Polina Anikeeva, Massachusetts Institute of Technology
Timothy Denison, Medtronic Inc.
Nick Melosh, Stanford University
Christelle Prinz, Lund University
Phase Holographic Imaging
BM08.01: Neural Tissue Imaging
Monday PM, November 27, 2017
Sheraton, 2nd Floor, Republic A
8:30 AM - *BM08.01.01
Towards Holistic Phenotyping of Intact Biological Systems
Kwanghun Chung 1 Show Abstract
1 , Massachusetts Institute of Technology, Cambridge, Massachusetts, United States
Holistic measurement of diverse functional, anatomical, and molecular traits that span multiple levels, from molecules to cells to an entire system, remains a major challenge in biology. In this talk, I will introduce a series of technologies including CLARITY, SWITCH, MAP (Magnified Analysis of Proteome), and stochastic electrotransport that enable proteomic and structural imaging for scalable, integrated, high-dimensional phenotyping of both animal tissues and human clinical samples. SWITCH enables over twenty rounds of relabeling of a single tissue with precise co-registration of multiple datasets by synchronizing key chemical reactions in tissue processing. With SWITCH, we demonstrated combinatorial protein expression profiling and high-dimensional quantitative analysis of the human cortex. MAP enables scalable superresolution proteomic imaging of large scale tissues by expanding intact organs four fold linearly while preserving their 3D proteome, nanoscopic architecture, and intercellular connectivity. Using MAP, we demonstrated molecular imaging of subcellular architectures and accurate tracing of densely packed neural projections. To speed up the labeling process in CLARITY, SWITCH, and MAP, we developed a novel electrokinetic method termed stochastic electrotransport, which enables immunolabeling of whole mouse brains within 1-3 days. We hope these new technologies to accelerate the phase of discovery in a broad range of biomedical research.
9:00 AM - BM08.01.02
Fiber-Shaped OLEDs for Effective Optogenetic Light Stimulation Tools
Seonil Kwon 1 , Hyuncheol Kim 1 , Seungyeop Choi 1 , Somin Lee 1 , Kyung Cheol Choi 1 Show Abstract
1 , Korea Advanced Institute of Science and Technology (KAIST), Daejeon Korea (the Republic of)
Optogenetics has emerged as a new stimulation method in neuroscience, to precisely control the activity of individual cells with light, using light-sensitive proteins such as channelrhodopsin-2 (ChR2), and halorhodopsin (NpHR). For light stimulation, most studies have used inorganic light emitting diodes (LEDs) and lasers because high optical power densities (1-10 mW mm-2) are typically required to provoke optogenetic responses.[1, 2] However, recently, organic LEDs (OLEDs) have been used as an alternative light stimulation source, and it has been proven that a low optical power density of 10 μW mm-2 is sufficient to elicit an action potential.[3, 4] OLEDs have appropriate properties for optogenetic light stimulation tools: fast response time, light weight, and low operating voltages. Their added flexibility can provide minimal cell invasion in in vivo experiments.
Here, we demonstrate fiber-shaped OLEDs with different diameters ranging from 300 μm to 90 μm - as thin as a human hair - which can serve as effective optogenetic light stimulation tools. Our previous work reported the fiber-shaped OLEDs, however, they had a lower intensity than comparable glass-based control devices. By revising the structure of the OLEDs, we achieved fiber-shaped OLEDs with an optical power density close to 90 μW mm-2, which is a high enough optical power density to trigger optogenetic responses. The fabricated devices showed main electroluminescence emission peaks at around 540 nm, which overlaps the activation spectrum of NpHR. In addition, the fiber-shaped OLEDs were encapsulated in an Al2O3 single layer after fabrication for stability testing. Their operational lifetime was measured to be over 80h in ambient air.
In conclusion, we have developed fiber-shaped OLEDs as thin as human hair with sufficient optical power density to evoke optogenetic responses. However, some challenges still remain before these OLEDs can be used in a biologically harsh environment, because OLEDs are very vulnerable to moisture and oxygen. Nevertheless, we believe that with advanced flexible encapsulation and packaging the proposed fiber-shaped OLEDs can provide opportunities to investigate neuron networks with minimally invasive effects on cells in vivo in the future.
Acknowledgement: This research was supported by Attachable Photo Therapeutics Center for e-Healthcare funded by the National Research Foundation of Korea (NRF) Grant of the Korean government (MSIP).
1. T. Bruegmann et al., Nat. Methods 2010, 7, 897.
2. S. Zhao et al., Nat. Methods 2011, 8, 745.
3. C. Murawski et al., Light, Energy and the Enviroment, OSA Techincal Digest (online) 2016, p. JW4A.9.
4. A. Steude et al., Sci. Adv. 2016, 2, e1600061.
5. S. Kwon et al., Adv. Electron. Mater. 2015, 1, 1500103.
9:15 AM - BM08.01.03
Simultaneous Profiling of Nucleotides, Proteins and Endogenous Fluorescence in Transparent Tissue Enabled by Flexible and Multifunctional Fixatives
Ritchie Chen 1 , Meg McCue 1 , Yonggyun Park 1 , Kwanghun Chung 1 Show Abstract
1 , Massachusetts Institute of Technology, Cambridge, Massachusetts, United States
Holistic understanding of complex biological systems, from single biomolecules to cell interactions across whole organs, will require integrated methodologies that can simultaneously probe both nucleotides and proteins in intact tissue. While several tissue preservation strategies, such as CLARITY, SWITCH, and MAP, have been explored to preserve individual molecular features (e.g endogenous fluorescence of protein reporters, mRNA transcripts, or protein antigenicity), a universal tissue clearing method to profile all biomolecule types remains to be developed. Here, we demonstrate how multifunctional cross-linkers with tightly regulated reaction kinetics can form cohesive tissue gels by binding together biomolecules of interest. We find that these flexible and multifunctional linkers protected proteins and nucleotides from deteriorating in harsh chemical conditions by forming both intra- and intermolecular bonds. This strategy, called SHIELD, enables simultaneous molecular profiling of nucleotides, proteins, and fluorescent reporters in intact tissue, such that correlative studies, from single transcripts to whole organ features, can be performed.
9:30 AM - *BM08.01.04
Optogenetic, Tissue Clearing, and Viral Vector Approaches to Understand and Influence Whole-Animal Physiology and Behavior
Viviana Gradinaru 1 Show Abstract
1 , California Institute of Technology, Pasadena, California, United States
Our research group at Caltech develops and employs optogenetics, tissue clearing, and viral vectors to gain new insights on circuits underlying locomotion, reward, and sleep. Genetically encoded tools that can be used to visualize, monitor, and modulate mammalian neurons are revolutionizing neuroscience. However, use of genetic tools in non-transgenic animals is often hindered by the lack of vectors capable of safe, efficient, and specific delivery to the desired cellular targets. To begin to address these challenges, we have developed an in vivo Cre-based selection platform (CREATE) for identifying adeno-associated viruses (AAVs) that more efficiently transduce genetically defined cell populations (Deverman et al, Nature Biotechnology, 2016). As a first test of the CREATE platform, we selected for viruses that transduced the brain after intravascular delivery and found a novel vector, AAV-PHP.B, that transduces most neuronal types and glia across the brain. We also demonstrate how whole-body tissue clearing can facilitate transduction maps of systemically delivered genes (Yang et al, Cell, 2014; Treweek et al, Nature Protocols, 2016) and how non-invasive delivery vectors can be used to achieve dense to sparse labeling to enable morphology tracing (unpublished). Since CNS disorders are notoriously challenging due to the restrictive nature of the blood brain barrier, the recombinant vectors engineered to overcome this barrier can enable potential future use of exciting advances in gene editing via the CRISPR-Cas, RNA interference and gene replacement strategies to restore diseased CNS circuits. In addition to control of neuronal activity we need feedback on how exactly the tissue is responding to modulation. We have worked on two related topics: optical voltage sensors and imaging of single molecule RNA in cleared tissue. Changes in RNA transcripts can also report on activity history of brain circuits. Preserving spatial relationships while accessing the transcriptome of selected cells is a crucial feature for advancing many biological areas, from developmental biology to neuroscience. Collaborators and us recently reported on methods for multi-color, multi-RNA, imaging in deep tissues. By using single-molecule hybridization chain reaction (smHCR), PACT tissue hydrogel embedding and clearing and light-sheet microscopy we detected single-molecule mRNAs in ~mm-thick brain tissue samples (Shah et al, Development, 2016) and by rRNA labeling we mapped the identity and growth rate of pathogens in clinical samples (DePas et al, mBio, 2016). Together these technologies can enable high content anatomical and functional mapping to define changes that affect cell function and health body-wide.
10:30 AM - *BM08.01.05
Designing Fluorescent Materials for Advanced Microscopy Experiments in Cells and Beyond
Luke Lavis 1 Show Abstract
1 , Janelia Research Campus, Ashburn, Virginia, United States
Specific labeling of biomolecules with bright, photostable fluorophores is the keystone of fluorescence microscopy. An expanding method to label cellular components utilizes genetically encoded self-labeling tags, which enable the attachment of chemical fluorophores to specific proteins inside living tissue. This strategy combines the genetic specificity of fluorescent proteins with the favorable photophysics of synthetic dyes. However, intracellular labeling using these techniques requires small, cell-permeable fluorescent materials, thereby limiting utility to a small number of classic, unoptimized dyes. We discovered a simple structural modification--incorporation of four-membered azetidine rings--that dramatically improves brightness and photostability while preserving other spectral properties and cell permeability. This novel substitution is generalizable to fluorophores from different structural classes, yielding a palette of synthetically tractable chemical dyes with high brightness and cell permeability. These improved versions of classic fluorophores can be further modified to fine-tune spectral and chemical properties for advanced imaging experiments in complex biological environments, ultimately allowing the in situ construction of neural indicators inside living animals.
11:00 AM - BM08.01.06
Simultaneous Electrophysiology and 2-Photon Imaging with Transparent Electronics for In Vivo Characterization of Neural Networks
Mary Donahue 1 , Attila Kaszas 2 , Gergely Turi 3 , Attila Losonczy 3 , Adam Williamson 2 1 , George Malliaras 1 Show Abstract
1 , ENS Mines-St. Etienne, Gardanne France, 2 Aix-Marseille Université, Institut de Neurosciences des Systèmes, Marseille France, 3 Department of Neuroscience, Columbia University, New York, New York, United States
Optical methods for the characterization of neural activity are used clinically and in rodent models every day. The most common of these methods are CT scans and fMRI. Although the spatial resolution of these scans is brain-wide, the temporal resolution is at best several seconds. This makes a robust analysis of the LFP compared to the millisecond and microsecond events of the firing of bursts and individual neurons impossible to resolve. As a result, the primary method for the characterization of neural activity remains electrophysiology with a temporal resolution perfectly acceptable for capturing the above mentioned activity.
However, electrodes provide a spatial resolution equal to the spacing between the individual electrodes and are invasively implanted. Modern imaging should in theory replace electrophysiology in the future. One extremely modern method is the 2-photon microscope, which has a continuous spatial resolution containing the whole area of 3D tissue measured and a temporal resolution also perfectly acceptable to capture the desired activity. Unfortunately, there has not been an electrode technology particularly compatible with 2-photon investigation to truly benchmark this modern method against the classical standard of electrophysiological measurement with electrodes.
Here we demonstrate the simultaneous use of state-of-the-art organic electrodes in combination with modern 2-photon optical imaging in vivo. The LFP and local bursting are identifiable simultaneously with both methods. This provides the first real test vehicle to compare classical electrophysiological clustering and analysis methods with modern optical investigation. Previously this was impossible due to optical limitations, i.e. opacity, traditional recording electrodes in addition to noise generated by the scanning of the laser. However, the organic microelectrode array utilizes transparent materials, allowing for 2- photon imaging, and is also unaffected by the scanning and fluorescence measurements stimulated by the scanning of the 2-photon’s laser system. We correlate the activity of a 3D in vivo neural network as measured by the 2-photon calcium signal to the cortical grid of organic microelectrodes.
11:15 AM - *BM08.01.07
MoNaLISA—A Faster and Gentler Super Resolution Approach for Live Whole Cell Imaging at the Nanoscale
Ilaria Testa 1 Show Abstract
1 , KTH Royal Institute of Technology, Stockholm Sweden
The formidable ability of fluorescent nanoscopy to image features closer than half the wavelength of light often comes at the expense of time and increased dose of energy for recording. We developed a gentle fluorescent nanoscope based on the reversible switch of fluorescent proteins, capable of resolving cellular structures within the whole cell at spatial resolutions down to between 40–60 nm using minimal light intensities (50-500 W/cm2). Our approach, named MoNaLISA for molecular nanoscale long term imaging with sectioning ability, is based on thousands of focal spots that switch and read-out the fluorescence signal emitted by reversible switchable fluorescent proteins. MoNaLISA illumination scheme happen in three steps and it is highly parallelized enabling acquisition time in the order of the 0.2–2Hz for large fields of view (50µm). The spatially modulated illuminations in ON-switching and read-out lead to images with tenfold enhanced contrast and intrinsic optical sectioning. MoNaLISA imaging is extendable to the whole range of reversible switchable fluorescent proteins without compromising image contrast. We demonstrate the general use of MoNaLISA in living cells and tissues such as human fibroblast, hippocampal neurons, colonies of mouse embryonic stem cells and organotypic slice culture.
BM08.02: High-Resolution, Multifunctional and Carbon Neural Interfaces
Monday PM, November 27, 2017
Sheraton, 2nd Floor, Republic A
1:30 PM - *BM08.02.01
Highly Integrated CMOS Microsystems to Interface with Neurons at Subcellular Resolution
Andreas Hierlemann 1 Show Abstract
1 Department of Biosystems Science and Engineering, ETH Zürich, Basel Switzerland
To understand how functions and characteristics of neuronal networks arise from the concerted interactions of the involved neurons, it is necessary to have methods that allow for interacting with neuronal functional subunits and ensembles - somas, axons, dendrites, single neurons, and entire networks - at high spatiotemporal resolution and in real time.1-3 Here, we demonstrate how CMOS high-density microelectrode arrays (HD-MEAs) featuring several thousands of electrodes (> 3’000 electrodes per mm2) 4-7 can be used to record from or stimulate potentially any individual neuron or subcellular compartment on the CMOS chip. High- and subcellular-resolution recordings of individual neurons in networks will be presented.
Extracellular electrical recordings by means of microelectrode arrays complement well-established patch clamp techniques 8,9 and optical or optogenetic techniques.10-13 The use of CMOS technology helps to overcome the connectivity problem of how to interface thousands of tightly-spaced electrodes, while, at the same time, it improves signal-to-noise characteristics, as signal conditioning is done on chip next to where the partially very small signals (< 10 µV) are generated.4-6 Several different approaches relying on open-gate field-effect transistors or metal electrodes have been pursued.4-7 There are high-density pixel-based approaches 4,5,7 and realizations based on a switch matrix concept.6,14,15
As one of the examples, a HD-MEA system featuring a sensing area of 3.85 × 2.10 mm2 hosting 26’400 electrodes of 7 µm diameter at a center-to-center pitch of 17.5 µm will be shown.6,15 The switch matrix allows for simultaneously routing user-configurable selections of electrodes to 1024 recording channels and 32 stimulation units at the array periphery. With this system we were able to record subcellular-resolution data in various preparations. Applications include research in neural diseases and pharmacology.
(1) Alivisatos, A. P., et al. ACS nano 2013, 7, 1850-1866.
(2) Marblestone, A. H., et al. Front Comput Neurosci 2013, 7.
(3) Buzsaki, G., et al. Neuron 2015, 86, 92-105.
(4) Berdondini, L., et al. Lab on a Chip 2009, 9, 2644-2651.
