Daryl R. Kipke University of Michigan
Stephanie P. Lacour University of Cambridge
Barclay Morrison Columbia University
Dustin Tyler Case Western Reserve University
U1: Surface Bio-Functionalization
Wednesday AM, April 11, 2007
Room 2010 (Moscone West)
9:30 AM - **U1.1
Modulate Cortical Tissue Response to Chronic CNS Electrode via Surface Immobilization of Anti-inflammatory Neuropeptide
Wei He 1 , George McConnell 1 , Thomas Schneider 1 , Ravi Bellamkonda 1 Show Abstract
1 Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia, United States
Implanted silicon microelectrode arrays (Si-MEAs) are neural implants with great potential to enhance both fundamental knowledge pertaining plasticity and physiology, as well as in the treatment of central nervous system (CNS) trauma by providing single-unit recordings in the adult cortex. One of the greatest obstacles to such potential is the instability of the implant-host interface due to astro-glial scarring response. The glial scarring adversely impacts the function of Si-MEAs by electrically and mechanically isolating them from the neurons. A common strategy is to locally release anti-inflammatory agents at the site of injury. Although such approach has been shown to successfully moderate host response during the acute phase, it might be inadequate to have long-term functional consequences limited by the drug release duration. The sustained chronic tissue response to the implant is a result of both foreign body reaction and mechanical mismatch induced micromotion. To address this issue, we functionalized the surface of Si-MEAs by immobilizing an anti-inflammatory neuropeptide a-melanocyte stimulating hormone (a-MSH) and evaluated the performance of the modified implant both in vitro and in vivo. Chemical composition of the modified surface was verified by X-ray photoelectron spectroscopy (XPS). The surface density of immobilized peptide was estimated using the sulfo-SDTB test. We observed that a-MSH grafted silicon surface inhibited the production of nitric oxide (NO) by lipopolysaccharide (LPS)-activated microglia in vitro, demonstrating that the immobilized neuropeptide remained biologically active. The gene expression of pro-inflammatory cytokines, tumor necrosis factor a (TNF-a) and interleukin-1 (IL-1), was measured by mRNA using real time quantitative reverse transcriptase polymerase chain reaction (RT-PCR). The results indicated that the immobilized a-MSH reduced the expression of both TNF-a and IL-1 in response to LPS activation. We implanted both bare and a-MSH immobilized silicon microelectrodes into adult rat brains. Reactive tissue response was assessed by quantitative immunohistochemistry for GFAP (astrocytes) and ED-1 (microglia). The presence of a-MSH reduced microglial reaction 1 week (~67% reduction) and 4 weeks (~50% reduction) following surgery in comparison with uncoated control electrode. The astrocytic response was also weakened 4 weeks post surgery. In situ hybridization results indicate that the observed anti-inflammatory effect might be associated with the reduced mRNA expression of pro-inflammatory cytokine TNF-a. These results suggest that surface immobilization of anti-inflammatory neuropeptide may provide a means, in combination with the local drug delivery approach, to attenuate long-term brain tissue response to chronic neural implants, leading to a stable implant-host interface.
10:00 AM - U1.2
Simultaneous Controlled-Release of Multiple Compounds from the Surface of an Implantable Neural Device.
Catherine Lo 1 , Paul Van Tassel 2 , Mark Saltzman 1 Show Abstract
1 Biomedical Engineering, Yale University, New Haven, Connecticut, United States, 2 Chemical Engineering, Yale University, New Haven, Connecticut, United States
Systems that provide controlled-release from the surface of an implantable neural device can improve its biocompatibility, enhance its interactions with cells, or provide local delivery of therapeutic agents. Here, a novel method is presented to combine the diverse interests by simultaneous release of multiple compounds from a layer of biodegradable nanoparticles adhered onto a single device surface. Test silicon substrates were initially modified by deposition of cationic poly-L-lysine polyelectrolyte, followed by immersion in an aqueous suspension of negative charged poly(lactide-co-glycolide) nanoparticles, which were previously loaded with drugs. The particles were driven by electrostatic interaction to self-assemble onto the device surface. The special feature of this system is in its versatility to incorporate a mixture of compounds that can be adhered onto the same surface. Specifically in this report, rhodamine B-loaded and fluorescein-loaded nanoparticles were used to visualize dual particle adsorption onto test substrates. Simultaneous release of rhodamine B and fluorescein were tracked by release of fluorescence.
