosis and therapy of polys and tumors. Despite its utilities, current endoscopes have certain limits in high resolution diagnosis and precise feedback therapy due to its large size, insufficient resolution, and restricted functions. To diagnose diseased sites precisely and treat specific abnormalities, a new integrated surgical system which is composed of various useful sensing and therapeutic features on small area of an endoscope tip is required. Here, we present a smart endoscope system integrated with transparent soft bioelectronics and theranostic nanoparticles (NPs) for diagnosis and therapy of the colon cancer. Transparent bioelectronics mounted on the endoscope camera provide impedance- and pH-based tumor sensing and RF ablation therapy, which enable accurate characterization and removal of small size and scattered colon cancers. Mechanical contact sensor and temperature sensor help the facile control of RF ablation treatment. In addition to transparent bioelectronics, theranostic NPs provide fluorescence-based mapping and localized photo- and chemo-therapy through targeted delivery to the cancer tissue and guided laser illuminations. This multifunctional endoscope realize effective diagnosis and therapy, which provides a closed-loop solution for the colon cancer treatment.

A number of technologies are currently available for the production of elastic, dynamically deformable circuits, which can be bended, stretched and released numerous times. In this case very often hyperelastic materials like PDMS (silicone rubbers) are used as circuit carriers. Our group has also developed such technologies. In our approach the stretchability of the circuit is achieved by providing metallic, meander shaped electrical interconnects between rigid or flexible components. These metallic interconnects can be produced from Cu sheets, used in standard Printed Circuit Board technology (metal thickness typically 18 or 35µm), or can be thin-film technology based, e.g. sputtered Au (thickness typically a few 100s of nm). Due to their meander shape these interconnections can be elongated while maintaining their electrical functionality.
There are applications however where the circuit still needs to take a random shape, but to some degree needs to maintain this shape during use. Examples of such applications in the medical field are smart lenses or prostheses, where the former is an example of a circuit which is still soft and deformable, but returns to the same original shape when no forces act on it, while the latter is an example of a rigid, non-deformable circuit. For these type of applications we have developed fabrication technologies where we replaced the carrier materials of our elastic circuits by thermoplastic materials like poly-urethanes, polycarbonates (PC), PET, polystyrenes, etc. The production process is to a large extent identical to the one for elastic circuits : the circuit is produced on a flat temporary carrier and finally transferred to its final carrier, which is now a thermoplastic polymer. Now one additional step is necessary, i.e. thermoforming from flat to the final circuit shape. The step consists of heating the thermoplastic carrier with embedded electronic circuit to temperatures above the glass transition temperature of the polymer, but below the melting temperature (in the range of 120 to 180 degC for most of the polymers), followed by vacuum or high pressure forming of the structure over a tool, determining the shape of the thermoplastic circuit, and finally cooling down and release of the circuit from the forming tool. Now essentially the interconnections need to sustain a single elongation only (as compared to elastic circuits). More details on design considerations, process details and applications will be provided in the symposium presentation.

Soft robots exhibit many attributes that are difficult, if not impossible, to realize with robots based on conventional rigid materials. Despite recent advances, soft robots remain tethered to hard robotic control systems and power sources. New strategies for creating completely soft robots, including soft analogs of these crucial components, are needed to realize their full potential. We present the first untethered operation of a robot comprised solely of soft materials. The robot is controlled with microfluidic logic that autonomously regulates the catalytic decomposition of an on-board monopropellant fuel supply. Gas generated from fuel decomposition inflates fluidic networks downstream of the reaction sites, resulting in actuation. The robot’s body and microfluidic logic are fabricated with molding and soft lithography, respectively, while the pneumatic actuator networks, on-board fuel reservoirs and catalytic reaction chambers needed for movement are patterned within the body by a multi-material, embedded 3D printing technique. Our integrated design and rapid fabrication approach enables the programmable assembly of multiple materials within this architecture, laying a foundation for completely soft, autonomous robots.

Biointerface devices and stretchable electronics typically include mechanically compliant materials such as polymer gels and elastomers. Such “soft matter” can be designed and manufactured to exhibit high toughness, such that the materials dissipate significant mechanical energy and undergo large deformations without fracturing. Those characteristics provide strong appeal for their use in diverse applications, such as biomedical devices, soft robotics, flexible hybrid electronics, and shock-absorbing equipment. Although the mechanisms of energy dissipation in polymers are extensively explored, those studies primarily focus on properties characteristic of the bulk viscoelastic material. The surface properties, such as adhesiveness of the material, can also influence the energy dissipation response and biointerface properties. It remains poorly understood, however, how surface adhesion and bulk viscous dissipation individually contributes to mechanical energy dissipation, largely because the surface and bulk properties are intrinsically coupled. For example, more viscous, or dissipative, polymers gels are typically more adhesive. Here, we develop a bilayered composite gel, in which a thick, viscoelastic polydimethylsiloxane (PDMS) gel is coated with a thin layer of PDMS elastomer. The PDMS elastomer, formed by crosslinking bottlebrush rather than linear polymer chains as in typically manufactured silicones, exhibits exceptionally low and controllable elastic moduli down to ~1 kPa, yet negligible adhesion compared to conventional PDMS gels because of its macromolecular design. With this hierarchical bilayer design, we demonstrate independent control of surface adhesion and bulk viscoelastic properties; this allows us to probe energy dissipation at fixed surface adhesion while varying the bulk viscoelastic properties, and vice versa. We measure the adhesive pull-off forces between a metallic sphere and the composite gels at different unloading rates, to quantitatively compare the interfacial adhesion in relation to other mechanical properties that define device performance and manufacturability. Additionally, with the same nanoindenter, we apply concentrated mechanical impacts at high strain rates and investigate the role of adhesion on the dissipation of impact energy. Together, these studies provide fundamental insights on the underlying mechanisms of energy dissipation in soft, adhesive polymers that are considered key candidates for scalable production of biointerfacial and flexible electronic devices.

The two essential components for a chemical reaction are reagents and reaction media. Chemical reagents can determine the chemical structure of the final reaction product. Reaction media, on the other hand, controls the reaction kinetics and defines the product morphology (e.g. size, shape, and surface texture) of the final products. In this study, we utilized a class of anisotropic medium, liquid crystals (LCs), as reaction media to create arrays of functional polymer nanofibers through a vapor-based polymerization process. When substituted [2,2]paracyclophanes were polymerized in LCs via chemical vapor deposition, the molecular alignment within the LCs guided the propagation of polymer chains and facilitated the formation of arrays of high-aspect ratio nanofibers with narrow size distribution. By tuning the properties of the LCs or polymerization parameters, we can control the size, shape, and surface chemistry of the nanofibers, as well as create helical nanofiber arrays. Altogether, this work establishes a platform technology that enables the creation of nanofiber arrays on complex geometries and can be used for the capture of biomolecules. Streptavidin was successfully immobilized on the polymer nanofiber arrays as a demonstration. Due to the high surface area, the amount of streptavidin binding on the nanofiber arrays was 15 times greater than that on polymer film. We believe that our work provides an avenue for designing functional polymer nanostructures to target a wide range of technological applications, including bio-sensing, affinity filtration, and catalyst supports.

Cells require adhesion to survive, proliferate and migrate, as well as for wound healing and many other functions. The strength of contractile cell forces on an underlying surface is a highly relevant quantity to measure the affinity of cells to a rigid surface with and without coating. By employing a self-designed setup, we show that these forces create surface stresses that are sufficient to induce measurable bending of macroscopic cantilevers [1]. In detail, a metal cantilever with and without coatings was employed as substrate for NIH 3T3 fibroblast cells. Prior to measurements, cells were seeded onto the cantilever and adhered, which results in a stress acting onto the cantilever. The resulting cantilever bending was determined with a laser beam reflected on the cantilever’s bottom and monitored with a position sensitive detector (PSD). Subsequently, trypsin was added to the cells to detach them. Consequently, contractile cell forces were not acting on the cantilever anymore and it relaxed to its initial without cells. For quantitative analysis, we performed finite element simulations on the beam bending to back up the calculation of contractile forces from cantilever bending under non-homogenous surface stress. In our study in vitro fibroblast adhesion and active contractions on the magnetic shape memory alloy Fe–Pd and on the L-lysine derived plasma-functionalized polymer PPLL [2] were determined. Results were compared with fibroblast adhesion on pure titanium cantilevers. We show that cells on Fe–Pd are able to induce surface stresses three times as high as on titanium cantilevers. A further increase was observed for PPLL, where the contractile forces are four times higher than on the titanium reference. Our findings consolidate the role of contractile forces as a meaningful measure of biomaterial performance.
[1] U. Allenstein, S. G. Mayr, M. Zink: Contractile cell forces deform macroscopic cantilevers and quantify biomaterial performance.
Soft Matter11, 5053-5059 (2015)
[2] U. Allenstein, F. Szillat, A. Weidt, M. Zink, S. G. Mayr: Interfacing hard and living matter: plasma-assembled proteins on inorganic functional materials for enhanced coupling to cells and tissue. Journal of Materials Chemistry B 2, 7739-7746 (2014)

Recent advances in soft electronics have attracted great attention due in large to its various potential clinical applications. Here, we present a soft and highly conductive rubber made of ligand-exchanged silver nanowires (Ag NWs) and a thermoplastic elastomer. The ligand-exchange reaction enabled the formation of a highly conductive and homogeneous nanocomposite of Ag NWs. By patterning the nanocomposite with serpentine-mesh structures, conformal lamination of devices on curvilinear epicardium and effective electrical stimulation over the entire ventricle even during vigorous heart motions were achieved. The epicardium-integrated device reduces inherent wall stress without compromising diastolic relaxation and improves hemodynamics through synchronized electrical stimulation. The high conductivity of the epicardial mesh enables rapid propagation of electrical signals over the entire epicardial surface and results in the global resynchronization pacing. This novel implantable bioelectronic system provides new opportunities in the clinical medicine.

Conventional medical tools for delivering cardiac electrotherapies have severe physical limitations, in terms of the non-conformal interfaces between the cardiac structures and the stimulating electrodes. Recently developed concepts for 3D multifunctional integumentary membranes (3D-MIM) open the path for building conformal interfaces between cardiac surfaces and medical electronics. The results presented here expand on these concepts to demonstrate 3D-MIM devices configured for cardiac electrotherapy. Here, fractal concepts enable large area, conformal electrodes suitable for delivering defibrillation shocks, but without compromising mechanical compliance and stretchability of the device. Advanced electrode materials, including nanotextured Pt-Ir alloys and PEDOT:PSS, are integrated in this platform to yield low-impedance electrical interfaces with the tissues. Co-integrated micro-sensors array allows precise monitoring of physiological responses during therapeutic processes. All the functional components are constructed in a thin, 3D elastic membrane that conforms to the entire surface of epicardium. Animal experiments on Langendorff-perfused rabbit heart demonstrate the the key features of these systems.