(5) Bertotti, G., et al. In Biomedical Circuits and Systems Conference (BioCAS), 2014 IEEE, 2014, pp 304-307.
(6) Ballini, M., et al. IEEE J Solid-State Circuits 2014, 49, 2705-2719.
(7) Eversmann, B., et al. IEEE J Solid-State Circuits 2003, 38, 2306-2317.
(8) Neher, E.; Sakmann, B. Nature 1976, 260, 799-802.
(9) Cole, K. S. Arch. Sci. physiol. 1949, 3, 253-258.
(10) Hochbaum, D. R., et al. Nat Methods 2014, 11, 825-833.
(11) Scanziani, M.; Häusser, M. Nature 2009, 461, 930-939.
(12) Peterka, D. S., et al. Neuron 2011, 69, 9-21.
(13) Grienberger, C.; Konnerth, A. Neuron 2012, 73, 862-885.
(14) Frey, U., et al. IEEE J Solid-State Circuits 2010, 45, 467-482.
(15) Müller, J., et al. Lab Chip 2015, 15, 2767-2780.
2:00 PM - BM08.02.02
Electrical and Biocompatibility Properties of Different Soft Intra-Cortical Implant Designs
Paul Villard 1 , Jean-Marie Mayaudon 1 , Cyril Zenga 1 , Anne Quesnel-Hellmann 1 , Lionel Rousseau 2 , Blaise Yvert 1 , Gaelle Piret 1 Show Abstract
1 Braintech Lab, INSERM, Grenoble France, 2 , ESIEE, Noisy-le-Grand France
Neuroengineering more efficient neural interfaces is crucial to develop better clinical rehabilitation solutions and for neural network exploration. Most of current intra-cortical implants are stiff and generate mechanical strain that results in complex cellular responses and instabilities in neural signal recording. Designing soft intra-cortical neural implant with a high density microelectrode array has therefore become essential to faithfully record several neural units overtime and to facilitate for instance, brain computer interface performances and the study of memory and plasticity. We developed a soft SU-8 polymer neural implant with 64 nanostructured gold 20µm electrodes and vary the design of the 2mm deep intra-cortical part of the implant. Leads were either 50µm, 20µm or 11µm wide with a straight or a wavy shape. We then evaluated the impact of different designs on electrical properties of the implant. In vivo biocompatibility tests in rodents were performed and astrocytes, microglia and cell density were analysed around the different implant lead types.
2:15 PM - BM08.02.03
Toward a Completely Resorbable Penetrating Neural Electrode—Fundamental Studies at the Metal/Coating Interface
Morgan Hawker 1 , Chengchen Guo 1 , David Kaplan 1 Show Abstract
1 Biomedical Engineering, Tufts University, Medford, Massachusetts, United States
Enormous potential exists for utilizing neural electrodes as both stimulation and recording devices in a multitude of applications. Penetrating neural electrodes can aid in the diagnosis and treatment of Parkinson’s disease, epilepsy, and traumatic brain injuries. Current electrode probe designs center around invasive, silicon-based materials. Although these devices are strong and conductive, the inability to modulate their flexibility and geometry severely limits their utility. Moreover, silicon-based electrodes do not exhibit appreciable in vivo degradation, often requiring post-implantation removal surgery. Such surgeries are undesirable as they increase infection risk and may cause tissue damage. Ideally, penetrating electrodes would completely degrade following stimulation or recording, mitigating the need for removal surgeries. Although a variety of transient devices have been developed within the neural electronics field, a fully transient penetrating neural electrode has yet to be realized. In the present work, we take steps to address shortcomings of current electrode technologies through the design of conductive, flexible constructs with tunable degradation in aqueous environments.
Magnesium metal has been selected as an initial electrode material, owing to its well-established biological relevance and conductivity. The trade-off between stable electrical stimulation/recording and degradation capabilities, however, represents a significant challenge for magnesium-based devices as the metal undergoes rapid hydrolysis in aqueous conditions. We address this challenge by passivating magnesium via coating strategies to provide short-term electrical stimulation/recording followed by complete device degradation. In this work, we utilized a multi-pronged coating approach centering on silk fibroin, owing to its ubiquitous biocompatibility, processing ability, desirable mechanical properties, and controllable degradation behavior in aqueous environments. These proof-of-concept transient devices provided a framework to develop a fundamental understanding of synergies between magnesium degradation and silk degradation. Specifically, we explored how tuning device chemical and physical properties alter degradation kinetics, as well as routes to improve coating conductivity by silk chemical modification. Preliminary findings assessing coating morphology, conformality, chemical composition, and crystallinity/secondary structure will be presented, pertaining to their impact on device performance. Additionally, we will present findings on device conductivity as a function of degradation. Ultimately, knowledge established in these fundamental studies will be used to inform the design of penetrating neural electrodes with completely tunable properties.
3:00 PM - BM08.02.04
Flexible and Implantable Graphene Based Neural Probes
Dmitry Kireev 1 , Pegah Shokoohimehr 1 , Vanessa Maybeck 1 , Bernhard Wolfrum 1 2 , Andreas Offenhaeusser 1 Show Abstract
1 Institute of Bioelectronics (ICS-8), Forschungszentrum Julich, Julich Germany, 2 Neuroelectronics, Munich School of Bioengineering, Technical University of Munich (TUM) & BCCN Munich, Munich Germany
Neuroprosthetics is a fairly new and hot research discipline, with a tremendous potential to improve the quality of life of people affected by brain injuries and diseases. However, the field is still in need of reliable tools for interfacing the brain and neuronal cells. Moreover, in order to fully study the brain and its electrical activities, functions and dysfunctions, it is necessary to have a large variety of functional tools. Implantable devices, that are stiff for insertion, yet flexible and soft while inside the body, can provide stable extracellular recordings with large signal-to-noise ratio (SNR) and have good spatio-temporal resolution. State-of-the-art devices are typically based on classic microelectrode arrays, which have a number of drawbacks. Fortunately, the field can be greatly reinvigorated by the development of graphene-based electronics and bioelectronics. The combination of flexibility, transparency, biological stability, and exceptional sensitivity of the graphene makes graphene-based devices almost perfect for interfacing with neuronal cell cultures or brain tissue. New kinds of devices, such as graphene microelectrode arrays (GMEAs)  and graphene field effect transistors (GFETs)  were developed in the recent years, and nowadays can be used for tissue interfacing and extracellular recordings. In vitro experiments show the excellence of these devices for extracellular recordings from the cardiac-like HL-1 cell line (with SNR over 100) . Moreover, cortical neuronal action potentials, their propagation and bursting were successfully recorded with the GFETs  and GMEAs . In this work we report on further developments of the graphene-based neuronal interfaces via fabrication of devices on thin polyimide probes in order to be used for in vivo prostheses. The layout and fabrication of GFETs and GMEAs facilitates simplified use for in vivo experiments. Large-scale fabrication techniques allow us to fabricate the devices cost-effectively, on a 4-inch wafer, with minimum graphene waste .
 D. Kireev, S. Seyock, M. Ernst, V. Maybeck, B. Wolfrum, and A. Offenhäusser, “Versatile Flexible Graphene Multielectrode Arrays,” Biosensors 7, 1, 2016.
 D. Kireev et al., “Graphene field effect transistors for in vitro and ex vivo recordings,” IEEE Trans. Nanotechnol. 17, 140–147, 2016.
 D. Kireev, et al., “Graphene transistors for interfacing with cells: towards a deeper understanding of liquid gating and sensitivity”. Submitted.
 D. Kireev, S. Seyock, J. Lewen, V. Maybeck, B. Wolfrum, and A. Offenhäusser, “Graphene Multielectrode Arrays as a Versatile Tool for Extracellular Measurements,” Adv. Healthc. Mater. 1601433, 2017.
 D. Kireev, D. Sarik, T. Wu, X. Xie, B. Wolfrum, and A. Offenhäusser, “High throughput transfer technique: Save your graphene,” Carbon N. Y. 107, 319–324, 2016.
3:15 PM - BM08.02.05
Flexible Boron-Doped Diamond Sensors for Neurotransmitter Detection—Fabrication and Characterization
Michael Becker 1 , Cory Rusinek 1 , Robert Rechenberg 1 , Wen Li 2 , Bin Fan 2 , Yue Guo 2 Show Abstract
1 , Fraunhofer USA Center for Coatings and Diamond Technologies, East Lansing, Michigan, United States, 2 , Michigan State University, East Lansing, Michigan, United States
In vivo neurotransmitter sensing has developed into a significantly prominent field over the course of the past two decades. With biocompatibility and ease of miniaturization, electrochemical methods are a powerful tool for these measurements. This has largely been completed with carbon fiber microelectrodes where several analytes such as dopamine and serotonin have been detected at very low levels. However, carbon fiber electrodes can be prone to fouling and thus, boron-doped diamond (BDD) has emerged as a material capable of long-term reliability and stability. While, BDD-coated tungsten (W) wires have been used for in vivo dopamine detection in mouse brains, a remaining issue is the significant difference in Young’s modulus from BDD (1050 GPa) and that of brain tissue (103- 105 Pa). The strain between a rigid implant and soft tissue has been thought to be a cause of irreversible tissue damage and negative immune response. Hence, a flexible and softer material is desired to prevent such damage from occurring and polymer-based neural implants have shown promise as a possible implantable device.
Though BDD is unable to be deposited directly on a polymer substrate, a wafer transfer process has been developed to transfer BDD grown on silicon (Si) substrates to flexible Parylene-C substrates (an FDA-approved and USP Class VI biocompatible polymer). The fabricated sensors included BDD working, reference and counter electrodes and were characterized using several analytes including Ferricyanide (Fe(CN)6 3-/4-), Ruthenium hexaaamine (Ru(NH3)6 2+/3+), and dopamine. Fast scan cyclic voltammetric (FSCV) and chronoamperometric measurements of dopamine were completed as well. These novel fabricated BDD sensors on Parylene-C open a new avenue of electrochemical-based neurotransmitter sensing with potential in vivo measurement capability.
3:30 PM - BM08.02.06
In Vivo Neurotransmitter Detection Using Intracortical Glassy Carbon Microelectrode Arrays
Elisa Castagnola 1 2 , Surabhi Nimbalkar 1 2 , Elena Zucchini 3 , Claudia Cea 1 2 , Stefano Carli 3 , Luciano Fadiga 3 4 , Sam Kassegne 1 2 , Davide Ricci 3 Show Abstract
1 MEMS Research Lab., Department of Mechanical Engineering, San Diego State University, San Diego, California, United States, 2 , Center for Sensorimotor Neural Engineering (CSNE), Seattle, Washington, United States, 3 Center for Translational Neurophysiology of Speech and Communication, Istituto Italiano di Tecnologia, Ferrara Italy, 4 Section of Human Physiology, University of Ferrara, Ferrara Italy
The possibility to electrochemically detect in vivo neurotransmitters such as dopamine and serotonin, represents an important topic of research as far as the intimate mechanisms of several brain pathologies are concerned. Dopamine (DA), for example, is a key neurotransmitter playing a pivotal role in a large variety of neurophysiological functions. Disruption of the secretion and uptake of this neurotransmitter leads to a variety of neurological and psychiatric disorders ranging from Alzheimer and Parkinson diseases, to chronic depression. Although it has been shown since many years that DA detection in vivo is feasible, the available techniques often lack in stability and spatial selectivity.
In this study, we address the problem by realizing 4-channels glassy carbon (GC) microelectrode arrays on a flexible substrate to simultaneously measure dopamine concentration in vivo in four different locations (220µm vertical distance) of the nucleus accumbens of the rat brain by background-subtracted fast scan cyclic voltammetry (FSCV). The GC offers a number of compelling advantages over existing microelectrode materials such as inertness, faster electrokinetics as compared to thin-film metals, long-term stability under electrical stimulation, and good surface modification capability. Our microelectrode array was made by micro-electro-mechanical systems fabrication process that allow the integration of GC microelectrodes into polyimide substrate through a pattern transfer technique introduced recently.
The ability of GC microelectrodes to detect DA was firstly assessed in vitro on artificial cerebrospinal fluid through FSCV, ramping the potential from -0.4V to 1.3V (Vs Ag/AgCl) and back at 400 V/s with a frequency of 10Hz. Largely, due to the electrochemical stability of GC, the background current caused by the charging of the double layer, can be digitally subtracted and revealed the oxidation peak of DA. We measured a linear range of DA concentration from 50nM to 1µM, the maximum expected concentration in vivo.
The functionality of the array was then validated in vivo by assessing the DA concentration in the nucleus accumbens of anesthetized rats during electrical stimulation of the medial forebrain bundle (MFB). The electrical stimulation of the MFB is known to activate the “reward system” and is constantly associated to an increase of DA in the n. accumbens. During the stimulation periods, a current increase attributable to DA release was detected by our array, showing DA concentrations compatible with the in vitro calibration results.
In conclusion, by this study, we demonstrated the feasibility of GC microarrays to detect neurotransmitters release. GC may thus offer a new opportunity to in vivo real-time neurotransmitter detection within multipurpose microarrays able to record and microstimulate at the same time the surrounding tissue in order to understand the intimate relations linking electrophysiological parameters with neurotransmitters release.
3:45 PM - BM08.02.07
Fabrication and Microassembly of a High-Density Carbon Fiber Neural Recording Array
Travis L. Massey 1 , Jason F. Hou 1 , Kristofer S.J. Pister 1 , Michel M. Maharbiz 1 Show Abstract
1 , University of California, Berkeley, Berkeley, California, United States
We present a 32-channel carbon fiber monofilament-based intracortical neural recording array fabricated through a combination of bulk silicon microfabrication processing and microassembly. This device represents the first truly two-dimensional carbon fiber neural recording array. The five-micron diameter fibers are spaced at a pitch of 38 microns, four times denser than the state of the art one-dimensional arrays. The fine diameter of the carbon fiber microwires affords both minimal cross-section and nearly three orders of magnitude greater lateral compliance than standard tungsten microwires. Both of these serve to minimize the adverse biological response to implanted devices, particularly compared to conventional implantable microelectrodes. The electrode pitch, in turn, has the potential to enable localization of individual units by detection at multiple adjacent sites, something traditionally the domain of polytrodes. The density, channel count, and size scale of this array are enabled by a microfabricated silicon substrate and a out-of-plane microassembly technique in which individual fibers are inserted through metallized and isotropically conductive adhesive-filled holes in the oxide-passivated silicon substrate. Insertion is eased and the fibers aligned to within five milliradians using an array of microfabricated funnels. The device is insulated in parylene for biocompatibility and electrical isolation, and the recording sites are electroplated with PEDOT:PSS to an impedance on the order of tens of kiloohms at 1 kHz. Further, this fabrication technique is scalable to a larger number of electrodes and allows for the potential future integration of microelectronics.
4:00 PM - BM08.02.08
2D Ti3C2 MXenes for High-Resolution Neural Interfaces
Nicolette Driscoll 5 6 , Kathleen Maleski 2 4 , Babak Anasori 2 4 , Andrew Richardson 1 , Lilia Escobedo 3 , Timothy Lucas 1 , Yury Gogotsi 2 4 , Brian Litt 5 7 6 , Flavia Vitale 5 7 Show Abstract
5 Center for Neuroengineering and Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania, United States, 6 Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania, United States, 2 A.J. Drexel Nanomaterials Institute, Drexel University, Philadelphia, Pennsylvania, United States, 4 Materials Science and Engineering, Drexel University, Philadelphia, Pennsylvania, United States, 1 Neurosurgery, University of Pennsylvania, Philadelphia, Pennsylvania, United States, 3 Chemical Engineering, Cornell University, Ithaca, New York, United States, 7 Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, United States
Microelectrode technologies are powerful tools to elucidate neural dynamics on fine spatial and temporal scales (~10-100 µm, 1ms) and understand mechanisms underlying brain function and disease. However, recording neural signals with a high signal-to-noise ratio from micron-scale electrodes remains a significant challenge. Nanoscale materials have attracted growing interest for use in neural interfaces because of the possibility of improving electrode performance via impedance reduction through effective surface area increase, without affecting the electrode footprint.