10:15 AM - U1.3
``Click" Functionalization of Vapor Deposited Polymer Thin Films for Patterned Surface Modification of Neural Recording Arrays
William O'Shaughnessy 1 , Nuria Mari-Buye 2 , Karen Gleason 1 Show Abstract
1 Chemical Engineering, MIT, Cambridge, Massachusetts, United States, 2 Chemistry, Institut Quimic de Sarria, Barcelona Spain
Recent research advances in the field of neuroprosthetics, including human trials, have brought the possibility of therapeutic use into the near term. One major impediment to moving this technology from the lab to the clinic is the ability to record from implanted neural arrays over an extended time period. While current implant technology allows for stable recording in the first year, a time scale of 25-50 years of active recording will be necessary for therapeutic use. This loss of function is mainly attributable to the formation of dense scar tissue around the probe not only immediately post-implantation but also over the life of the implant. Long term damage is due to continual breaching of the blood brain barrier as a result of micromotions of the probe within the brain. Finite element modeling has demonstrated that this damage could be almost entirely eliminated if the probe were anchored to the cellular matrix surrounding it. One approach to achieving this goal is the covalent attachment of cellular adhesion peptides, such as laminin, to the probe surface. In this work, an initiated chemical vapor deposition (iCVD) synthesized polymeric coating has been developed to allow patterned tethering of peptides to the surface of neural implants. The material, poly(pentaflourophenyl methacrylate) or pPFM, is deposited through all dry free radical polymerization of the vinyl moiety within the monomer. The use of iCVD to create the coating ensures conformal, pinhole free coverage of the device. The fluorophenyl side group present in pPFM is an excellent leaving group for nucleophillic addition of amines. This provides a methodology for single step, or “click”, covalent attachment of adhesion peptides, or any primary amine containing molecule, to the surface of the coating. The reaction proceeds very rapidly, allowing for patterned modification of the surface through microcontact printing (μCp). Patterned surface modification has been demonstrated through μCp of fluorescently labeled amine followed by optical imaging. Samples were repeatedly rinsed before imaging to ensure covalent attachment of functional molecules. In addition, as the material is deposited through iCVD, it is easily copolymerized with an electrically insulating barrier material deposited by the same technique. This approach eliminates any possible coating adhesion issues, and ensures that the peptides remain attached to the implant.
10:30 AM - **U1.4
Improving Biocompatibility of the Neural Probes by Surface Immobilization of Biomolecules
Xinyan Cui 1 2 3 Show Abstract
1 Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania, United States, 2 McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States, 3 Center for Neural Basis of Cognition, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
Silicon based implantable neural electrode arrays are known to experience failure in long-term recording. Several strategies are being taken in our lab to improve their biocompatibility and integration within the host brain tissue. First strategy is immobilization of biomolecules such as L1 and laminin on the silicon surfaces to promote attachment and growth of neurons. Laminin, an ECM protein that interacts with a variety of cell types, is known to be an excellent substrate for neuronal attachment and growth. L1 is a neuron cell adhesion molecule specifically promoting neurite outgrowth and neuronal survival. We routinely purify L1 from murine brains using an immunoaffinity column. Silane chemistry and heterofunctional coupling agent, 4-Maleimidobutyric acid N-hydroxy succinimide ester (GMBS), were used to covalently bind the biomolecules on the silicon surfaces. In our in vitro model, silicon dioxide wafers were used to mimic the surface of the neural probe. After binding of the biomolecules, polyethylene glycol (PEG)-NH2 was used to inactivate the reactive GMBS and to inhibit non-specific protein adsorption and cell adhesion. Primary murine neurons and astrocytes were used to evaluate the modified surfaces. Both L1 and laminin promoted neuronal growth, while the L1-PEG surfaces showed better neurite outgrowth (p<0.05). In the astrocyte culture, laminin-PEG surfaces promoted astrocyte growth, while L1-PEG surfaces were not permissive to astrocyte growth. For the in vivo studies, the Michigan neural probes were used. After surface treatment, four groups of probes (L1-PEG immobilized, Laminin-PEG