To establish the human-machine interface, including wearable, implantable, and ingestible devices, electronic signals in electronic devices and chemical signals in human body are commonly required to communicate with each other. In living organisms, chemical signals released by secreting cells, including hormones, cytokines, and neurotransmitters, can activate the target cells. On the other hand, electrical signals are associated with the flow of charge in integrated circuits. Conventional approaches to build a connection between devices and human body involves indirect translation from biomarkers to electrical output, including electrochemical reaction, phase transition, and responsive materials, or direct translation, including EEG, ECG, EMG, to name a few. The direct electrophysiological monitoring relies on some specific cells, like cardiomyocytes and neurons, which can generate and respond to electrical impulses by themselves. However, most conventional human-machine interface involves a complex or elaborated system while achieving few specific functions. In contrast, synthetic biology enabled genetic engineered cells can accomplish programmable, versatile applications, including novel healthcare diagnosis and therapy, in a relatively simple manner. Most of these applications of living cells is restricted to research stage and in vivo environment due to demanding condition for viable cells, and biosafety concerns towards genetic modified cells. This dilemma can be well solved by designing a robust, biocompatible cellular host to bring the living cells towards a real world device. Here, we report a novel design of living device that can detect chemical cues from external environment, and allow cell communication between neighbored channels in the device. This is achieved by the hydrogel-elastomer hybrid as a containment for the genetic engineered cells. The hydrogel upper layer provides the window for cell growth and communication, the robust interface between hydrogel and elastomer ensure there is no leakage of genetic modified cells and eliminate the biosafety concerns, and the patterns on inert elastomeric substrate provide micro-niches for cells. Without involving any conducting materials and stiff components, the living device can detect the chemical signal which comes from the environment and go through a cascade of biochemical reactions to produce a fluorescent output. Diffusion-based direct chemical signal transmission excludes the need to modulate the chemical signal to electrical signal. Meanwhile, the flexible, freestanding device can be conformally laminated on human skin or any other curvilinear surfaces. To bring the synthetic-biology-based gene editing technique to real life beyond the laboratory, we further demonstrate this technology with applications of a wearable sensor patch conformally mounted on human forearm, and fingerprint-like monitors adhered to gloves.

Continuous monitoring of electromyography (EMG) and the electrical and/or optical stimulation of muscle are important in treating neuromuscular dysfunctions. The rigidity of conventional implantable devices, however, can cause damage in muscular tissue during its movement due to mechanical mismatch between device and soft tissue and trigger severe immune responses, particularly at the device-tissue interface. Furthermore, the non-conformal contact of rigid devices leads to low signal-to-noise ratio of sensing and insufficient stimulation. To overcome these limitations, soft implantable devices based on flexible/stretchable electronics were developed as a potential solution. Here, we introduce a multifunctional cell-sheet-graphene hybrid device comprised of C2C12 myoblast sheet, mesh-patterned graphene nanomembrane, and sub-micron polyimide (PI) membrane. Mesh patterned graphene nanomembrane serves as a smart cell culturing substrate and a soft monitoring and stimulating device. The buckled structure enhanced stretchability of the device. The stretchable and transparent device enable efficient electrical and/or optical stimulations with simultaneous recording. The therapeutic effect of the hybrid on implanted site could be observed by the regeneration of damaged muscles. Integrated cell sheet can also dramatically reduces the recruitment of CD68-positive macrophages at the implanted site and maintains the tissue-device interface intact over the extended period of time. This multifunctional cell-sheet-graphene hybrid device would provide a number of new opportunities in new areas of implantable bioelectronics for skeletal muscles.

One of the most challenging task in toxicology and diagnostics is monitoring cell responses induced by external stress by simple and reliable devices. Methods currently used for cell viability detection lack mainly of the real-time monitoring and are often cumbersome requiring a significant degree of specialization. Here, we present and discuss a solution based on Organic Electrochemical Transistors (OECT) [1] that is very sensitive, portable and allows in-vitro monitoring of cellular stress and death dynamics. A549 adenocarcinoma cells line were cultivated on the micro-porous membrane of Transwell supports, that were directly integrated in the OECT. Cellular response was investigated under the effect of external stress, induced by drugs [2] or an hyperosmotic environment. The sensing performance has been qualified by monitoring both the time-dependent and the dose-dependent evolution of the device electrical output. We could optimize the response in different regimes of stress also by comparing with more standard and qualified methods such fluorescence microscopy and MTT assay. Results were interpreted by modelling the ionic diffusion taking place into the Transwell-OECT device and validated by correlating the device response with traditional biological methods. Future applications of this Twell-OECT include the development of sensors for monitoring cell death dynamics with cost effectiveness, portability and ease of use, paving the way toward point-of- care diagnostics.

[1] Scalable and Flexible Bioelectronics and Its Applications in Medicine. S. Iannotta, P. D'Angelo, A. Romeo, G. Tarabella. Large Area and Flexible Electronics, 485-540. Wiley VCH Verlag GmbH & Co.
[2] Drug-induced cellular death dynamics monitored by a highly sensitive organic electrochemical system. A. Romeo, G. Tarabella, P. D’Angelo, C. Caffarra, D. Cretella, R. Alfieri, P. G. Petronini, S. Iannotta. Biosens. Bioelectron., vol. 68, pp. 791–797, 2015.

This talk will give an overview of our research into the development of new materials and materials-based characterisation approaches for regenerative medicine [1-3]. The ability to control the cell-material interface offers exciting possibilities for stimulating growth of new tissue for example through the development of conductive polymer scaffolds. By applying state of the art materials-based approaches we can also better elucidate the cell-material interface for applications in cardiac tissue engineering. Recent examples from our group will be presented.

References
[1] E. T. Pashuck, M. M. Stevens "Designing Regenerative Biomaterial Therapies for the Clinic."
Science Translational Medicine.2013. 4 (160) 160sr4.
[2] Chiappini C, De Rosa E, Martinez JO, Liu X, Steele J, Stevens MM, Tasciotti E.
“Biodegradable silicon nanoneedles delivering nucleic acids intracellularly induce localized in vivo neovascularization.” Nature Materials. 2015. 14(5):532-9.
[3] M. D. Mager, V. LaPointe, M. M. Stevens “Exploring and exploiting chemistry at the cell surface.”
Nature Chemistry. 2011. 3(8): 582-589.

The ability to create materials with well-controlled structures on micrometer length scale has been widely studied for development of microdevices to precisely deliver therapeutic agents. While anti-inflammatory drugs have been widely used to reduce reactive tissue response to implanted electrodes in the brain, the development of efficient drug encapsulation and contorted release have been challenging due to (1) inefficient methods of drug encapsulation and (2) undesirable burst and uncontrollable rate of the drug release.
In this study, we have developed a novel method for fabrication of dexamethasone (DEX)-loaded microspheres coated with conducting polymers with high drug-encapsulation efficiency and on-demand drug release capability. The fabrication process includes electrojetting of drug-loaded microspheres and electrochemical polymerization of conducting polymers around the microspheres to create PPY microcups. First, DEX-loaded poly (lactide-co-glycolide) (PLGA) microspheres were electrosprayed on gold substrates with an applied electrical field of 100kV.m^-1. Then, conducting polymer PPY was electrochemically polymerized around PLGA microspheres with a current density 0.5 mA.cm^-2 in 4 different deposition times (i.e. from 2 to 6min) from a solution of 0.2M PY and 0.2M sodium-p-styrenesulfonate. The diameter of PLGA microspheres was 3.45±0.31µm. The height of PPy microcups was 0.5±0.14 , 2.5±-0.15, 2.75±-0.15, and 3±0.15µm and the opening size of PPy microcups was 3.38±1.05, 3.55±0.79, 2.3±0.85, and 1.7±0.91µm² for four different electrodeposition times. PPy microcups have been actuated using electrical stimulation (i.e. cyclic voltammetry, voltage between -0.8 and 0.4V with scan rate ranged from 10 to 1000mV/s) in order to produce on-demand release of DEX from PPy microcups. The triggered release profile of DEX will be quantified using HPLC system at wavelength of 242nm. We have hypothesized that DEX release profile can be precisely tuned by opening size of PPy microcups and electrical stimulation parameters. We are investigating the release profile of DEX respect to size of microcups and electrical stimulation parameters and in future we will study the active release of nerve growth factors from PPY microcups.

Considering the limited physiological relevance of 2D cell culture experiments, significant effort was devoted to the development of materials that could more accurately recreate the in vivo cellular microenvironment, and support 3D cell cultures in vitro. One such class of materials is conducting polymers, which are promising due to their compliant mechanical properties, compatibility with biological systems, mixed electrical and ionic conductivity, and ability to form porous structures. In this work, we present a single component, macroporous hydrogel made from poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) via an ice-templating method. [1] PEDOT:PSS scaffolds offer tunable pore size, morphology and shape through facile changes in preparation conditions, and are capable of supporting 3D multi-cell type culture due to their biocompatibility and tissue-like elasticity. Furthermore, these platforms are functional: they exhibit excellent electrochemical switching behavior and significantly low impedance. The electrochemical activity enables impedance based sensing and label free detection of cells. While being an integral part of the tissue, the conducting polymer serves as a bioelectronic tool with integrated sensing capability.

[1] A. M.-D. Wan, S. Inal, T. Williams et al., Journal of Materials Chemistry B, 2015, 3, 5040

Introduction
Allergy is a kind of closest disease in the world, which is widely infected and induced by various allergen sources. Our group previously reported the monitoring of type I cell allergic reaction by ion-sensitive field effect transistor (IS-FET), and consequently considered the histamine as one of the main signal sources secreted from allergy reaction [1]. Then, to detect histamine specifically by FET, we chemically modified the gate sensing surface of the FET device by histamine-template molecularly imprinted polymer (MIP-gate FET). In this study, we report the improved MIP-gate FET showed the highly selective detection of histamine against similarly structured molecule, nicotinamide.

Methods
Extended-gate Au electrode was modified by MIP through UV-bulk polymerization. To improve the selectivity of histamine-template MIP, we used 2-(trifluoromethyl) acrylic acid (TFMAA) as functional monomer to strongly interact with histamine in the pre-polymer solution. The use of TFMAA was previously reported by the T. Takeuchi group as an improved reagent for amino-carboxylic interaction [2]. We used N, N’-methylenebisacrylamide (MBAA) as cross-linker, which strategically makes MIP hydrophilic and hopefully avoid the adhesion of proteins, which are considered to be main competent for the allergy detection. As a measurement, a change in the gate surface potential was monitored by FET real-time monitoring system when histamine or the competent was added to the solution. The pH was controlled around 7.4 by phosphate buffered saline (PBS).