MXenes are a new family of two-dimensional nanoscale materials that offer a unique combination of high electrical conductivity (6500 S/cm), hydrophilicity, strength, flexibility, and volumetric capacitance (300-400 F/cm3).1 The outstanding electrical properties of MXenes, coupled with their ease of processing and casting as thin films, make them a promising candidate materials for high-resolution neural interfaces. Here, we present the first demonstration of titanium carbide (Ti3C2) MXene as an electrode material for multi-channel neural microelectrode arrays.
We fabricated parylene C-based electrode arrays for both cortical surface and depth recordings, by integrating MXene wet processing with conventional microfabrication techniques.
For surface recordings, 3x3 micro-electrocorticography (µECoG) arrays of both gold and Ti3C2 were fabricated with 50 µm x 50 µm contacts. For depth recordings, 10-channel stereotrode-configuration probes were fabricated with 25 µm diameter recording sites, with Ti3C2 and gold contacts side-by-side for comparison.
We found a remarkably low magnitude impedance at 1 kHz for the Ti3C2 electrodes as compared to gold devices of same sizes: 48 ± 35 kΩ vs. 206 ± 36 kΩ for the µECoG electrodes, and 343 ± 78 kΩ vs. 1000 ± 440 kΩ for the depth electrodes.
To evaluate whether improved impedance characteristics would result in higher signal quality, we tested the electrodes in vivo in anesthetized rats. The µECoG electrodes were placed on the exposed cortex and the depth electrodes were inserted so that the contacts spanned first the hippocampus, and were subsequently retracted to span the cortex. The Ti3C2 electrodes successfully recorded physiological signals from the rat’s brain and analysis of the in vivo data showed significantly reduced baseline and 60 Hz noise for the Ti3C2 electrodes when compared to gold electrodes of the same size.
Ongoing work includes in vivo recording with the depth electrodes with the aim of recording unit activity across the layers of the hippocampus and transcallosal evoked potentials in the cortex. To our knowledge, this work represents the first demonstration of MXenes as an electrode material for in vivo neural recording and we believe MXene shows significant potential to enhance the performance of microelectrodes beyond current capabilities.
1. Anasori, B. et al., Nature Reviews Materials, 2017. 2(2) 16098.
Polina Anikeeva, Massachusetts Institute of Technology
Timothy Denison, Medtronic Inc.
Nick Melosh, Stanford University
Christelle Prinz, Lund University
Phase Holographic Imaging
BM08.03/BM07.04/BM09.03: Joint Session I: Flexible and Stretchable Electronics for Neural Interfaces
Tuesday AM, November 28, 2017
Sheraton, 2nd Floor, Grand Ballroom
8:30 AM - *BM08.03.01/BM07.04.01/BM09.03.01
Soft and Stretchable Epidermal Electronics and Biosensors for Personalized Medicine
Roozbeh Ghaffari 1 Show Abstract
1 Center for Bio-Integrated Electronics, Simpson Querrey Institute for BioNanotechnology, Northwestern University, Evanston, Illinois, United States
Soft bioelectronics systems enabled by recent advances in materials science are approaching the softness and curvilinear format of human skin. These systems are referred to as 'epidermal electronics' by virtue of their stretchable form factors and 'skin-like' mechanics compared to conventional packaged electronics and sensors. Here we present recent results for an emerging class of fully-integrated epidermal electronics. These devices incorporate arrays of sensors, microprocessors, memory and wireless connection (via Bluetooth low energy) configured in ultrathin, stretchable formats for continuous monitoring of neuromuscular and biomechanics signals. Quantitative analyses of strain distributions and circuit performances under mechanical stress highlight the utility of these systems in clinical operating rooms or in the home. We conclude with pilot clinical studies showing the utility of these epidermal systems in neurophysiological monitoring compared to clinical standards of care in operating rooms.
9:00 AM - BM08.03.02/BM07.04.02/BM09.03.02
Syringe-Injectable Mesh Electronics Integrate Seamlessly with Minimal Chronic Immune Response in Central Nervous System
Tao Zhou 1 , Guosong Hong 1 , Tian-Ming Fu 1 , Xiao Yang 1 , Robert D. Viveros 1 , Charles M. Lieber 1 Show Abstract
1 , Harvard University, Cambridge, Massachusetts, United States
Seamless integration of minimally-invasive electrical probes into animal tissues is of central importance to both neuroscience research and biomedical applications. Previously we designed ultra-flexible mesh electronics that can be injected into animal brains through syringes. Here we report systematic histology studies of the interface between ultra-flexible mesh electronics and central nervous system. We also conducted histology studies of conventional electrical probes implanted in mice brain for comparison. Compared with conventional electrical probes, mesh electronics introduces little or no inflammation to brain tissues after chronic implantation. Unlike conventional rigid probes, which introduce depletion regions in brain tissues, neurons and axons surrounding the mesh electronics exist at endogenous tissue levels. More intriguingly, axons and neuron somata even penetrate into the interior of mesh electronics, allowing for the formation of seamless interfaces between brain tissues and mesh electronics. Seamless incorporation of minimum invasive ultra-flexible mesh electronics with tissues allows for a wide range of applications, including recordings, stimulation and repairing of the brain and other tissues such as spinal cord, opening a new window for brain-machine interfaces and cyborg animals.
9:15 AM - BM08.03.03/BM07.04.03/BM09.03.03
Dynamic Devices for Neural Interfacing
Christopher Proctor 1 , Vincenzo Curto 1 , Jolien Pas 1 , Adam Williamson 2 , George Malliaras 1 Show Abstract
1 , Ecole des Mines St Etienne, Santa Barbara, California, United States, 2 , Aix Marseille University, Marseille France
Significant advances have been made in the last two decades in interfacing electronic devices with the nervous system. Organic electronic materials in particular have emerged as ideal materials for interfacing with the brain due to their flexibility, biocompatibility and moreover their electronic and ionic conductivity. To that end, significant research efforts are being pursued to develop minimally invasive, implantable organic electronic devices integrating recording, stimulating, and drug delivery features. Here we report recent developments towards such dynamic devices for neural interfacing that take full advantage of the favorable properties offered by conducting polymers and polymer substrates. It is shown that thin, flexible devices can incorporate microfluidic channels to enable new sensing and therapeutic functionalities. Furthermore we show such features also open the door to novel implantation strategies that can reduce inflammatory tissue response as well as the surgical footprint required for implantation. We anticipate this work will accelerate the development of a new generation of devices for neural interfacing.
9:30 AM - BM08.03/BM07.04/BM09
10:00 AM - BM08.03.04/BM07.04.04/BM09.03.04
Microfluidic Actuation of Flexible Microelectrodes for Neural Recording
Daniel Vercosa 2 3 , Flavia Vitale 1 , Alex Rodriguez 3 , Sushma Sri Pamulapati 1 , Frederik Seibt 4 , Eric Lewis 3 , Stephen Yan 5 , Krishna Badhiwala 5 , Mohammed Adnan 1 , Micheal Beierlein 4 , Caleb Kemere 3 5 6 , Matteo Pasquali 1 7 , Jacob Robinson 3 2 5 Show Abstract
2 Applied Physics Program, Rice University, Houston, Texas, United States, 3 Department of Electrical and Computer Engineering, Rice University, Houston, Texas, United States, 1 Department of Chemical and Biomolecular Engineering, Rice University, Houston, Texas, United States, 4 Department of Neurobiology and Anatomy, McGovern Medical School at UTHealth, Houston, Texas, United States, 5 Department of Bioengineering, Rice University, Houston, Texas, United States, 6 Department of Neuroscience, Baylor College of Medicine, Houston, Texas, United States, 7 Department of Chemistry, The Smalley-Curl Institute, Rice University, Houston, Texas, United States
New tools for the recording and stimulation of neurons are key to advancing basic neuroscience research and developing new treatments for neural dysfunction. Despite tremendous advances, chronic electrodes for high-resolution electrical recording and modulation of neural activity at the cellular level still rely on rigid metal or silicon materials, which poorly match soft brain tissue and cause extensive acute and chronic injury, eventually leading to electrode encapsulation and the loss of signal over the scale of weeks or months.
Flexible electrodes and ultra-small microwires have been shown to significantly reduce brain damage during chronic implantation and increase the quality and longevity of neural recordings compared to rigid electrodes. However, unsupported flexible electrodes easily buckle on contact with the brain and require temporary stiffening agents to overcome the force of implantation. These agents increase the device footprint and may cause additional damage to the brain during implantation.
Here, we present the microfluidic drive, a novel solution to precisely actuate and implant flexible electrodes without changing the profile of the implanted electrode. After constructing a multi-layer polydimethylsiloxane (PDMS) microfluidic device to constrain electrodes, we utilize viscous fluid flow to push electrodes into tissue. The viscous fluid distributes force along the length of the electrode, allowing it to enter the brain without buckling. Computational analysis on electrodes made from flexible carbon nanotube fibers (CNTfs) suggests that implantation using the microfluidic drive increases the critical buckling force of CNTf microelectrodes by three-fold compared to standard methods.
The device’s hydraulic design with embedded valves enables precise control of the electrode position with minimum fluid output. In vitro experiments in brain phantoms show that microfluidic actuated CNTf electrodes can be implanted up to a 4-mm depth with 30 µm precision, while keeping the total volume of fluid ejected with the electrode below 0.5 µL.
10:15 AM - BM08.03.05/BM07.04.05/BM09.03.05
Hybrid Integration of Stiff Active Electronic Components on Stretchable Carrier Substrate
Florian Fallegger 1 , Aaron Gerratt 1 , Stephanie Lacour 1 Show Abstract
1 , Bertarelli Foundation Chair in Neuroprosthetic Technology, Laboratory for Soft Bioelectronic Interfaces, Centre for Neuroprosthetics, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne Switzerland
Most implantable neuroprostheses consist of electrodes reading neural signals and/or stimulating the neural tissues. These sites are usually treated as passive components in the system with raw signals treatment and logic processing being traditionally performed by external electronic circuits. To increase electrode density and signal bandwidth, closer integration of electronic hardware is being explored.
Here, we explore how to integrate (CMOS) active electronic components with soft surface electrodes embedded in thin silicone membranes. This hybrid integration combines conventional microfabrication techniques with innovative polymer processing techniques. The system consists of three main parts to enable the transition from the hard components to the stretchable substrate: the chip integrated with a soft via material, a stiff platform to isolate the component and contacts area from strain, and stretchable interconnects.
The hard components are picked and placed manually or semi-automatically and then embedded in a PDMS matrix. The stiff platform consists of 150μm thick SU8 disk integrated under the chips. The components are electrically contacted with a “soft via” consisting of a composite of platinum microparticles and PDMS, self-aligned to the contacts by screen-printing. Interconnects consist of stretchable gold thin films patterned by shadow masking then assembled in a multilayer structure in order to achieve simple circuits. The different layers (i.e. CMOS Integrated chip, soft vias and multiple layers of interconnects) are aligned and bonded using a custom-made alignment tool.
The hybrid circuit is characterized mechanically up to global uni-axial strain of 30% showing that the stiff components do not experience local strain greater than 0.2%. Furthermore the strain profile at the surface of the circuit, running from the mechanically-isolated rigid chips to the fully stretchable carrier is smooth suppressing any peak strain at the rigid-elastic interface. The developed method allows contacting thin (< 250μm) but rigid chips with contact sites with sizes in the range of 100μm to 100s μm. This system enables functions such as multiplexing or addressing individual electrode sites with a switch matrix scheme, which will allow for an increase in the number of electrode sites.
10:30 AM - BM08.03.06/BM07.04.06/BM09.03.06
Three-Dimensional Silicon Mesostructures for Biointerfaces
Yuanwen Jiang 1 , Bozhi Tian 1 Show Abstract
1 , University of Chicago, Chicago, Illinois, United States
Silicon-based materials exhibit biocompatibility, biodegradability as well as a spectrum of important electrical, optical, thermal and mechanical properties, leading to their potential applications in biophysical or biomedical research. However, existing forms of silicon (Si) materials have been primarily focused on one-dimensional (1D) nanowires and two-dimensional (2D) membranes. Si with three-dimensional (3D) mesoscale features has been an emerging class of materials with potentially unique physical properties. Here, we incorporated new design elements in traditional synthetic methods to prepare various forms of 3D Si mesostructures and studied their functional biointerfaces with cellular components. In the first example, an anisotropic Si mesostructure, fabricated from atomic gold-enabled 3D lithography, displayed enhanced mesoscale interfacial interactions with extracellular matrix network. This topographically-enabled adhesive biointerface could be exploited for building tight junctions between bioelectronics devices and biological tissues. Another Si mesostructure with multi-scale structural and chemical heterogeneities, was adopted to establish a remotely-controlled lipid-supported bioelectric interface. We further adapted the bioelectric interface into the non-genetic optical modulation of single dorsal root ganglia neuron electrophysiology dynamics. Our results suggest that the dimensional extension of existing forms of Si could open up new opportunities in the research of biomaterials manufacturing and application.
10:45 AM - BM08.03.07/BM07.04.07/BM09.03.07
Wireless Photometers for In Vivo Behavioral Studies in the Deep Brain
Luyao Lu 1 , Philipp Gutruf 1 , Li Xia 2 , Dionnet Bhatti 2 , Michael Bruchas 2 , John Rogers 1 Show Abstract
1 , Northwestern University, Evanstan, Illinois, United States, 2 , Washington University in St. Louis, St Louis, Missouri, United States
Monitoring the neural dynamics at the cellular level in behaving animals is a central goal of modern neuroscience. This is critical to understand neural computations and communications that create diverse brain functions. Current Ca imaging techniques such as fiber photometry provides some capabilities for recording neuron activities in animals during behaviors. However, the rigid optical fibers are not mechanically compliant with soft brain tissues, and the wired set up will restrict movements of animals, therefore impeding studies of natural behaviors. Here we present an integrated wireless photometry device capable of recording calcium transient activity in awake, freely behaving animals. The wireless photometry platform consists of a microscale inorganic light-emitting diode (μ-ILED) and a microscale inorganic photodetector (μ-IPD) for stimulating and recording Ca fluorescence, a detachable transponder, a control unit, a miniature power supply and an external receiver system. These μ-ILED and μ-IPD mount on ultrathin, flexible kapton substrate with overall dimensions (~350 μm wide and ~150 μm thick) significantly smaller than fiber optic cables. The wireless data transmission fully eliminates physical tethers and reduces motion artifacts. Detailed in vivo studies demonstrate that the wireless photometry platform allows high fidelity recording of calcium fluorescence in the deep brain, with results that are comparable or better than those obtained from fiber photometry system.
11:00 AM - *BM08.03.08/BM07.04.08/BM09.03.08
Wireless, Implantable Optoelectronics for Stimulating, Inhibiting and Monitoring Neuronal Dynamics in the Deep Brain
John Rogers 1 Show Abstract
1 , Northwestern University, Evanston, Illinois, United States
The recent development of materials and design designs for flexible, filamentary optoelectronic probes opens up opportunities for wireless stimulation, inhibition and monitoring of neuronal dynamics in the deep brain regions of freely-moving, untethered animals. This talk summarizes some of the latest results in this field of research, with a focus on fluorescence photometers that integrate sub-mm scale light sources and photodetectors on narrow, needle-shaped polymer supports, suitable for delivery into the brain at sites of interest. The ultrathin geometry and compliant mechanics of these probes allow minimally invasive implantation and stable chronic operation. In vivo studies in freely moving animals demonstrate high fidelity recording of calcium fluorescence in the deep brain, with measurement characteristics that match or exceed those associated with the most advanced, tethered fiber photometry systems. The capabilities in optical recordings of neural dynamics in untethered, freely moving animals have potential for widespread applications in neuroscience research.
