Natalie Stingelin, Imperial College London
Roisin Owens, Ecole National Superieure des Mines de St. Etienne
Paul Meredith, University of Queensland
Fabio Cicoira, Ecole Polytechnique de Montreal
Symposium Support Aldrich Materials Science
Ecole Polytechnique Montreal
Royal Society of Chemistry
Z2/AA2: Joint Session: Bioelectronics: Neural Applications
Mohammad Reza Abidian
Tuesday PM, April 22, 2014
Moscone West, Level 2, Room 2005
2:30 AM - Z2.01/AA2.01
AlGaN/GaN Acetylcholinesterase-Modified Field-Effect Transistors for Monitoring of Myenteric Neuron Activity
Gesche Mareike Muentze 1 Ervice Pouokam 2 Julia Steidle 2 Wladimir Schaefer 1 Kai Roeth 1 Alexander Sasse 1 Martin Diener 2 Martin Eickhoff 1
1Justus-Liebig-Universitamp;#228;t Giessen Giessen Germany2Justus-Liebig-Universitamp;#228;t Giessen Giessen GermanyShow Abstract
AlGaN/GaN high electron mobility transistors (HEMTs) are promising candidates for the application as transducers in biosensors. The chemical stability and biocompatibility  of GaN surfaces as well as their high pH-sensitivity  serve as the basis for this application. By covalent immobilization of enzymes on the gate area of an AlGaN/GaN HEMT one obtains an enzyme-modified field-effect transistor with the type of enzyme defining the specificity of the biosensor. Essential to this concept is the formation of an acid or a base as a product of the enzymatic reaction. The pH-change is then detected by the AlGaN/GaN HEMT in terms of a change in the gate-source voltage ΔUGS at constant channel current, giving rise to the sensor signal. The enzyme used in the experiments presented here is acetylcholinesterase (AChE) which produces acetic acid during its enzymatic reaction by decomposing the neurotransmitter acetylcholine (ACh). Thereby, the preparation of such an acetylcholinesterase-modified field-effect transistor (AcFET) is accomplished via a wet chemical process [3, 4].
Here, the characteristics of AcFETs were analyzed by measuring ΔUGS in dependence of the concentration of administered acetylthiocholine iodide, an ACh analogue, and evaluated applying a kinetic model  that yields microscopic parameters representing both the enzymatic activity (by the Michaelis constant KM) and the transistor/enzyme/electrolyte system (by the normalized exchange rate constants across the respective interfaces).
The utilization of AcFETs allows for monitoring of the release of the neurotransmitter ACh and, hence, the activity of neurons. This is shown here on the example of myenteric neurons from 5-8 days old Wistar rats, cultured on the gate area of the AcFETs, with the release of ACh induced by a potassium chloride stimulus. The recorded AcFET signal due to the chemical stimulus is related to the enzymatic activity of the covalently immobilized AChE.
Concluding, on the one hand our results show that AcFETs based on AlGaN/GaN HEMT structures provide a suitable platform not only for the realization of a specific biosensor but also for the analysis of the functionality of immobilized AChE. On the other hand we have been able to monitor the activity of myenteric neurons non-invasively and thus converting a biological into an electrical signal.
 G. Steinhoff et al., Adv Funct Mater 13 (2003), 841
 G. Steinhoff et al., Appl Phys Lett 83 (2003), 177
 B. Baur et al., Appl Phys Lett 87 (2005), 263901-1
 K. Gabrovska et al., Int J Biol Macromol 43 (2008), 339
 S. Glab et al., Analyst 116 (1991), 453
2:45 AM - Z2.02/AA2.02
Characterization of Conjugated Polymer/Electrolyte Interfaces for Full Control of Cellular Activity by Visible Light
M. R. Antognazza 1 S. Bellani 1 2 N. Martino 1 2 M. Porro 1 G. Lanzani 1 2
1Center for Nanoscience and Technology of IIT@PoliMi Milano Italy2Politecnico di Milano Milano ItalyShow Abstract
Combined systems of semiconducting polymers and aqueous electrolytes are emerging as the new frontier of organic electronics, with many promising applications in biology, neuroscience and medicine. A detailed characterization of polymer/water interfaces is thus urgently needed. In particular, the combined effect of contact with electrolytes and visible illumination should be taken into account, since many applications rely on exposure to light, or are meant to work in ambient room light conditions.
In this work, we first extensively characterize the chemical-physical processes occurring in thin films of poly(3-hexylthiophene) exposed to water saline solutions and visible light. Through combination of different spectroscopic techniques, we demonstrate that prolonged contact with saline solutions does not add further degree to photo-activated doping processes of the polymer; instead, it turns out that the reduced number of oxygen molecules present in water, compared to open air, acts as a limiting factor, thus fully validating the use of semiconducting polymers in contact with electrolytes.
