Symposium SM6 : Transient and Biologically-Inspired Electronics

Innovation in the fabrication of metallic-based implantable micro-scale bioelectronics has been challenging owing to high impedance and low charge storage capacity that result in both low signal-to-noise ratio and low charge injection electrode-tissue interfaces. Additionally, such devices without anti-inflammatory compounds are less likely to maintain their efficacy due to fibrous encapsulation associated with reactive tissue responses to the implanted electrode. Thus, there is considerable incentive to fabricate devices capable of delivering therapeutic compounds while maintaining electrical performance. Poly(pyrrole) (PPy) has gained significant interest for biomedical applications owing to its excellent biocompatibility, electrical properties, and mechanical actuation. Poly(lactic-co-glycolic) acid (PLGA) is biodegradable and biocompatible, making it an ideal matrix for drug encapsulation. In this research, we have produced hollow PPy microcups from template PLGA microspheres on gold (Au) electrodes, which were fabricated on Si wafers. Briefly, 4/2wt% PLGA/benzyltriethylammonium chloride was dissolved in chloroform and electrosprayed on the electrodes using an applied electrical field of 100kVm^-1. PLGA was then coated with PPy/poly(styrenesulfonate) using an applied current density 0.5mA/cm² for 5 different time durations. The template spherical PLGA was then dissolved in chloroform to create hollow PPy microcups. These microspherical cups are relatively monodisperse in size, with an average diameter of 3.45±0.31µm, Furthermore, Impedance spectroscopy and cyclic voltammetry were performed to investigate the impedance and charge storage capacity of PPy microcups. The size and shape of PPy microcups were characterized using Field-Emission SEM. The hollow PPy microcups decreased the impedance from 445 ± 63 Ω on bare gold to 354 ± 39 Ω for 8 min deposition of PPy microcups, a difference of 20% at 1kHz. The additional area obtained by removal of the PLGA cores significantly increased the effective surface area of electrode, thus lowering the impedance. The PPy microcups also significantly enhanced the charge storage capacity from 2.5 mC/cm² to 47.5 mC/cm², nearly 95%. In conclusion, we successfully demonstrated: (1) electrochemical deposition of PPy around the electrosprayed PLGA microspheres, (2) degradation of PLGA microspheres to fabricate hollow PPy microcups, and (3) improvement of electrical properties of Au electrodes by decreasing impedance and increasing charge storage capacity. This study demonstrates the potential of our conductive microstructures for neural interfacing and neural regeneration while retaining functionality for drug delivery. Future studies will focus on the incorporation of bioactive compounds such as nerve growth factor and antitumor agents for controlled drug delivery using electrical actuation of PPy microstructures.

Thermal conductivity and elastic constants of water-soluble polymers are critically important properties for their applications in unconventional electronics and biomedical therapies. Here, we use time-domain thermoreflectance (TDTR) and acoustic waves to measure the thermal and elastic properties of thin films of water-soluble polymers and polymer blend. The obtained thermal conductivity varies approximately by a factor of 2, with the highest values approaching 0.4 W m^-1 K^-1, appearing among those with the capability to form hydrogen bonds by themselves. The elastic constants are found to positively correlate with the thermal conductivity, enabling the extraction of an effective atomic density (of full excitation) around 3×10²² cm^-3 based on the minimal thermal conductivity model. We do not observe significant increase of thermal conductivity for the water-soluble polymer blend involving hydrogen bonding. These results serve as an initial step to understand the thermal transport in water-soluble polymers, and are practically helpful for using them in electronic and other applications.

In this talk, I will discuss our recent progress in pressure sensor design, fabrication and applications.

Electronics of tomorrow will be imperceptible and will form a seamless link between soft, living beings and the digital world. This new form of ultra-conformable electronics places severe physical requirements on the active components that constitute modern foil-like electronic systems. Weight and flexibility become key figures of merit for large area electronics such as robotic skin, as they critically influence the mechanical response and perception of the artificial sensory system. With less than 2 μm total thickness, imperceptible electronic foils are light (≈3-5 gm^-2) and unmatched in flexibility, they are operable with radii of curvature below 5 µm, yet highly durable and withstand severe crumpling without any performance degradation. These are prerequisites for intimate contact with soft, biological tissue or organs and complex, arbitrarily shaped 3D free forms that enable applications spanning medical, safety, security, infrastructure, and communication industries.
This talk introduces a technology platform for the development of large-area, ultrathin and lightweight electronic and photonic devices, including organic solar cells^[1], light emitting diodes^[2], active-matrix touch panels^[3], implantable organic electronics^[4], imperceptible electronic wraps^[5] and “sixth-sense” magnetoception^[6] in electronic skins. Solar cells, less than 2 µm thick, endure extreme mechanical deformation and have an unprecedented power output per weight of 10 W/g and more. Highly flexible, stretch-compatible polymer light emitting diodes for display applications and ambient lightning conform to arbitrary 3D free-forms and provide electrical functionality in yet unexplored ways through simple and cost-effective fabrication. Tactile sensor arrays based on active-matrix organic thin film transistors can be operated at elevated temperatures and in aqueous environments as an imperceptible sensing system that ensures the smallest possible discomfort for patients requiring medical care and monitoring. E-skins with GMR-based magnetic field sensors equip the wearer with an unfamiliar sense that enables perceiving of and navigating in magnetic fields. These large area sensor networks build the framework for electronic foils and artificial sensor skins that are not only highly flexible but become highly stretchable and deployable when combined with engineered soft substrates such as elastomers, shape memory polymers or tissue-like hydrogels. New concepts for powering thin, light and stretchable electronic appliances will be discussed, including low-cost air-stable perovskite solar panels^[7].

