Focused Session Q-6
Materials Nanotechnologies for Implantable Neural Interfaces

Q-6:IL01  Semiconductor Nanowires for Neural Interface Applications
C.N. PRINZ, Division of Solid State Physics, NanoLund and Neuronano Research Center, Lund University, Lund, Sweden

Semiconductor nanowires have been increasingly used in a broad range of bio-applications. In this talk, I will review the work undertaken in Lund towards the use of nanowires for neural interface applications. We have shown in vitro that neurons from the PNS and CNS thrive on vertical arrays of nanowires, whereas the growth of glial cells on such arrays is limited compared to when cultured on flat substrates. In the rat brain, we have shown that the presence of nanowires of length 5 µm and above elicits a long lasting tissue inflammation, whereas the reaction to the injection of shorter nanowires is similar to the reaction to the injection of vehicle solution. We developed nanowire-based neural electrodes that were able to perform acute recordings of single unit action potentials in the rat cortex.


Q-6:IL02  Carbon Nanotube Technology for Flexible Neuronal Interfacing
Y. HANEIN, School of Electrical Engineering, Tel Aviv University, Tel Aviv, Israel

A lingering technological bottleneck in the field of neuro-prosthetic devices is the realization of soft, micron sized electrodes capable of injecting enough charge to evoke localized neuronal activity without causing neither electrode degradation nor tissue damage. In recent years we have developed a new flexible neuronal micro electrode device, based entirely on carbon nanotube technology, where both the conducting traces and the stimulating electrodes consist of conducting carbon nanotube films embedded in a polymeric support. The use of carbon nanotubes bestows the electrodes flexibility, and excellent electro-chemical properties. As opposed to contemporary flexible neuronal electrodes, this technology is both robust and the resulting stimulating electrodes are nearly purely capacitive. Recording and stimulation tests with chick retinas were used to validate the advantageous properties of the electrodes and demonstrate their suitability for high-efficacy neuronal stimulation applications. The CNT electrodes were further modified with quantum dots converting them to bio-mimetic, photo-sensitive pixels for artificial retina applications.


Q-6:IL05  Tissue Engineering Conducting Polymer Coatings for Implantable Neural Interfaces
R. GREEN, Biomedical Engineering, UNSW, Sydney, Australia

Fibrous scar tissue and fluid encapsulation about chronically implanted neural electrodes is often a result of insertion trauma and poor electrode/tissue integration, which adds a layer of electrical resistance between the device and the target neural tissue. Tissue engineered electrodes aim to deliver a living cellular layer to interface bionic devices with target tissue by establishing synaptic connections between the electrode and target nerve. A significant challenge in developing this technology is to engineer a polymeric, conductive electrode material that can both pass electricity and support growth and function of complex neuronal networks. To achieve this objective an electrode construct has been designed by integrating conductive polymers with biosynthetic hydrogels. A combination of non-degradable and degradable polymeric components have been nanostructured and integrated with biomolecules that can support neuronal cell survival and growth. These structures are based on the conductive polymer poly(ethylene dioxythiophene) (PEDOT) and the hydrogel poly(vinyl alcohol) (PVA). Addition of covalently linked, degradable gelatin and sericin to the PVA has been shown to support survival of primary neural cells for up to 21 days post-encapsulation.


Q-6:L06  A Direct Comparison of Glassy Carbon and PEDOT-PSS for High Charge Injection and Low Impedance Neural Interfaces
M. VOMERO¹, E. CASTAGNOLA², S. DE FAVERI², E. MAGGIOLINI², I. REMBADO², L. FADIGA^2,3, S. KASSEGNE¹, D. RICCI², ¹MEMS Research Lab., Department of Mechanical Engineering, College of Engineering, San Diego State University, San Diego, CA, USA; ²CTNS@UniFe, Istituto Italiano di Tecnologia, Ferrara, Italy; ³Section of Human Physiology, University of Ferrara, Ferrara, Italy

Materials interfacing the brain in neural applications with long-term and high-fidelity performance capabilities are still sought after. Glassy Carbon (GC) and Poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT-PSS) have proved to be promising materials for neural interfaces as, with respect to conventional metal electrodes, they show higher conductivity, better electrochemical stability, greater mechanical properties and looks very promising for in vivo recordings. We present here for the first time a direct comparison of electrochemical, biocompatibility and in vivo performance of GC and PEDOT-PSS using electrocorticography microelectrode arrays on a flexible polyimide substrate. The GC microelectrodes were microfabricated using a traditional negative lithography processes followed by pyrolysis. Then PEDOT-PSS was selectively electrodeposited on the desired electrodes. Electrochemical performance of the two materials was evaluated through electrochemical impedance spectroscopy and cyclic voltammetry. Biocompatibility was assessed through in-vitro studies evaluating cultured cells viability. The in-vivo performance of the GC and PEDOT-PSS electrodes was directly compared by simultaneously recording the same neuronal activity during somatosensory stimulation in rat.