In addition, we demonstrate that the recently demonstrated technique of cell stimulation by polymer photo-excitation (CSP) represent a versatile platform for full-optical control of cell excitation/inhibition. We report examples of functional interfaces between several combinations of conjugated polymers and different cell cultures (HeK cells, astrocytes, neuronal networks). A detailed model of the mechanisms occurring at the polymer/electrolyte interface and leading to cell photoexcitation, based on electrical and optical measurements, will be finally presented and critically discussed
3:00 AM - *Z2.03/AA2.03
Conducting Polymer Devices for In-Vivo Electrophysiology
George Malliaras 1
1Ecole des Mines Gardanne FranceShow Abstract
A visible trend over the past few years involves the application of conducting polymer devices to the interface with biology, with applications both in sensing and in actuation. Examples include biosensors, artificial muscles, and neural interface devices. The latter are of particular interest, as conducting polymers offer several distinct advantages compared to incumbent technologies, including mechanical flexibility, enhanced biocompatibility, better signal-to-noise ratio and capability for drug delivery. As such, they promise to yield new tools for neuroscience and enhance our understanding on how the brain works. After a brief introduction, I will present a few examples of electrodes and transistors for applications ranging from recording brain activity inside the skull to cutaneous recordings of muscle movement. In vivo performance, electrical characteristics and properties such as mechanical flexibility and biocompatibility will be discussed.
3:30 AM - Z2.04/AA2.04
Ultra-Small Intracellular Bioelectronic Probes for Live-Cell Action Potential Recording
Xiaojie Duan 1 Tian-Ming Fu 2 Charles M. Lieber 2 3
1Peking University Beijing China2Harvard University Cambridge USA3Harvard University Cambridge USAShow Abstract
The miniaturization of bioelectronic intracellular probes opens up opportunities to study functional structures inaccessible by existing methods and to interrogate biological systems with minimal invasiveness. Here, we report the design, fabrication and demonstration of the intracellular bioelectronic probes with size down to sub-10-nm regime based on a nanowire-nanotube heterostructure, in which nanowire FET detectors are synthetically-integrated with the nanotube cellular probes. Water-gate measurements together with numerical simulations show that devices with probes sizes as small as 5 nm, which approaches the size of a single ion channel, have sufficient time response to resolve fast electrical signals in live cells. The use of phospholipid modification enabled spontaneous penetration of the cell membrane by the nanotube probe, and allowed full-amplitude, stable recording of intracellular action potentials by these ultra-small bioelectronic probes. Furthermore, simultaneous multi-site recording from both single cells and cell networks, and the recording of low frequency transmembrane potential demonstrated the capability, robustness and reliability of these ultra-small bioelectronic probes for intracellular interrogation and their potential for neural and cardiac activity mapping.
3:45 AM - Z2.05/AA2.05
Controlling Action Potential Firing of Neurons Using a Magnetothermal Genetic Toolkit in vivo
Ritchie Chen 1 Michael Christiansen 1 Polina Anikeeva 1 2
1Massachusetts Institute of Technology Cambridge USA2Massachusetts Institute of Technology Cambridge USAShow Abstract
Debilitating neurological disorders such as Parkinson&’s disease and essential tremor are often treated via electrical stimulation using implantable devices. However, such procedures are highly mechanically invasive as well as not specific to cell type. Conversion of alternating magnetic fields in the radiofrequency range into heat via hysteretic power loss in superparamagnetic nanoantennas has been used to remotely control gene transcription in vivo and action potential firing in vitro. This actuation of TRPV1, a heat-sensitive calcium ion channel, with magnetothermal conversion may lead to minimally-invasive deep brain stimulation therapies. However, the timescale required - tens of seconds - suggests that further optimization to this magnetothermal approach is needed to shorten the actuation time to biologically relevant timescales.
Recently, we have applied a dynamic hysteretic model to optimize the magnetic nanomaterials properties, which allowed us to achieve record heat dissipation rates in magnetic nanoparticles (MNPs) at physiologically safe driving conditions. We find that iron oxide nanoparticles ~22 nm in diameter can reach temperature changes needed to trigger TRPV1 an order of magnitude faster than what was previously achieved at field frequencies and amplitudes relevant to magnetic hyperthermia. By sensitizing neurons to heat using a viral delivery system for TRPV1 DNA, we demonstrate how the heat dissipative abilities of our MNPs can be harnessed for minimally invasive deep brain stimulation therapies in vivo. Such an approach has implications towards remote control of biological functions at a single-cell level.
4:30 AM - *Z2.06/AA2.06
Soft Neural Electrode Implants
Stephanie Lacour 1
1EPFL Lausanne SwitzerlandShow Abstract
Mechanical cues affect cell behavior. In vitro, neurons and supporting cells show distinct response to substrate stiffness and topography. In vivo, and in particular for long-term implantations, the physical properties of the implant are key to maintain a stable, non-damaging, connection between the nervous tissue and the electrodes. The mechanical mismatch at the soft neural tissue to hard implant material interface combined with local micromotions induces an inflammatory reaction by immune cells, the generation of fibrotic tissue and/or a scar capsule, withdrawal or death of the nearby neurons and progressive loss of electrode contact, and thus implant failure.