Result and future plan
First, the gate surface potential of MIP-gate FET was monitored when histamine and nicotinamide were separately added to the solution. As a result, although both histamine and nicotinamide were quantitatively detected as a negative shift of surface potential, the absolute value of the potential shift was significantly larger for histamine addition. Thus, the selectivity for detection of histamine was enhanced by MIP. In addition, the detection sensitivity, which indicates signal shift for histamine concentration, was also improved compared with the MIP-gate FET from previous method. For the next step, we will further consider the improvement of MIP by covalent method, and hopefully apply the sensor for specific cell allergic detection.

References
[1] H. Y. Yang et al., MRS Fall Meeting (2015).
[2] J. Matsui, O. Doblhoff-Dier, and T. Takeuchi, Analytica Chimica Acta, 343 (1997) 1-4.

Transient electronics is an emerging technology whose key characteristic is an ability to physically disappear in physiological environments in a controlled manner after a period of stable operation. Potential applications include zero-waste environmental sensors and temporary biomedical implants to avoid second surgery. Biodegradable electronics built using water soluble, biocompatible active and passive materials can provide multifunctional operations for diagnostic and therapeutic purposes, such as monitoring neural networks, assisting wound healing process, etc. Biodegradable power supply is an essential component for many such systems, which still remains as a challenge, and primary batteries represent versatile options that can complement these and other possibilities. The water-activated primary batteries that we report here involve constituent materials that are all degradable, environmentally benign and biocompatible. Systematic studies reveal the achievable performance and the electrode characteristics at the device/bio-fluids interface. Biocompatibility of the degradation products is investigated, and the battery system is demonstrated for practical usages, including powering of light-emitting diodes (LEDs) and radio transmitters for wireless communication.

Transparent energy conversion and storage devices have recently attracted increasing attention due to their great potential as integrated power sources for displays and windows in buildings, automobiles and aerospace vehicles. On the other hand, mechanical stretchability coupled with optical transparency of the energy storage devices is required for many other applications, ranging from self-powered rolled-up displays to self-powered wearable optoelectronics. Superior stretchability of the aerosol synthesized single-walled carbon nanotube (SWCNT) films, integrated in such devices, may find broad applications in stretchable electronics, as well as energy storage electrodes.
Several configurations were fabricated and tested, with the best achieved specific capacitance of 17.5 F g^-1. Our first fabricated and tested TSSs with liquid 2 mol/dm³ H₂SO₄ electrolyte showed capacitance about 3.2 F g^-1 and allowed to apply 50% of strain. This limitation can be explained by the presence of non-stretchable separator and leakage of liquid electrolyte. In order to solve this problem, TSS based on PVA-H₂SO₄ gel electrolyte was developed, which showed specific cell capacitance of 7.4 F g^-1. In order to increase durability to stretching of such TSS another technique was performed based on pre-stretching of the electrodes with the deposited gel electrolyte. A total device transmittance up to 75% was achieved for supercapacitors made from the assembly of two PDMS/SWCNT electrodes and a gel electrolyte in between. The transparent supercapacitor has a specific capacitance of 17.5 F g^-1 and can be stretched up to 120% with practically no variation in the electrochemical performance after 1000 stretching cycles and 1000 charging-discharging cycles.
In this study, stretchable all-solid supercapacitors based on aerosol synthesized single-walled carbon nanotubes have been successfully fabricated and tested. High quality SWCNT films with excellent optoelectrical and mechanical properties were used as the current collectors and active electrodes of the stretchable supercapacitors. The capacitance of SWCNT based TSSs remained nearly unchanged, even after stretching and charging-discharging cycles with practically no variation in the electrochemical performance. Therefore, these newly-developed transparent and stretchable supercapacitors are promising for various power-integrated stretchable optoelectronic systems.

Lactate is one of the most important metabolites produced during anaerobic glycolysis process. Intense physical exercise leads to higher lactate production in blood which could eventually lead to muscle pain. Diseases such as cancer, sepsis, diabetes and cardiovascular diseases could also cause lactic acidosis. Measuring lactate concentration is thus of utmost importance to reflect physical condition.
Here we introduce a flexible amperometric biosensor fabricated with silver nanoparticle-based electrode for non-invasive detection of sweat lactate. The biosensor was fabricated by modifying silver nanoparticle-based electrode with lactate oxidase as oxidation catalyst, bovine serum albumin for enzyme immobilization and glutaraldehyde as cross-linker, which was coated with Nafion to enhance selectivity against interfering electroactive anions such as ascorbate. Cross-serpentine shaped silver nanoparticle based electrode was fabricated for the application of stretchable electrode on flexible polyethylene terephthalate (PET) substrate. Sodium Hypochloride was used to fabricate in-sensor pseudo Ag/AgCl reference electrode which evinced its long term potential stability against a standard commercial Ag/AgCl reference electrode. Scanning Electron Microscopy (SEM) revealed the well-modified surface morphology and chloridization proclivity of silver nanoparticles on electrodes. The catalytic response of the sensor showed linear response to lactate ranged from 0 to 25 mM. This non-invasive electrochemical sensor also demonstrates excellent resiliency against mechanical deformation and little temperature fluctuation which leads the potential sweat lactate sensing application on human epidermis.

Reference
M. A. Abrar, Y. Dong, P. K. Lee and W. S. Kim*, “Bendable Electro-chemical Lactate Sensor Printed with Silver Nano-particles” under review in Scientific Reports

Neural recording devices often fail after a year, primarily due to biological failures including glial scarring and neural cell death.[1] A leading hypothesis suggest that these biological failures are caused by long term overproduction of reactive oxygen species due to “frustrated phagocytosis," resulting in oxidative stress in the tissues surrounding implants.[2] The current study conjugates antioxidant drugs to pro-drug molecules for extended local treatment of oxidative stress. Systemic treatment with resveratrol, an antioxidant upregulation drug, reduces glial scarring and neuronal cell death around electrodes, but results in some negative side effects suggesting that local long-term delivery of resveratrol may be a promising strategy.[3] We explore the novel conjugation of pterostilbene, a related antioxidant [4], for this application as well.

In this work, resveratrol and pterostilbene were conjugated to succinic acid to form novel pro-drug molecules. Conjugation was performed by ring opening synthesis in which resveratrol, or pterostilbene, was reacted with succinic anhydride. The successful formation of each compound was verified by mass spectroscopy, showing the molecular weights at 328.1 for resveratrol-succinic acid and 356.1 for pterostilbene-succinic acid. FTIR characterization of both products showed a new peak at 1698 cm^-1, which was not seen in any starting materials and is consistent with the formation of a new carbonyl group. HNMR and CNMR analyses showed the presence of the predicted structures, indicating that the reactions yielded only the expected products and their unreacted reagents. The conjugation of antioxidant drugs, resveratrol and pterostilbene, to succinic acid was shown to produce a functional pro-drug. Characterization of the reaction products indicates the preservation of the molecular structure of the drugs for controlled release. Local treatment with the pro-drug molecules synthesized in this study, resveratrol-succinic acid and pterostilbene-succinic acid, may be a viable strategy for integration of device-tissue interfaces.

[1] J. C. Barrese, N. Rao, K. Paroo, C. Triebwasser, C. Vargas-Irwin, L. Franquemont, and J. P. Donoghue, “Failure mode analysis of silicon-based intracortical microelectrode arrays in non-human primates.,” J. Neural Eng., vol. 10, no. 6, p. 066014, 2013.
[2] K. a. Potter-Baker and J. R. Capadona, “Reducing the ‘Stress’: Antioxidative Therapeutic and Material Approaches May Prevent Intracortical Microelectrode Failure,” ACS Macro Lett., vol. 4, pp. 275–279, 2015.
[3] K. A. Potter, A. C. Buck, W. K. Self, M. E. Callanan, S. Sunil, and J. R. Capadona, “The effect of resveratrol on neurodegeneration and blood brain barrier stability surrounding intracortical microelectrodes,” Biomaterials, vol. 34, no. 29, pp. 7001–7015, 2013.
[4] D. McCormack, Denise; McFadden, “A Review of Pterostilbene Antioxidant Activity and DiseaseModification,” OxidativeMedicine Cell. Longev., vol. 2013, 2013.

Carbon microfiber (CMF) electrodes are commonly used for studying the chemical signaling of neurotransmitters in the brain through fast scan cyclic voltammetry (FSCV). At present, these electrodes are constructed in a glass seal containing a single CMF that is ~100 μm long and ~7 μm in diameter. Because of this configuration, the resulting electrodes are bulky, thereby limiting them to single site measurements. In addition, the process involving the fabrication of the existing electrodes is mostly manual. The limited precision of such fabrication methods introduces significant probe-to-probe variability in surface geometry, thereby complicating the calibration and measurement processes. Here, we demonstrate a new multi-electrode sensor platform, in which the CMF electrodes are co-integrated with an advanced silicon readout circuit. We also discuss the effect of various process and measurement parameters such as sensor size and the input voltage signal waveform on the key performance metrics of the multi-electrode sensor platform. Strategies for realizing multielectrode neural probes for measuring the chemical signals in the brain will be discussed.

The silicon readout circuit was designed and fabricated using a 65nm complementary metal-oxide semiconductor (CMOS) technology. The chip consists of multiple readout channels, in which the size of each channel is approximately 150 μm × 450 μm. The CMOS chip underwent post-processing in order to integrate the CMF working and counter electrodes on the top surface of the chip. We first utilized a Langmuir-Blodgett assembly method to achieve an aligned array of CMFs on the surface of the chip. Next, multiple electron-beam lithography and metal deposition steps were done to form the ohmic contacts and precisely define the active sensing region of the CMF electrodes.

Capacitance-voltage measurements were conducted to study the equivalent electrical circuit model at electrode-solution interface. From these measurements, we extracted the parameters of the circuit model including the electrical double layer capacitance and the pseudo capacitance. Such an accurate circuit model is critical for the proper design of the readout circuit to (i) guarantee the stability of the circuit, and (ii) increase the overall sensitivity of the sensor platform. We have also performed a series of systematic experiments to examine the sensitivity of our multi-electrode sensor platform for in vitro detection of dopamine. In particular, we present the effect of traditional and extended waveforms for performing FSCV on the sensitivity of the CMF sensors. Further, the area dependent sensitivity of CMF electrodes will be discussed. Finally, we discuss our results on the fabrication of multielectrode neural probes using our new sensor platform.

In summary, our new sensor platform opens up the possibility for creating next-generation neural probes that are capable of recording chemical signals with high spatiotemporal resolution.