Q-6:L08  Investigation of HfO2-based Capacitive Transducers for Neuron Interfacing
G. TALLARIDA¹, S. SPIGA¹, A. CORNA², L. GELMI¹, A. LAMPERTI¹, M. FANCIULLI^1,2, ¹Laboratorio MDM - CNR-IMM, Agrate Brianza, Italy; ²Dipartimento di Scienza dei Materiali, Università degli Studi di Milano Bicocca, Milano, Italy

A valuable route for the fabrication of biohybrid systems connecting natural and artificial neurons is the integration of transducers arrays into CMOS technology, thus allowing high spatial resolution, massive parallel recording and fast processing of signals. To avoid toxic electrochemical reactions at the electronic-biological interface, stimulation/reading of neural signal should be achieved without charge exchange between electrodes and the neural tissue, e.g. by exploiting displacement currents across capacitive transducers. For capacitive transducers with improved characteristics, we investigated HfO2-based thin dielectric films deposited on TiN. The charge storage capacity of the metal-oxide system and electrochemical potential window are studied in PBS. Chemical stability following prolonged operation in electrolyte is investigated by ToF-SIMS. Our study show that HfO2-based films are highly attractive as passivation layers for their chemical and electrochemical stability. The large potential window in PBS allows a wide operation bias range for the transducers, compatible with CMOS circuitry, within which capacitance in virtually constant. These characteristics holds also for very thin films (5nm) that provide capacitance density of nearly 2μF/cm2 on flat devices.


Q-6:L12  Soft and Leaky Encapsulation Materials for Neural Interface Devices
A. JOSHI-IMRE, A. GARCIA SANDOVAL, R. MODI, S. COGAN, W. VOIT, The University of Texas at Dallas, Richardson, TX, USA 

Soft and flexible thin film materials are desirable for the packaging of chronic neural interface devices. Softness is valued for being tissue friendly, and flexibility is required to facilitate bending, torsion, and perhaps stretching (especially in peripheral applications). We are developing thin film microfabrication processes to build cuff electrodes using medical grade silicone and custom thiol-ene acrylate thermoset polymers [T. Ware et al., “Thiol-ene/acrylate substrates for softening intracortical electrodes,” J Biomed Mater Res Part B 102 p1-11, 2013]. As electronic insulators in aqueous environment, these materials are inherently leaky, while their exact performance is primarily dependent on their adhesion property to the current carrying conductor and the characteristics of the electric current. Here we present experimentally measured mechanical properties for 20 to 100 micrometer thick ribbons of pure materials, as well as for ribbons with embedded electrical wiring. We also present leakage current measurements under (inside a ribbon in between wires) and across these thin film materials. Leakage current measurements were repeatedly performed in order to evaluate aging in a physiologically relevant condition (37 °C, phosphate buffered saline).


Q-6:IL15  Systemic Inhibition of Innate Immunity Pathways Improves Intracortical Microelectrode Performance
J.R. CAPADONA, J.K. HERMANN, M. RAVIKUMAR, Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA; Advanced Platform Technology Center, L. Stokes Cleveland VA Medical Center, USA

Intracortical microelectrodes allow the activity of single or small neuronal populations to be analyzed over time, which can be used to control external assistive devices in patients suffering from paralysis. However, challenges still remain in maintaining quality neural signals for extended periods. One of the most accepted hypotheses for loss of chronic recordings is that the inflammatory response results in the reduction of viable neurons at the tissue-electrode interface. Several studies have indicated a dominant participation of microglia and macrophages in facilitating this response. Here, we report on the role of a specific microglia co-receptor that is a major component in the recognition and removal of infiltrating serum proteins within the central nervous system, cluster of differentiation 14 (CD14). The current study uses both transgenic mice and a small molecule antagonist (IAXO) to investigate the effectiveness of CD14 as targets for improving microelectrode performance. Our results indicate that both inhibition of CD14 as well as administration of IAXO improve neural recording, and promise a translation therapeutic approach to improving the stability of neural recordings.