immobilized, PEG immobilized and unmodified control) were implanted randomly in the left and right cortex of Fisher 344 rats. After 1 or 4 weeks the rat brains were sectioned, immunofluorescently stained for neurons, astrocytes, and microglia around the probe site. Reactivity around the implant site was quantified using integrated gray-scale intensity of the confocal fluorescence images. The stained tissue sections of the L1-PEG probes showed a significant increase (p<0.01) of neurofilament when compared to unmodified and PEG controls. Astrocyte reaction around L1-PEG was significantly lower than all the other groups (p<0.05). There was no difference in microglia responses in all the test conditions. Our result suggests that the immobilized L1-PEG improved survivability of neurons around the insertion site, and in some cases promoted neurite ingrowth toward the implant. Better neuronal density and reduced astrocyte reactivity around the neural probes may lead to more stable and higher quality neural signals in chronic recording.Other strategies such as controlled release of anti-inflammatory drugs and seeding of neural stem cells will be briefly introduced. The ultimate solution may be a combination of multiple approaches.
U2: Electrode Materials and Functionalization
Wednesday AM, April 11, 2007
Room 2010 (Moscone West)
11:30 AM - U2.1
Characterization of Reactively Sputtered Iridium Oxide Films for Neural Stimulation.
Sandeep Negi 1 , Rajmohan Bhandari 1 , Richard Normann 2 , Florian Solzbacher 1 2 3 Show Abstract
1 Department of Electrical and Computer Engineering, University of Utah, Salt Lake City, Utah, United States, 2 Department of BioEngineering, University of Utah, Salt Lake City, Utah, United States, 3 Department of Materials Science and Engineering, University of Utah, Salt Lake City, Utah, United States
Neural stimulation plays a key function for neuroprosthetic implant. The artificial stimulation of living tissue requires transfer of an external electrical signal from an implantable microelectrode to the neural cells. The limitation encountered by the microelectrodes implanted in cortical tissue is their robustness and charge injection capacity. Many noble metals such as platinum, gold, palladium, iridium and many non-noble metals such as tungsten, tantalum, titanium, have been investigated for such applications. Iridium oxide, termed as “valence change oxides”, is potentially the most promising one due to its higher charge injection capacity. Iridium oxide can be deposited by electrochemical activation of iridium metal (AIROF), by thermal decomposition of an iridium salt on a metal substrate (TIROF), by electrochemical deposition (EIROF) or by reactive sputtering from an iridium target (SIROF). Conventionally an electrochemical process is utilized to oxidize the top layer of iridium in the Utah Electrode Array (UEA) which is used for neuroprosthetic implant to form AIROF which is a time consuming process. In this paper, SIROFs are investigated for neural recording and stimulating electrodes. The iridium oxide thin films studied were deposited by D.C. reactive sputtering of pure iridium target in presence of oxygen and argon plasma. Test structures were fabricated using lift-off technique. These test structures are circular disc of diameter from 50 to 800 um. SIROF was deposited on these circular discs using lift-off technique. The SIROF was deposited on a stack of either Ir/Au/Ti or Ir/Pt/Ti or Ir/Ti electrode sites. Different metal sites were used to investigate affect of substrate material on charge injection capacity. An optimal combination of sputtering parameters such as sputtering pressure and power was established that yields low stress and uniform thickness films. A full factorial design of experiment was run to procure low stress and thickness uniformity in Ir, Au, Ti and Pt thin films. The minimum stress achieved for Ir, Au, Ti and Platinum was -57, -38 -13, -25 MPa respectively for 200 nm thickness of each film. The thickness, the deposition rate and the stress of the films was measured using Tencor profiler and stress was calculated from Stoney formula. SIROFs are denser and physically more robust than AIROF and are likely to exhibit a higher electronic conductivity. The surface morphology was examined by SEM and surface roughness was studied by AFM. The XRD technique was used to analyze phase formation and degree of crystallization of the films.Electrochemical characterization of SIROF was done by cyclic voltammetry (CV) and Impedance Spectroscopy (EIS). The effect of SIROF thickness (50 to 500 nm), electrode area (2000 to 500,000 um2) and, on different substrate (platinum, titanium and gold) on the electrochemical and charge-injection properties was investigated.