[1] M. Kaltenbrunner et al, Nature Communications 3, 1-7 (2012)
[2] M. White et al, Nature Photonics 7, 811 (2013)
[3] M. Kaltenbrunner et al, Nature 499, 458 (2013)
[4] J. Reeder et al, Advanced Materials 26, 4967 (2014)
[5] M. Drack et al, Advanced Materials 27, 34 (2015)
[6] M. Melzer et al, Nature Communications 6, 1-8 (2015)
[7] M. Kaltenbrunner et al, Nature Materials 14, 1032 (2015)

Highly traumatic skeletal muscle injuries that involve peripheral nerve damage require over a year for repair. While healing, denervated muscles quickly undergo atrophy, which significantly affects functional recovery of motor reinnervation. The common clinical treatment for atrophy uses functional electrical stimulation. However, conventional transcutaneous electrodes are not optimal for cases requiring peripheral nerve repair and can induce significant damage. Intramuscular electrodes are rarely used clinically because of the invasiveness of the approach and the prohibitively large electrode arrays necessary to induce denervated muscle contraction. Conventional epimysial (i.e. on the muscle surface) electrodes are sometimes bulky and unable to meet the stringent needs of peripheral nerve repair. Meanwhile, little information with regard to the time course of nerve regeneration and motor reinnervation has been collected. There remains a need for an effective, continuous interface that is suitable for stimulation of denervated muscle and for the real-time in vivo monitoring of the nerve regeneration time course. Additionally, it is still unclear what the optimal stimulation protocols should be. The objective of this research was to develop an integrated therapeutic/diagnostic approach for improved nerve repair. The central hypothesis is that reduction of muscle denervation and atrophy will promote functional recovery. Here, an implantable microelectrode was developed that provides surface neuromuscular stimulation during long-term denervation. The design consists of embedding an array of gold-based microelectrodes within a thin substrate of biocompatible poly(dimethylsiloxane) elastopolymer with low water permeability. This prototype was tested for biocompatibility, surface conformability, electrode impendence, and capability of in vivo recording.

The fabrication of new nanoscopic materials combining biomolecules with organic polymers is of high interest both because it allows the addition of important chemo-physical properties to the biomolecular nanotemplates, which can then be exploited in a variety of functional components, and because of their possible integration in biological systems.
Supramolecular methods exploiting the high structural order of biomolecules and the conductive properties of conjugated organic polymers are versatile construction tools for the assembly of electronic devices components by bottom-up approaches. Here we show how conductive polymers can be used to coat proteins superstructures, such as amyloid fibers,^{[1, 2]} or to be incorporate into model lipid membranes,^[3] by exploiting non-covalent interactions. The self-assembled nanostructures are investigated by means of advanced scanning probe microscopy techniques, such as conductive atomic force microscopy (C-AFM), which allows to simultaneously visualize the morphology and the local conductive properties at the nanoscale. Electrical conduction within the nanostructures opens fascinating perspectives for accessing electronic and ionic processes within biosystems in a non-destructive manner, possibly enabling new modes of observing biological processes.

[1] A. Elfwing, F. G. Bäcklund, C. Musumeci, O. Inganäs and N. Solin, Decorated Protein Nanowires with conductive properties, J. Mater. Chem. C, 3, 6499, 2015.
[2] F. Bäcklund, A. Elfwing, C. Musumeci, F. N. Ajjan, V. Babenko, W. Dzwolak, N. Solin, O. Inganäs, PEDOT-S coated protein fibril microhelices, in preparation.
[3] P. Johansson, D. Jullesson, A. Elfwing, S. I Liin, C. Musumeci, E. Zeglio, F. Elinder, N. Solin, and O. Inganäs, Electronic polymers in lipid membranes, Sci. Rep. 5, 11242, 2015.

Melanins are biomacromolecules responsible for the pigmentation of many plants and animals. The biological functions of melanins, also present in the inner ear and the substantia nigra of the human brain, go far beyond coloration and include photoprotection, anti-oxidant behavior, and metal chelation. Melanins are also intensively studied for their involvement in melanoma skin cancer and Parkinson's disease. In the class of melanins, eumelanins are the most ubiquitous form in humans and the most studied by material scientists.
Processing melanins in thin film form is a condition to easily assemble it into devices. Modifying the substrates where films are overgrown through surface chemistry help in overcoming challenges such as the poor solubility of melanin and its chemical heterogeneity. We probed the redox and photoredox properties of eumelanin thin films in presence of a number of electrolytes containing metal cations with low to high binding affinity to melanin to study the interplay between the charge transfer and the chelation properties in the pigment. The study is relevant to demonstrate biodegradable and biocompatible electrochemical energy storage devices but also to dvance the knowledhe on the functional role of melanin in biological systems (considering that it has been reported that binding of reactive metal ions by melanin reduces the oxidative stress on the human body).

Bio-templated synthesis of functional nanomaterials has received increasing attention for applications in energy, catalysis, bio-imaging, and other technologies. This approach is justified by the unique abilities of biological systems to guide the sophisticated assembly and organization of molecules and materials into distinctive nanoscale morphologies often highly desirable to achieve physicochemical properties for specific purposes. Here, we present a high-performance, flexible nanogenerator using BaTiO₃ (BTO) nanocrystals templated with a genetically modified, filamentous M13 virus. The virus-templated BTO nanostructure with high crystallinity and effective piezoelectricity is synthesized with the biological self-assembly. The anisotropic M13 shape can realize well-distributed BTO-based nanogenerator which produces the electrical outputs up to ~300 nA and ~6 V. These results demonstrate a new possibility of bio-templated nanostructures for a flexible energy harvesting applications. I will also review some biological and biotemplated approaches for piezoelectric generation.

Electronic systems which are controllably transient (that vanish when receiving a trigger signal) are potentially useful for a number of applications including environmental monitoring and personal data security. This report will describe an approach based on stressed glass which is capable of disintegrating high-performance off-the-shelf electronic systems in a rapid and programmable manner. Using ion-exchange chemical tempering large stresses can be built into thin glasses, by simply immersing the substrates into a bath of molten salt (typically potassium nitrate), allowing the ions from the bath to exchange with those present in the glass (typically sodium). This process produces a stable, toughened glass as the outer compress-stress region prevents cracking from surface defects. Under certain conditions the ion exchange process can also provide sufficient stored strain energy (up to ~ 1 GPa of surface stress) to promote significant crack branching, causing the glass to rapidly fragment into small pieces which disperse over a wide area when triggered. Such stress-engineered glass substrates are used here to form the basis of a transient electronics technology, where the stored strain energy is used to controllably and rapidly fragment not only the glass substrate but also any thin electronic components processed onto it.