We propose a new process for fabricating highly stretchable and transparent electrodes, where the micro-grid of a gallium-based liquid metal is embedded within a transparent elastomeric matrix. Although metal oxide-based transparent electrodes are being employed in various commercial applications extensively, there has been an increasing demand for not only transparent but also stretchable electrodes, for more versatile applications in future displays or wearable systems. In previous approaches, stretchable and transparent electrodes have been obtained mainly by dispersing carbon nanotubes or metal nanowires on an elastomeric substrate, but it is still difficult to achieve high reliability and reproducibility especially for large-area applications. Although transparent grid structure of solid metals such as Cu or Ag has been demonstrated to enable highly reproducible and low-cost fabrication of large area electrodes, it can provide only flexible (or bendable) but not stretchable characteristics. In the present work, we demonstrate a new technique for producing highly stretchable and transparent liquid-metal mesh structures, utilizing photolithography-based patterning and transfer processes for the eutectic gallium-indium liquid alloy (EGaIn). By combining the roll-printing technique with the classical lift-off process based on photolithography, we produced fine mesh patterns of EGaIn on a rigid Si substrate with the line-width as narrow as ~20μm and the line-pitch varying from 400 to 1000μm. Then, by transferring the liquid metal grid onto a stretchable polydimethylsiloxane (PDMS) substrate, we finally obtained stretchable and transparent electrodes with the sheet resistance below 10 Ω/sq and transmittance over 80% at the wavelength of 550 nm. Those electrodes demonstrated good stretchability with the initial sheet resistance maintained even after 1,000 cycles of 50% repeated stretching, which shows that the liquid metal can provide high stability against fatigue failures. Being highly compatible with conventional microfabrication processes and based on beneficial characteristics of the liquid metal as a fluidic conductor, this new method is expected to be useful in various applications requiring transparent electrodes with both low-resistance and high stretchability. This work was supported by Institute for Information & communications Technology Promotion (IITP) grant funded by the Korea government (MSIP) (B0101-16-0133, The core technology development of light and space adaptable energy-saving I/O platform for future advertising service).

Epidermal pressure sensor is an important element in wearable devices for monitoring real-time physiological signals in medical application or exercise conditions, in which the application of soft electronic material is essential. Since the successful realization of surface-based electric contact pressure sensor, the complicate fabrication process increases the cost of the device and are not environmentally friendly during manufacturing, as well as the sensor does not fully take good advantage of the elastomer electrical properties. It has been desired to form a cost-effective conformable pressure sensor so as to exploit it extraordinary sensing performance and biocompatible properties. In this work, we report a novel stretchable pressure sensor based on microstructured silver - polydimethylsiloxane (Ag-PDMS) composite elastomer. The strategy for improving the sensing properties is by using the compression-induced percolation and microstructure electric-contact wherein bulk and contact electrode can both work together. The potentialities of the microstructured Ag-PDMS elastomer as stretchable pressure sensor were tested for its epidermal pressure sensing capabilities. The effect of the microstructured Ag-PDMS stretching and bending on its applied pressure response is also studied, and it is found that the sensor can have a good robustness with high sensitivity. Since the silver volume fraction in PDMS is tunable, therefore the pressure sensitivity of microstructured Ag-PDMS composite is also tunable. The excellent sensing properties of microstructured Ag-PDMS, together with its advantages of large area fabrication and versatility in detecting various pressure signals, make microstructured Ag-PDMS elastomer a good potential for epidermal pressure sensor in wearable device applications.

The creation of artificial skin that shows the tactile-sensing capability of human skin has been a big challenge in tactile sensor research. In spite of intensive effort in this area, all existing approaches are constrained to a narrow pressure regime in terms of both sensitivity and stability. Thus, in order to overcome the limitations of existing reports and to find a scientific breakthrough point, the exact understanding of the cutaneous somatosensory receptors (Merkel cell-neurite complexes, Pacinian corpuscles, Meissner's corpuscles and Ruffini endings) as well as an interlocked structure at the epidermal/dermal junction in human skin is strongly required.
In this talk, inspired by the physiological tactile sensing mechanism of human skin, we describe a homeostatic and ultrasensitive stretchable artificial skin based on an ionic mechanotransducer, in which we directly addressed the sophisticated physiological tactile sensing mechanism of human skin. To this end, we emulated the ionic mechanotransduction channel with a piezocapacitive ionic mechanosensory system that engages in ion migration when the polymer matrix is deformed under a mechanical non-equilibrium state. The artificial skin is unprecedented in its ability to sustain a high sensitivity over a wide spectrum of pressure (10nF kPa^-1 at 0-30kPa) with homeostatic operation at an ultralow-voltage (1mV). We also described that this novel artificial skin sensor allows for voice identification, health monitoring, daily pressure measurements and even measurements of a heavy weight beyond capabilities of human skin.
We believe that if we can directly mimic a physiological sensing mechanism in other functional skin receptors (thermoreceptor, muscle-spindle stretch receptor, etc.), we will encounter a multimodal artificial skin that is capable of simultaneously perceiving various stimuli, such as temperature, humidity, posture and movement.

Although thermochromic displays are flexible, cheap and simple to fabricate, its use is limited to simple on/off display because the resolution and shape of thermochromic indicator is predefined by conductive heater array, which act as a block to use thermochromic display as free shape and interactive display. Here, we present a selectively actuated thermochromic display using pressure responsive current source array. This device consists of thermochromic indicator panel and resistive pressure sensor array as a current source to activate joule heating layer connected to thermochromic layer. By applying pressure to thermochromic panel, joule heating layer is partially connected to electrode on pressure sensor array and acts as current bridge between separated electrodes. Current causes joule heat, which activates thermochromic color changing. The device can be used as interactive display that indicates magnitude of pressure visually without any external processing. We investigate the relation between external force and color changing.

In this research, we design the silver nanocrystal (Ag NC) thin films for the skin direct mountable and wearable strain sensor device to monitor the human motion and activities. We investigate the electrical and electromechanical properties of Ag NC thin films with different ligand treatments. In the case of inorganic ligands treatment, Ag NC thin films show very low resistivity of 1 x 10^-4Ωcm, and exhibit strain insensitive resistance behavior, with the gauge factor less than 1.5. However, in the case of the organic ligands treatment, the Ag NC thin films show relatively high resistivity of ~ 1Ωcm and show strain sensitive resistance behavior with the gauge factor up to 70. Structural, chemical, and optical analyses were performed to understand this phenomenon. The inorganic ligand treated Ag NC thin films show sintered Ag NC structures with the almost no gap between each NCs, which is the origin of the low gauge factor. However, the organic ligand treated Ag NC thin films show a clear gap between each NCs without any sintering or grain growth. The hopping transport of carriers through this gap is turned out to be the origin of the high gauge factor, as the hopping transport is dramatically affected by the interparticle distance. As the inorganic treated Ag NC thin films is highly conductive and show almost no resistance change even up to the extreme strain of 10%, the materials was used to fabricate electrodes. We use the active strain sensor with the organic ligand exchanged AgNCs which shows high gauge factor even with 0.1% strain gauge.
Finally, we fabricated the 4 x 4 strain device arrays using only with one material of AgNCs but with the different treatments for bioelectronic applications. The row and column electrode lines were formed by inorganic ligand exchanged Ag NC thin films, and 16 sensing parts were made by organic ligand exchanged Ag NC thin films using by multi step photolithography. The fabricated multi cell strain sensor device was processed by all solution based techniques at low temperature without expensive vacuum based techniques, providing a pathway to realize the high performance bioelectronics devices.

Sensors to detect motion with high precision using sensors has been extensively studied in diverse engineering research fields. In order to adapt electronic devices to human body, various studies have been carried out. In most case, the existing sensors, however, are opaque due to the limitation of the materials they use. Transparent devices have strong adaptability in various fields such as display panels, but have not gained much academic interests. In this paper, we present a high sensitive pressure and strain sensor based on a transparent epilayer, Indium-Tin Oxide (ITO), deposited on a transparent PET substrate. This sensor system exhibits ultra-sensitivity (with gauge factor about 4000 at strain of 2%) and transparency (up to 89% at wavelength of 560 nm). Also, we introduce transparent pressure sensor matrix with 89% transparency and sensitivity of 0.21 kPa^-1 at pressures from 0 to 30 kPa and 1.91 kPa^-1 in the range from 30 kPa to 70 kPa. We demonstrate detecting pressure and finger motions by using this transparent sensor, which boasts broad applications including touchscreens and detecting complex motion of human.

Rapid and accurate detection of pathogens is paramount to human health. Spectroscopic techniques have been shown to be viable methods for detecting various pathogens. Enhanced methods of Raman spectroscopy can discriminate unique bacterial signatures, however many of these require precise conditions and do not have in vivo replicability. Common biological detection methods such as rapid antigen detection tests have high specificity, but do not have high sensitivity. Here we developed a new method of bacteria detection that is both highly specific and highly sensitive by combining the specificity of antibody staining and the sensitivity of spectroscopic characterization. Bacteria samples, treated with a fluorescent antibody complex specific to Streptococcus pyogenes, were volumetrically normalized according to their Raman bacterial signal intensity and characterized for fluorescence, eliciting a positive result for samples containing Streptococcus pyogenes and a negative result for those without. The normalized fluorescence intensity of the Streptococcus pyogenes gave a signal that is up to 16.4 times higher than that of other bacteria samples for bacteria stained in solution and up to 12.7 times higher in solid state. This method can be very easily replicated for other bacteria species using suitable antibody-dye complexes. In addition, this method shows viability for in vivo detection as it requires minute amounts of bacteria, low laser excitation power, and short integration times in order to achieve high signal.

Creating artificial muscle that emulates the capability of human muscle has been a big challenge in stretchable haptic research. In particular, ionic electroactive polymer (i-EAP) actuator has been regarded as a promising candidate for mimicking human muscle due to low operational voltage and mechanical flexibility. Artificial muscles by i-EAP actuators, however, suffer from keeping displacement and stability consistent in high operation frequencies, which comes from slow ion migration into active channel. In this manner, engineering of an optimal ion transport in the ionic films as well as mechanical properties of actuators is strongly required to allow fast actuation under electrical stimuli in the solid-state.
In this talk, we describe an unprecedented high-speed i-EAP actuator by engineering microstructure of ion channel at the interface of ionic elastomer and flexible conducting polymer electrode, Poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT:PSS). To this end, the PEDOT:PSS electrodes are formed onto both sides of ionic elastomer with an optimal content of ions using well-controlled spray-coating method. The actuator implemented by us was successfully operated with a large displacement up to 4mm (strain=0.55%) at an operating frequency of 0.1Hz under an applied voltage of 1.5V. Further, the actuator shows high-speed response under the bending strain of 0.15% and the displacement of 0.92mm even at frequency of 30Hz, which is equivalent to 100 folds improvement compared to the values reported in the literature. This result indicates that controlling an interpenetration depth of PEDOT:PSS chains into the ionic elastomer not only decreases an internal resistance between two electrodes, but also forms more effective and microstructured ion conducting channel, thereby leading to larger displacement and faster response of actuators even under low voltage bias.
We believe that high-speed i-EAP actuator demonstrated by us will be an effective way to implement human-interactive smart haptics capable of recognizing the human-environment interface and a novel engineering design for smart artificial muscle capable of physiologically actuating under electrical stimuli.