We hypothesize that microfabricated electrode implants mechanically matched to the surrounding tissue may be a robust technological route for chronic synthetic neural implants. To do so, soft electrode implants are prepared with silicone elastomers. With elastic moduli as low as 10skPa, elastomers are some of the softest materials still compatible with MEMS-like fabrication processing. Furthermore their surface can be engineered in the form of large-area matrix of elastic micron-sized pillars thereby producing an interface with even lower stiffness.
We will review the materials and fabrication process to produce soft neural electrodes then illustrate the potential of this “soft technology” in the context of peripheral nerve interfaces and spinal cord electrode implants.
5:00 AM - Z2.07/AA2.07
An Organic Cell Stimulator and Sensing Transistor Architecture for Electrophysiological Recording of Primary Neural Cells
Valentina Benfenati 1 Simone Bonetti 1 Assunta Pistone 2 Saskia Karges 1 Guido Turatti 3 Michela Chiappalone 4 Anna Sagnella 2 Giampiero Ruani 1 Roberto Zamboni 3 Michele Muccini 1 3
1Consiglio Nazionale delle Ricerche (CNR), Istituto per la Sintesi Organica e la Fotoreattivitamp;#224; (ISOF) Bologna Italy2Consiglio Nazionale delle Ricerche (CNR), Istituto per lo Studio dei Materiali Nanostrutturati (ISMN) Bologna Italy3E.T.C. s.r.l Bologna Italy4Fondazione Istituto Italiano di Tecnologia (IIT) Genova ItalyShow Abstract
The development of advanced biomedical devices capable of real-time stimulation and recording of neural cells bioelectrical activity is a demand to improve our understanding of the functional mechanisms of the Nervous System and the need for effective in vitro drug screening targeted to neuropathophysiologies.
Organic semiconductor materials which combine long-term biocompatibility and mechanical flexibility are suitable candidates for neural cell interfacing. Of particular relevance is the study of the effect of the material interface interaction with neural cells, namely neurons and astrocytes. In particular, the material interface should support the cells adherence and promote their growth and differentiation on the device structure. The cell bioelectrical activity should be preserved, avoiding alteration of the electrophysiological properties due to the interaction with the organic semiconductor. Here, we show that primary neurons and astroglial cells can adhere, grow and differentiate on a suitably engineered perylene-based field-effect transistor platform, while maintaining their firing properties even after a prolonged time of cell-culturing. The development of transparent Organic Cell Stimulating and Sensing Transistors (O-CSTs) that provide bidirectional stimulation and recording of primary neurons is also reported. We demonstrate that O-CST enables depolarization and hyperpolarization of primary neurons membrane potential. The transparency of the device also allows the optical imaging of the modulation of the neural cell signalling. The O-CST device enable extracellular recording from neurons with maximal amplitude-to-noise ratio 16 times better than a micro electrode array (MEA) system on the same neuronal preparation. Our organic cell stimulating and sensing device paves the way to a new generation of devices for stimulation, manipulation and recording of neural cell bioelectrical activity in vitro and in vivo.
Supported by EU-FP7-ITN Olimpia, Firb-Futuro in Ricerca, SILK.IT
5:15 AM - Z2.08/AA2.08
Nanodevice for Intracellular Signal Recording and Stimulation
Jun Yan 1 Prema Chinnappan 1 Smith Woosley 1 Shyam Aravamudhan 1
1North Carolina Aamp;T State University Greensboro USAShow Abstract
The goal of this project is to develop a nanoprobe device for intracellular electrical signal recording and stimulation of neuronal cells. This paper presents a platform that integrates “Fin” shaped nanoelectrodes and cell microprinting technology. The “Fin” shaped nanoeletrodes were designed to increase the electrode area and conductance so as to reduce the signal loss seen in the case of traditional circular nanopillar designs. The microprinting technology, in turn enables controlled number and volume of cells to be printed on top of the nanoeletrodes in order to realize ease in cell penetration.