Through control of experimental parameters (glass thickness, ion exchange temperature, and time) the mechanical properties, frangibility and final fragment size of the glass has been optimized, leading to substrates that fragment into small, difficult-to-detect pieces with average particle size < 100 μm on their longest dimension. Electronic circuits can be processed onto the glass either through micro-fabrication directly onto the glass (amorphous and polycrystalline Si as well as metal oxide based devices have been studied) or by transfer, bonding and thinning of pre-fabricated devices onto the stressed substrate (single crystal silicon and compound semiconductor based devices will be described). As the included electronic layers are typically thin (< 10 μm), crack propagation from the substrate into these layers is observed, showing that the stress energy stored in the glass can be used to fragment and disperse the thin, well adhered layers processed onto it. Controllable electronic triggering of fragmentation is achieved through resistive heating, thermally shocking the glass and causing rapid (within a few seconds) and complete disintegration of the included electronics when a logical trigger signal is received.

Silicon (Si) is a widely used material in biomedical research because it is biocompatible and biodegradable, and it exhibits a spectrum of important electrical, optical, thermal and mechanical properties. For example, Si-based systems can sense electrical activities of the brain in flexible and adhesive configurations, and deliver growth factors in vivo to induce angiogenesis. However, physical modulation (e.g., eliciting neural action potentials by passing current) of soft and curvilinear biological components with Si is still limited to bulky or interconnected systems, where rigid and single crystalline Si materials are typically used for device fabrication or implementation. New Si-based forms that are unique in composition, structure, and property have the potential to overcome this limitation and open up unexpected new avenues for research and device manufacturing. In this talk, I will introduce a group of phospholipid-supported and silicon-based transient bioelectric devices. Our results show that the devices permit non-genetic, fast, low power and sub-cellular optical control of the electrophysiological activities in single dorsal root ganglia neurons with single spike precision.

New ideas in materials science, mechanical engineering, manufacturing technologies and device designs establish the foundations for a class of electronics that can insert into the body, perform a desired function and then vanish via processes of bioresorption, all in a controlled manner. This talk summarizes the key enabling materials and describes their use at the system level in biomedical devices that address clinical unmet needs in programmable drug release and in treatment of traumatic brain injury.

Transient electronics represents an emerging class of technology that exploits materials and/or device constructs that are capable of physically disappearing or disintegrating in a controlled manner at programmed rates or times. Inorganic semiconductor nanomaterials such as silicon nanomembranes/nanoribbons provide attractive choices for active elements in transistors, diodes and other essential components of overall systems that dissolve completely by hydrolysis in biofluids or groundwater. This talk describes materials, mechanics, and design layouts to achieve this type of technology in stretchable configurations with biodegradable elastomers for substrate/encapsulation layers. Experimental and theoretical results illuminate the mechanical properties under large strain deformation.

A testbed example includes a bioresorbable drug delivery vehicle that allows on-demand, localized release of drugs in precisely controlled, patient-specific time sequences. The wirelessly operated, implantable drug delivery system offers such capabilities in a form that undergoes complete bioresorption after an engineered functional period, thereby obviating the need for surgical extraction. The device architecture combines thermally actuated lipid membranes embedded with multiple types of drugs, configured in spatial arrays and co-located with individually addressable, wireless elements for Joule heating. The result provides the ability for externally triggered, precision dosage of drugs with high levels of control and negligible unwanted leakage. In vitro and in vivo investigations reveal all of the underlying operational and materials aspects, as well as the basic efficacy and biocompatibility of these systems.

This presentation will discuss the degradation chemistry of nanostructured porous silicon relevant to implantable in vivo systems. Porous silicon is a high surface area nanomaterial that is prepared by electrochemical anodization of crystalline silicon in HF-containing electrolytes. We will focus on three aspects of the chemistry: The reactive surface hydrides that are generated during the electrochemical preparation, Si-Si bonds, and Si-O bonds. Reactions to trigger or control the programmed degradation of porous silicon will be discussed. The use of silicon nanoparticles as in vivo imaging agents and drug delivery vehicles will be highlighted.

Recent advances in design of materials has enabled design and synthesis of transient materials and structures capable of maintaining stable mechanical and electrical properties for a desired and preset amount of time; and, undergo fast and complete degradation and deconstruction once transiency is triggered. Transiency in solvent-triggered devices are strongly dependent on chemical and physical interactions between the solvent and the device, as well as those within the device itself, among its constituent components. Such interactions can be utilized as a means to program and control the mechanics and extent of transiency in complex transient electronics.
Mechanics of transiency of prototypical transient circuits demonstrate strong dependence on the transiency characteristics of the substrate. Furthermore, electronic properties of soft electronics depend on mechanical properties of the substrate. This talk describes recent advances in (1) correlations between electrical and mechanical properties of soft transient electronics, (2) mechanics of transiency of complex electronics, and (3) integration of non-transient materials in transient electronics with examples in passive and active soft transient electronics and structures.

The use of natural or nature-inspired materials in electronic applications is becoming relevant as disposable electronics become ubiquitous in the era of Internet of Things. Utilization of natural materials in disposable electronics is an environmentally responsible approach that reduces not only over-reliance on materials of non-renewable origins but also the amount of e-waste that overwhelmed landfills in many countries. Thin films based on extracted, formulated, and processed Aloe vera gel have been used as both active and passive regions for electronic applications. In particular, the bipolar resistive switching effect observed in thin film spin-coated from Aloe vera gel suggests its potential application in memory devices. Using Al as the top electrode, the bipolar resistive switching effect is governed by the space-charge-limited conduction (SCLC) mechanism. Nevertheless, a change in the switching effect from SCLC mechanism to filamentary conduction mechanism can be observed as silver is used as the top electrode. These observations indicate that top electrode materials play a vital role in determining the underlying charge conduction mechanism. In this work, the charge conduction mechanisms governing the switching effects in Aloe vera gel films are investigated by varying the top electrode materials (Al, Ag, Cu, Au, and Pt). The changes in charge conduction mechanism are proposed and discussed based on current density-voltage measurements. The innate biodegradability and biocompatibility of Aloe vera can bring closer the ultimate goal of sustainable development via “all-natural” transient electronics.