As the internet of things (IoT) has risen as the gold market, many applications have started to embed various sensors to products such as healthcare devices and bio electronics. Pressure sensor, one of diverse sensors, can be used to detect various strains by comparing the change of resistance. The pressure sensor is usually composed of the metal; however, the metal-based pressure sensor previously shown low flexibility due to its material limitation. To solve this problem, many studies have been investigated using a modification of mechanical design such as a horseshoe structure, an island-bridge structure, etc. However, in order to fabricate these structures, most researches used photolithography resulting in higher fabrication cost and complexity. In this study, we fabricated the island-bridge pressure sensor consisting of metal-island with carbon nanofiber (CNF) using the intrinsic segregation property of the CH₃NH₃PbI₃ film. This will give a solution to the pressure sensor with a simpler method and lower cost than the conventional pressure sensor.
For the fabrication of metal-island, each concentration (low, medium, and high) of the CH₃NH₃PbI₃ solution was spin coated onto the polyethylene phthalate substrate resulting in intrinsic segregation surface. Then, Al was deposited using the reactive frequency sputtering, and etched in water for 20 min in ultra-frequency sonication due to the high solubility of CH₃NH₃PbI₃ in water. For the pressure sensor, CNF was spin coated on the metal-island film for connecting the each metal-island. To investigate the bi-directional pressure sensor, we performed the resistance change test under external forces. As a result, the relative change of resistance was ~120% under upward force and ~60% under downward force.

We report a bio-inspired conductive membrane with micro-scale hierarchical porosity, nano-scale electrical pathways, and tissue-like softness. Our membrane conductors have unique bendable and stretchable conducting properties. Polycaprolactone (PCL) membrane was coated by molecularly controlled layer-by-layer (LBL) assembly with several types of soft polymers and carbon nanotubes. Since the membranes have asymmetrical porous architecture, electrical connections could be differently increased on the micro-pore surface along the bending direction. Moreover, synergetic effect of 3D porous and elastic nature of the template membrane and stable interconnected LBL coating of conductive SWNTs could provide effective conductivity under the both bending and stretching deformation. Our novel platform as a conducting membrane will provide a significant solution to solve long-lasting challenges for biomedical conducting applications.

To fully understand how the brain functions, scientists rely on the technological developments for studying brain activities with simultaneous electrical, chemical and mechanical signaling from the cellular level to the circuit and behavioral level. In the past few decades, silicon-based neural probes, owing to their miniature size, high density and good signal to noise ratio (S/N), have significantly advanced the field of neuroscience by allowing researchers to study neuronal interactions in a complex network via electrical stimulation and recording. However, their long-term application is limited as probe implantation injury results in glial scarring, an inflammatory response, and neuronal death; factors that lead to progressive S/N degradation. In addition, traditional silicon-based neural probes are unable to differentiate neuronal signals. Therefore, there is a great need for innovative technology facilitating flexible and multifunctional probes. Among emerging innovations, thermal drawing process, widely used in drawing optical fibers in the telecommunication industry, has been demonstrated as a novel scalable fabrication method for flexible polymer fibers. It can integrate multi-materials and multi-functions, such as micro-electrodes, microfluidic channels and optical waveguides. Nevertheless, fiber-based neural probes have all the functionalities restricted to the tip, where surface area is planar and limited (diameter < 400 um), thus it restricts the study of neuron signaling in the context of neural circuits. In order to address this issue and realize functionalization along the length of the fiber, the biggest challenge is to precisely position, locate and machine fibers that are as thin as human hair. Here, we poineered a femtosecond (Fs) laser micromachining technique which, thanks to its non-thermal ablation, allows for the patterning of sub-micron features independent of the material. With this technique, we are able to create high-precision 3D structures and patterns at specific sites along the length of the fiber, for example square openings, spiral patterns or grooves. Therefore, polymer fiber based neural probes with depth dependent multimodality are developed via exposing electrodes, microfluidic channels and optical waveguides with controlled opening sizes and patterns at specific locations along the fiber. It realizes simutaneous electrical recording, optical stimulation as well as chemical delivery to different brain regions. This is a big step towards our ultimate goal of studying neuronal activities in a network and establishing the causal link between the neuronal activities and behavior output.

Electronics for future requires active and electrically stable performance under the large strain condition so as to utilize for the applications in electronic sensors, stretchable displays, energy related devices, and smart clothing. However, good conductivity and stretchablilty are the parameters that are hard to attain simultaneously so there are many attempts to overcome this limitation. For example, carbon nanotubes based nanostructures, conductive filler-elastomers composite and liquid metal and rubber interpenetrating networks are widely studied.
Recently, among those approaches, many reports show that highly stretchable circuits can be designed using conductive composites which show good conductivity at tens of strain range. Conductive fillers used in these systems are Ag nanoparticles, Ag nanowires and Au nanosheets. Rubbery block copolymers combined with these conductive materials retains metal networks so that helps conductivity to be preserved at large strains. Up to date, to describe conducting behaviors of various dimension conductive fillers in the elastomers, percolation theory is proposed by theoretical and simulation studies. But, nanoscale mechanisms by direct observation in this aspect have not yet reported so far. So the fundamental origin of conductivity changes of conductive composite during highly strained range (above 100%) or numerous cycle test remains unsolved. Moreover, according to the modulus difference of each block copolymer in the composites that holds together each filler, the stress and strain distribution in composite during deformation will be varied naturally. But this aspect has been neglected in this field although this is one of the major factors maintaining nanomaterial networks and conductivity against the fracture. In this sense, we will discuss mechanodynamics of electrode materials network during deformation by in situ Transmission Electron Microscopy (TEM) straining experiment to complement undiscovered part of the percolation theory. Also, effects of micro domain and modulus variation of block copolymers to the networks between fillers during straining and its correlation with electrical behaviors will be investigated simultaneously by Small Angle X-ray Scattering (SAXS). These basic studies of stretchable electrodes will broaden our knowledge of mechanical behaviors of filler-block copolymer composites and will be expected to utilize as a novel strategy of designing conductive composite material for better performance.

Picosecond (ps) laser fabrication offers novel design and fabrication opportunities for implantable electrodes. Through cold ablation metal foils can be thinned down to several µm and subsequently be coated in parylene C. These electrode arrays feature different thicknesses in one assembly to allow simple implantation transversally through a nerve while also offering high structural strength. However, in terms of charge delivery these electrodes have the disadvantage that established electrode coatings like iridiumoxide cannot be used due to incompatible fabrication processes.
We introduce controlled corrosion of platinum foils via excessive pulsing as means to increase the active electrode surface to overcome stimulation limitations.

The presented electrode arrays have been fabricated from a 25 µm thick platinum iridium foil which was thinned and cut with a LUMERA LASER Rapid10 ps laser system to 10 µm at points of interest. Deposition of Parylene C was carried out within in a SPECIALITY COATINGS SYSTEMS PDS 2010 process chamber.
In a first step the electrode arrays were characterized in terms of electrochemical impedance spectroscopy (EIS) with a SOLARTRON 1260&1287 potentiostat and frequency analyzer as well as with a PLEXON PLEXSTIM Electrical Stimulator system for their maximum charge injection capacity. Controlled corrosion was achieved by pulsing the electrodes following a corrosion map for platinum alloys. By setting either the top and/or bottom limit of the voltage response outside the water window different states of passivation, corrosion or platinum black formation were achieved.

An increase in maximum charge injection capacity from initially 75 μC/cm² to 450-550 μC/cm² could be observed. EIS measurements however showed a change in the underlying electrode model based on the Randles’ cell from a standard R||C-R electrode model towards the appearance of constant phase elements (CPE).

Feasibility of removal of electrode material instead of addition of a coating to improve electrochemical behavior in flexible laser fabricated electrode arrays has been shown. However, long term studies have to be conducted to prove stability for medical applications.

Ionic transport is of increasing significance to enable controlled interplay between technical and biological systems. It allows on one hand the realization of novel electronic devices (ionic resistors, ionic bipolar transistor, and memristors) and on the other hand direct contacts to biological systems and individual cells with controlled electrochemical potential.
Hydrogels offer attractive properties as ionic transport media for such bio-inspired applications. Depending on the polymeric matrix and its manufacturing process their ionic (ion selectivity, transport resistance) and mechanical properties (strength, flexibility, and elasticity) can be adjusted to the needs of the intended application.
Dynamic ionic processes are the main key to transportation and communication via the cell membrane. In biomedical applications artificial passive ionic channels of hydrogels can adjust the ionic transport resistance, ion selectivity and thus ionic flux. Based on the thermodynamic diffusion process of the ions in the hydrophilic channel, the ionic resistance is determined by geometry and polymeric matrix. By applying voltage along the ionic channel the transport of the ions can be supported or restrained by the electrical field with respect to polarity.
Hydrogels like polyacrylic acid (PAA) have a flexible, stretchable appearance and structural biocompatibility. The preparation of the PAA hydrogel bases on photo induced polymerization of a mixture of acrylic-acid monomers, a photo-initiator (DMPA - Dimethoxyphenylacetophenone), and a crosslinking additive (PEG550DMA - Polyethylene glycol dimethacrylate). The investigations focus the ionic flux with respect to the properties of dissolved ions, in particular the ion radius and valence, and the polymeric structure, set by the chemical composition and process of the hydrogels. Therefore PAA-ribbons with two reservoirs for the liquid electrolyte were produced. A source-measuring-unit applies a DC-Voltage over Ag/AgCl- Electrodes, which are dipped in the electrolyte. The measured current can be distinguished in an electrical and ionic part. Since the electrical current is constant, given by the electrical resistance of the hydrogel ribbon without wetting with the electrolyte the ionic flux can be determined. Preliminary data indicate an ionic flux of aqueous NaCl (0.1 M) through the hydrogel of 5.9 pg/(mm^2 s V).

Strategies to combine the mechanical properties of elastomers and the biocompatibility and high water content of hydrogels to obtain enhanced hybrid materials have been previously reported. However, these hybrid materials are seldom tunable and are prone to delamination (unless porous elastomers are used) due to lack of adhesion and different surface chemistries of the individual components. Enabled by our recently-developed method to make a strong bond between hydrogels and elastomers, we present in this talk a strategy to make hydrogel sheets with highly tunable modulus, ranging from 40kPa to 800kPa. These hydrogel-elastomer structures are resistant to delamination upon stretching and retain useful properties of both hydrogels and elastomers. Moreover, due to the presence of an elastomer layer, these hydrogel sheets are non-permeable to small molecules. Taking advantage of this property, we demonstrate pH sensing and drug delivery to two different environments using our non-permeable hydrogel sheets, novel capabilities that can be harnessed for wearable devices, healthcare and biomedical applications.