11:45 AM - U2.2
Electroactive Polymers for Neural Interfaces – New Materials
Maria Asplund 1 , Elin Thaning 1 , Hans von Holst 1 , Olle Inganäs 2 Show Abstract
1 School of Technology and Health, Royal Institute of Technology, Huddinge Sweden, 2 Applied Physics, Department of Physics, Chemistry and Biology, Linköping Sweden
One of the main inhibitors of neural controlled prosthesis and artificial sensing today is the lack of electrode materials suitable for prolonged implantation and stimulation. Conducting polymers have, during the last ten years, emerged as a field of great expansion. Rapid progress have lead to the development of stable organic electronic materials possible to use within a wide set of applications. This has opened up new possibilities for using these materials within medical devices, for example within the area of neural communication electrodes. One of the polymers often suggested is poly(3,4-ethylenedioxythiophene) (PEDOT) because of its excellent stability and conductivity properties. There are several ways to produce PEDOT from its monomer. The polymerization process can be tuned to regulate properties like porosity, wettability and chemical composition. The use of organic electronic materials for the improvement of neural electrode interfacing has already been studied by several groups and promising results have been shown concerning their behavior as electrodes. The in vitro biocompatibilty of PEDOT has been shown by several authors and cells have been successfully grown on top of PEDOT layers. When polymerizing PEDOT, the surfactant polystyrene sulphonate (PSS) is often used as anion for its beneficial effects on the polymerization process. The use of PSS is well established working with organic electronics, but it is also a choice not all unproblematic when it comes to creating a friendly environment for neural cells, especially because of its acidic properties. There is, however, no reason to suspect that other ions could not be chosen instead of PSS as counterion, and can be tailored to provide optimal conditions for implanted electrodesTo identify and evaluate new materials for neural electrodes, three charged biomolecules which are already present in abundance in living tissue, fibrinogen, hyaluronic acid (HA) and heparin, has been paired with PEDOT as candidates for this purpose. We have shown that it is possible to electropolymerize EDOT from aqueous solutions containing these biomolecules as anions. Cytotoxicity agar diffusion tests on fibroblast cells were performed on these composites and compared to the cellular response to PEDOT:PSS. Initial testing indicated a toxic response to PEDOT:PSS that was less severe than the response to the positive control. No toxic response was however seen for any of the PEDOT:biomolecular composites. The fact that none of the biomolecular compounds showed any toxic reaction is encouraging for future efforts on exploring these new materials.
12:00 PM - **U2.3
Biologically-Functionalized and Biologically-Derived Conducting Polymers for Interfacing Biomedical Devices with Living Tissue
David Martin 1 2 3 , Laura Povlich 2 , Mohammad Abidian 3 , Jeffrey Hendricks 3 , Sarah Spanninga 2 , Rickard Axelsson 4 , Jae Cho 1 , Jinsang Kim 1 2 3 Show Abstract
1 Materials Science and Engineering, The University of Michigan, Ann Arbor, Michigan, United States, 2 Macromolecular Science and Engineering, The University of Michigan, Ann Arbor, Michigan, United States, 3 Biomedical Engineering, The University of Michigan, Ann Arbor, Michigan, United States, 4 Applied Physics, University of Linkoping, Linkoping Sweden
We have been investigating the use of electrochemically-deposited conducting polymers such as poly(3,4-ethylenedioxythiophene) (PEDOT) for interfacing a variety of electronic biomedical devices such as cortical probes, cochlear implants, retinal prostheses, cardiac pacemakers, and deep-brain stimulators with living tissue. We have been studying the use of biologically active molecules such as anti-inflammatory agents and neurotrophic proteins that can be doped into the polymer matrix or encapsulated in nanofibers or nanoparticles. Quantitative measurements of the mass transport in and out of these films under an externally applied bias have been obtained using a quartz crystal microbalance. We have also demonstrated that the conducting polymers can be synthesized in the presence of living cells both in-vitro and in-vivo. We have confirmed that a synthetic variant of melanin can be electrochemically deposited on metal electrodes using 3,4-dihydroxy-L-phenylalanine (L-dopa), although its electrical activity is not as high as PEDOT. Recently we have developed a new class of functionalized EDOT monomers that now make it possible to create peptide-modified polymers and copolymers.