The overarching goal of neuroscience is to target and discover the relationships between the functional connectivity-map of neuronal circuits and their physiological or pathological functions. In the past, extracellular microelectrode arrays (MEAs) have been used to record and stimulate a population of excitable cells for months in-vivo (Kipke et al.). The recorded spikes (signal) by extracellular electrodes, though informative, do not provide the source mechanism for neuron firing; because the extracellular recordings do not record synaptic signals (subthreshold). On the other hand, intracellular recording can help study the functions of “silent” neurons and neuroplasticity (Spira et al.). In this respect, the current intracellular recording technologies include a sharp or patch electrode to measure only a few neurons. For recording a record large number of neurons, technologies such as gold mushroom-shaped microelectrodes (Hai et al.), vertical nanowire electrode arrays (Robinson et al.) and nanoFET technology (Tian et al.) are currently under development. The gold mushroom-shaped electrodes in order of microns are invasive for smaller cells with no successful recording on rat hippocampal neurons and primary rat cardiomyocytes. The vertical nanowire electrode arrays show high electrode impedance which causes large signal loss. The nanoFET show higher noise levels and the manipulation of a single nanotube to penetrate a single cell are very challenging. In this work, we present the design and fabrication of “Fin” shaped nanoelectrode which seeks to overcome the restrictions between electrode impedance and electrode size. Compared to the 3x3 array of 150 nm diameter nanowire electrodes, the “Fin” electrodes reduces impedance by factor of ten. 150 nm thick fins are seen to be less damaging compared to mushroom-shaped electrodes. We demonstrate the ability of microprinting technology to print viable neuronal PC12 cells onto pre-defined areas such as within the reservoir with nanoelectrodes. The relationship between the electrode geometry and neuronal cell viability is studied. Finally, the intracellular neuronal activity (action potential) with and without sub-threshold (10-40mV) electrical stimulus, along the effect of electrode surface coating on signal coupling is presented.
5:30 AM - *Z2.09/AA2.09
Biomedical Applications of Organic Bioelectronics
Agneta Richter-Dahlfors 1
1Karolinska Institutet Stockholm SwedenShow Abstract
Due to their structural kinship to proteins, carbohydrates and nuclei acids, the use of organic conducting polymers in biomedical research and medical applications is highly intuitive from a biological and chemical perspective. The availability of organic chemistry toolkits to functionalize and adapt these molecules, convenient processing techniques like soft lithography, electrodeposition or vapor phase polymerization as well as the possibility to reversibly modify their chemical and electrical properties by switching between the redox states of the conducting polymer backbone qualifies them as interesting materials for the development of functional tissue-device interfaces.
Using organic electronic devices with different designs and polymer bases, one can achieve control of cell growth and attachment on different levels. On a surface switch based on the conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT) doped with tosylate (PEDOT:tosylate) we show modulation of epithelia formation by presenting electrochemically oxidized versus reduced surfaces as substrates for cell attachment. By further modification of the device, adding a channel and gate electrode, an organic electrochemical transistor (OECT) is developed, which allows for active control of epithelial cell-density gradients along the channel. Electronic control of cell release was demonstrated in a similar devices using the self-doping compound PEDOT-S:H.
Organic electronic devices can also be designed to facilitate modulation of cell signaling in a biomimetic fashion. Electrical actuation of neuronal cells in a three dimensional nano-fiber scaffold is achieved on an electrospun scaffold coated with PEDOT:tosylate. The unique property of organic electronics to utilize both electrons and ions as charge carriers is used in the organic electronic ion pump (OEIP). When addressed electronically, the OEIP translates electronic signals into electrophoretic migration of ions or neurotransmitters. The precise, spatiotemporally controlled delivery of signaling substances in absence of liquid flow was demonstrated as a novel interface to modulate mammalian senses.
This presentation will highlight the potential of communication interfaces based on conjugated polymers in generating complex substrate signaling to control cell and tissue physiology. Organic electronic devices will have widespread applications across basic medical research fields as well as future applicability in medical devices in multiple therapeutic areas.
Z3/AA3: Joint Poster Session: Bioelectronics: Neural Applications, Nanoelectronics and Natural/Biocompatible Materials
Tuesday PM, April 22, 2014
Marriott Marquis, Yerba Buena Level, Salons 8-9
9:00 AM - Z3.01/AA3.01
Towards Scalable Solid-State Nanoelectrode Arrays for Neural Recordings
Tara Bozorg-Grayeli 1 Katie G. Chang 1 J. Nathan Hohman 1 Matt R. Angle 1 2 Nicholas A. Melosh 1
1Stanford University Stanford USA2Max Planck Institute for Medical Research Heidelberg GermanyShow Abstract
The study of interconnectivity within neural networks is limited by the existing experimental techniques for massively parallel electrical recordings. Multielectrode arrays and patch clamps are the current standards for recording neuronal membrane potentials; however, neither offers the combination of sensitive, long-duration recordings. Developing solid-state devices via scalable fabrication techniques requires thoughtful design informed by the conditions at cell surfaces. To achieve sensitive, long-term recordings, we target biomimetic integration of probes with the plasma membrane, using a layered structure we describe as “stealth probes.” Stealth probes are solid-state nanostructures that can span cell membranes, forming electrically tight seals against the phospholipid bilayer structure. The junction between probe and cell is both mechanically stable and offers high resistance against ion exchange between cytoplasm and media. Gigaohm-level leak resistance is the critical need for non-invasive intracellular measurements with the scalability of a multielectrode array. Through cell-probe interface modeling, we have identified the parameters required for sensitive cellular electrical recordings, and are employing fabrication techniques to target devices accordingly. We have developed a hybrid on-wire lithographic approach to fabricate biologically compatible, individually addressable solid-state nanoelectrode arrays. Here, we describe device fabrication and the necessary parameters for sensitive electrophysiological recordings. We focus on the electrical characteristics of the probes, the relationship between device impedance and signal-to-noise ratio, and the requirements necessary for immediate deployment of the technology for experiments in neuroscience.