Animal bodies are mainly composed of hydrogels — polymer networks infiltrated with water. Most biological hydrogels are mechanically flexible yet robust, and they accommodate transportations (e.g., convection and diffusion) and reactions of various essential substances for life – endowing living bodies with exquisite functions such as sensing and responding, self-healing, self-reinforcing and self-regulating et al. To harness hydrogels’ unique properties and functions, intensive efforts have been devoted to developing various biomimetic structures and devices based on hydrogels. Examples include hydrogel valves for flow control in microfluidics, adaptive microlenses activated by stimuli-responsive hydrogels, color-tunable colloidal crystals from hydrogel particles, complex micropatterns switched by hydrogel-actuated nanostructures , responsive buckled hydrogel surfaces, and griping and self-walking structures based on hydrogels . In particular, as unprecedented amounts of electronic devices are being integrated with human body , hydrogels with similar physiological and mechanical properties as human tissues represent ideal matrix/coating materials for electronics and devices to achieve long-term effective bio-integrations. However, owning to the weak and brittle nature of common synthetic hydrogels, existing hydrogel electronics and devices mostly suffer from the limitation of low mechanical robustness and low stretchability. On the other hand, while hydrogels with extraordinary mechanical properties have been recently developed , it is still challenging to fabricate tough hydrogels into stretchable electronics and devices capable of novel functions. The design of robust, stretchable and biocompatible hydrogel electronics and devices represents a critical challenge in the emerging field of soft materials, electronics and devices.
Here we report a set of new materials and methods to integrate stretchable conductors, rigid electronic components, and drug-delivery channels and reservoirs into biocompatible and tough hydrogel matrices that contain significant amounts of water. The resultant hydrogel-based electronics and devices are mechanically robust, highly stretchable, biocompatible, and capable of multiple novel functions. We show that the design of robust hydrogel-solid interfaces is particularly important to the functionality and reliability of stretchable hydrogel electronics and devices. Programmable delivery and sustained release of drugs can be achieved by controlling the flow of drug solutions through selected channels and reservoirs in hydrogel matrices at both undeformed and highly stretched states. We further demonstrate novel applications including a stretchable LED array encapsulated in biocompatible hydrogel matrix, and a smart hydrogel wound dresser that is highly stretchable, transparent, and capable of sensing temperatures at different locations on the skin and sustained release of various drugs to specific locations accordingly.

Rapid quantification of ions in bodily fluids is important for preventive care (nutrition) as well as pathology diagnostics. For example, a potassium levels in blood below 3 mM is indicative of abnormal heart rhythms. We are developing electrochemical micronutrient sensing platforms based on voltammetric solid state ion-sensing, using potassium (K⁺) as our first target. Paper-based analytical platforms are useful for point-of-care measurements because of their simplicity, low cost, portability and disposability[1,2]. They would be an alternative to customarily used ion-selective electrodes, which are fragile, more costly, and subject to biofouling[3].
The proposed potassium quantification is based on the measurement of shift in the redox potential of an electroactive layer (Prussian blue) as a function of concentration in K⁺[4,5]. We explored the best conditions for electrodepositing Prussian blue using commercial screen-printed electrodes and successfully tested aqueous solutions containing K⁺ in the range of 0 to 1 M. We also investigated interferences from other electrolytes such as sodium ions. We implemented the assays on paper-based electrochemical devices obtaining flexible and disposable ion sensing tools with an average relative standard deviation of less than 10 % out of 13 independent paper-based devices manually fabricated.
The next steps of the project include the tests of human serum samples throughout the relevant health range (3.5-5 mM).

References:
[1] Maxwell, E. J.; Mazzeo, A. D.; Whitesides, G. M. MRS Bull. 2013, 38, 309.
[2] Nie, Z. H.; Deiss, F.; Liu, X. Y.; Akbulut, O.; Whitesides, G. M. Lab Chip 2010, 10, 3163.
[3] Lan, W.-J.; Zou, X. U.; Hamedi, M. M.; Hu, J.; Parolo, C.; Maxwell, E. J.; Buhlmann, P.; Whitesides, G. M. Anal. Chem. 2014, 86, 9548.
[4] Ho, K.-C.; Lin, C.-L. Sens. Actuators, B 2001, 76, 512.
[5] Ang, J. Q.; Li, S. F. Y. Sens. Actuators, B 2012, 173, 914.

This paper presents the results of lamination of organic solar cells and light emitting devices using a combined experimental, computational and analytical approach. The effects of applied lamination force (on contact between the laminated layers) are studied before estimating the crack driving forces associated with the interfacial cracks (at the bi-material interfaces). The critical interfacial crack driving forces associated with the separation of the thin films, after layer transfer, are then estimated to predict the condition for successful lamination using a combination of experiments and computational models. The results are then used to provide guidelines for the lamination of low-cost electronic devices.

An ideal skin-like sensor will be light-weight, flexible, and scalable. In working toward these goals, recent efforts in skin-like sensing have focused on the use of micro-scale active components in arrays of patterned transistors. While this approach maintains high sensitivity in transmitted measurements, it requires complex fabrication. Furthermore, patterned grids of wires for sensing touch require an increasing number of interconnects and real estate on the devices. This work presents a passive approach for scalable skin-like sensing based on resistive networks of capacitors. The scalable sensors are simple to fabricate with laser-based ablation of metallized paper to vaporize material and create distinct conductive regions or traces. This technique permits patterning of resistive and capacitive components in a single layer. With the designed patterns shown in this work, it is possible to detect human touch through the patterned capacitive buttons and distinguish multiple points of contact with only two wired leads.
Detection of multiple points of touch is possible using swept-frequency identification, and this work details an approach to modeling the frequency response of human touch. To model the sensing of human touch and design the passive circuitry, the authors build libraries of look-up-tables, in which the frequency response of human touch on a single button is equivalent to that of a frequency-dependent resistor and capacitor in series. In addition, this work demonstrates the fabrication and characterization of arrayed touch sensors. One example includes a wearable skin-like device that is capable of detecting touch at multiple locations with only two wired leads. Another example consists of a device for detecting applied droplets of water. The final example demonstrates how two wired leads are capable of detecting touch from 31 distinct buttons laid out in the format of a conventional keypad.
Overall, this work demonstrates a new scalable technique for disposable sensors. The sensors – made of paper – are also biodegradable and renewable for minimal impact on the environment. Future applications might include wearable human-machine interfaces, interactive art and architecture, or smart sensing embedded in civil infrastructure for detection of moisture and leaks.
Key words: artificial skin, touch sensor, paper-based electronics

Electrically conductive fibers are not a new technology. Patents for conductive fibers for antistatic fabrics and floor coverings have been published in the late 1970s. However, these materials could barely be considered conductive, having high resistance values. A more modern resurgence in the interest in textile fibers that conduct electricity has occurred in the last decade or so. This interest is mainly due to the discovery of graphene and carbon nanotubes (CNTs) and the astounding electrical properties that it provides. This allows for textiles that are structurally strong as well as able to carry electrical current without much internal resistance. These advances are useful because in the field these textiles have a variety of potential uses, mainly the ability to be sensors for a variety of measurement types. Sensors such as conductive fibers for measuring joint movements, unobtrusive vital sign detection systems, and the ability to detect damage in a textile or composite material are all uses for conductive fibers that have been investigated. In the context of flexible body armor, which is mainly made of Kevlar weaves, the ability to electronically detect damaged fibers could be useful in assessing whether or not the integrity of the armor has been compromised. Other types of biological and structural sensors will be investigated as well. The main topics of this research are to investigate different coating methods and materials in order to make Kevlar a conductive fiber and secondly to test these manufactured fibers both structurally against untreated (stock) Kevlar and electrically against other types of conductive fibers/conductive materials.
Kevlar by and large is an insulator and is known for its low thermal conductivity. The first part of this study will be to investigate methods and procedures to dye Kevlar KM2 yarns in order to make them conductive. Current methods call for coatings with CNTs or graphene nanoribbons. The methods will be developed in-house in our Advanced Materials and Structures Laboratory (AMSL). The infusion of graphene nanopowders as well as graphite flakes will also be investigated.
The second part of this study involves first determining the base resistivity range of the fibers that are produced and investigating the relationship between stress applied to the fibers, the strain exhibited by the fibers, and the change in resistance as these fibers are strained. An Instron tensile test machine outfitted with fiber clamps in conjunction with a four-probe resistance testing multi-meter would be used to perform these kinds of tests. Preliminary tests have been performed on proprietary conductive fibers supplied by NASA. Currently there needs to be more construction on this experimental aspect of the setup; results are not conclusive since data recording by the multi-meter needs to be synchronized to the time-load-displacement data output by the Instron machine to achieve accurate results.

The development of nanotechnology for the improvement in the performance of existing devices and adding novel functionalities is significant recently. Within the field of bioanalytics, nanosensors based on graphene with delicate sensitivities down to the level of single molecule and fast responding analysis time lead to the possibility of rapid and potentially price reasonable point-of-care diagnostics for medical screening application. Existing sensing platforms are predominantly device that transduces the signal through specific molecular conformation via the functionalization of the sensor surface with the specific binding molecules preferentially binding to the target molecule, inducing a change in the property in functionalized surface of the sensor. However it is challenging to collect in-situ imaging information of the affinity of specific binding molecules to the target molecule on the nanoscale in liquid environment for the improvement in the nanosensor performance due to the limitation of TEM in thin solid samples.

Rapid development in liquid cell TEM leads to the possibility of studying the correlation of the affinity of specific binding molecules to the target molecule on the nanoscale and detection performance in real time. We collected in-situ imaging results of an active biosensors consisting of chose neuropeptide Y (NPY) as target molecule, N2 peptide grafted Au nanoparticle as the biomarker and functionalized CVD synthesized graphene containing tethered P1N3 peptide in liquid cell TEM experiments and analyzed the binding process among these three different protein molecules to form linear bioconjugate (P1N3/NPY/N2-g-Au NPs) grafted to the graphene on the nanoscale in real time. The relationship of the ability of binding NPY molecule and biomarker to functionalized graphene and the performance of this active biosensor can be established quantitatively by the measurement of these in situ videos. Results showed 1. Surface property of graphene dominates the amount of tethered P1N3/NPY/N2-g-Au NPs bioconjugates 2. Tethered bioconjugates and cup shaped NPY self-assembly nanostructures coexist 3. Tethered Au nanoparticles vibrate on few nm scales. 4. The motion of these NPY nanostructures exhibits water thickness dependence. We observed rotation; vibration and free motion of these cup shaped nanostructures 5. Nucleation, growth and dissolution of gold NPs driven by the electron-water interactions take place by adjusting electron doses.