Melanins, biomacromolecules responsible for the pigmentation of many plants and animals, feature antioxidant, thermoregulative, photoprotective, and free radical quenching properties. Metal chelation properties are imparted by the two indolic building blocks[1]. This wide set of properties, together with intrinsic biodegradability, biocompatibility and mixed ionic-electronic conduction[2,3], make melanin an interesting candidate in organic bioelectronics.
The growth of dendrites in hydrated eumelanin thin films, deposited between Au electrodes under bias (1V), has been reported[4], and further investigated by our research group. Once the dendrites bridged the 2 electrodes, a sudden change in conductance took place, similar to resistive switching memory devices based on electrochemical metallization: Electrochemical Metallization Memory Cells, ECM, where from the dissolution of the Active Electrode a metal filament forms through an ion conductive layer. While previous studies addressed the dissolution of metals in contact with eumelanin for interelectrode distances of 6-10μm, we herein report a study about the phenomena happening for distances of 50-100nm. At such distances the overlapping of the space charge layers at the interface pigment-metal is believed to take place, thus dramatically influencing the phenomena occurring in the channel. Here we studied 2 configurations: planar (eumelanin deposited between 2 electrodes photolithographically pre-patterned on a substrate) and vertical (eumelanin sandwiched between 2 electrodes). The former allows to study the dendrite growth, the latter is actually used in nanoelectronics. The metals used for the electrodes were Au, Pd and Ag, for their relevance in microelectronics, and Fe and Cu for their relevance in melanin-based biological systems. Transient current measurements were performed at the relative humidity (90%) and electrical bias (1V) favorable to the dendrite growth (direct biasing)[4]. A systematic study was carried out over the possibility and the time required to erase the dendrites by reversing the bias. The interelectrode area was observed, after direct and reverse biasing, by means of Atomic Force Microscopy (AFM), Scanning Electron Microscopy (SEM) and NanoIR™ (combination of nanoscale IR spectroscopy and atomic force microscopy); the composition and the morphology of the nanostructures present were compared to those forming at higher interelectrode distances and the effect of reverse biasing was assessed. The results of this research improve the current understanding on the eumelanin-metals interactions and can give a first insight over the innovative possibility of using a biomaterial as the ion conductive layer of an ECM.[1]M. d’Ischia et al., Pigm Cell Melanoma R, 28, 5, 520-544, 2015 [2]B. Mostert et al., Proc. Natl. Acad. Sci., 109, 23, 8943–8947, 2012 [3]C. J. Bettinger et al., Biomaterials, 30, 17, 3050–3057, 2009 [4]J. Wünsche et al., Adv. Funct. Mater., 23, 45, 5591–5598, 2013

Neural interfaces are increasingly applied for the treatment of neurological disorders and diseases such as Parkinson’s disease, epilepsy, paralysis, and chronic pain. An ideal neural interface should seamlessly integrate into the nervous system and reliably function for long periods of time. The quality performance of these technologies ultimately rests on the specifics of the martial design that, in turn, enables a long-lasting functional interface. The challenge for materials science is to apply nanotechnology strategies for development of innovative biomaterials that closely mimic neural tissue characteristics and hence, cause minimal inflammation and neuronal cell loss. As a result, many nanoscale materials not originally developed for implantable neural applications have become attractive candidates to record neural signals, stimulate neurons, regenerate axons, and deliver drugs and biomolecules to nervous system. In this seminar, I will introduce some of the material-based approaches that we have developed within the past few years to improve long–term efficacy of neural interfaces. I will focus on synthesis, fabrication, and application of electroactive nanostructured materials including conducting polymer nanotubes and bioactive nanofibers for drug delivery to the brain, chronic neural recording, neurochemical sensing, and axonal regeneration.

Ingestible electronic devices have the potential to obviate many of the challenges associated with chronic implants such as risk of infection, chronic inflammation, and costly surgical procedures. Examples of ingestible electronics include edible cameras, ingestible event monitors, and integrated smart drug delivery systems. Ingestible devices have made great advances in the early detection and improved treatment of disease by using commodity polymers and off-the-shelf electronic components. However, currently available materials fundamentally limit how these devices can be used. The potential clinical impact of ingestible electronics could be increased by expanding the application-specific materials toolbox for this class of medical devices. This talk will describe recent advances in bioinspired materials for potential use in edible devices. Examples include flexible biodegradable elastomers as structural polymers and melanin-based pigments as materials for on-board energy storage. Structure-property-processing relationships for these medical materials will be emphasized and prospective uses for these application-specific materials will be discussed.

Organic electronics has a remarkable potential for the development of electronic products that are non-toxic, environmentally friendly, and biodegradable. An ideal solution for the production of such devices involves the fabrication of electronics either from natural materials, or from materials that have been proved to be biodegradable or biocompatible.
We continued our research on naturally occurring molecules for organic electronics applications by careful investigating the natural, insect-laid resin Shellac. We analyzed the processibility, film forming characteristics, surface morphology, resistance to degradation and dielectric properties of various grades of refined (solvent extracted) Shellac: Kushmi and Bysakhi Shellac, secreted by the insect Kerria Lacca in India, as well as Thai Shellac, secreted by the insect Kerria Chinensis in Thailand. We also investigated an aqueous Shellac solution (ammonium shellac salt) obtained from our partner in Germany. Flexible films of Shellac were cast and their flexibility exploited for substrates in the fabrication of organic electronic devices. We demonstrate that flexibility is preserved even when exposed up to 30 minutes to temperatures approaching 200 deg. C. Such substrates are ideal for the fabrication of electronics that require post-fabrication heat treatment of the active layers in order to increase their performance (e.g. metal oxides semiconductors, bulk-heterojunction solar cells, etc). We have demonstrated fully-biodegradable devices and inverter circuits featuring natural substrate and dielectric Shellac and naturally occurring semiconducting layers (Indigo, Tyrian Purple) and showed that the success of implementing these novel class of ‘green’ technologies to field effect transistors could be successfully extended to organic photovoltaic field.