BM08.04/BM07.05/BM09.04: Joint Session II: Conductive Polymers for Biointerfaces
Tuesday PM, November 28, 2017
Sheraton, 2nd Floor, Grand Ballroom
1:30 PM - *BM08.04.01/BM07.05.01/BM09.04.01
Skin-Inspired Electronic Materials and Devices
Zhenan Bao 1 Show Abstract
1 , Stanford University, Stanford, California, United States
Flexible organic electronics have attracted considerable attention over the past decade. Stretchable electronics represent another type of optoelectronic devices that are intrinsically elastic, that is they are foldable, twistable, and stretchable while maintaining performance, integrity and durability. Incorporated into devices, properly designed stretchable materials may result in more robust devices under bending and strain compared to flexible but not stretchable materials. For intrinsically stretchable electronics, it is desirable to have intrinsically stretchable materials, ranging from stretchable conductors, stretchable dielectric to stretchable semiconductors. In this talk, I will present various molecular design concepts for realizing stretchable electronic polymers without compromising electronic properties. Some applications of such materials will also be presented.
2:00 PM - BM08.04.02/BM07.05.02/BM09.04.02
Measuring Evoked Electrocorticography on Cortical Surface of Optogenetics Rat Using Transparent Organic Electro Chemical Transistors
Wonryung Lee 1 , Dongmin Kim 1 , Naoji Matsuhisa 1 , Masaki Sekino 1 , Tomoyuki Yokota 1 , George Malliaras 2 , Takao Someya 1 Show Abstract
1 , The University of Tokyo, Tokyo Japan, 2 Department of Bioelectronics, Ecole Nationale Supérieure des Mines, Gardanne France
Optogenetics tools have been developed to control spatial and temporal neuronal function for making it possible to investigate complex neural circuitry. In general, it is hard to measure evoked response while strong light stimulation directly applying on the device due to light artifact, and nontransparent metallic wires.
In this work, we developed world first transparent organic amplifier and measured evoked electrocorticography (ECoG) signals from rat which has light sensitive neuron by using 3-μm-thick flexible transparent organic electro-chemical transistors (OECTs) with small light artifact. The trans-conductance (gm) of OECTs showed 1.1 mS with 70 μm/20 μm channel dimension. The transparent OECTs was fabricated on 1.2-μm-thick parylene (diX-SR) substrate. The 70-nm-thick Au grid for source/drain of OECTs deposited on the substrate, while it showing 60% transparency. The mechanical stability of Au grid was tested by applying compression. The sheet resistance of Au grid film changed 3 Ω/sq to 7 Ω/sq after 50% compression, while sheet resistance of ITO (70 nm) changed 80 Ω/sq to 400 Ω/sq at same condition. The SU-8 for passivation layer was patterned. The PEDOT:PSS for active material of OECTs was patterned by etching process .
The applicability of transparent OECTs was demonstrated by measuring light evoked signal on optogenetic rat . The cortical surface was stimulated by laser at a wavelength of 473 nm through the transparent and non-transparent OECT. The transparent OECT could record evoked ECoG (ΔIds/gm = 700 µV) which has double amplitude of bio response from non-transparent OECT (ΔIds/gm = 350 µV) at the same light intensity (40 mW). Finally, non-light artifact was confirmed by control experiment using non optogenetic rat. The light artifact was less than peak to peak noise level (100 nA). The non-light artifact can be obtained because of wide bandgap and high capacitance of PEDOT:PSS. We concluded that measuring evoked ECoG on optogenetic rat showed that possibility of transparent OECTs for investigation on more complicate neural circuit.
 M Braendlein et al, Advanced Materials 29, 13 (2017).
 E Boyden, et al Nature Neuroscience 8, 1263 (2005).
2:15 PM - BM08.04.03/BM07.05.03/BM09.04.03
Biodegradable and Biocompatible Force Sensor Based on a New Piezoelectric Polymer to Monitor Important Bio-Physiological Pressures
Thanh Nguyen 1 Show Abstract
1 , University of Connecticut, Storrs, Connecticut, United States
Measuring vital bio-physiological pressures such as trans-pulmonary pressure, intra-articular pressure, intra-abdominal pressure, intra-ocular pressure, intra-cranial pressure etc. is important for monitoring health status, preventing dangerous internal force build up in impaired organs, and enabling novel approaches of using mechanical stimulation for tissue regeneration. Pressure sensors are often required to be implanted and directly integrated with native soft tissues and organs, therefore they should be flexible and at the same time, biodegradable to avoid any invasive removal surgery, which could damage the interfaced tissues. There has been recent achievements of biodegradable force sensors which are based on either Silicon piezo-resistive probe or capacitive biopolymer. Although exhibiting excellent sensing performance, these devices rely on (1) passive materials which need to be electrically powered, (2) exotic electronic materials (e.g. Silicon), which have not been confirmed to be completely degradable and safe for use inside human body, and (3) complex clean room micro-fabrication processes. Recently, triboelectric sensors fabricated with biodegradable polymers have been reported. Yet, friction-induced triboelectric charges, while ideal for energy harvesting, are often susceptible to variation of force-response due to the delay of charge dissipation in the sensor. Here, for the first time, we present the study and processing of a novel piezoelectric biopolymer of poly-l-lactid acid (PLLA) and create a biodegradable PLLA force-sensor which only relies on medical materials, used commonly in FDA-approved implants, to monitor tiny biological forces. The sensor is able to sensitively detect a wide range of pressure from 1 – 18 kPa, relevant to many biological pressures such as intracranial pressure (0 – 2.7 kPa), intraocular pressure (0 - 5.3 kPa), and intrabladder pressure (0 - 3.92 kPa). With 150 µm thick poly-lactide (PLA) encapsulators, we show the sensor can sustain its performance inside a buffer solution for 2-3 days. As a proof of concept, we implanted this sensor into a mouse thorax to measure trans-pulmonary/trans-diaphragmatic pressure of the animal for detection of respiratory disorder from obstructive pulmonary diseases. This novel biodegradable force-sensor, based solely on common medical biomaterials, offers an extremely useful tool to monitor important biological pressures. The sensor could be also integrated with native/engineered tissues and organs, forming a bionic self-sensing systems which could enable many applications in regenerative medicine, drug delivery, and medical devices.
2:30 PM - BM08.04/BM07.05/BM09
3:00 PM - BM08.04.04/BM07.05.04/BM09.04.04
Organic Bioelectronic Materials and New Opportunities for Neural Interfacing
Jonathan Rivnay 1 Show Abstract
1 , Northwestern University, Evanston, Illinois, United States
Direct measurement and stimulation of electrophysiological activity is a staple of neural interfacing for mapping of circuits, diagnosis and/or therapy. Such bi-directional interfacing can be enhanced by the low impedance imparted by organic electronic materials that show mixed conduction properties (both electronic and ionic transport). Many high performance bioelectronic devices are based on conducting polymers such as poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate), PEDOT:PSS. However, new structure-property and device based design rules have led to a new class of formulations/materials. The incorporation of glycol side chains into carefully selected backbone motifs, for example, has enabled a new class of high performance bioelectronic materials that feature high volumetric capacitance, transconductance >10mS (device dimensions ca. 5μm), and steep subthreshold switching characteristics. We explore the implications of these new materials for neural interfacing, including the effect of device operation regimes, and their effect on recording sensitivity and power consumption.
3:15 PM - BM08.04.05/BM07.05.05/BM09.04.05
New Approach for High Performance PDMS Based Electrodes for Neuronal Recording and Stimulation
Aline Renz 1 , Klas Tybrandt 1 2 , Flurin Stauffer 1 , Greta Thompson-Steckel 1 , Janos Voros 1 Show Abstract
1 , ETH Zürich, Zürich Switzerland, 2 , University Linköping, Linköping Sweden
New approaches for the fabrication of stretchable electronic implants in healthcare applications have attracted increased attention in the past years. Enhancement of the implant-tissue interface to both reduce the foreign body response as well as achieve improved electrode properties has been the main focus of many new devices. Stretchable implants have shown promise in their ability to reduce the foreign body response, however, there are still many limitations to the successful implementation of these devices. Specifically, achieving the combination of reliable electrical recording, as well as stimulation have yet to be established to gain long-term stable implants.
Here we present a new microelectrode array fabrication method, in which electrodes with controllable diameters ranging from 30 µm to 1 mm and tunable height can be generated on PDMS. These porous nanomaterial-based electrodes exhibit stable stimulation characteristics for several thousand pulsing repetitions, and demonstrate excellent impedance values of approximately 4 kΩ at 1 kHz for a 30 µm electrode. Additionally, this method can be used for a broad range of electrode designs. Overall, these electrodes can be utilized for the recording and stimulation of electrically excitable cells and tissues for both in vitro as well as in vivo applications.
3:30 PM - BM08.04.06/BM07.05.06/BM09.04.06
Soft and Intrinsically Stretchable Inkjet-Printed Transistor Arrays with Sub-Volt Operation for Skin-Like Bioelectronics
Francisco Molina-Lopez 1 , Theo Gao 1 , Ulrike Kraft 1 , Yeongin Kim 1 , Yuxin Liu 1 , Zhenan Bao 1 Show Abstract
1 , Stanford University, Stanford, California, United States
Soft and stretchable electronic materials are receiving increasing attention in the fields of biology and biomedicine. Part of the reason for this interest resides in their mechanical properties, which match those of human body and other living organisms, allowing intimately integration with them in a minimally invasive manner. On the other hand, printing electronics presents the possibility of additive low-cost deposition and patterning of a wide range of solution-processed functional materials at ambient conditions and over large areas. These characteristics suit the requirements for integration of stacked organic electronic materials in the fabrication of skin-like electronics. Among the different printing methods, inkjet has special interest as it is a digital fabrication method with the capability of depositing materials on-demand and without physical contact, facilitating prototyping and patterning on different surface topologies.
In this work, we present a soft and stretchable array of transistors with sub-volt operation for application in skin-like bioelectronics. The transistors are composed of stacks of intrinsically stretchable functional materials, namely networks of semiconducting carbon nanotubes (CNTs), ionic dielectric and conducting and stretchable PEDOT:PSS. Since these materials can be only processed from solution and do not withstand high temperatures, inkjet printing has been used to facilitate their integration at ambient conditions (below 60°C) on an elastomeric substrate. Each material of the system was first formulated as an inkjet-printable ink using orthogonal solvents, and subsequently deposited and patterned using a commercial lab-scale tabletop inkjet printer for electronics. Good resolution of few tens of micrometers over large-areas of several cm2 was achieved for every printed material. The double-layer capacitor effect of the utilized ionic gate dielectric permitted over 1 µm-thick irregular printed films to operate below 1 volt and without risk of gate current leakage. Sub-volt operation is paramount in bioelectronics to avoid water splitting and to emulate neuron synapsis behavior. Furthermore, Inkjet printing-patterning of the gate dielectric suppressed cross talk between neighboring transistors. High mobility and large on/off current ratio were achieved for the printed transistors by fine-tuning the CNT network density through controlling the number of printed passes. The excellent electrical properties of the fabricated transistors along with their mechanical softness and the versatility offered by the non-contact and maskless nature of inkjet printing, makes this system a promising general platform easily customizable for different applications in bioelectronics. Indeed, the potential of the fabricated transistors array to work as a soft wearable system for neuron interfacing will be tested, advancing the new generation of brain-machine interfacing devices and prosthetics with sensing capabilities.
3:45 PM - BM08.04.07/BM07.05.07/BM09.04.07
Organic Electronics for High-Resolution Electrocorticography of the Human Brain
Dion Khodagholy 2 , Jennifer Gelinas 1 , Gyorgy Buzsaki 3 Show Abstract
2 Electrical Engineering, Columbia University, New York, New York, United States, 1 , Columbia University, New York, New York, United States, 3 Neuroscience Institute, NYU Langone Medical Center, New YorK, New York, United States
Localizing neuronal patterns that generate pathological brain signals may assist with tissue resection and intervention strategies in patients with neurological diseases. Precise localization requires high spatiotemporal recording from populations of neurons while minimizing invasiveness and adverse events. We describe a large-scale, high-density, organic material–based, conformable neural interface device (“NeuroGrid”) capable of simultaneously recording local field potentials (LFPs) and action potentials from the cortical surface. We demonstrate the feasibility and safety of intraoperative recording with NeuroGrids inanesthetized and awake subjects. Highly localized and propagating physiological and pathological LFP patterns were recorded, and correlated neural firing provided evidence about their local generation. Application of NeuroGrids to brain disorders, such as epilepsy, may improve diagnostic precision and therapeutic outcomes while reducing complications associated with invasive electrodes conventionally used to acquire high-resolution and spiking data.
4:00 PM - BM08.04.08/BM07.05.08/BM09.04.08
Real Time Monitoring of 3D Cell Cultures In Vitro Using Conducting Polymer Scaffolds
Charalampos Pitsalidis 1 , Magali Ferro 1 , Donata Iandolo 1 , Isabel del Agua 1 , Sahika Inal 2 , Roisin Owens 1 Show Abstract
1 , Ecole des Mines de Saint-Etienne, Gardanne France, 2 , King Abdullah University of Science and Technology, Saudia Arabia (KAUST), KAUST Saudi Arabia
Three-dimensional (3D) cell cultures are sought to improve the physiological relevance of cell-based assays and provide a better alternative to animal testing compared to the conventional cell-monolayer based cultures. We report herein an in vitro toxicology screening platform based on 3D conducting polymer scaffolds consisting of poly(3,4-ethylene dioxythiophene (PEDOT). The conducting scaffolds are used concurrently as a biocompatible host to support 3D cell cultures as well as an electrode to electrically probe cell behavior. Dynamic electrochemical impedance spectroscopy of the 3D conducting scaffolds reveal in real time the different features of the cell culture including adhesion, growth and proliferation. By tuning the composition parameters and the microstructural properties of the fabricated scaffolds we were able to provide a suitable 3D environment for the cells without affecting the electrical sensing capability of the device. The proposed platform tested with various cell types including fibroblasts and epithelial cells represents a nondestructive and label-free in-situ cell-based toxicity screening platform, paving the way towards next generation in vitro toxicology assays toward the reduction of animal tests.
4:15 PM - BM08.04.09/BM07.05.09/BM09.04.09
Elastic Microelectrodes for Bioelectronic Recording from Peripheral Nerves
Tobias Cramer 1 , Francesco Decataldo 1 , Davide Martelli 2 3 , Marta Tessarolo 1 , Mauro Murgia 4 , Beatrice Fraboni 1 Show Abstract
1 Department of Physics and Astronomy, University of Bologna, Bologna Italy, 2 Department of Biomedical and Neuromotor Sciences-Physiology, University of Bologna, Bologna Italy, 3 Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, Victoria, Australia, 4 Istituto per lo Studio dei Materiali Nanostrutturati (CNR-ISMN), Consiglio Nazionale delle Ricerche, Bologna Italy
Monitoring of bioelectric signals in peripheral nerves is crucial to gain understanding of how the autonomic nerve system controls specific body functions related to disease states such as inflammatory response.1,2 In order to achieve long-term, chronic recordings, that do not interfere with nerve function or animal behaviour, a low-invasive wireless electrode technology has to be developed.
In this work, we present our efforts to achieve a wireless peripheral nerve interphase based on stretchable electrodes to record from the splanchnic and renal nerve in rats. Polydimethylsiloxane (PDMS) is used as elastic substrate and encapsulation material for electrodes and interconnects made of thermally evaporated Ti/Au. A kinked electrode shape has been introduced to facilitate the surgical procedure to position and fix the electrodes at the nerve. An electropolymerized layer of the doped organic semiconductor Pedot:Pss is deposited on the electrodes to reduce impedance and improve signal quality. The impact of strain on electronic and morphologic properties of the electrode are investigated. In in-vivo recordings, bioelectronic signals are amplified and digitized by a subdermal battery operated transmitter. We show that our electrode is able to record neural activity of peripheral nerves during chronic experiments in free moving animals.