Sustained release of drug formulations in buccal region of the oral cavity have been gaining popularity and medical acceptance worldwide. Major challenges for such patches are biocompatibility, drug loading capacity, drug release efficiency, directionality of drug release and finally controlled time dependent biodegradation, which are yet to be handled efficiently. At this very end, we have prepared novel polymer-graphene (PolyGraphene) based drug loaded medi-patches and hosted them in natural polysachharide, chitosan based patches for better effect. Polycaprolactone (PCL) was melted and mixed with graphene (GR) via hydro-thermo-evaporation method to prepare medi-patches with (Nic-PCL and Nic-GR-PCL) or without loaded drug (PCL and GR-PCL), Niclosamide, a known inhibitor for cancer stem-like cells via STAT-3 (Signal Transducers and Activators of Transcription) inhibition pathway. Furthermore, medi-patch was integrated with a highly sensitive biosensor to study the behavioural response during drug release. Au based µ-electrodes were fabricated using an e-beam evaporator.
The scanning electron microscopic (SEM) investigation revealed the layered structures of prepared medi-patches and raman spectroscopic data showed distinguished features of all components in medi-patches. These medi-patches were found to be responsive in releasing Nic in time dependent manner where GR found to be playing the role of release controller. MTT and trypan blue assay revealed that patches devoid of Niclosamide were very safe to be used with cells giving only 2 to 4% dead cell population after 48h incubation. Cells treated with medi-patches were 45±2.5% dead when treated with Nic-GR-PCL whereas cell death with Nic-PCL was reported as 35±5% by trypan blue assay at 72h time point. Developed sensor with electronic circuitry will be looped with Bluetooth module for monitoring of signals during drug release. Thus, highly potential mucoadhesive medi-patches for inhibition in stem like cell population have been prepared with unique ability of tracking drug release. This medi-patche could be extended to decrease in CD44 positive cells in cell population to make it promising product for anti-stem like cancer therapy via mucoadhesion.

Organic electrochemical transistors (OECTs) are excellent candidates for an application in bioelectronics devices, e.g. for sensing, drug delivery and brain activity measurements. Poly (3,4-ethylenedioxythiphene) (PEDOT) doped with anion is a conducting polymer that has been mostly used as an active material for the fabrication of OECTs. Flexible and stretchable substrates are good candidates for a large array of biological applications, where they are used as a support/base for the interface between the world of electronics and the world of biology. We fabricated OECTs with a channel made of PEDOT doped by Tosylate (PEDOT:Tos) nanofibers on flexible polyethylene terephthalate (PET) and stretchable polydimethylsiloxane (PDMS) substrates. The commonly used anionic dopant polystyrene sulfonate (PSS) of PEDOT was replaced by non-polymeric tosylate dopant. Furthermore, PEDOT:PSS thin films were replaced by nanostructured PEDOT:TOS fibers, with high porosity and high surface to volume ratio in order to achieve a high current modulation at low operating voltage and reversibility of the doping/dedoping process. The combination of a versatile technique like electrospinning and the vapor phase polymerization (VPP) was exploited to obtain the PEDOT nanofibers [1].
In order to achieve oxidant fibers, a mixture containing the carrier polymer poly(vinylpyrrolidone) (PVP) (Mw = 1,300,000), the oxidant iron tosylate (Fe(III)Tos) in butanol and a base inhibitor imidazole was electrospun on the channel of a pre-patterned OECT device. Polymerization was carried out in the VPP chamber containing the EDOT monomer, under passive vacuum of 45 mbar, using the VPP technique. The morphology of the fibers was characterized using transmission electron microscopy (TEM), scanning electron microscopy (SEM), and atomic force microscopy (AFM). The conductivity of fiber mats was measured with the four-point probe method. The diameters of the obtained fibers were around 400-700 nm. The electrical characterization of PEDOT nanofiber transistors (transient, transfer, output characteristics) was carried out. The electrochemical analysis like cyclic voltammetry and electrochemical impedance spectroscopy was investigated. Our results, besides opening new opportunities to study the operating mechanism of OECTs, pave the way to new exciting bioelectronics applications.

[1] Laforgue, A., & Robitaille, L. (2010). Production of conductive PEDOT nanofibers by the combination of electrospinning and vapor-phase polymerization. Macromolecules, 43(9), 4194-4200.

There is considerable interest in the in-vitro study of growth and guidance of biological cells in simulated “near in-vivo” environments. It has already been shown that neural guidance can be enhanced by careful patterning of semiconductor microtubes^1–3 and ripples⁴ on the growth substrate.
By using multiphoton lithography in conjunction with traditional semiconductor processing techniques we have created 3D structures for the growth of neural cells. We present results of the seeding and growth of cortical neuron cells on patterned Si nanomembranes (NMs) transferred onto glass substrates. Cultures are also carried out on NMs suspended on 3D fabricated gelatin structures. These structures and the fact that the NMsare extremely compliant⁵ present the cells with a 3D environment where neurite growth characteristics and dynamics are known to be different than in classical 2D culture environments. We demonstrate selective seeding and growth of neurite cells on 3D fabricated and patterned Si NMs. These NMs could potentially be used for electrical measurements while simultaneously carrying out live cell optical imaging.
Patterned polymer substrates with stiffness grading are prepared using conventional and multiphoton lithography. These are then covered with ultrathin Si NMs, which appear transparent⁵ while at the same time presenting an impervious and chemically identical surface to cells under investigation. Raman spectrography and time-lapse optical measurements on such surfaces allow us to study in real time the interaction and behavior of cells on substrates having stiffness variations.
The growth of biological cells on these 3D structures opens an exciting new area of study that allows us to combine techniques from biology and materials engineering.

1. Yu, M. et al. Semiconductor nanomembrane tubes: Three-dimensional confinement for controlled neurite outgrowth. ACS Nano 5, 2447–2457 (2011).
2. Bausch, C. S. et al. Guided neuronal growth on arrays of biofunctionalized GaAs/InGaAs semiconductor microtubes. Appl. Phys. Lett. 103, 2013–2016 (2013).
3. Froeter, P. et al. Toward intelligent synthetic neural circuits: Directing and accelerating neuron cell growth by self-rolled-up silicon nitride microtube array. ACS Nano 8, 11108–11117 (2014).
4. Cavallo, F., Huang, Y., Dent, E. W., Williams, J. C. & Lagally, M. G. Neurite Guidance and Three- Dimensional Con fi nement via Compliant Semiconductor Sca ff olds. ACS Nano 8, 12219–12227 (2014).
5. Cavallo, F., Grierson, D. S., Turner, K. T. & Lagally, M. G. ‘Soft Si’: Effective Stiffness of Supported Crystalline Nanomembranes. ACS Nano 5, 5400–5407 (2011).

Support: DOE

This work reports a new type of the transfer printing with tunable adhesion of soft silicone elastomer stamp, which proved to be an effective and reliable technique to fabricate stretchable electronics. In our fabrication, a UV laser marker was introduced to direct write high-resolution circuits on the commercial available copper thin film. Further, this technique can be easily adapted to a mass production with a significant lower initiation cost of facility and infrastructure.
The stretchable electronics is a multidisciplinary filed of electronics, mechanics and materials science. The most conductor, as an essential part of the electronic system, is hard brittle material. It is a challenging task that make the hard brittle material stretch. George Whitesides used sputtering method to process electrode in PDMS. Due to the stress does not match, there were many cracks in the metal after stretching [1]. The scholars in Princeton introduced a concept of pre stretching. When pre stretching PMDS is released, surface waves of thin gold films were made on an elastomeric substrate with built-in compressive stress. These waves can be stretched flat they function as elastic electrical conductors [2]. Then the scholars from the European union put forward a simple moulded-interconnect-device technology for the construction of elastic point-to-point interconnections, based on 2-D spring-shaped metallic tracks, which are embedded in a highly elastic silicone [3]. While Rogers from UIUC combined the SOI thin film circuits fabrication technique and silicone transferring technique by adjusting the adhesion force due to the speed of transferring stamp movement [4].
In this work, by changing the adhesion of elastic base and the structure of copper, we achieved a high stretchable performance printed circuit boards. Using laser to cut the copper and getting the pattern. Then we use the ecoflex and pdms to manufacture the receiving substrate, which is gradient and ridge structure. By the viscosity difference between donor substrate and receiving substrate, the pattern copper can transfer from donor substrate to receiving substrate. Then the electronic component is integrated on the circuit. At the last, the electronic circuit is packaged.The strecyability can be reached 25% with 10000 cycyling with any failure

[1] Bowden N, Brittain S, Evans A G, et al. Spontaneous formation of ordered structures in thin films of metals supported on an elastomeric polymer[J]. Nature, 1998, 393(6681):146--149.
[2] Lacour S P, Wagner S, Huang Z, et al. Stretchable gold conductors on elastomeric substrates[J]. Applied Physics Letters, 2003, 82(15):2404-2406.
[3] Brosteaux D, Axisa F, Gonzalez M, et al. Design and Fabrication of Elastic Interconnections for Stretchable Electronic Circuits[J]. IEEE Electron Device Letters, 2007, 28(7):552-554.

Abstract
Recently, our group developed a new way to tune softness, stretchability and stickiness of PDMS, which resulting a so-called S3-PDMS [1]. In concretely, varying the amount of PEIE fraction, mixing speed, or curing temperature and time, it is possible to obtained PDMS-based elastomer with different softness, stretchability and stickiness. Therefore, in order to adapt to a mechanical hybrid structure with mechanical rigid islands to host and protect rigid chips and soft surroundings and soft wires, we adjust our elastomer’s softness to achieve such a structure for electronics while keeping the good material compatibility and lowering the stress between the rigid and soft areas.

For device fabrication, we make some rigid chips array connected by meander copper wires or liquid alloy. And in structure, chips are encapsulated with higher Young’s modulus elastomer while liquid alloy or copper wires are encapsulated with lower Yung’s modulus PDMS-based elastomer. The two PDMS areas are connected by time difference, in other words, one area is semi-cured to get ready to connect with another after fully cured. For liquid alloy pattern, spray printing with a pattern mask is good for a line array, and direct printing can improve the resolution. Finally we obtained a crosswise Young’s modulus gradient structure packaging with chips and wires. This structure has a good mechanical stress buffering to ensure the whole device compatible and stable. For the data we get currently, the device can be stretched to 20% elongation and cycled up to 10000 times. This technique will be useful for making highly reliable epidermal electronics that needs some structure to adapt our body motion and observe physiological signal.

Reference
[1] Jeong S H, Zhang S, Hjort K, et al. PDMS-Based Elastomer Tuned Soft, Stretchable, and Sticky for Epidermal Electronics[J]. Advanced Materials, 2016.DOI:10.1002/adma.201505372

Stretchable and transparent conductors (STCs) are basic components of critical soft electronic devices that enable humans to interact with devices in new ways. Stretchable touch screens that enable visual/tactile interactions, wearable solar cells which functions as portable energy sources, and conformal optogenetic implants which provide much effective cures are examples in which STCs are requisites. Developing optically transparent conductors that are stretchable is challenging because of the trade-off relationship among transparency, conductivity, and stretchability. Ag nanowire networks are considered one of the strong candidates for stretchable transparent conductors due to its superior transparency and conductivity. Most studies reported so far are about uniaxially stretchable conductors and very few studies have been attempted to create electrodes that are stable under biaxial mechanical deformations.