Active implantable medical devices (AIMDs) can be used to diagnose and/or treat disease that challenging human life. Most of them are chronic implants that are typically intended to stay in the human body for permanent use. The recent emergence of biodegradable implantable electronics, such as bioresorbable sensors, wireless data transmitters and transient actuators, has the potential to preserve electronic activity while avoiding surgical removal and reducing chronic inflammation. If an external energy source is required for effective operation, then a biocompatible and biodegradable battery would be ideal.

With the surge of interest in miniaturized AIMDs, implantable power sources with small dimensions and biocompatibility are in high demand. We have developed a biocompatible polymer electrolyte-enabled compact Mg-air battery with a total thickness of 300 µm when coupled with polypyrrole (PPy) cathode.¹ The biocompatible electrolyte is made of choline nitrate (ionic liquid) embedded in a biopolymer, chitosan. This polymer electrolyte is mechanically robust and offers a high conductivity of 8.9×10^-3 S cm^-1. This battery can offer a volumetric power density of 3.9 W L^-1. Given its small dimension and biocompatibility, this battery may be a promising power source for miniaturized AIMDs.

We further demonstrate a partially biodegradable cathode material composed of silk fibroin and PPy.² It is prepared by chemically coating a PPy layer onto one side of the silk substrate. It shows a conductivity of ~1.1 S cm^-1, and demonstrates a 82% mass loss after 15 days incubation in 1.0 mg mL^-1 buffered protease XIV solution. It can offer an energy density of 4.70 mW h cm^-2 when coupled with a bioresorbable Mg alloy in phosphate buffered saline electrolyte. Our work highlights the feasibility of realizing a biodegradable battery that could provide appropriate power with a designed degradation profile. Developments in the area of biodegradable battery structures together with implantable medical devices will open up new possibilities for biomedical research and clinical care.

References

[1] X. T. Jia, Y. Yang, C. Y. Wang, C. Zhao, R. Vijayaraghavan, D. R. MacFarlane, M. Forsyth, G. G. Wallace. Biocompatible ionic liquid-biopolymer electrolyte enabled thin and compact biocompatible magnesium air batteries. Acs Appl. Mater. Interfaces 2014, 6, 21110.

[2] X. T. Jia, C. Y. Wang, C. Zhao, Y. Ge, G. G. Wallace. Towards biodegradable Mg-air bioelectric batteries composed of silk fibroin-polypyrrole film. Adv. Funct. Mater. 2015, In press.

Single-molecule field-effect transistors (smFETs), created from point-functionalized exposed-gate carbon-nanotube transistors, are miniature electrical circuits small enough to capture and probe individual biomolecules like proteins and nucleic acids. These devices can monitor fluctuations in molecular conformation or charge-state, in real-time and over a broad range of time scales, which makes them capable to investigate biomaterials and fundamental biochemical mechanisms at the molecular level. Here we present real-time probing of the conformational activity of single-stranded DNA using smFETs. We covalently bind an individual strand of human telomeric DNA to the carbon nanotube sidewall and monitor its folding and unfolding through changes in the nanotube electrical conductance. Human telomeric DNA consists of multiple repeats of the GGGTTA sequence and folds into a G-quadruplex tridimensional configuration stabilized by monovalent cations like K⁺ or Na⁺. In the presence of such ions, we observe quantized fluctuations between high and low states in the conductance of DNA-functionalized nanotubes, which we are able to assign to the unfolded and folded conformations of DNA, respectively. We discuss the effect of the nature and concentration of cations on the folding dynamics of the DNA. In particular, we find that the folded G-quadruplex structure is 30 times more stable in potassium than sodium cations. These results pave the way to investigate various biomolecules at the individual scale and to build functional electronics using individual biomolecules as building blocks.

Organic bioelectronics are based on soft materials that can conduct both electronic and ionic carriers making them ideal for translating addressing electronic signals to complex ionic outputs and vice versa. These devices have been mainly oriented towards biomedical applications for controlling physiology, therapy, neural prosthetics and in vitro diagnostics. Here we report, for the first time, the coupling of organic electronics with plants. With electronic ion pumps we were able to control the growth pattern of young plant seedlings by delivering hormones to the roots with high spatiotemporal resolution. As a next step, taking a non-conventional approach, we used the vascular system and organs of a plant to manufacture organic electronic devices in vivo having the internal structure of the plant as integral part of the device. We therefore demonstrate analog and digital organic electronic circuits and devices manufactured in living plants. This is the first example where electronic functionality is added to plants. Recent results on new materials and device concepts will also be discussed. 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.

In recent years, soft organic materials have raised conspicuous interest in the bioelectronics community as several novel biosensing and bioactuation devices have been proposed to address specific biomedical applications, e.g. neural recording and stimulation, artificial retina implants, controlled drug delivery and tissue regeneration.^[1] In this context, organic electronic devices and systems based on edible materials are emerging as a potentially pervasive platform technology. Indeed, research in this direction opens to a set of new medical devices designed to operate within the gastrointestinal tract, acting as biosensors and bioactuators, as well as tools to monitor patients compliance to medications.^[2] By all means, the integration of this technology with standard pharmaceuticals would naturally benefit of low-cost, easily up-scalable material deposition techniques, such as solution-based processes.
In this work, we exploit ink-jet printing to realize edible p-type and n-type transistors on a commercially available pharmaceutical capsule. The materials employed are either biocompatible, nature based or commonly used in the food industry. PEDOT:PSS, a very well known biocompatible conducting polymer, constitutes the transistors’ bottom-contacts and top-gate electrode. Alternative conductive materials can be adopted, e.g. graphene obtained by Liquid-Phase Exfoliation or edible gold and silver. Shellac, a biodegradable bug secreted resin, acts both as smoothing layer and dielectric.^[3] Hydrogen-bonded organic pigments such as quinacridone, indigoids and perylene derivatives are natural candidates for the semiconducting layer thanks to both interesting electronic transport properties and high biocompatibility.^[4] Indeed, these pigments can be chemically synthesized with cleavable solubilizing tert-butoxycarbonyl (t-BOC) groups, which are removed after deposition by means of exposure to trifluoroacetic acid (TFA) vapors. The t-BOC groups removal activates the latent H-bonds of the pigments which become completely insoluble and therefore exhibit an extremely low toxic potential, even lower than common food colorings.
The devices produced constitute an interesting approach for the integration of ingestible electronic systems with traditional pharmaceuticals and may act as platforms for future works on the emerging class of edible biomedical devices.