12:30 PM - **U2.4
Electrically-conductive Micropatterns that Promote Cell Adhesion and Neurite Extension.
G. Tayhas R. Palmore 1 , Sung-Yeol Kim 1 , Hyun-Kon Song 1 , Diane Hoffman-Kim 1 Show Abstract
1 , Brown University, Providence, Rhode Island, United States
We recently demonstrated a new strategy to modify polypyrrole with biological molecules that relies on a polyanionic dopant containing reactive functional groups. Specifically, chemical guidance cues for neurons were tethered to polypyrrole via covalent bond formation with reactive functional groups of the polyanionic dopant. This strategy overcomes several shortcomings found in other approaches used to modify conducting polymers by providing a doping procedure that insures efficient utilization of the biomolecule-of-interest without having to (i) synthesize new monomers with reactive functional groups or (ii) functionalize the conductive polymer post-electrodeposition. Consequently, an important feature of this new strategy is that it can be extended to other conducting polymers (i.e., poly(3,4-ethylenedioxythiophene) that are polycationic. In this presentation, we show how our strategy has been advanced beyond controlling the location of neuron adhesion and neurite outgrowth to modulating quantitatively the density of cells and their neural processes within micropatterned substrates. Details on the preparation of these substrates will be presented, including their spectroscopic, microscopic and immunochemical characterization. The density of hippocampal neurons and neurites will be shown to be proportional to the surface concentration of the biological cue. The number of cells adhered to areas outside of the micropattern will be shown to decrease as the density of the guidance cues within the micropattern increases until a physical limit of cell density is achieved.
U3: Electrode Materials and Encapsulation
Wednesday PM, April 11, 2007
Room 2010 (Moscone West)
2:30 PM - **U3.1
Neuronal Interfacing Using Vertically Aligned Carbon Nanofiber Arrays.
Nance Ericson 1 , Timothy McKnight 1 , Anatoli Melechko 2 , Charles Britton 1 , Simpson Michael 2 , Zhe Yu 3 , Barclay Morrison 3 Show Abstract
1 Engineering Science & Technology Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee, United States, 2 Material Science & Technology Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee, United States, 3 Biomedical Engineering Department, Columbia University, New York, New York, United States
Vertically aligned carbon nanofibers (VACNFs) hold significant promise as a new material interface for electroanalytical and electrophysiological coupling with neuronal tissue. VACNFs may be readily integrated into microfabricated devices to provide discrete, individually addressed sensing and/or stimulating electrodes at active probing dimensions approaching <100 nm2. In addition to providing predictable electrochemical response, the morphological characteristics and chemical composition of VACNFs contribute to a biocompatible interface. They may also be tailored using a variety of post synthesis surface modifications to promote improved biocompatibility, tissue integration, or to provide electroanalytical sensitivity to specific molecular species. Flexible films of VACNFs, which preserve the high aspect ratio morphology of these electrodes as well as their spatial distribution, can be mated with high density microelectronics, such as CMOS integrated circuits, to form complex monitoring and stimulating systems enabling both electroanalytical and electrophysiological assays. We report recent progress in the synthesis of VACNF arrays and their integration into systems for neuroscience applications including the development of flexible films of electroactive VACNF arrays and their incorporation with low-temperature CMOS substrates. Experimental results will be presented demonstrating both action potential monitoring and neurotransmitter detection using VACNF systems in neuronally-differentiated cell culture. In addition, VACNF performance for electrophysiological stimulation and recording from organotypic hippocampal slice cultures will be compared to data obtained using commercially available microelectrode arrays. Future systems based on VACNF arrays and integrated circuits may provide new strategies for highly miniaturized, programmable, and efficient multi-mode neuroprosthetic interfaces.