9:00 AM - Z3.02/AA3.02
Incorporation of Biomolecules in Micropatterned Films of Conducting Polymers for Neuronal Cell Adhesion and Growth
SooHyun Park 1 Darian Nocera 1 Mohammad Reza Abidian 1 2 3 Sheereen Majd 1 4
1Penn State University University Park USA2Penn State University University Park USA3Penn State University University Park USA4Penn State University University Park USAShow Abstract
Conducting polymers (CPs) are easy to process and have tunable physical and chamical properties including conductivity, volume, color, and hydrophobicity. Therefore, these organic polymers are attractive in a broad spectrum of biomedical applications ranging from implentable electornics, and biosensing to tissue engineering and drug delivery. Among CPs, polypyrrole (PPy) is particularly appleaing for biomedical applications due to its biocompatibility and excellent stability. PPy can be electropolymerized into thin films and serve as substrates for in vitro cell cultures. Patterned films of conductive polymers, particularly with various surface chemistries, provide an excellent platform to study cellular behavior. We recently introduced a unique and verstaile method for direct patterning of PPy films on gold substrates. In this method, we employed an agarose hydrogel stamp as a carrier of polymer precursor solution including pyrrole and dopants. Upon placement of the stamp on an electrode and subsequent application of a current, the polymerization of pyrrole only occurred in the contact areas between the topographically-patterned hydrogel and the gold substrate. We demonstrated the capability of this method to generate positive patterns of PPy films with different sizes and geometries in a single-step and solution-free process. More importantly, we demonstrated that the posts on a hydrogel stamp can deliver different monomer/dopant combinations to create a patterned PPy film with different and addressable surface chemistries in a parallel fashion.
Here, we aim to apply this innovative and multifaceted technique to cage bioactive molecules within the CP network by simply adding the desired biomolecules to the polymer precursor solution that is applied for inking the hydrogel stamp. We hypothesize that the biocompatible agarose gel stamps can safely deliver the bioactive molecules during the electropolymerization process, leading to the entrapment of these molecules within the CP film. We tested this hypothesis by incorporation of D-biotin molecules into PPy network and confirmed the presence of D-biotin in these films by fluorescence immunohistochemistry and ATR-FTIR. Most importantly, we demonstrated that this hydrogel-mediated electrodeposition technique can create spatially addressable patterned films of PPy decorated with multiple different proteins and biomolecules in one-step process. Currently, we are employing these bio-functionalized PPy films to control and study neuronal cell adhesion and differentiation. The goal of this study is to apply these biofunctionalized PPy films to control stem cell fates for applications in neural tissue engineering.
9:00 AM - Z3.03/AA3.03
ldquo;In vivordquo; Test of Titanium Alloy Devices Regarding Aluminum Release
Julia Claudia Mirza 1 Oscar Martel Fuentes 1 Cora Vasilescu 2
1University of Las Palmas de Gran Canaria Las Palmas de Gran Canaria Spain2Physical-Chemistry Institute Bucharest RomaniaShow Abstract
Ever since the pioneer titanium alloy (Ti6Al4V) has been used as biomaterial, lack of biocompatibility has been extensively reported and propelled research on improved materials with appropriate mechanical behavior and adequate biocompatibility. Studies have indicated that vanadium produces oxides harmful to the human body; in order to replace vanadium containing Ti alloys, Ti-6Al-7Nb was developed. Today this alloy is the preferred choice for cementless total joint replacements. It is very important to produce a nanostructured bioactive metal implant with appropriate mechanical properties and we applied a chemical and thermal treatment that converts the surface of titanium alloy into bioactive surface. Therefore, bioactive Ti6Al7Nb might represent an alternative for advanced orthopedic implants under load-bearing conditions.
Eleven mini-pigs weighting around 50 kg, with free access to food pellets and water, were the experimental animals for this study. Ten of these pigs (one is the control) were anesthetized and after shaving, disinfection and draping, a straight 3 cm incision was made and the implants (plate and pin) were implanted into the epiphyses of the tibiae. Surgical procedures were performed bilaterally. At 6 months after implantation, the mini-pigs were sacrificed.
After sacrifice, the segments of the proximal tibia epiphyses containing the implanted plates and pins were cut off, fixed in phosphate-buffered formalin and dehydrated in serial concentrations of ethanol after which they were embedded in polyester resin and then cutted and grounded to a thickness of 75-100 µm. With these samples SEM-EDX examinations were made. The aluminium content was measured by electrothermal atomic absorption spectrometry in different organs: brain, fat, kidney, spleen and liver.