Here we present Ag NW-based transparent conductors that are biaxially stretchable. We have developed a facile method to control the structure of nanowire networks in an isotropic manner that releases applied strains so that the nanowires can better retain the conductive nanowire network. Strain tests and cyclic tests showed that samples prepared by our method have high strain tolerance regardless of the direction of stretching and simultaneous biaxial stretching. They showed superior performance compared to straight Ag NW networks and even the ones prepared using the commonly known pre-strain method. Scanning electron microscope (SEM) was utilized to analyze the cause of improved electrical stability under biaxial stretching in our developed electrodes. Prepared Ag NW networks were directly applied to a resistive strain sensor which was attached to an elbow to test the angles between arms. An in-house measurement system was built to simultaneously measure resistance of strain sensor and the angles between the arms. The angles and resistance values roughly exhibited a one-to-one relationship, meaning the sensor was highly reliable and reproducible. The demonstrations suggest the prepared Bi-Ag NW-based strain sensor has the potential to reliably sense/measure movement of arms and to be applied in biaxially deforming circumstances. We anticipate our findings could potentially be applied to other metal nanowires for stretchable optoelectronic applications.

Implantable electrodes have been widely used for biomedical research and therapy. Due to size and mechanical mismatch between electrodes and live cells and tissues, existing probes face many challenges in performance and biocompatibility. Different materials, geometry and strategies have been proposed to solve these challenges, but it is still a difficult task to reconcile the request for scaling down the size of probe, maintaining the mechanical strength for implantation surgery, while having the core structure flexible for bettering interfacing with cells. Here we propose a new strategy to address this challenge by integrating flexible structures on a supporting ultra-small silicon shaft, which features the in situ formation of flexible three-dimensional electrodes without any additional etching process by the integration of biodegradable sacrificial layer. Complex three-dimensional microstructures for tissue-electronics integration can also be realized by engineering the geometry and anchor points. In addition, we will demonstrate controlled positioning and releasing of a whole polymer film probe of sub-10 micrometer thickness which would allow accurate deep implantation of fully flexible probes for the first time.

Complete mapping of neural activity requires individually addressing densely packed neurons, which presents a great challenge well beyond the capability of existing techniques. Specifically, implanted electrodes record in vivo bio-potentials with sub millisecond temporal resolution, but are far from reaching the desired recording-site density to gain circuit-level understanding of neural activity, mostly due to the large electrode dimensions and the consequential low implantation density. Here we report a novel nano-electronic approach to drastically reduce the dimensions of in vivo neural electrodes. By using substrate-less, multi-layer design and state-of-the-art E-beam lithography techniques, we fabricated neural probes with cross-section down to 5 µm², hosting multiple, individually addressed electrodes. The small volume per electrode potentially allows for implanting one electrode per 30 µm in all three dimensions with less than 1% tissue-displacement ratio. We implanted these ultra-small probes into mouse brains with sub-cellular surgical footprint, and used them to record local field potentials and single-unit action potentials from the somatosensory cortex. We studied the tissue-probe interface by in vivo two-photon imaging and post-mortem histology and observed seamless bio-integration. We demonstrated a variety of electrode designs for different applications. The unprecedented small dimensions of our probe open up new opportunities for high-density neural recording by overcoming current physical limits in implanted neural electrodes.

Advanced capabilities in electrical recording and stimulation are fundamental to clinical treatment of neurological and heart rhythm diseases as well as to progress in fundamental neural and cardiac sciences. The most sophisticated hardware systems for this purpose utilize geometrically conformal electronics that achieve high speed, high resolution electrophysiological mapping through direct interfaces between arrays of thin metal pads and the contacting cardiac tissue. Although such technologies can be effective, the measurement interfaces pose significant risks due to electrical leakage currents that arise from penetration of bio fluids through the metal and into an underlying layer of electronics that provides for amplification and multiplexing. Here we present a solution to this challenge that exploits the use of an ultra-thin, biocompatible dielectric layer that completely seals a platform of underlying flexible silicon electronics, where electrophysiology occurs via direct capacitive coupling to the channel regions of silicon nanomembrane transistors, without any direct metal contact. Systematic studies of the materials and the electronic characteristics highlight the advantages of such systems. High resolution electrophysiological mapping in normal, paced, and arrhythmic conditions in Langendorff hearts ex vivo and on rat auditory cortex in vivo demonstrate the capabilities, with quantitative validation against control measurements performed using optical techniques. The results suggest a realistic pathway towards flexible, biocompatible electronic implants for research and clinical use, with potential for broad utility.

The use of optogenetics to control spatial and temporal neuronal function has made it possible to investigate complex neural circuitry. However, it is difficult to detect biological signals on a dynamically moving muscle using conventional rigid electrodes without delamination from the surface of the muscle. Flexible devices have been developed as promising tools for free moving animal monitoring due to their high flexibility and biocompatibility. Although it is difficult to record ms-scale induced signal using conventional organic transistor, recently 4-μm-thick organic electrochemical transistors (OECTs) have shown promising characteristics with micro-second scale temporal response and large signal-to-noise ratio (SNR) due to local signal amplification [1]. Because of this high SNR capability, OECTs have been used in EEG, ECoG. These processes only measure relatively slow signals [1,2]. So far, there has been no report on the measurement of bio signals at high temporal resolution (ms-scale) using OECTs.
In this work, we evoked muscle movement in a rat with a surgically implanted, light sensitive neuron and successfully measured the evoked action potential using 2-μm-thick flexible OECTs placed directly on the moving muscle tissue. The OECTs were fabricated on 600-nm-thick parylene (Dix-SR) substrates. Gold patterning on this substrate formed the source/drain of the OECTs. Another 600-nm-thick layer of parylene was deposited for passivation. The active layer, poly (3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS), was patterned using double-parylene-lift-off process[1]. The trans-conductance of these OECTs was 1.5 mS with 100 μm/100 μm channel dimension. The motor nerve of transgenic rat [3] was stimulated by laser at a wavelength of 473 nm. We applied repetitive light stimulations at 1,2,5,10 Hz. The OECT recorded evoked action potentials which is about 1 mV during 5 ms. As a control experiment, the conventional needle electrode was used to measure the bio signals with same frequency stimulation. The signal shape was similar with data from OECTs. We concluded that OECTs can successfully measure ms-scale evoked action potentials on moving muscle tissue, and showed the potential for more complicated medical applications of OECTs.
[1] D Khodagholy, et al Nature Communications 4, 1575 (2013).
[2] J Rivnay, et al Science Advances 1, 4 (2015).
[3] E Boyden, et al Nature Neuroscience 8, 1263 (2005).

The rapid advancement of knowledge in neural sciences has led to a vast number of potential treatments for neurological ailments. Many of these, such as neural stimulation and recording, require the use of implantable electronics. For many years the state of the art were rigid devices manufactured from silicon, tungsten or other materials. While acutely effective, these implants lacked chronic stability due to the mechanical mismatch between brain tissue and the substrate. Recently, large steps forward have been made with the development of softening polymeric devices. These devices are rigid enough for lithographic processing and insertion into the body, but then soften to minimize chronic damage to the surrounding tissue. This work reports the design of thiol-isocyanate substrates that improve upon previous thiol-ene/acrylate substrates. Prior to implantation the substrate has a modulus surpassing 2 GPa which decreases to as low as 5 MPa in vivo, allowing for exceptionally thin devices to be implanted. The new substrates resist degradation that previous chemistries were susceptible to by eliminating ester linkages from the polymer backbone. This enables long-term recording and stimulation of neural signals. Importantly, the thiol-isocyanate substrates are many times tougher than previous softening substrates due to extensive hydrogen bonding, which enables surgeons to more easily implant devices and reduces the likelihood of mechanical device failure. The substrates withstand standard lithographic processing for complex microelectronics, and multi-channel neural recording devices are demonstrated using existing methods. These developments were enabled by the use of thiol-isocyanate chemistry, which promises to combine the simple processing and shape memory behavior achieved through thiol-ene chemistry with the superior mechanical performance of polyurethanes, representing yet another large step forward towards the proliferation of chronically viable smart neural devices.

While the majority of the neural engineering efforts of the past decade have focused on interfaces with the brain, fundamental understanding of the spinal cord neural dynamics remains limited by the tools capable of recording and modulation in this organ. In addition to its sophisticated neurophysiology, flexibility and repeated deformations of the spinal cord present a challenge to engineering of implantable devices. Fueled by advances in optogenetics, optoelectronic probes have recently enabled cell-specific neural stimulation compatible with concomitant recording of neural activity. The mechanics of the spinal cord, however, remain difficult to match with hard materials traditionally used in optoelectronics.
Here we address the elastic modulus mismatch by designing flexible multifunctional neural probes capable of conforming to the spinal cord geometry and mechanical properties, while providing optical stimulation and neural recording.
We mimicked the fibrous and flexible morphology of the spinal cord and fabricated all-polymer fibers that consist of a polycarbonate (PC) and cyclic olefin copolymer (COC) waveguide and carbon-polyethylene (CPE) composite electrodes. The polymer fiber probes enabled low-loss light transmission 0.5-2 dB/cm even under repeated deformation at bending radii < 1 mm. The conductive polymer composite electrodes exhibited tip impedance 1-3 MΩ suitable to record local field potentials. To further reduce the impedance, we have fabricated concentric device by dip coating PC/COC waveguides (~100 µm in diameter) with a 1 µm thick conductive mesh of silver nanowires (AgNWs). The devices were then encapsulated with a layer of poly(dimethylsiloxane) (PDMS) to a total diameter of 130 µm to protect the AgNW mesh from degradation, while maintaining high flexibility (under review). Exposed AgNW mesh ring-electrodes possessed low impedance (~200 kOhm) and were capable of recording isolated action potentials in the mouse spinal cord with high signal-to-noise ratio (SNR 7±1) and low noise level (10 ±3 μV). We also applied the dip coating approach to fibers made of cyclic olefin copolymer elastomers (COCE). COCE is a rubbery material allowing us to produce stretchable electrodes for neural recording. The COCE/AgNW fiber electrodes maintained their conductivity at 100 % extension strain, and could be deformed repeatedly without hysteresis at 20 % strain.
We demonstrated the utility our devices for recording and optical stimulation in the spinal cord of transgenic mice expressing the light sensitive protein channelrhodopsin 2 (ChR2). Furthermore, we found that optical stimulation of the spinal cord with the polymer fiber probes induces on-demand limb movements. Finally, we illustrated that the modest dimensions and high flexibility of our devices permit chronic implantation into mouse spinal cords with minimal damage to the neural tissue.