[1] Rivnay, J., et al. (2013). Chemistry of Materials, 26(1), 679-685.
[2] Irimia-Vladu, et al. (2010). Advanced Functional Materials, 20(23), 4017-4017.
[3] Irimia-Vladu, M., et al. (2013). Green Chemistry, 15(6), 1473-1476.
[4] Glowacki, E. D et al. (2013). Advanced Materials, 25(11), 1563-1569.

DNA is one of the most fascinating biomaterials today and it is a promising molecule for applications in molecular electronics. Moreover, DNA is currently used in the diagnosis of many diseases and a clear picture of the conductance of these molecules could open the doors for the design of diagnostic tools that could be read electronically, thus improving the sensitivity and reducing costs. Although results of DNA conductance reported in the literature span a huge range and differ by orders of magnitude, some consensus has been achieved in the charge transport mechanisms. However, to date, conductance modulation by controlling the structure in different DNA forms has not been systematically studied. The B-form typical for dsDNA is a right-handed double helix and it has been extensively studied. The A-form is the prototypical structure for dsRNA and it can be induced in dsDNA by dehydration.

Herein we report conductance measurements of short dsDNA molecules using the STM-break junction method¹. We study dsDNA conductance as function of length and structure. The structure is changed from B-form to A-form by adding ethanol during the experiment. Results demonstrate that A-form dsDNA is ~10 times more conductive than B-form in these GC rich sequences. This large conductance increase is fully reversible, and by controlling the chemical environment, the conductance can be repeatedly switched between the two values. Length dependent conductance studies of the two conformations suggest that hopping is the dominant charge transport mechanism in these guanine-rich sequences. Ab initio electronic structure calculations coupled with Green’s Function transport calculations of the two conformations indicate that the HOMO is extended through the entire chain in the A-form DNA case, and this extended orbital results in a higher conductance². These results are consistent with single molecule conductance measurements in A-form DNARNA hybrids³.

We also report results from electrochemical experiments with methylene blue functionalized DNA in order to obtain information about the interfacial charge transfer kinetics for the different structures in oligonucleotides ensembles covalently bound to electrodes⁴. These results correlate the structural modulation of single molecule conductance with the electrochemical signal of DNA functionalized electrodes and demonstrate DNA as a promising molecular switch for molecular electronics applications.

References

1.Xu BQ, Tao NJ. Measurement of single-molecule resistance by repeated formation of molecular junctions. Science 301, 1221-1223 (2003).
2.Artés JM, Li Y, Qi J, Anantram MP, Hihath J. Conformational gating of DNA conductance. Nature Communications (2015). In press.
3.Li Y, Artés JM, Hihath J. Long-range charge transport in adenine-stacked RNA:DNA hybrids. Small (2015). In press.
4.Artés JM, Matharu Z, Hihath J, Seker E. Correlating single molecule conductance and electrochemical rate constants in DNA and RNA. In preparation.

Redox reactions and electron transfer are unifying themes in all biological energy conversion strategies, including respiration. Metal-reducing bacteria gain energy by extracellular electron transport to external solids, such as naturally abundant minerals or even synthetic electrodes, which substitute for oxygen or the other common soluble electron acceptors of respiration. This process is one of the earliest forms of respiration on Earth, and has significant environmental and technological implications. By performing electron transfer to or from synthetic electrodes instead of minerals, such microbes can be used as biocatalysts for converting the energy stored in diverse chemical fuels to electricity or vice versa. Since microbial extracellular electron transport naturally evolved to interact with inorganic systems, a physics-based understanding may enable the transmission and control of signals at hybrid living/synthetic interfaces, creating new materials that combine the replication, self-repair, and precise biochemical control of a natural system with the vast toolbox of nanotechnology.

But how can a bacterium transport electrons to an external surface micrometers away? In contrast to solid-state systems, where the charge transport physics is well understood, comparatively little is known about the physics of biological charge transport over cellular length scales. Here, we will describe how bacteria organize redox sites on outer cell membranes, and along quasi-one-dimensional filaments known as bacterial nanowires, to facilitate long-range charge transport. The approaches taken include microfluidic fluorescence assays, single-cell respiration measurements, scanning tunneling microscopy of individual redox molecules, kinetic Monte Carlo simulations, and nanofabrication-enabled measurements of transport along individual bacterial nanowires produced by the bacterium Shewanella oneidensis MR-1. Based on these measurements, we propose that extracellular electron transport is facilitated by an incoherent multistep charge hopping mechanism along heme chains. In addition, we report a comprehensive characterization of the composition and structure of bacterial nanowires, demonstrating that these structures are lipid-based extensions of the outer membrane and periplasm that include the multiheme cytochromes responsible for extracellular electron transport.

The field of organic electronics has made available materials with a unique combination of attractive properties, including mechanical flexibility, mixed ionic/electronic conduction, enhanced biocompatibility, and capability for drug delivery. I will present examples of organic-based devices for recording and stimulation of brain activity, highlighting the connection between materials properties and device performance. I will show that organic electronic materials provide unparalleled opportunities to design devices that improve our understanding of brain physiology and pathology, and can be used to deliver new therapies.

Organic light-emitting diode (OLED) microdisplays are a new type of optoelectronic device that finds applications in electronic viewfinders, video cameras, or personal video players. Typically, they comprise of several hundred thousand individual top-emitting OLED pixels deposited on top of a driver backplane. Here, we demonstrate a completely novel application of OLED microdisplays, namely to use them as platform for cell biology and optical cell manipulation. In our study, each OLED pixel of the displays has a size of 6 µm x 9 µm, dimensions that allow resolving, addressing and interfacing single living cells and even parts of individual cells. The displays also provide high temporal resolution with response times <10 µs which enables investigation of fast cellular processes, e. g. activity of ion channels. Advanced thin film encapsulation prevents OLED degradation despite nearly direct contact (< 2 µm) with cell culture medium.