All the results revealed that the plates and pins are in direct contact with newly formed bone without any intervening soft tissue layer. No aluminium accumulation occurs during the experiment and we regard it as one of the advantages of this implant in consideration for clinical applications.
9:00 AM - Z3.04/AA3.04
Functionalization of Conducting Polymers with Silk-Inspired Peptides to Develop Robust Materials for Biomedical Applications
Tyler Albin 1 Melany Fry 1 Amanda Murphy 1
1Western Washington University Bellingham USAShow Abstract
Conducting polymers (CPs) have been the subject of significant research in recent years for their optical and electronic properties, as well as their potential use in biomedical applications. Medical procedures requiring electrical stimuli have traditionally used metallic compounds, which have severe issues with tissue compatibility. CPs are a promising replacement to metals in these applications due to their biocompatibility, electrical conductivity, and range of chemical and physical properties. However, standard CPs are typically brittle and difficult to process into 3D structures which has limited their use. We aim to develop new CPs that incorporate a peptide motif based on an amino acid sequence found in silk fibroin that is capable of self-assembly and is responsible for the characteristic strength of silk. We hypothesize that hydrogen bonding between chains of the peptide functionalized conducting polymers will influence the 3D organization and improve mechanical strength while retaining biocompatibility. To make such materials we are investigating two complimentary approaches: 1) assembling and polymerizing peptides containing a thiophene-based monomer or 2) functionalizing a pre-made polymer with silk peptides. Here, we present the synthesis of silk-inspired peptides coupled to 3,4-ethylenedioxythiophene (EDOT) monomers, the characterization their electrochemical properties, and their capability to self-assemble. We also demonstrate the ability to incorporate these thiophene-peptide conjugates into copolymers with EDOT.
9:00 AM - Z3.05/AA3.05
SiC Protective Coating for Photovoltaic Retinal Prosthesis
Xin Lei 1 2 Stuart Cogan 4 Ludwig Galambos 1 Philip Huie 2 3 Keith Mathieson 5 Theodore Kamins 1 James Harris 1 Daniel Palanker 2 3
1Stanford University Stanford USA2Stanford University Stanford USA3Stanford University Stanford USA4EIC Laboratories Norwood USA5University of Strathclyde Glasgow United KingdomShow Abstract
Implantable biomedical devices such as emerging MEMS-based neural prostheses require long-term stability in the human body. Since these devices cannot be protected with conventional metal or ceramic enclosures, a conformal encapsulation that provides chronic protection against water and ion ingress is necessary to achieve this goal. Commonly used materials include some urethanes, silicones, ceramics and metals. Amorphous silicon carbide (a-SiC) was proposed as a protective coating due to its biocompatibility and low dissolution rate in saline compared to other commonly used dielectric materials for IC passivation, such as silicon nitride (SiNx) and silicon dioxide. In addition, the deposition, patterning and etching of SiC are compatible with standard CMOS processing. These factors provide a strong incentive to investigate the potential of a-SiC as a protective coating for implantable devices.
In this study, we examined the properties of a-SiC deposited at 325°C by plasma enhanced chemical vapor-phase deposition (PECVD). We focused on three properties of a-SiC that are critical to its success as a protective coating: dissolution rates in accelerated saline tests, pinholes, trench coverage and barrier properties. The existence of any pinhole in the SiC layer will expose the underlying materials to the physiological medium causing them to dissolve, adversely affecting functionality of electrical devices, and inducing biological response in the human body. We performed a fast pinhole test by immersing the device in selective SiO2 and Si etchants and found that SiC films as thin as 200nm protected the front surface of MEMS devices completely with no evidence of pinholes. We demonstrated that SiC is able to cover most of the regions inside deep trenches (with an aspect ratio of 6:1), while a small number of pinholes were identified on the sidewalls. Further research is needed to eliminate these pinholes.
To test stability of the silicon device with polysilicon-filled trenches protected by a-SiC in the biological medium, we soaked both protected and unprotected devices in saline at 87°C for 12 days, which is equivalent to ~ 1 year at the human body temperature. SEM images showed that devices without a-SiC coating degraded significantly, while devices with a SiC coating stayed mostly intact. We also examined the forward and reverse I-V characteristics of pn junctions underneath the SiC coating before and after soaking, and observed no significant difference. These results indicate that a-SiC provided an effective barrier for our MEMS-based retinal prosthetic implants.