1. D. Martelli, S. T. Yao, M. J. McKinley and R. M. Mc Allen, Reflex Control of Inflammation by Sympathetic Nerves, Not the Vagus, J Physiol 592.7, 1677-1686 (2014).
2. D. Martelli, D. G. Farmer, and S. T. Yao, The Splanchnic Anti-Inflammatory Pathway: Could It Be the Efferent Arm of the Inflammatory Reflex?, Exp Physiol 101.10, 1245-1252 (2016).
Polina Anikeeva, Massachusetts Institute of Technology
Timothy Denison, Medtronic Inc.
Nick Melosh, Stanford University
Christelle Prinz, Lund University
Phase Holographic Imaging
BM08.05: Organic and Hybrid Electronics at the Neural Interface
Wednesday AM, November 29, 2017
Sheraton, 2nd Floor, Republic A
8:30 AM - BM08.05.01
Novel Polymer Coating for Improving Tissue Integration of Neural Interfacing Device
Bingchen Wu 1 , Asiyeh Golabchi 1 2 , Xinyan Cui 1 2 3 Show Abstract
1 , University of Pittsburgh, Pittsburgh, Pennsylvania, United States, 2 , Center for the neural basis of cognition , Pittsburgh, Pennsylvania, United States, 3 , McGowan Institute for Regenerative Medicine, Pittsburgh, Pennsylvania, United States
The integration of implantable neural electrodes within neural tissue is a crucial factor affecting recording and stimulation capability for implantable neural electrodes. Surface coatings are developed for the non conductive and conductive regions of neural interface devices respectively to reduce foreign body response and improve neuron-electrode interactions. For the non-conductive portion of the neural probe, we developed a catechol based zwitterionic polymer poly[(methacryloyloxy)ethyl]-dimethyl-(3-sulfopropyl) ammonium-catechol] (PSBMA-catechol) coating to inhibit nonspecific protein adsorption an cell adhesion. For the conductive electrode sites, a novel conducting polymer poly[2-methylene-2,3-dihydrothieno (3,4-b) (1,4) dioxine] (PEDOT-EM) coating was developed which allow facile biofunctionalizaton of the PEDOT to improve neuron adhesion. The antifouling coating was formed via co-deposition of polydopamine (PDA) and PSBMA-catechol. The stability of polymer films were tested by soaking polymer film in PBS for 4 weeks. Thickness and water contact angle of polymer films were measured at four different time points: pre-soaking, post-soaking 1 week, 2 weeks, and 4 weeks. The antifouling effectiveness of polymers were examined by 3T3 fibroblast cell culture and fibrinogen absorption test. Regarding PEDOT-EM, galvano-static (GS) were used to prepare PEDOT and PEDOT-EM film and compare electrochemical properties. The post-functionalization capability of PEDOT-EM was investigated through attempts to immobilize biomolecules on polymer film using thiol-ene ‘click’ chemistry. PDA-PSB co-deposition produced stable polymer films with an average thickness remain relatively constant (from 3.35±1.5nm pre-soaking to 2.86±0.74nm after 4-weeks of soaking) and a stable water contact angle of 23.28°±3.54°. For the PEDOT-EM, the optimized film showed decreased impedance from uncoated gold electrode at low frequency range (≤100Hz). DNA aptamers containing a thiol end was successfully attached to PEDOT-EM as confirmed with square wave voltammetry detection. Primary neuron cell culture showed positive neuron attachment and neurite outgrowth on PEDOT-EM immobilized with laminin protein. In vivo experiments were performed on mice implanted with PDA-PSB coated probes and the inflammatory host tissue response was compared to uncoated probes by quantitative histological analysis. In the immediate area (100µm) around the probes, the intensities of the IgG staining (indicating blood brain leakage) and glial scar markers were significantly lower around the PDA-PSB coated probes. at depth 500-1000 µm than the uncoated controls. When properly combined, these two novel polymer coatings have the potential to significantly improve recording or stimulation performance of implanted electrodes during chronic applications.
8:45 AM - BM08.05.02
Deep Brain Stimulation (DBS) Electrodes Based on Conducting Polymers
Côme Bodart-Le Guen 1 , Arunprabaharan Subramanian 1 , Gaia Tomasello 1 , Steen Brian Schougaard 2 , Florin Amzica 3 , Fabio Cicoira 1 Show Abstract
1 , Ecole Polytechnique de Montreal, Montreal, Quebec, Canada, 2 Chemistry, Université du Québec à Montréal, Montreal, Quebec, Canada, 3 Dentistry, Université de Montréal, Montréal, Quebec, Canada
Neurological degenerative diseases represent one of the major problems in the public’s health. The development of novel tools devoted to early diagnosis and treatment of these diseases is an important and urgent medical need. Deep brain stimulation (DBS) via implanted intracerebral electrodes, is a key technology in neuroprosthetic applications. However, the efficiency and biocompatibility of the probes are far from being ideal. Organic bioelectronics offers unprecedented opportunities for a novel design of neural electrodes, able to both record and stimulate neurons. Conducting polymers have emerged as ideal candidates for neurological electrodes, particularly suitable for being interfaced with the nervous tissue. Indeed, π-conjugated polymers, besides being mechanically soft, sustain mixed electronic/ionic transport, particularly suitable for interfacing the ionic current in cell membranes. Conducting polymers coated metal microelectrodes, with respect to bare electrodes, show lower impedance, required to ensure and maintain an efficient charge during stimulation and to improve signal to noise ratio as well as lower stimulation voltage threshold, beneficial for tissue safety. In our work we have coated DBS microelectrodes made of W and Pt/Ir with electropolymerized PEDOT:PSS and PEDOT:PF6 exploring different deposition conditions and achieving improved electrical and mechanical performances demonstrated by in-vivo tests. The morphology of the film has been characterized and measured through Scanning Electron Microscopy (SEM). The electrical performances and stability have been studied using cyclic voltammetry (CV) in aqueous media (Ringer’s solution). Measurements of the temporal frequency-dependent complex impedance have been conducted via Electrochemical Impedance Spectroscopy on conducting polymer coated and bare DBS electrodes.
9:00 AM - *BM08.05.03
Crosslinking Conjugated Polymers for Improved Long-Term Mechanical Performance in Neural Interfacing Applications
David Martin 1 , Bin Wei 1 , Jinglin Liu 2 , Jing Qu 1 , Liangqi Ouyang 3 , Chin-Chen Kuo 1 , Vivek Subramanian 1 Show Abstract
1 , University of Delaware, Newark, Delaware, United States, 2 Actives to Products, Dow AgroSciences LLC, Indianapolis, Indiana, United States, 3 Biomolecular and Organic Electronics, Linkoping University, Linkoping Sweden
We have been recently investigating the design, synthesis, and characterization of various types of chemical crosslinking agents for improving the long-term performance of electrochemically deposited conjugated polymers such as poly(3,4 ethylene dioxythiophene) (PEDOT) and poly(3,4-propylenedioxythiopene) (PProDOT). These materials are being actively investigated for a variety of neural interfacing applications. We have investigated branched comonomers such as EPh with several EDOT units arranged around a central aromatic core. EPh causes an increase in mechanical stiffness but quickly leads to a loss of charge transport efficiency. The PEDOT-EPh copolymers also dramatically change color, consistent with a loss of their extended bond conjugation along the chain backbone. We have also studied the behavior of POSS-ProDOT units that have eight ProDOT moieties attached, one on each corner of the silsequioxane cage. The POSS-ProDOT comonomer introduces crosslinking in PEDOT without significantly disrupting charge transport. The optimal mechanical properties of PEDOT-co-POSS-ProDOT were seen at intermediate levels of ProDOT composition (~3 wt%); films with higher crosslinker contents were brittle and delaminated from the solid substrate.
9:30 AM - BM08.05.04
Edible Neuroprosthetic Devices
Laura Ferlauto 1 , Paola Vagni 1 , Diego Ghezzi 1 Show Abstract
1 STI IBI-STI LNE, EPFL, Geneva Switzerland
With the ultimate goal of avoiding infections due to a prolonged stay and risks related to surgical retrieval, functional silicon-based electronic devices able to dissolve within the biological environment have been engineered in the past few years. These advancements, in combination with the present trend of incorporating polymers as flexible substrate or for drug-release purposes in bioengineering devices, have led to the idea of fully polymer-based transient electronic devices. Our aim is indeed to fabricate probes for neural signal recording entirely based on biocompatible and biodegradable polymers. In the specific case, we rely on Polycaprolactone (PCL) as substrate and Poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (Pedot:PSS) as conductive conjugated polymer. With these materials as building blocks, a series of passive neural probes were fabricated and implanted in mice brains (visual cortex area) to assess their in-vivo durability. Several time-points (1, 3, 6 and 9 months) have been established for the implants analysis in order to have a better comprehension of the degradation process within the biological environment and the response of the biological environment itself to the insertion of an external object. Preliminary results show that after one month of implantation the astrocytes are visibly activated as expected, whereas there is no evidence of activated microglia. Further results demonstrate that after 3 months of implantation the PCL layer starts to show signs of bulk degradation. In the near future, implantation of active neural probes will give insight also on the recording capability of the devices.
9:45 AM - BM08.05.05
Electrochemically Controlled Drug Release from a Conducting Polymer Hydrogel Composite for Neural Interfaces
Carolin Kleber 1 2 , Jean Chammas 1 2 , Dunia Abed el Hafez 1 2 , Karen Lienkamp 2 , Jürgen Rühe 1 2 , Maria Asplund 1 2 Show Abstract
1 , BrainLink-BrainTools Center, University of Freiburg, Freiburg Germany, 2 Department of Microsystems Engineering (IMTEK), University of Freiburg, Freiburg Germany
Controlled delivery of drugs and biomolecules from conducting polymer coated electrodes present a promising approach to reduce inflammatory tissue reactions in the vicinity of neuroprosthetic devices. Common weaknesses of such delivery systems, however, include the limited incorporation of larger and higher concentrated biomolecules. Conducting polymer hydrogel (CPH) coatings present a promising strategy to address this challenge. CPHs are material composites consisting of a conducting polymer grown within a hydrogel matrix. Thereby, the conducting polymer enables the capability of electrochemically controlled drug delivery and the hydrogel component offers a water-based and voluminous depot to store larger amounts of biomolecules. In this work, we introduce a novel CPH system, which facilitates the actively controlled release of the model substance Fluorescein and is more potent when compared to the standard release system PEDOT/PSS.
The CPH used in this work consists of the conducting polymer poly(3,4-ethylene dioxythiophene) (PEDOT) and the hydrogel P(DMAA-co-5%MABP-co-2,5%SSNa) (PDMAAp). The PDMAAp/PEDOT was coated on microfabricated probes according to procedures described elsewhere . Fluorescein was used as a model substance since it can be easily detected and quantified by fluorometry. The release functionality of the CPH was investigated by actively incorporating and releasing Fluorescein by electroactivation using a range of different parameters including pulsing, sweeping and constant potentials.
The novel CPH material enables the electrochemically controlled drug release of Fluorescein. Furthermore, substantially higher quantities of the model drug were released from CPH films when compared to PEDOT/PSS controls. Thereby, the PDMAAp/PEDOT composite presents a suitable candidate as drug delivery system for neural interfaces. The potential to serve as drug delivery system for larger biomolecules and more specific applications will be explored in future studies.
 C. Kleber, K. Lienkamp, J. Rühe, M. Asplund, An interpenetrating, microstructurable and covalently attached conducting polymer hydrogel for neural interfaces, Acta Biomaterialia 58 (2017) 365-375.
10:30 AM - *BM08.05.06
Organic Transistor Architectures for Neural Cells Stimulation and Sensing
Michele Muccini 1 , Valentina Benfenati 2 , Stefano Toffanin 1 Show Abstract
1 , CNR-ISMN, Bologna Italy, 2 , CNR-ISOF, Bologna Italy
The development of innovative bioelectronic devices for monitoring nerve cells activity with improved biocompatibility, sensitivity and spatiotemporal resolution is a stringent condition to understand brain physiology and pathophysiology. We have already demonstrated that primary neurons can adhere, grow and differentiate on a suitably engineered perylene-based thin-film transistor platform, while maintaining their firing properties even after a prolonged time of cell-culturing . Moreover, we implemented the platform called organic cell stimulating and sensing transistor device (O-CST) for stimulating the neuronal cells and recording the bioelectrical activity . Here, our recent activity concerning the validation of O-CST for the study and manipulation of ion channels and calcium signaling in non excitable (glial) cells and on the study of sensing and transduction mechanisms of O-CST will be presented.
O-CST is biocompatible with astrocytes and its operation lead to an exclusive increase in the astroglial inward whole-cell conductance that we could attribute to specific ion channel. We also found that O-CST stimulation evokes an intracellular calcium increase, which can be monitored by calcium imaging due to the O-CST's transparency. Notably, by a combination of patch-clamp, calcium imaging and computational analyses, we show that the evoked current and calcium response are dependent on the O-CST device architecture.
Furthermore, by performing Electrical Impedance Spectroscopy (EIS), we propose the working principles of the sensing mechanism of the O-CST architecture by introducing a suitable equivalent circuit. We succeeded in validating a macroscopic model by achieving surface potential maps of the organic layer surface after the device biasing in wet conditions . Collectively, our results confirm the potential of O-CST for selective manipulation of bioelectrical activity of neural cells and describe a model that is straightforward to discriminate the different processes occurring at the interphase between the electrolyte and the organic layer which rule the ions-electrical transduction mechanism in the device.
 Toffanin S., Benfenati V., Muccini M. et al., J Mater Chem, 2013, 1, 3850-3859.
 Benfenati V., Toffanin S., Muccini M. et al., Nature Materials, 2013, 12, 672-680.
 Lago N., Muccini M., Toffanin S., et al., Organic Electronics, 2016, 35, 176–185.
11:00 AM - BM08.05.07
Photopatternable Shape Memory Polymer for Quick and Reliable Fabrication of Neural Devices
Jonathan Reeder 1 , Kejia Yang 1 , Eric Eisner 1 , Benjamin Perez 1 , Iakov Rachinskiy 1 , Francesca Daigle 1 , Walter Voit 1 Show Abstract
1 , University of Texas at Dallas, Richardson, Texas, United States
Shape memory polymers (SMP) are attractive substrates for neural devices because of their ease of processability, dramatic changes in modulus, and high capacity to recover their initial configuration. However, creating patterns into SMPs for devices is time-consuming and rarely produces consistent results using the current method, reactive ion etching (RIE). This work explores a novel polymer that exhibits similar mechanical properties as shape memory polymers but eliminates the need to fabricate devices with RIE. First, poly(Bisphenol A Diglycidyl Ether-alt-1,4-Butanedithiol) was synthesized and then crosslinked with Tris(4-hydroxyphenyl)methane triglycidyl ether. Adding photoinitiator photosensitized the polymer, before spin coating it onto glass slides, and selectively patterning the polymer with contact lithography. By changing the ratios of chemicals, the SMP's properties can be tailored for specific applications. Various characterization techniques were also used such as scanning electron microscopy to image the films, profilometry to measure the film thickness, and differential scanning calorimetry and dynamic mechanical analysis to characterize the thermomechanical properties. Designing this photopatternable SMP enables engineers and scientists to fabricate reliable devices quickly and without the hassle of reactive ion etching.