3:00 PM - U3.2
A Novel Carbon Nanotube Nano-probe
Su Huan-Chieh 1 , Yew Tri-Rung 1 Show Abstract
1 , National Tsing-Hua University, Hsinchu Taiwan
This paper reports a novel carbon-nanotube (CNT) nano-probe as an electrode for future invasive biological applications. The nano-probe consists of a CNT synthesized on a Si microtip by chemical vapor deposition. The CNT nano-probe morphology was identified by scanning electron microscopy (SEM). The physical and electrical properties of the CNT nano-probe in 3M KCl buffer solution were also investigated, including the CNT structural, composition, and electrical signal variation after long-term usage. To study the feasibility for future invasive biological application, the toxicity of the CNT nano-probe was studied. The CdSe/ZnS quantum dot labeling on CNT nano-probe, developed in this group, was also included for the real-time observation of CNT nano-probe under fluorescent optical microscope during biological application.
3:15 PM - U3.3
Vertically-Aligned Carbon Nanofiber Array as a 3D Multifunctional Material for Neural Electrical Interfaces
Jun Li 1 , Barbara Nguyen-Vu 1 , Edward de Asis 2 , Hua Chen 1 , Alan Cassell 1 , Russell Andrews 1 , Cary Yang 2 , M. Meyyappan 1 Show Abstract
1 , NASA Ames Research Center, Moffett Field, California, United States, 2 Center for Nanostructures, Santa Clara University, Santa Clara, California, United States
Developing biomaterials that closely mimic the natural tissue microenvironment with complex chemical and physical cues is essential for improving the function and reliability of implantable devices, especially neuroprosthetic devices that require direct neural-electrical interfaces. Here we demonstrate that free-standing vertically aligned carbon nanofiber (VACNF) arrays can be used as a multifunctional 3D brush-like material that interfaces with neurons. VACNFs are grown selectively on pre-fabricated microcircuits using plasma enhanced chemical vapor deposition (PECVD). Due to its 3D nanostructure and large effective surface area, VACNF arrays possess desirable electrical properties such as the large capacitance and low impedance, desired for optimizing stimulation efficacy. We have developed a method to further coat each CNF with a thin (on the order of tens of nanometers) conformal electrical conductive polymer (ECP) film in order to improve the chemical, electrical, and mechanical properties for neural electrical interfaces. This unique core-shell nanostructure helps to maintain the integrity of both the CNFs and polymer film in the biological environments. Biocompatibility before and after ECP coating has been studied using PC12 cells, a model neuronal cell type derived from the rat pheochromocytoma. Various ion dopants and surface functionalization have been investigated. The materials generally show good biocompatibility with an additional collagen coating. No acute toxicity from either the CNF or the ECP film has been found. PC12 cells cultured with nerve growth factor (NGF) on VACNF substrates can form extended neural network with distinct morphology on the VACNF arrays with and without ECP coating, reflecting the change in mechanical properties. The soft 3D VACNF ECP-coated architecture provides a new platform to fine-tune the topographical, mechanical, chemical, and electrical cues at sub-cellular level. Electrical stimulation and recording studies have been performed on rat hippocampal brain slices. Electrochemical detection of dopamine release upon electrical stimulation has been demonstrated with both carbon microelectrode and inlaid VACNF arrays using rat striatal slices. Further development of this technology by combining all these modalities into a multiplex close-loop system for deep brain stimulation, and neuroprostheses are in progress.
3:30 PM - **U3.4
Biopassivation Coatings by Initiated Chemical Vapor Deposition fromTrivinyltrimethylcyclotrisiloxane.