As a proof-of-concept, we investigated the blue light-controlled locomotion (phototaxis) of the green alga Chlamydomonas reinhardtii. As a direct result of the small size of the individual pixels of our OLED displays, this approach allows one to study the behaviour of individual cells. We found that the phototactic response of the C. reinhardtii depends on the optical power provided by the OLEDs and we were able to clearly distinguish different strains by their different phototactic behaviour.

C. reinhardtii is a famous biological model organism and, in addition, it is the natural source of the photoreceptors that are at the centre of the fast-growing field of optogenetics, a method that combines genetic manipulation and light exposure to gain control over cells or tissue, specifically to investigate processes in selected neurons without altering the behaviour of other nearby neuronal cells. We will show preliminary data on the use of OLED microdisplays to control membrane voltage in genetically modified cells expressing optogenetic constructs.

A. Steude, M. Jahnel, M. Thomschke, M. Schober, M.C. Gather, “Controlling the movement of single live cells with high density arrays of microscopic OLEDs”, Advanced Materials DOI10.1002/adma.201503253 (published online)

The cell-compatible field effect transistors (FETs) have drawn tremendous attention due to the growing interest in developing bio-electronic interfaces. The key challenge has been securing high-performance electronic devices with excellent bio-compatibility, low operation voltage, long-term stability under water, and etc. Here, we report an electrolyte-gated thin film transistors (EGTFTs) based on solution-processed metal oxide semiconductors directly interfacing with cells. The fabricated transistor devices exhibited impressive electrical performance such as very low operational voltage ( 10⁷), high transconductance (> 1.0 mS) and long-term operational lifetime (>7 days). Furthermore, cell viability, proliferiation, morphology, and electrophysiological functions were verified by culturing several different types of mammalian cells directly on top of indium-galium-zinc oxide (IGZO) semiconductor surface. More importantly, the stable operation of devices directly integrated with live biological entities showed the proof-of-concept for oxide electronic material-based cellular sensors. We expect that our device may serve as a versatile bio-electronic interface such as drug screening platform or human-friendly implantable electronics.

Light can be use for controlling cell activity, with high space and time resolution and a virtually infinite number of configuration, free from wiring constrains. Yet there are draw backs, such as light absorption and scattering, hampering delivery into deep tissues, and a fundamental limitation: by and large living cells are transparent. In this talk we will briefly review the state of our research regarding organic bio interfaces for inducing light sensitivity in cells, both in vitro and in vivo. The coupling mechanism of the biotic/abiotic interface is still far from being understood, attempts to shed light will be introduced. The possible application of dispersed interfaces, obtained by spreading organic nanoparticles into living tissues will be discussed. Finally an update on the artificial retina project will be presented, as one of the most appealing application of this emerging technology.

Pancreatic beta cells play a crucial role in controlling glucose homeostasis as one of the most important nutrient sensors and the site for storage and secretion of insulin. In particular, an increase in blood glucose induces membrane depolarization leading to insulin secretion. Generally, the use of extracellular electrodes permits recording of these electrical signals over prolonged time in intact cells. However, interfacing cells to electrodes remains a major problem in terms of sensitivity and specificity.
During the past years conducting polymers have become extremely popular among the scientific community as one of the most promising candidates for the next generation biology interfacing devices, in vitro as well as in vivo. Especially, poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT: PSS) has the unique feature to conduct both electronically and ionically, offering a new pathway of interaction between biological systems and electronics. Furthermore, it demonstrates ease of processability and chemically tunable properties in contrast with its inorganic counterparts. In this work we use PEDOT:PSS covered microelectrode arrays (MEAs) to monitor in real-time the electrophysiological activity of pancreatic islet beta cells in response to glucose and hormones. With the use of a conducting polymer in vitro platform, we were able to record slow waves oscillations (SW) and Actions Potentials (APs), both from disassociated human and mouse islet cells. We also examined the prospect of performing similar recordings with the use Organic Electrochemical Transistors (OECTs). OECTs, due to the local amplification that they provide, have proven able to offer superior signal to noise ratio as compared to passive electrodes.
Our findings demonstrate that PEDOT: PSS permits electrode recordings and paves the way for its use in pancreatic cell electrophysiology. In the long term, our PEDOT:PSS platform shall enable the study and the decoding of the endogenous algorithms used by pancreas islets to maintain glucose homeostasis.

Proton conducting materials play a central role in a diverse array of renewable energy and bioelectronics technologies. Thus, a great deal of research effort has been expended to develop improved artificial proton conducting materials, including ceramic oxides, solid acids, porous solids, polymers, and metal-organic frameworks. Within this context, proton conductors from naturally occurring proteins have received relatively little scientific attention, despite advantages that include intrinsic biocompatibility, structural modularity, tunable physical properties, ease and specificity of functionalization, and generalized expression/purification protocols. We have recently characterized the cephalopod structural protein reflectin with a diverse array of electrical and electrochemical techniques and found that this material is an effective proton conductor, with figures of merit that compare favorably to those of artificial analogues. Our findings may hold implications for the development of the next generation of biologically-inspired proton conducting materials.

We will reort on the recent progresses of large-area, ultraflexible, and ultrasoft electronic sensors. Our works focus on integration technologies of thin-film, ultraflexible electronics comprising ultrasoft gel electrodes, thin-film amplifier, Si-LSI wireless platform, thin-film battery, and information engineering, which are imperceptible active sensors. Here we would like to demonstrate the applications of the patch-type wearable bio-signal sensor, which can clearly monitor brain wave (Electroencephlogram: EEG) from a forehead, whose EEG signal intensity is in the order of micro-volts. Furthermore, the sensor can simultaneously monitor electrocardiogram (ECG) and electrooculogram (EOG) with changing the location of the sensors, whose signal intensities are in the order of mille-volts. The remaining technical challenges and the future prospects of the patch-type bio-signal monitoring system will be also discussed from the aspect of materials, devices, circuit design, and integration technologies from materials to information processing.