11:15 AM - BM08.05.08
Rapid Femtosecond Laser Patterning of 3D PEDOT:PSS Devices Enhance Coupling in Bioelectronics
Francesca Santoro 1 , Yoeri van de Burgt 3 2 , Scott Keene 3 , Bianxiao Cui 1 , Alberto Salleo 3 Show Abstract
1 Chemistry, Stanford University, Stanford, California, United States, 3 Material Science and Engineering, Stanford University, Stanford, California, United States, 2 , Technische Universiteit Eindhoven , Eindhoven Netherlands
Interfacing soft materials with biological systems holds considerable promise not only for building sensitive biosensors and diagnostic tools, but also for recording biological processes in live cells. Recording devices are typically made of hard materials (metals, silicon-based semiconductors) and their stiffness limits the coupling with soft biological tissues (i.e. brain). In the last decades, conjugated polymers have been proven to be excellent conductive materials useful for a wide variety of applications (van de Burgt et al., 2017) and can have low Young’s moduli. In this way, devices like organic transistors or multi (organic) electrode arrays with various geometries can be easily coupled with cells and record action potentials as well as send electrical stimuli. However, the interface between cell and organic substrate is not well studied, despite its crucial role in the effectiveness of the device. On top of that, well-known cell adhesion enhancements such as nano-grooves have not yet been implemented on these surfaces due to the difficulties in obtaining these structures in soft materials. Additionally, determining and characterizing enhancement of cell adhesion at the nanoscale is challenging. Here we demonstrate a novel rapid femtosecond laser patterning technique to produce 3D micropatterns in PEDOT:PSS organic electrodes and show that we can successfully enhance cell adhesion of electrogenic cells such as cardiomyocytes/neuronal cells on organic surfaces. For that, a novel characterization method is used to study the coupling between 2D and 3D laser-patterned organic-based devices and cells, combining electrochemical impedance spectroscopy (EIS) with a novel scanning electron microscopy/focused ion beam (SEM/FIB) method (Belu et al., 2016; Zhao et al., 2017).
van de Burgt, Y., Lubberman, E., Fuller, E.J., Keene, S.T., Faria, G.C., Agarwal, S., Marinella, M.J., Alec Talin, A., and Salleo, A. (2017). A non-volatile organic electrochemical device as a low-voltage artificial synapse for neuromorphic computing. Nat. Mater. 16, 414–418.
Belu, A., Schnitker, J., Bertazzo, S., Neumann, E., Mayer, D., Offenhäusser, A., and Santoro, F. (2016). Ultra-thin resin embedding method for scanning electron microscopy of individual cells on high and low aspect ratio 3D nanostructures. J. Microsc. 263, 78–86.
Zhao, W., Hanson, L., Lou, H.-Y., Akamatsu, M., Chowdary, P.D., Santoro, F., Marks, J.R., Grassart, A., Drubin, D.G., Cui, Y., et al. (2017). Nanoscale manipulation of membrane curvature for probing endocytosis in live cells. Nat. Nanotechnol. advance online publication.
11:30 AM - BM08.05.09
Monitoring the Electrical and Metabolic Activity of Living Cells by Means of Flexible Organic Devices
Andrea Spanu 1 , Mariateresa Tedesco 2 , Fabrizio Antonio Viola 1 , Piero Cosseddu 1 , Sergio Martinoia 2 , Annalisa Bonfiglio 1 Show Abstract
1 , University of Cagliari, Cagliari Italy, 2 , University of Genova, Genova, GE, Italy
Electrophysiological monitoring of neuronal assemblies both in vitro and in vivo is of great importance in disciplines like computational neuroscience, brain-machine-interfaces, and pharmacology. To date, the two main types of electrophysiological tools (i.e. Micro Electrode Arrays and devices based on the Ion Sensitive FET), though widely employed, present issues such as the high cost of production, the rigidity of the materials, and the need of a reference electrode in the liquid medium where the sensing takes place. Here we demonstrate that an Organic Charge Modulated FET device, besides been flexible, low cost, transparent, and reference-less, is able to sense different parameters of biomedical interest depending on how a particular part of its structure (called sensing area) is functionalized. We therefore propose here an OCMFET specifically designed to sense both electrical activity of electroactive cells (such as cardiomyocytes and neurons) and metabolic cellular activity in vitro. We will demonstrate that the charge perturbation induced by the cellular electrical activity on the OCMFET sensing area leads to a marked variation of the output current of the device, giving the possibility to clearly record cardiac and neuronal field potentials. Moreover, we will also demonstrate that the same structure can be employed for monitoring pH fluctuations of the culture medium induced by cells metabolic activity, thus giving important clues on cells conditions and viability. In fact, in the particular application of in vitro electrophysiology, an alteration of the acidity of the culture medium can induce changes in the electrical behavior of the cell culture itself, thus representing a parameter of interest in pharmacological testing. The sensing mechanism relies on the presence of a plasma activated, sub micrometric (750 nm) layer of Parylene C deposited on the sensing area. Besides turning the device pH-sensitive, the presence of such a sensing layer makes the sensing area an ideal surface for cell growth and development. The proposed device has been fully characterized as a pH sensor, and, in order to prove the possibility of using it for in vitro applications, the device was preliminary tested with 3T3 cells (an immortalized fibroblast cell line), in an experiment aimed at inducing and measuring a variation of their metabolic activity, which have been monitored by measuring the (low-buffered) medium acidification. The presented results represent the first example of direct metabolic monitoring using an organic field effect transistor and it is an interesting example on how organic electronics can pave the way to innovative low-cost, multi-sensing approaches to in vitro electrophysiology and pharmacology.
11:45 AM - BM08.05.10
Biocompatible, UV Curable Acrylate Functionalized Polysiloxane for an Advanced Neural Probe and Its Structural Mechanical Analysis
Woojin Jung 1 2 , Minah Suh 3 2 , Tae-il Kim 1 2 3 Show Abstract
1 School of Chemical Engineering, Sungkyunkwan University (SKKU), Suwon-si Korea (the Republic of), 2 Center for Neuroscience Imaging Research (CNIR), Institute for Basic Science (IBS), Suwon-si Korea (the Republic of), 3 Department of Biomedical Engineering, Sungkyunkwan University (SKKU), Suwon-si Korea (the Republic of)
As neural engineering is rapidly developed, and becoming more complex, the importance of polymeric biomaterials is getting more important. Moreover, the emerging of Optogenetics requires good optical, mechanical and biocompatible property for those biomaterials.  Therefore, biomaterials for modern, complex neural engineering need to satisfy four requirements; high transparency, biocompatibility, easy processability, proper mechanical property. However, current polymeric biomaterials do not fulfill them. Here, we suggest a UV-curable polysiloxane acrylate which shows biocompatibility, proper mechanical property, and extremely high transparency. Firstly, we successfully demonstrated a hierarchical structure with extremely simple process achieved by combining conventional, and unconventional lithography. Secondly, we performed immunohistochemistry and cell viability test. It shows excellent biocompatibility. Transparency is measured, and it shows extremely high transparency at the visible-NIR range. Finally, we showed the high flexibility of it. It has 1.3 GPa of modulus, and 38 MPa of fracture strength. Based on this material, an extremely thin neural probe is fabricated as an application. It shows high flexibility but enough strength for brain implantation, which means only minimal tissue damage occurs. The neural probe was successfully implanted into a living mouse brain with minimal tissue damage, and local field potential was successfully recorded. Taken together these results suggest that the UV-curable polysiloxane acrylate might have excellent potential for being used for advanced neural engineering.
BM08.06: Flexible and Stretchable Neural Interfaces
Wednesday PM, November 29, 2017
Sheraton, 2nd Floor, Republic A
1:30 PM - *BM08.06.01
Conductive Rubber Mesh for Electromechanical Cardioplasty
Dae-Hyeong Kim 2 1 Show Abstract
2 Center for Nanoparticle Research, Institute for Basic Science, Seoul Korea (the Republic of), 1 , Seoul National University, Seoul Korea (the Republic of)
Recent advances in soft electronics have attracted great attention due in large to its various potential clinical applications. Here, we present a soft and highly conductive rubber mesh made of ligand-exchanged silver nanowires (Ag NWs) and thermoplastic elastomer (styrene-butadiene-styrene; SBS). The ligand-exchange reaction enabled the formation of a highly conductive and homogeneous nanocomposite of Ag NWs. By patterning the nanocomposite with serpentine-mesh structures, conformal lamination of devices on curvilinear epicardium and effective electrical stimulation over the entire ventricle even during vigorous heart motions were achieved. The epicardium-integrated device reduces inherent wall stress without compromising diastolic relaxation and improves hemodynamics through synchronized electrical stimulation. The high conductivity of the epicardial mesh enables rapid propagation of electrical signals over the entire epicardial surface and the global resynchronization pacing therapy. This novel implantable soft electrode array provides new opportunities in the clinical medicine.
2:00 PM - BM08.06.02
Ester-Free Thiol-Ene Shape Memory Polymers for Neural Interfaces
Seyed Mahmoud Hosseini 1 , Melanie Ecker 1 , Kutter Kupke 1 , Walter Voit 1 Show Abstract
1 , The University of Texas at Dallas, Richardson, Texas, United States
Thiol-ene/acrylate shape memory polymers (SMPs) got a lot of interest for biomedical application due to their tunable thermo-mechanical properties. Recently, the Voit group has developed softening thiol-ene/acrylates for neural interfaces. These types of polymers are rigid during insertion to the body but become soft during the recording. Thus, they reduce the mechanical mismatch that otherwise would exist between the bioelectronic device and native tissue.
One drawback of the first generations of SMPs is, that they have ester groups in their backbone and may undergo hydrolysis under chronic in vivo conditions. Therefore, we have synthesized an ester-free thiol-ene/acrylate and tailored the glass transition temperature (Tg) to be above body temperature in the dry state, but below when soaked. Hence, the softening temperature is near to the body temperature. In addition, we have performed accelerated aging tests on this polymer in aqueous media and compared it with the previous generation to prove that this type of SMP is more stable and more convenient for implantable bioelectronics devices. We have studied the mass loss, change in thermomechanical behavior and optical changes over time.
2:15 PM - BM08.06.03
Engineering Metal Nanomesh as Microelectrodes and Interconnects for Transparent Neural Interfaces
Kyung Jin Seo 1 , Hui Fang 1 Show Abstract
1 , Northeastern University, Boston, Massachusetts, United States
Measuring neural signals with high temporal resolution and spatial resolution requires innovative electrophysiological sensing techniques. By adapting nanosphere lithography, we developed transparent and flexible gold nanomesh interconnects and microelectrodes, which enables electrical stimulation and recording along with optical imaging. Specifically, we demonstrated a 15-nm-thick Au nanomesh electrode with 8.14 Ωcm2 normalized impedance, >65% average transmittance over a 300−1100 nm window, and stability up to 300 bending cycles. Compared to previous transparent devices with graphene and indium tin oxide (ITO), nanomesh electrodes possess superior properties including low electrical impedance, high transparency, good cell viability, superb flexibility, and low light-induced artifacts. Our recent results of nanomesh with low impedance coatings further demonstrated significant improvements in the electrode performance, on both the impedance and charge injection limit. Together these results demonstrate the applicability of using metal nanomesh under biological conditions and broad applications in brain mapping and neural stimulation.
Kyung Jin Seo*, Yi Qiang*, Ismail Bilgin, Swastik Kar, Claudio Vinegoni, Ralph Weissleder, and Hui Fang. (2017), “Transparent Electrophysiology Microelectrodes and Interconnects from Metal Nanomesh” ACS Nano, 11(4), 4365-4372 (* denotes equal contributors)
3:30 PM - BM08.06.04
Design and Validation of a Foldable and Photovoltaic Wide-Field Retinal Prosthesis
Laura Ferlauto 1 , Marta Airaghi Leccardi 1 , Naïg Chenais 1 , Thomas Wolfensberger 2 , Kevin Sivula 3 , Diego Ghezzi 1 Show Abstract
1 Medtronic Chair in Neuroengineering, École Polytechnique Fédérale de Lausanne, Geneva Switzerland, 2 , Hôpital Ophtalmique Jules Gonin, Lausanne Switzerland, 3 Laboratory for Molecular Engineering of Optoelectronic Nanomaterials, École Polytechnique Fédérale de Lausanne, Lausanne Switzerland
In the last two decades, several retinal prostheses have been developed to fight blindness in people affected by outer retinal layer dystrophies. To date, a few hundred blind patients worldwide have received retinal implants. In this field, one of the most important open questions concerns how to increase both visual acuity and visual field with the same device.
Here we present a novel foldable and photovoltaic wide-field retinal prosthesis that advances the current state of the art in several aspects. The active array covers a retinal surface of 13 mm in diameter, affording restoration of the visual field up to ~46 degrees. Moreover, it is foldable to limit the scleral incision and it self-opens once released into the eye. It has a hemispherical shape to match the curvature of the eye, thus remaining in tight contact with the retina and minimizing the distance between the electrodes and the retinal cells over its entire surface. Lastly, it operates according to a photovoltaic principle via 2215 stimulating pixels. In its central area of 5 mm it embeds 967 pixels, twice than the estimated value required for being useful in daily activities.
Laboratory tests show that the prosthesis is not cytotoxic, while accelerated ageing shows a lifetime of at least 2 years. These advances provide a realistic solution towards the improvement of both visual acuity and visual field in blind patients.
3:45 PM - BM08.06.05
Intrinsically Stretchable Transistor Arrays and Functional Circuits for Future Neuron Interface
Sihong Wang 1 , Jie Xu 1 , Jong Won Chung 1 , Zhenan Bao 1 Show Abstract
1 , Stanford University, Stanford, California, United States
For human integrated or implanted electronic applications, transistors as the core component in electronic systems needs to have comparable mechanical properties with human skin and tissues, such as low modulus, good stretchability and flexibility. Therefore, a new generation of thin-film transistors that can function under large strain are highly desirable. Besides the device structural engineering approaches, the realization of stretchable electronics based on the development of intrinsically stretchable electronic materials could offer a number of important advantages, including larger strain tolerance, higher device density and simpler fabrication. In order to construct stretchable circuits and functional systems utilizing the intrinsically stretchable materials, the fabrication technology of stretchable transistor array is critically important. With polymer as the primary material system for the intrinsically stretchable semiconductors and dielectrics, the traditional fabrication processes for Si-electronics are not compatible. In this work, we developed the first all-solution-processed fabrication strategy that gives the first stretchable transistor array based on polymer semiconductor and dielectrics. This innovative fabrication process gives the record-high device density, a yield almost 100%, and little performance variation among individual devices. With the intrinsic stretchability of the materials, this array can keep its original performance without any degradation under a large strain up to 100%. In order to reveal its practical applicability in the development of next-generation electronics, this stretchable transistor array is further as active matrix for skin conformable tactile sensing array on hand plam. In another demonstration, prototypes of stretchable logic circuits have been realized based on this stretchable transistor array. This advancement can lead to next generation of neural interface electronics with a lot better mechamical compatibility and electrical functionality,
4:00 PM - BM08.06.06
Controlled Engineering of Bioelectronics Interfaces Using Organic Mixed Monolayers
Roger Woerdenweber 1 , Aleksandr Markov 1 , Nikolaus Wolf 1 , Xiaobo Yuan 1 , Dirk Mayer 1 , Vanessa Maybeck 1 , Andreas Offenhaeusser 1 Show Abstract
1 , FZ-Juelich, ICS-8, Juelich Germany
Modifying the surfaces of oxides using self-assembled monolayers offers an exciting possibility to tailor their surface properties for various research fields ranging from organic electronics to bioelectronics applications. The simultaneous use of different molecules in particular can extend this approach since the surface properties can be tuned via the ratio of the chosen molecules. This requires the composition and quality of the monolayers to be controlled on an molecular level – i.e. on the nanoscale. In this contribution, we present a method of modifying the surface and surface properties of silicon oxide by growing self-assembled monolayers comprising various compositions of two different molecules – (3-aminopropyl)-triethoxysilane (APTES) and (3-glycidyloxypropyl)-trimethoxysilane (GLYMO) – by means of in situ controlled gas-phase deposition. For the in situ monitoring and control of the deposition a special electronic molecular sensor system was developed that allows a precise control of the growth of the molecular layer. The properties of the resulting mixed molecular monolayers (e.g. effective thickness, hydrophobicity, and surface potential) exhibit a perfect linear dependence on the composition of the molecular layer. Finally, by coating the mixed monolayers with poly(L-lysine) PLL and fibronectin using these substrates in cell culture experiments, we were able to show that the density of PLL on the surface as well as the live/dead ratio of the rat cortical neurons (on PLL) and maturation of HL-1 cardiac muscle cells (on fibronectin) can also be tailored by the APTES–GLYMO ratio. We therefore believe that this technology could represent an ideal tool for engineering surfaces for bioelectronics purposes, such as improving cell adhesion, cell proliferation or bioelectronics sensors.