Q-6:L16  Recording High Frequency Neural Signals using Conformable and Low-impedance ECoG Electrodes Arrays coated with PEDOT-PSS-PEG
E. CASTAGNOLA¹, M. MARRANI², E. MAGGIOLINI¹, S. DE FAVERI¹, F. MAITA², L. PAZZINI², D. POLESE², A. PECORA², L. MAIOLO², L. FADIGA^1,3, D. RICCI¹, ¹CTNS@UniFe, Istituto Italiano di Tecnologia, Ferrara, Italy; ²CNR-IMM Istituto per la Microelettronica e i Microsistemi, Rome, Italy; ³Section of Human Physiology, University of Ferrara, Ferrara, Italy 

Electrocorticography (ECoG) is receiving growing attention for both clinical and research applications thanks to its reduced invasiveness and ability of addressing large cortical areas. These benefits come with a main drawback, i.e. a limited frequency bandwidth. However, recent studies have shown that spiking activity from cortical neurons can be recorded when the ECoG grids present the following combined properties: (I) conformable substrate, (II) small neuron-sized electrodes with (III) low-impedance interfaces. We introduce here an ad-hoc designed ECoG device for investigating how electrode size, interface material composition and electrochemical properties influence the ability to record high frequency neural signal components. Contact diameterreduction down to 2 µm was possible thanks to a specific coating of a (3,4-ethylenedioxytiophene)-poly(styrenesulfonate)-poly-(ethyleneglycol) (PEDOT-PSS-PEG) composite that drastically reduces impedance and increases electrical and ionic conductivities. In addition, the extreme thinness of the polyimide substrate (8 μm) and the presence of multiple perforations through the device ensure an effective contact with the brain surface and the free flow of cerebrospinal fluid. In-vivo validation was performed on rat somatosensory cortex.


Q-6:L17  Interface Investigation of Electrogenic Cells on 3D Laser-patterned PEDOT Structures
F. SANTORO¹, G.C. FARIA^2,3, Y. VAN DE BURGT², A. SALLEO², B. CUI¹, ¹Department of Chemistry, Stanford University, Stanford, CA, USA; ²Department of Material Science and Engineering, Stanford University, Stanford, CA, USA; ³Sao Carlos Physics Institute, Sao Paulo University, Sao Carlos, Brazil

Interfacing OECT’s with ionic barriers and biological systems holds considerable promise not only for building sensitive biosensors and diagnostic tools, but also for recording biological process in live cells and neurons. In fact, organic transistors or multi (organic) electrode arrays can record action potentials from electrogenic cells as well as send electrical stimuli to trigger certain electrical patterns within cells. Traditional devices are planar, and a cleft between cells and device typically forms, affecting the recorded signal quality. Recently, 3D modifications of the electrode surface have been successfully proposed for traditional metal electrodes. Here, we present a novel patterning method using a direct-write femtosecond laser process, to create well-defined micro patterns into PEDOT:PSS films. The direct-write technique is straightforward and does not involve complicated lithography or etching steps while the ultrafast nature of the process ensures a high resolution and low impact. Electrogenic cells can sense 3D cues inducing spatially guided outgrowth and stretching. Furthermore, we investigate the effective interface of electrogenic cells by using an innovative embedding procedure for scanning electron microscopy and focused ion beam sectioning. By doing so, we can effectively visualize the point contacts of the cell membrane on to the 3D PEDOT structures. These in vitro morphological studies represent the first step towards a 3D implantable organic electrodes.


Q-6:L18  A Nanoscale Interface Directs Alignment of a Cell-assembled Extracellular Matrix to Template Neurite Outgrowth
J. SCHWARTZ¹, S.B. BANDINI¹, G.M. HARRIS², L.S.F. ADLER¹, A.O. PARIKH¹, J. SPECHLER³, C.B. ARNOLD³, H. WANG⁴, J.E. SCHWARZBAUER², ¹Department of Chemistry, Princeton University, Princeton, NJ, USA; ²Department of Molecular Biology, Princeton University, Princeton, NJ, USA; ³Department of Mechanical and Aerospace Engineering, Princeton University, Princeton, NJ, USA; ⁴Department of Neurologic Surgery, Mayo Clinic, Rochester, MN, USA

Tissue regeneration requires directing the assembly of cells and their extracellular matrix (ECM) into arrangements that possess native physical and mechanical properties. We have prepared an interface that templates aligned cell spreading to yield confluent layers of cells across an entire two-dimensional surface. Here, a volatile zirconium alkoxide complex is vapor deposited onto a surface pattern prepared by a novel shadow masking process; the substrate is then heated to form surface-bound, 10-70 nm thick zirconium oxide patterns, which are treated with 1,4-butanediphosphonic acid to give monolayer patterns of the zirconium phosphonate. NIH 3T3 fibroblasts attach to these patterns, spread, and form aligned, confluent monolayers across the entire surface; they assemble an ECM in which the fibronectin fibrils are highly aligned. Decellularization yields spatially aligned matrix attached to the polymer surface. Biologic function is illustrated by oriented neurite outgrowth along the aligned matrix fibrils, which supports the goal of developing a platform for integrating spatially directed cell behavior with a device for nerve regeneration. In this context, shadow mask patterning in 20-micron wide stripes has been applied to the inside surface of polymeric “nerve conduit” tubes.