9:00 AM - Z3.06/AA3.06
New Strategies to Optimize Conductivity and Morphology of Silk-Conducting Polymer Composites
Sean Severt 1 Isabella Romero 1 Amanda Murphy 1
1Western Washington University Bellingham USAShow Abstract
Biocompatible materials capable of conducting electricity have numerous biomedical applications including use as electrodes for neurological stimulation and recording, artificial muscles, and stimuli-responsive sensors. Conducting polymers (CPs) such as poly(pyrrole) and poly(thiophene) are advantageous for these applications as they are biocompatible, and their chemical and physical properties can be easily tuned. A major hurdle in the development of practical biomedical devices utilizing conducting polymers is dealing with the poor mechanical properties of the bulk polymers. The conjugated π-system of CPs that allows electron flow also results in the bulk material being stiff and brittle, complicating the fabrication of three-dimensional electrodes. In order to improve the mechanical properties of CP networks, we have established methodology for the fabrication of composites materials made of (poly)pyrrole interpenetrating into a flexible silk fibroin scaffold. Silk fibroin is a well-studied biomaterial capable of being processed into a variety of forms, such as films, hydrogels, and 3D scaffolds. Here we present new electropolymerization strategies to increase the conductivity and versatility of these silk-CP composites, and methods to tailor their surface morphology to maximize performance.
9:00 AM - Z3.07/AA3.07
Three-Dimensional Analysis of CLARITY Brain-Polymer Hybrids by Raman Scattering and Two-Photon Microscopy
Ariane Tom 1 Andrey Malkovskiy 2 Zhenan Bao 3 Karl Deisseroth 1 4
1Stanford University Stanford USA2Stanford University Stanford USA3Stanford University Stanford USA4Stanford University Stanford USAShow Abstract
Optical analysis of deep brain structures has remained an elusive challenge, due to the presence of highly scattering, randomly distributed, dense lipid bilayers surrounding neurons. Though laser scanning coherent anti-Stokes Raman scattering (CARS) microscopy has been successful in rendering three-dimensional (3D) spatial resolution in live cells and tissues, light dispersion still reduces laser intensity and signal quality, and prohibits imaging of deeper targets without first making incisions to access the tissue. This problem may be addressed by using a newly developed technology, known as CLARITY, which enables unprecedented resolution of detailed structural and molecular information of intact biological systems. During CLARITY sample preparation, intact tissue (such as whole brains) can be transformed into nanoporous tissue-polymer hybrids, which are then made transparent using electrophoretic lipid removal. The final product of CLARITY is tissue that has been stabilized through effective replacement of structure-maintaining lipids with a hydrogel covalently bonded to proteins. The resulting transparency of the tissue-polymer hybrid permits true high resolution, 3D analysis of neural networks and biomolecular architecture by much simpler, less damaging, and cost-effective imaging techniques. In this study, we investigated polymer formation and hybridization within tissue using confocal Raman scattering, complemented by two-photon fluorescence microscopy. This work represents the first demonstration of three-dimensional Raman spectral mapping of brain tissue, providing a new perspective on the distribution and identity of protein and polymer bonds. Information from these maps can be correlated with biological features identified using appropriate staining techniques and two-photon microscopy, and can be employed to quantitatively explore the influence of key reactants on CLARITY tissue-polymer hybrid properties. These results will be significant in helping to tune the CLARITY platform for various applications, and provide a deeper understanding of how polymers form and crosslink within tissues.
9:00 AM - Z3.08/AA3.08
High Performance Organic Electronic Circuits Based on Hydrogen-Bonded Molecules
Cigdem Yumusak 1 2 Meltem Akcay 1 Halime Coskun 1 Eric Daniel Glowacki 1 Niyazi Serdar Sariciftci 1
1Johannes Kepler University of Linz Linz Austria2Yildiz Technical University Istanbul AustriaShow Abstract
Natural-origin hydrogen-bonded molecular solids such as the indigo and its derivatives are very promising semiconducting materials because of remarkable physical and chemical properties as well as biocompatibility and biodegradability. With mobility in the range of 1 cm2/Vs and stable operation in air, they are competitive with many synthetic materials. In recent years, we have demonstrated that it is possible to produce green electronic devices using the indigo compounds. In this report, we bring our recent works into practical implementations of electronic circuits, such as complementary-like voltage inverters and ring oscillators, where indigo and its derivatives are remarkable for their air stability.
9:00 AM - Z3.09/AA3.09
Integration of Carbon Nanotube Network Transistor and Tethered Lipid Bilayer on SiO2 Surface for Single-Ion Channel Recording
Weiwei Zhou 1 Tae-Sun Lim 1 Phi Pham 1 Peter John Burke 1
1UC Irvine Irvine USAShow Abstract
As an artificial cell membrane on solid wafer surface, supported-lipid bilayer (SLB) is one of most promising biological platform in biophysics research because it opens possibilities to study the fundamental properties of cell membrane by modern surface-based characterization techniques and advanced nanotechnology. In the meantime, carbon nanotubes (CNTs), as a typical one-dimensional molecular system, have been attracted enormous attentions for their remarkable electrical properties and CNT-based field effect transistors (FETs) have shown high sensitivity in bio- or chemical sensors. However, a challenge is how to engineer graphene&’s sensitivity to a specific analyte of interest.