Polyhydroxybutyrate (PHB) is a biopolymer produced by some bacteria as a means of storing energy. This polymer can be enzymatically degraded by a variety of bacteria, fungi, and algae. In the absence of a suitable enzyme (PHB depolymerase), PHB shows good chemical and thermal stability (with a T_m of ~170 °C), barrier properties, and biocompatibility. Due to these properties, PHB is a good candidate for use as a substrate or matrix material in a conducting composite for degradable electronic devices.
In this presentation, work on the processing, characterization, and degradation of both pure PHB and PHB-graphene composites will be presented. We have recently developed a method to solvent cast PHB from acetic acid, and have found that the casting temperature has a strong impact on the crystallinity, optical properties, and mechanical properties of the films. Samples cast at the lowest temperatures have the lowest crystallinity, and correspondingly the lowest modulus (~1.2 GPa) and highest strain to failure (~9%). We have further studied the stability of the films over time, and found that as the samples age, there is a conversion of crystals from a metastable to stable state, resulting in a slower degradation rate.
To engineer conducting PHB composites, we have created solution-processed blends of PHB-graphene. Samples processed at similar temperatures with the same solvent were found to have percent crystallinities (~65% to 80%) similar to those of pure PHB films. A relatively low resistivity (~ 10^-2 – 10^-1 Ω cm) was achieved at a graphene loading of 10 % wt. As graphene and graphene oxide have been suggested to be cytotoxic to some cell types (including bacteria), there was some question as to whether bacterial degradation of the films would be possible; however our results show that the composite films are quite degradable. These materials could form the basis of environmentally-degradable electronic devices, or be incorporated into bacteria or enzyme sensors. Results will be presensted showing how these degradable materials can be used for the remote sensing of enzymes or PHB depolymerase-producing bacteria through integration into the dipole loop of an RFID tag.

Based on self-assembly and mimicking strategies occurring in nature, peptide nanomaterials play a unique role in a new generation of hybrid materials for the electronics of the 21^st century. This work describes the functionalization of diphenylalanine-based micro/nanostructures (FF) with blue-emitting conducting polymers of the polyfluorene (PF) family [1]. The FF:PF polymer nanocomposites are synthesized by a liquid-vapor phase method. Electron microscopy images reveal di-octyl substituted PF (PF8) to bind better to the FF micro/nanotubes in comparison with ethyl-hexyl PF (PF2/6), which influences its optical properties. Molecular dynamics simulations of FF nanotubes with monomeric units of PFs show that PF8 favors greater proximity to the grooves on the surface of the nanotubes due to a higher van der Waals interaction energy compared to PF2/6. The FF:PF nanocomposites are further utilized in light-emitting diodes. Biodegradability tests from FF:PF8 nanocomposite films show more than 80% weight loss in two hours by enzymatic action compared to PF8 pristine films, which do not degrade. Self-assembly of FF nanostructures with organic semiconductors opens up a new generation of biocompatible and biodegradable materials in organic electronics and photonics.

[1] S. Khanra, T. Cipriano, T. Lam, T. A. White, E. Fileti, W. Alves, and S. Guha, Adv. Mater. Interfaces 2, 1500265 (2015).

Polyphthalaldehyde has garnered interest over the past couple of years due to its rapid depolymerization both in solution and solid-state. It has been used as a small signal amplification polymer as well as a substrate for transient electronics. In this work, we investigate the thermal behavior of cyclic polyphthalaldehyde (cPPA) and ways that we can modulate that behavior. We also developed physically transient electronics which can be destroyed in response to temperatures as low as 80 ^oC while leaving behind very low polymeric residue (< 2 wt%). cPPA has a low ceiling temperature (-40^oC) and is self-stabilized due to its cyclic structure at room temperature. Thermogravimetric analysis reveals that cPPA rapidly depolymerizes and evaporates above 150 ^oC. With knowledge of its acid sensitive backbone, we explored the effect of a thermoacid generator to lower this degradation temperature to as low 75 ^oC for complete evaporation in 25 min. We demonstrate that cPPA can be used as a degradable substrate for Mg electrodes and as a destructible electrical path in circuits. We also investigate the use of cPPA as a sacrificial material that can be used to ‘transfer print’ circuits onto arbitrary substrates.

There are several diseases causing a degeneration of the human retina and a significant vision loss or even blindness. Some of these diseases predominantly affect only the photoreceptors, whereas other neuronal retinal cells seem to be present and functional. Several groups have shown that in these cases retinal prostheses can be developed to induce a signal that is forwarded to the visual cortex of the human brain. The aim of this talk will be to explain anatomic and physiologic details of ophthalmologic disorders that could be overcome by the implantation of new materials for retinal prostheses.

DNA:RNA hybrids are important biological components in gene replication, transcription and expression. However, little is known about charge transport though this mixed oligomer. To understand the electrical properties of these crucial hybrids, we systematically study the conductance of individual DNA:RNA hybrids and the transport properties of these mixed oligonucleotides by systematically changing both their length and sequence. In this work, the conductance of the oligonucleotide duplexes is directly measured using the Scanning Tunneling Microscope (STM)—break junction technique in aqueous solutions. This approach, which has previously been used to obtain reproducible conductance values for dsDNA has been adopted to directly measure individual DNA:RNA hybrid duplexes by linking them in between the tip and substrate in an STM. This setup allows us to rapidly obtain thousands of individual conductance measurements for statistical analysis, which determines the most probable conductance of a single molecule. Our recent work performs measurements on RNA:DNA sequences with various numbers of A:T or G:C base pairs. With poly A:T sequences, the conductance of DNA:RNA hybrid is weakly length dependent. And, in G:C rich sequences, we found the conductance of DNA:RNA hybrid is ~10 times higher than the dsDNA duplex with the same sequence. Thus, this result provides us a better understanding of the fundamental charge transport mechanisms in DNA:RNA hybrids. Additionally, beyond these fundamental studies, we will also present measurements of biologically relevant RNA sequences when hybridized to their DNA compliment. The measurement of these hybrids may provide the basis for developing label-free, RNA-based, electrical diagnostic tools that exploit the electrical properties of the oligonucleotide duplexes.