 
Q-6:IL19  Narrowing the Physical Mismatch between Neural Implants and Neural Tissues
S.P. LACOUR, Laboratory for Soft Bioelectronics Interfaces, Centre for Neuroprosthetics, School of Engineering, EPFL, Lausanne, Switzerland 

Low modulus elastic materials in conjunction with stretchable metallization enable the evolution of neural electrode arrays towards conformal bioinspired interfaces. These ultra-compliant devices are engineered to establish a synergy with living tissue to reactivate, repair, restore, or replace diminished/lost physiological functions due to disease or injury of the nervous system. Creating ultra-compliant neural electrodes, however, requires not only elastic substrates but also integration of electrode site coatings, interconnects, passivation layers and reliable connectors to electronics hardware, which can survive the mechanical deformations encountered during implantation or normal operation of the device. Here we present our approach to building soft microelectrode arrays with the enhanced mechanical compliance compared to current long-term neural implants. The soft neurotechnology is capable of bidirectional communication with the neural tissues and so over months of implantation. Using concepts from rapid prototyping, we have ensured that the fabrication process is easily adapted to produce implants for various anatomical sites.


Q-6:IL20  Ultracompliant Electrodes for Next-generation Brain-machine Interfaces
C.J. BETTINGER, Carnegie Mellon University, Pittsburgh, PA, USA 

The next-generation of brain-machine interfaces will ideally overcome many of the challenges associated with mechanical and chemical mismatches between natural tissue and synthetic devices. This talk will describe how bioinspired catechol networks can harmonize these asymmetries. First, the use of catechol-bearing hydrogels in transfer printing of electronic structures to ultracompliant hydrogel substrates will be presented. Photocrosslinkable hydrogels composed of poly(2-hydroxyethylmethacrylate-co-dopamine methacylate)-co-poly(ethyleneglycol)diacrylate (P(HEMA-co-DMA)-PEGDA) are prepared and characterized. The adhesive properties of P(HEMA-co-DMA)-PEGDA were measured using force-distance measurements across a range of substrate materials. These functionalized hydrogels are then used as substrates that permit transfer printing of microelectronic structures to swollen hydrated networks. Next, the use of catechol-bearing melanin networks as redox-active biologically-derived materials for improved charge injection will also be described. Future applications will be discussed.


Q-6:IL23  SiC-based Neural Interfaces for the Central Nervous System
C.L. FREWIN, S.E. SADDOW, University of South Florida, Tampa, FL, USA

The potential impact of neuro-compatible implantable devices to assist millions who suffer from brain and spinal cord injury or limb loss is tremendous, both in restoring patient health, as well as quality of life. Until now, no known reliable solution to this challenge has been found, with most of the current technology relying on non-neuro-compatible materials such as silicon, tungsten, or platinum, and polymer insulators. Silicon Carbide (SiC) and, in particular 3C-SiC, appears to be an ideal material to meet this challenging application: the evidence of bio- and hemocompatibility is increasing; it is a semiconductor that allows for tailored doping profiles and the seamless integration of electronics with the implants; it is highly durable, even within harsh, corrosive environments; SiC is also an excellent thermal conductor. For the first time, a comprehensive analysis of 3C-SiC for neural device applications has been performed and is reported here.
 
 
Poster Presentation

Q-6:HP03  E-microscopy of Micro-structured Cell/Biosensor Interface
G. PANAITOV, E. NEUMANN, A. OFFENHAUSSER, PGI-8, Research Center Jülich GmbH, Jülich, Germany

Micro- or nano-structuring is often used in biosensors in order to improve cell/sensor adhesion. We apply 3-dimensional gold micro-spines to enhance the contact between the cells and device electrodes. The quality of cell/device interface was investigated by scanning electron microscopy (SEM) and focused ion beam (FIB) sectioning. The conventional sample preparation for e-beam microscopy requires the chemical fixation of cells and the following dehydration by critical point drying (CPD) or, alternatively, by epoxy embedding. Each of these preparation steps can potentially deliver some specific artefacts at the interface between the soft cell membrane and the solid electrode material. In order to identify these kind of artefacts we compare conventional cell samples with cells fixed alternatively by quick plunge freezing. The advantage of cryo-fixation is, that, it is extremely rapid, which can prevent, within milliseconds, the intracellular movements of macromolecules and other substances. Another hand, problems may appear if freezing a biological sample contacting to the surface of biosensor. Due to different thermal expansion coefficients of solid and biological materials, it may lead to additional artefacts at the interface area.