Here, we incorporate ion channel membrane proteins gA and α-HL in an SLB on a functionalized all-semiconducting nanotube network, where SLB forms an insulating barrier on FET surface. The nanotube transistor as a charge sensor only detects the ions or biomoleculars through ion channels. Nonetheless, due to the nature hydrophobic surface of carbon nanotube, lipid bilayer doesn&’t form a continuous film on high-density nanotube network surface. At the same time, the main drawback of solid supported lipid bilayer is the very limited distance between solid substrate and lipid bilayer, usually only up to 1nm. Therefore, it is crucile to utilize surface functionalization for fabricating a robust lipid bilayer on surface and spacing the membrane up from the substrate. Our functionalization strategy is using silane molecular as a linker to covalently bind with substrate and lipid monolayer. The space distance can be delicately tuned by changing the length of silane molecular. The second layer lipid layer can be easily formed on the tethered lipid surface by vesicle fusion or directly dropping lipid ethanol solution. The quality of lipid membrane is estimated by fluorescence recovery after photobleaching (FRAP), atomic force microscopy (AFM) and impedance spectroscopy. Moreover, combining with microfluidic channel, we are able to detect single ion channel activity. Dynamic opening and closing of the pores is observed through measurement of the current from the nanotube network, through the nanopores, and into solution. The all-semiconducting nanotube network devices are compatible with microfabrication process, opening a window for massively parallel manufacturing of nanotechnology for a variety of applications in electrophysiology and biosensors.
9:00 AM - Z3.10/AA3.10
Electrolyte-Gated Organic/Nanoparticles Synapstor (Synapse-Transistor) for Biocompatible Synapse Prosthesis
Simon Desbief 1 Adrica Kyndiah 2 Mauro Murgia 2 Tobais Cramer 2 Fabio Biscarini 3 2 David Guerin 1 Stephane Lenfant 1 Fabien Alibart 1 Dominique Vuillaume 1
1IEMN-CNRS Villeneuve d'Ascq France2ISMN-CNR Bologna Italy3Univ. Modena and Reggio Emilia Modena ItalyShow Abstract
We have recently demonstrated how we can use charge trapping/detrapping in an array of gold nanoparticules (NPs) at the SiO2/pentacene interface to design a SYNAPSTOR (synapse transistor) mimicking the dynamic plasticity of a biological synapse. This device (memristor-like) mimics short-term plasticity (STP)  and temporal correlation plasticity (STDP, spike-timing dependent plasticity) , two "functions" at the basis of learning processes. A compact model was developed , and we demonstrated an associative memory, which can be trained to present a pavlovian response .
Here we develop an electrolyte-gated version of this device for biocompatible applications. We report on a detailed understanding of the electrical behavior of these synapstors in physiologically relevant conditions. We compare synapstors operated by the traditional bottom gate structure in air and by a water-electrolyte gate geometry. We show that the increased capacitance of the pentacene/water interface leads to a large improvement of the synapse-like behavior of these devices. STP of comparable amplitude (about 50% of the total output current) is observed at a reduced working voltage (i.e. spike voltage of 0.4V in water, instead of 10 V in air). Moreover, the typical dynamic time response of the synapstor is also decreased by about a factor 10 (ca. 0.2s instead of ca. 2-5s). These last results represent major improvements towards the use of these organic/NPs synapstor in biocompatible application e.g. as synapse prosthesis.
This work has been financially supported by the EU 7th framework programme [FP7/2007-2013] under grant agreement n° 280772, project "I ONE”.
 F. Alibart et al., Adv. Func. Mater. 20, 330 (2010).
 F. Alibart et al., Adv. Func. Mater. 22, 609-16 (2012).
 O. Bichler et al., IEEE Trans. Electron. Dev. 57(11), 3115-3122 (2010).
 O. Bichler et al., Neural Computation 25(2), 549-566 (2013).
9:00 AM - Z3.12/AA3.12
Characterizing Material Properties of Biocompatible, Silk-Based Polypyrrole Electromechanical Actuators
Nathan P Bradshaw 1 Jesse Larson 1 Sandra Roberts 1 Amanda Murphy 1 Janelle Leger 1
1Western Washington University Bellingham USAShow Abstract
Materials capable of controlled movements that can also interface with biological environments are highly sought after for biomedical devices such as valves, blood vessel sutures, cochlear implants and controlled drug release devices. Here we report the synthesis of films composed of a conductive interpenetrating network of the biopolymer silk fibroin and poly(pyrrole). These silk-PPy composites function as bilayer electromechanical actuators in a biologically-relevant environment, can be actuated repeatedly, and are able to generate forces comparable with natural muscle (>0.1 MPa), making them an ideal candidate for interfacing with biological tissues. We will discuss the mechanical properties and actuation performance of these promising devices under biologically relevant conditions.
9:00 AM - Z3.13/AA3.13
Synthesis and Characterization of Melanin in DMSO under Different Conditions
Erika S. B. Uhle 1 Marina P. Silva 1 Joao V. Paulin 1 Augusto Batagin 1 Eduardo R. Azevedo 2 Carlos F.O. Graeff 1