Polina Anikeeva, Massachusetts Institute of Technology
Timothy Denison, Medtronic Inc.
Nick Melosh, Stanford University
Christelle Prinz, Lund University
Phase Holographic Imaging
BM08.07: Nanostructured Neural Interfaces
Thursday AM, November 30, 2017
Sheraton, 2nd Floor, Republic A
9:00 AM - *BM08.07.01
Nanoelectronic Tools for Brain Science
Charles M. Lieber 1 Show Abstract
1 , Harvard University, Cambridge, Massachusetts, United States
Nanoscale materials enable unique opportunities at the interface between the physical and life sciences, for example, by integrating nanoelectronic devices with cells and/or tissue to make possible communication at the length scales relevant to biological function. In this presentation, I will overview a new paradigm for seamlessly merging nanoelectronic arrays and circuits with the brain in three-dimensions (3D), syringe-injectable mesh electronics. First, the design and properties of the mesh electronics with micrometer feature sizes and effective bending stiffness values similar to neurons and neural tissue will be described. Second, I will describe quantitative time-dependent histology studies demonstrating the absence of a tissue immune response on at least a year time-scale, as well as interpenetration of neurons and neurofilaments through the open mesh electronics structures. Third, I will report electrophysiology data demonstrating the capability to track and stably record from the same single neurons and neural circuits for more than a year. Fourth, I will describe several ‘applications’ of the unique mesh electronics capabilities that provide new insight into fundamental brain science problems, including aging and vision. Finally, the prospects for future advances of these nanoelectronic tools for overcoming complex challenges in neuroscience through the development of precision electronic therapeutics and brain-machine interfaces will be discussed.
9:30 AM - BM08.07.02
Semiconductor Nanowires—A Promising Tool for Designing Neural Implants
Gaelle Piret 2 , Henrik Persson 1 , Stina Oredsson 1 , Maria-Thereza Perez 1 , Christelle Prinz 1 Show Abstract
2 , INSERM/UJF/CHU, Grenoble France, 1 , Lund University, Lund Sweden
Semiconductor nanowires have been increasingly used in a broad range of bio-applications. In this talk, the work undertaken in our lab towards the use of nanowires for neural interface applications will be reviewed. We have shown that patterns of vertical nanowires can guide and sort axons1,2,5. We have also shown that PNS and CNS neurons thrive when cultured on vertical arrays of nanowires3–5, whereas the growth of glial cells on such arrays is limited compared to when cultured on flat substrates4,5. Phase holographic microscopy live cell imaging shows that the proliferation and motility of cells cultured on nanowire arrays are greatly affected by the nanowires6,7, which may at least partially explain the different effects of nanowires on neurons and glial cells. Taken together, these results suggest that arrays of semiconductor nanowires are promising nanomaterials for designing neural interfaces that support neurons steadily over time while limiting the formation of a glial scar.
(1) Prinz, C.; Hällström, W.; Mårtensson, T.; Samuelson, L.; Montelius, L.; Kanje, M. Axonal Guidance on Patterned Free-Standing Nanowire Surfaces. Nanotechnology 2008, 19 (34), 345101.
(2) Hallstrom, W.; Prinz, C. N.; Suyatin, D.; Samuelson, L.; Montelius, L.; Kanje, M. Rectifying and Sorting of Regenerating Axons by Free-Standing Nanowire Patterns: A Highway for Nerve Fibers. Langmuir 2009, 25 (8), 4343–4346.
(3) Hällström, W.; Mårtensson, T.; Prinz, C.; Gustavsson, P.; Montelius, L.; Samuelson, L.; Kanje, M. Gallium Phosphide Nanowires as a Substrate for Cultured Neurons. Nano Lett. 2007, 7 (10), 2960–2965.
(4) Piret, G.; Perez, M. T.; Prinz, C. N. Neurite Outgrowth and Synaptophysin Expression of Postnatal CNS Neurons on GaP Nanowire Arrays in Long-Term Retinal Cell Culture. Biomaterials 2013, 34 (4), 875–887.
(5) Piret, G.; Perez, M.-T.; Prinz, C. N. Support of Neuronal Growth Over Glial Growth and Guidance of Optic Nerve Axons by Vertical Nanowire Arrays. ACS Appl. Mater. Interfaces 2015, 7 (34), 18944–18948.
(6) Persson, H.; Købler, C.; Mølhave, K.; Samuelson, L.; Tegenfeldt, J. O.; Oredsson, S.; Prinz, C. N. Fibroblasts Cultured on Nanowires Exhibit Low Motility, Impaired Cell Division, and DNA Damage. Small 2013, 9 (23), 4006–4016.
(7) Persson, H.; Li, Z.; Tegenfeldt, J. O.; Oredsson, S.; Prinz, C. N. From Immobilized Cells to Motile Cells on a Bed-of-Nails: Effects of Vertical Nanowire Array Density on Cell Behaviour. Sci. Rep. 2015, 5 (November), 18535.
9:45 AM - BM08.07.03
Selective Neuro-Modulation Using Inkjet-Printed Thermo-Plasmonic Gold Nanorods
Hongki Kang 1 , Hyunjun Jung 1 , Jee Woong Lee 1 , Yoonkey Nam 1 Show Abstract
1 Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon Korea (the Republic of)
Thermal stimulation has activity modulation effects on neural networks: activation or inhibition of neural activities. Application of the thermal stimulation therefore can be used for numerous neural interface applications: from experimental platforms to study neural activities for various purposes to treating neural diseases. Applying heat in noninvasive way is especially required in these applications. Among various ways to deliver heat, utilization of metal nanoparticles for thermo-plasmonic effect is a very promising method as heat can be remotely generated. Especially, biocompatible gold nanorod specifically designed for absorbing longer wavelength (e.g. near infrared light) to improve tissue penetration depth is a very good example. In order to apply the thermal stimulation using the plasmonic nanoparticles with spatial selectivity and controlled intensity, therefore, suitable patterning method that can precisely pattern the plasmonic nanoparticles needs to be developed.
In this work, we show how we can apply inkjet printing process of plasmonic nanoparticles for selective neuro-modulation. We used biocompatible inkjet printing process we previously developed to precisely pattern the plasmonic gold nanorods on biocompatible polyelectrolyte coated substrates. Using this fabrication technique and material combination, we show that micron-resolution heat (near single cell resolution) can be generated by the thermo-plasmonics effect. Spatial temperature profile measurement around the micro-thermo-plasmonic heat source reveals the transient behavior of single micro heat source. This single heat source behavior can be used to precisely model temperature profile around multiple heat sources. We also show that large-area heat image with precisely varying intensity can be easily generated on flexible substrates while maintaining the high spatial resolution.
Lastly, we demonstrate that the heat pattern generated by the inkjet-printed gold nanorods can selectively suppress spontaneous spike activities in hippocampal neuronal network. The inkjet printing process was applied to 60-channel planar microelectrode array (MEA) chips on which hippocampal neurons are cultured in vitro. We then illuminated near infrared light to the MEA chip while recording spontaneous extracellular spike activities from the neuronal network, and observed that only those neuronal spike signals near the printed micro-thermo-plasmonic heaters are showing significant activity suppression. In addition, we also demonstrate that the locally generated heat pattern can temporarily disconnect spontaneous activity synchronization within the neuronal network activities while still maintaining partially synchronized neuronal activities in non-thermally stimulated areas. These selective neuro-modulation methods in neural interface can be useful for selectively turning off or isolate particular hyperactive neural cells that may be associated with neural diseases.
10:30 AM - *BM08.07.04
Membrane Curvature at the Nano-Bio Interface
Bianxiao Cui 1 , Wenting Zhao 1 , Francesca Santoro 1 , Hsin-ya Lou 1 , Allister McGuire 1 Show Abstract
1 , Stanford University, Stanford, California, United States
The interaction between the cell membrane and the contacting substrate is crucial for many biosensors such as sensors for electrophysiology recording. We are interested in exploring nanotechnology and novel materials to improve the membrane-surface interactions. Recently, we and other groups show that vertical nanopillars protruding from a flat surface support cell survival and can be used as subcellular sensors to probe biological processes in live cells. Vertical nanopillars deform the plasma membrane inwards and induce membrane curvature when the cell engulfs them, leading to a reduction of the membrane-substrate gap distance. We show that vertical nanoelectrodes offer unique enhanced signal detection for electrophysiological measurement in cells. We also found that the high membrane curvature induced by vertical nanopillars significantly affects the distribution of curvature-sensitive proteins and stimulates several cellular processes in live cells. Our studies show a strong interplay between biological cells and nano-featured surfaces, which is an essential consideration for future development of interfacing devices.
1. 1. Zhao W, Hanson L, Lou HY, Akamatsu M, Chowdary P, Santoro F, Marks JR, Grassart A, Drubin DG, Cui Y, Cui B, Nanoscale manipulation of membrane curvature for probing endocytosis in live cells, Nature Nanotechnology, accepted (2017).
2. Hanson L, Zhao W, Lou HY, Lin ZL, Lee SW, Chowdary P, Cui Y, Cui B, Vertical nanopillars for in situ probing of nuclear mechanics in adherent cells, Nature Nanotechnology, 10, 554-562, (2015).
3. Lin ZL, Xie C, Osakada Y, Cui Y, Cui B, Iridium Oxide Nanotube Electrodes for Intracellular Measurement of Action Potentials, Nature Communications, 5, 3206 (2014).
4. Xie C, Lin ZL, Hanson L, Cui Y, Cui B, Intracellular recording of action potentials by nanopillar electroporation, Nature Nanotechnology, 7, 185-190 (2012).
5. Hanson L, Lin ZL, Xie C, Cui Y, Cui B, Characterization of the Cell-Nanopillar Interface by Transmission Electron Microscopy, Nano Letters, 12, 5815-5820 (2012).
11:00 AM - BM08.07.05
A Nanoladder Platform Promoting Neural Regeneration
Chen Yang 1 Show Abstract
1 , Boston University, Boston, Massachusetts, United States
Disruption of nerve connections between the brain and the rest of the body caused by spinal cord injury could result in paralysis. Recovery is challenging due to failure in spontaneous neural regeneration. None of current clinical treatment targets neural regeneration and only limited functional recovery has been reported. Nanomaterials have been harnessed to promote neuronal growth in vitro. In this work, we present a new nanomaterial scaffold, interfacing and stimulating neural systems mechanically. Specifically, inspired by the hierarchically organized axon bundles in the spinal cord, we developed a “nanoladder” structure composed of a longitudinal micrometer-diameter fiber and multiple nanoscale protrusions to both guide macroscale neural growth and facilitate neurite formation at the subcellular level. Directional and promoted neurite growth is shown on the nanoladder structure. Directional growth and functional connection of organotypic spinal slices are confirmed through fluorescence labeled imaging and electrophysiology measurements on the nanoladder platform. We also demonstrated that such nanoladder concept can be used to further create self-folded injectable scaffold for in vivo studies and clinical tests.
11:15 AM - BM08.07.06
Genetically-Targeted Brain-Machine Interface
Jia Liu 1 , Ariane Tom 2 , Fikri Birey 3 , Charu Ramakrishnan 2 , Sergiu Pasca 3 , Zhenan Bao 1 , Karl Deisseroth 2 3 4 Show Abstract
1 Chemical Engineering, Stanford University, Stanford, California, United States, 2 Bioengineering, Stanford, Stanford, California, United States, 3 Psychiatry and Behavioral Sciences, Stanford University Medical School, Stanford, California, United States, 4 , Howard Hughes Medical Institute, Stanford, California, United States
Interfacing with living neural circuits using high-speed electrophysiological tools has contributed substantially to basic neuroscience as well as to clinical neurology and psychiatry. However, the limited ability of these devices to interface with the intact living brain with specificity for cell types prevents both deeper understanding of neural circuit function and much-needed precision for clinical intervention. Here, we present an unprecedented approach for a direct formation of electrical connections with targeted cells through the convergence of genetic engineering and polymer chemistry. With this method, novel genetically-targeted electronics are intrinsically assembled at the surface membrane of neurons both within functional neural tissue and in human 3D brain cultures derived from stem cells. This approach advances the field toward cell type-resolution electrical tuning of local neuronal activity, via bridging brain regions to external recording devices by precisely-defined high-speed pathways. Moreover, by enabling assessment and control of neural activity via fast genetically-targeted electrical connections, this technology may help broadly advance the understanding of neural circuit operation in health and disease, new treatment strategies for neuropsychiatric disease, and acceleration of the path toward specifically-enhanced sensation, cognition, and performance.
11:30 AM - *BM08.07.07
Silicon-Based Biophysical Tools for Extracellular and Intracellular Modulations
Yuanwen Jiang 1 , Ramya Parameswaran 1 , Bozhi Tian 1 Show Abstract
1 , University of Chicago, Chicago, Illinois, United States
Electrical and optical interfacing of semiconductor-based materials and devices with biological components can be used for probing cellular biophysics. Signaling and communication in biological systems occurs primarily through discrete and organized mesoscale structures and their networks. However, current biophysical tools for quantitative studies at this length scale have been rather limited. Semiconductor systems can be designed to have diverse material structures, allowing ample device configurations and related biophysical signal transduction mechanisms. Our lab has developed multiple semiconductor-based systems that address a variety of biophysical problems. The new tools are not only highly efficient when recording from or signaling to biological nanostructures, but may also ultimately blur the distinction between the natural and artificial interfaces, leading to unexpected breakthroughs. In this talk, I will introduce a few examples of silicon-based extracellular and non-genetic neuro- and cardiac modulations. Additionally, I will discuss the applicability of Si nanowires as intracellular devices for the control of cytoskeletal dynamics and chemical signaling. This research has the potential to address a wide range of scientific questions in inter- and intracellular signaling, organelle dynamics, and spatiotemporal organization of bioelectric and biomechanical pathways.
BM08.08: Magnetic Neural Modulation
Thursday PM, November 30, 2017
Sheraton, 2nd Floor, Republic A
1:30 PM - *BM08.08.01
Approaches and Materials for Remote Magnetothermal Deep-Brain Neuromodulation
Rahul Munshi 1 , Idoia Castellanos-Rubio 1 , Arnd Pralle 1 Show Abstract
1 Physics, State University of New York at Buffalo, Buffalo, New York, United States
Methods to remoted activate or silence specific neuronal activity in-vivo are valuable tools for unraveling the connection between behavior and brain circuits. If translatable to human application they also hold great potential as diagnosis and treatment tools. We explore magnetothermal activation and silencing of neuronal activities by local heating around superparamagnetic nanoparticles upon exposure to external alternating magnetic fields heated. The approach is tetherless and minimally invasive apart from delivering the nanoparticles. The application requires solving a series of material science challenges: synthesis of superparamagentic nanoparticle of specific size with maximal heat-generation capabilities (specific loss power), pacifying and stabilizing these nanoparticles for in-vivo delivery, yet permitting highly specific targeting to selected cells and self-assembly for increase efficacy. We will discuss our solutions to these challenges and present the application in controlling deep brain circuits in mice. We demonstrate activation of circuits by coupling the heating with heat-sensitive cation channels. Our results show robust that motor cortex and striatum neurons can be activated and lead to distinct motor behaviors, and that this is repeatable and robust. In addition, we demonstrate magnetothermal silencing of neurons in the Ventral Tegmental Area, leading to abolishing of a place preference. We evaluate duration and repetition rate of alternating field dosage required to generate memory retention of the demonstrated aversion.
2:00 PM - BM08.08.02
Enhancing Coil Design for Micromagnetic Brain Stimulation
Giorgio Bonmassar 1 , Laleh Golestanirad 1 , J. Deng 2 Show Abstract
1 A. A. Martinos Center, Harvard Medical School, Massachusetts General Hospital, Charlestown, Massachusetts, United States, 2 Center for Nanoscale Systems, Laboratory for Integrated Science and Engineering, Faculty of Arts and Sciences, Harvard University, Cambridge, Massachusetts, United States
Micromagnetic stimulation (μMS) has shown promise as a means of revolutionizing stimulation of the human nervous system. The technology uses sub-millimeter sized coils to stimulate neuronal tissue by means of magnetic induction; stimulation is achieved by generating a dispersed magnetic flux density (~0.1 Tesla) in a focal region of tissue by discharging a time-varying current through a microscopic coil. Placed within or in close proximity to excitable tissue, µMS induces a localized current gradient sufficient to activate neurons, as demonstrated in vitro by activating retinal ganglion cells . Recently, we have also shown that µMS is capable of activating neuronal circuitry at system level, using acutely implanted micro coils to activate neurons of the inferior colliculus in rodents . Micromagnetic stimulation (μMS) has several advantages over electrical stimulation. First, μMS does not require charge-balanced stimulation waveforms as in electrical stimulation. In μMS, neither sinks nor sources are present when a current is induced by the time-varying magnetic field, thus μMS does not suffer from charge buildup as can occur with electrical stimulation. Second, magnetic stimulation via μMS is capable of activating neurons with specific axonal orientations. Moreover, as the micro coils can be completely coated we expect to significantly increase biocompatibility with the use of implantable grade polymers such as parylene. Finally, we show that μMS can reduce the excessive power deposition into the tissue during magnetic resonance imaging (MRI), given that the coating can be a dielectric and thus insulated from the brain tissue. μMS technology was first developed in our laboratory and is entirely based on commercial components off the shelf, which are readily available to researchers. However, commercial inductors are designed to maximize efficiency (Q-factor), which consists in trapping the generated magnetic field to minimize its losses. Furthermore, they do not allow for multiple coil design in small and complex 3D geometries as it is often needed in neuroscience applications. In this work, we fabricate and test nanoscale coil structures for next generation μMS devices. Such devices could potentially become the brain and heart stimulators of the future with their contactless ability to deliver the neuronal stimulation needed for therapeutic efficacy in patients in need of implantable cardioverter-defibrillators or pace-makers, or patients with Parkinson’s disease, epilepsy, etc.
 G. Bonmassar, S. W. Lee, D. K. Freeman et al., “Microscopic magnetic stimulation of neural tissue,” Nature communications, vol. 3, pp. 921, 2012.
 H.-J. Park, G. Bonmassar, J. A. Kaltenbach et al., “Activation of the central nervous system induced by micro-magnetic stimulation,” Nature communications, vol. 4, 2013.
2:15 PM - BM08.08.03
Tuning Heat Sources for Application in Magnetothermal Neurostimulation
Idoia Castellanos-Rubio 1 , Rahul Munshi 1 , Arnd Pralle 1 Show Abstract
1 Physics, State University of New York at Buffalo, Buffalo, New York, United States
Modifying neuronal activities by controlled heat transfer to genetically modified or wild type cells can potentially be of therapeutic significance for ailments like epilepsy and addictions. In radiofrequency magnetic fields, superparamagnetic particles can be tailored to act as confined low dimensional heat sources for such application. Here, we inquire how the geometrical distribution of heat sources on and around the cell membrane can facilitate signal transduction and trigger behavioral changes in mice. Tagging the nanoparticles with a fluorescent dye enabled us to systematically study the temperature evolution by monitoring fluorescence intensity changes. We explore heating of nanoparticles suspended in inter cellular spaces and compare it to two dimensional sheets of membrane targeted nanoparticles. Particles, pre-arranged in sheet configuration and confined within polymer matrices allow for area density control and prolonged retention time. We fabricated such particle embedded polymer discs and characterized them on cells.
3:00 PM - BM08.08.04
Magnetic Hyaluronic Acid Hydrogel for Magneto-Mechanical Stimulation of Dorsal Root Ganglion Neurons via Mechano-Sensitive Ion Channels
Andy Tay 1 , Alireza Sohrabi 1 , Stephanie Seidlits 1 , Dino Di Carlo 1 Show Abstract
1 Bioengineering, University of California, Los Angeles, Los Angeles, California, United States
Tools for specific, localized and remote neural stimulation are useful for mapping neural circuits and neuromodulation. However, electrical and chemical tools cannot provide specific stimulation to densely-packed neural tissues. While optogenetics allows specific targeting of neurons, it is invasive for deep neural structures. These limitations motivated the emergence of new tools like thermogenetics and magnetogenetics. Nevertheless, the former risks heating tissues at >43 oC and the latter theoretically provides insufficient magnitude to gate mechano-sensitive channels (MSCs) with small ferritin nanoparticles (~10 nm).
Here we describe a biocompatible, magnetic hydrogel composed of hyaluronic acid (HA) for acute and chronic mechanical stimulation of primary rat dorsal root ganglion (DRG) via PIEZO2 and TRPV4.
This hydrogel is synthesized by reacting 4-arm-polyethylene-glycol-vinyl-sulfone (PEG-VS) with HA-thiol, the main component of the brain/spinal cord extracellular matrix (ECM) and 1 µm fluorescent thiol-functionalized-magnetic microparticles. The biomechanical properties of the hydrogel were optimized to have similar storage modulus (~150 Pa) as the brain/spinal cord ECM. We could also apply forces between 50-1100 pN with the gel using a 2 T permanent magnet.
We found no significant difference in cytotoxicity and metabolic activities of neurons grown on 2D PLL-coated coverslips, 3D HA gels and 3D magnetic HA gels with or without acute/chronic mechanical stimulation. Neurite outgrowth/branching and calcium level were similar across different conditions.
PIEZO1, PIEZO2, TRPV4 and N-type Ca2+ are the only MSCs that have been shown to be activated by mechanical forces. After verifying the specificity of antibodies, we performed immuno-labeling and found that DRG neurons express high density of PIEZO2 and TRPV4 channels but not PIEZO1 and N-type Ca2+.
Acute stimulation induced calcium influx in DRG neurons with on average 50% increase in Ca2+ fluorescence. Ca2+ influx was unaffected by ω-conotoxin, a specific inhibitor of N-type Ca2+ or Yoda1, a specific agonist of PIEZO1. However, there was dramatic quenching of Ca2+ influx with Ruthenium red that inhibits PIEZO2 and TRPV4.
Using the magnetic HA gel, we also found that chronic mechanical stimulation of DRG neural networks reduced the expression of mechano-sensitive PIEZO2 channels, consistent with previous findings that neural networks actively maintain homeostasis in the presence of continual excitation by downregulating their expressions of MSCs.
In conclusion, we fabricated magnetic HA hydrogels with similar biochemical/physical properties to brain/spinal cord ECM. Acute mechanical stimulation induced calcium influx via PIEZO2 and TRPV4 and chronic stimulation modulated the expression of mechano-sensitive PIEZO2 channels. We believe that the magnetic HA gel has potential for use in neural stimulation, pain modulation and mechano-transduction.
3:15 PM - BM08.08.05
Wireless, Scalable, Transgene-Free, Magnetomechanical Neural Stimulation via Magnetic Vortex Magnetite Nanodisks
Alexander Senko 1 , Danijela Gregureć 1 , Pooja Reddy 1 , Siyuan Rao 1 , Michael Christiansen 1 , Po-Han Chiang 1 , Dekel Rosenfeld 1 , Seongjun Park 2 , Polina Anikeeva 1 3 Show Abstract
1 Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States, 2 Electrical Engineering and Computer Sciences, MIT, Cambridge, Massachusetts, United States, 3 Research Laboratory for Electronics, MIT, Cambridge, Massachusetts, United States
A wireless magnetomechanical technique has been developed for magnetic nanoparticle-based neural stimulation. Unlike magnetothermal neural stimulation, which relies on heat dissipation from magnetic nanoparticles in radio-frequency alternating magnetic fields and requires genetic modification of neurons to sensitize them to heat, this approach does not necessitate transgenes, making it potentially safer for clinical applications. While previously reported magnetomechanical stimulation techniques employ magnetic field sources positioned within several hundred microns of the targeted cells, the field required for this technique is produced at the scale compatible with live animal experiments using a simple solenoid and a 200 W audio amplifier. This simplified stimulation setup and increased stimulated volume are enabled by magnetic particles with volumes hundreds of times larger than conventional superparamagnetic nanoparticles, but which have favorable colloidal properties due to their disk shape. These magnetite nanodisks possess a magnetic vortex state, which nearly eliminates stray field and results in less inter-particle attraction compared to spherical magnetic particles of similar volume. The neural stimulation technique enabled by these magnetic nanodisks has been demonstrated to robustly induce calcium influx in sensory neurons within whole dorsal root ganglion culture. Such minimally invasive neural stimulation techniques may facilitate basic studies and development of future therapies for neurological disorders.
3:30 PM - BM08.08.06
Wireless Neuromodulation of Targeted Cells Using Magnetoelectric Materials
Amanda Wickens 1 , Benjamin Avants 2 , Jacob Robinson 1 2 3 Show Abstract
1 Applied Physics Program, Rice University, Houston, Texas, United States, 2 Department of Electrical and Computer Engineering, Rice University, Houston, Texas, United States, 3 Department of Bioengineering, Rice University, Houston, Texas, United States
Chronic neuromodulation for treating neurological disorders and probing neural circuits is growing in popularity; however, testing new stimulation paradigms in animal models like rats and mice often requires lightweight, wireless neuromodulation technologies that
can target specific brain areas. Many wireless stimulators designed for humans and NHPs are too large for experiments in mouse models due to the weight of batteries or receiver coils, requiring significant redesign. Here we present a new approach for wireless neuromodulation that uses a material to convert magnetic fields that freely penetrate the brain into an electric field that stimulates nearby neurons. Because these materials act as targeted wireless stimulators, they can be made small enough to be implanted in mice. To create these biocompatible
“magnetoelectric” materials we fabricated a film of a piezoelectric material polyvinlydene fluoride bonded to a magnetostrictive film of Metglas. We then encapsulated the final films to make them biocompatible. These films can generate voltages above three volts
under resonant conditions using alternating magnetic fields with an amplitude of about 1 mT. With these magnetoelectric films we demonstrate that a simple film is able to stimulate cellular activity in vitro in excitable HEK cells. Based on this proof of concept
work, we fabricated magnetoelectric “micro-films” that weigh less than 20 mg and are compatible with studies in freely moving mice.
Our results show that magnetoelectric materials offer great promise for wireless electrical stimulation of specific brain areas. The basic understanding of magnetoelectric neural stimulation also be used to develop novel magnetoelectric materials or geometries (such as nanoparticles or nanofibers) to achieve even more targeted and less invasive wireless neural stimulation technologies.
BM08.09: Poster Session
Friday AM, December 01, 2017
Hynes, Level 1, Hall B
8:00 PM - BM08.09.01
Highly Sensitive Implantable Transient Dopamine Sensor for the Brain
Hyun-Seung Kim 1 , Suk-Won Hwang 1 Show Abstract
1 Graduate School of Converging Science and Technology, NBIT, Korea University of Science and Technology (KIST), Seoul Korea (the Republic of)
Dopamine is a neurotransmitter released by the brain that plays a critical role in the way our brain controls various our body systems. Excess or deficiency of dopamine levels is the cause of several neurological diseases such as Parkinson’s disease, schizophrenia. However, currently established dopamine sensors are inappropriate for applying to the real human body because most dopamine sensor systems are composed of toxic materials for detection as biomedical applications.
Here, we report a highly sensitive FET-based dopamine sensor, for which all of the constituent materials are biocompatible and mostly biodegradable in bio-fluids for direct detection in human brain in the future, eliminating the need for secondary operation. We synthesized biocompatible metal/conducting polymer hybrid nanoparticles using biodegradable transition metal ‘Iron (Fe)’ for catalyst and biocompatible conducting polymer ‘Polypyrrole (PPy)’ for sensor transducer via a bottom-up approach. The biocompatible metal/conducting polymer hybrid nanoparticles (NPs) are formed by electrostatic adsorption and reduction reaction with carboxylated polypyrrole (CPPy) in Fe precursor solution. The prepared Fe_CPPy NPs were characterized by TEM, UV-Vis, FT-IR, and XPS. The TEM images of CPPy NPs and Fe_CPPy NPs, and the UV-Vis spectra of all of the NPs displayed broad absorption band in the range of 400 - 1100 nm revealed well-defined NP structures decorated with metal catalyst. The FT-IR spectra of synthesized NPs has two absorption peaks observed at 1700-1800 cm-1 and 2900-3100 cm-1, and each of those peaks is associated with the stretching vibration of C=O and acid O-H in carboxylic acid group, respectively. The XPS spectrum showed C, O, N, Fe peaks in accordance to the presence of PPy and Fe as a metal catalyst and present an atomic percent of an essential component.
The catalytic performance of synthesized Fe_CPPy NPs was evaluated by high performance liquid chromatography (HPLC) with dopamine oxidation reactions. The results of catalytic dopamine oxidation demonstrated its capability as a catalyst compared to Pt_CPPy NPs and the oxidation product of dopamine (=dopamine o-quinone) was verified by UV-Vis, 1H-NMR and FT-IR.
The Fe_CPPy NPs are then immobilized on NH2 (amine) - functionalized biodegradable electrode through the formation of amide bond between the carbonyl carbon on carboxylated nanoparticle surface and the amine group on chemically treated electrode surface in neutral pH condition, whose current-voltage (I-V) characteristic involves a linear relationship between the applied voltage and output current as an ohmic behavior.
8:00 PM - BM08.09.02
Chemically-Derived Iridium Oxide Films as Bio-Stimulating Electrodes for Implantable Silicon-Based Devices
Kuang-Chih Tso 1 , Han Yi Wang 1 , Yi-Chieh Hsieh 2 , PuWei Wu 2 , Po Chun Chen 3 , Jyh Fu Lee 4 Show Abstract
1 Graduate Program for Science and Technology of Accelerator Light Source, National Chiao Tung University, Hsinchu Taiwan, 2 Department of Materials Science and Engineering, National Chiao Tung University, Hsinchu Taiwan, 3 Department of Materials and Mineral Resources Engineering, National Taipei University of Technology, Taipei Taiwan, 4 , National Synchrotron Radiation Research Center, Hsinchu Taiwan
The fabrication of implantable bio-electronics devices has attracted considerable attention recently for their promising potentials to cure/remedy patients with impaired functionality in selective organs. One of the critical components for such devices is the bio-electrodes that act as the interface allowing interchanges of electrical signatures between neurons and electrical circuits. During the past ten years, our group has been developing wet chemical based synthetic methods to fabricate IrO2thin films on Si-based electronic devices. Our unique process enables selective deposition onto exposed contact areas leaving those inert areas passivated. Relevant deposition mechanism is investigated using X-ray absorption spectroscopy. Materials and film characterization are carried out and discussed.