W. O’Shaughnessy 1 , David Edell 2 , Karen Gleason 1 Show Abstract
1 Chemical Engineering, MIT, Cambridge, Massachusetts, United States, 2 , InnerSea Technology, Bedford, Massachusetts, United States
One major barrier to clinical utilization of neuroprosthetics remains the encapsulation and biopassivation of the implants. Current technology shows significant degradation of implant functionality within the first year due to scar tissue buildup at the implant site. In addition, implant coating methodologies presently in use require coating thicknesses of 10-25 μm in order to provide the required electrical insulation. These coatings significantly increase the diameter of the neural probe shanks, often only 50-100 μm when uncoated, and consequently the amount of neural damage upon implantation. In this work, biopassivation coatings are synthesized by initiated chemical vapor deposition (iCVD) from the monomer trivinyltrimethylcyclotrisiloxane. The iCVD method creates the coating directly on the surface of the substrate and uses mild reaction conditions allow for full retention of all siloxane ring moieties within the resulting polymer. This polymer can only be synthesized by iCVD due the combination of its controlled structure and insolubility in all common solvents. The all-dry deposition process generates a highly cross-linked matrix material in which over 95% of the vinyl moieties present on the monomer units have been reacted out to form linear polymerized hydrocarbon chains. While each hydrocarbon backbone chain averages 8.9 monomer units in length, as evaluated by X-ray photoelectron spectroscopy analysis, each monomer unit is involved in three independent chains, resulting in polymer films of such high molecular weight that they are completely insoluble. Kinetic analysis of the deposition process indicates that the film formation rate is limited by the adsorption of reactive species to the deposition substrate, with an apparent activation energy of -23.2 kJ/mol with respect to the substrate temperature. These results are consistent with a surface growth mechanism, ideal for the coating of nonuniform or high aspect ratio substrates. The material possesses a resistivity of 4 X 1015 ohm-cm, allowing for insulating coatings of only 5 μm in thickness. In addition, the material is flexible and extremely adherent to silicon substrates, making it ideal for insulating both silicon neural probes and their lead wires. This polymer coating has been demonstrated to retain its electrical properties in a simulated biological environment for over two years, and has been shown compatible with neural cells through in vitro testing.
U4: Encapsulation Materials
Wednesday PM, April 11, 2007
Room 2010 (Moscone West)
4:30 PM - U4.1
A Biomimetic Approach to Adaptive Nanocomposites for Cortical Electrodes
Dustin Tyler 1 3 , Jeffrey Capadona 1 2 3 , Otto van den Berg 2 , Stuart Rowan 2 1 , Christoph Weder 2 1 Show Abstract
1 , L. Stokes CVAMC, Cleveland, Ohio, United States, 3 Biomedical Engineering, Case Western Reserve University, Cleveland , Ohio, United States, 2 Macromolecular Science and Engineering, Case Western Reserve University, Cleveland , Ohio, United States
Cortical electrodes are used to record the activity of individual neurons. These recorded signals can control robotic and prosthetic limbs, and suggests the potential for stroke victims and patients with severe spinal cord injury to regain control of non-responsive limbs. One limiting factor of current technology is the decrease in the quality of the recorded signals over time. A possible cause for this effect is the mechanical mismatch of the electrodes with the cortical tissue. While a high modulus electrode is advantageous for insertion, a rigid electrode causes micro-motion, micro-damage, and chronic astrocyic response once implanted into the brain tissue. For successful long-term use of cortical electrodes the chronic mechanical mismatch must be addressed, while retaining required properties for proper insertion.We here report on the development of adaptive, mechanically-dynamic polymer nanocomposites, which may eventually serve as ‘smart’ substrates for cortical electrodes. The nanocomposites designed in this study were modeled after the natural three-phase defense mechanism for the mechanical reinforcement of the skin of echinoderms. The nanocomposites are composed of cellulose whiskers obtained from tunicates (TW, approximate dimensions 1 mm x 10 nm) as a high-aspect ratio, high-strength reinforcing agent within an elastomeric polymer matrix of an ethylene oxide–epichlorohydrin (EO–EPI) copolymer. Investigation towards the mechanism for mechanical reinforcement was first conducted with aqueous suspensions of TW. Composites were then made by either solution casting polymer-TW dispersions, or by diffusing polymers into a cellulose sol-gel with a pre-assembled cellulose network; followed by solvent evaporation and compression molding. We demonstrated that these nanocomposites display a TW density-dependent increase in shear modulus from ~ 3 MPa to nearly 1 GPa with up to 35% TW (w/w). Through modest aqueous swelling of the nanocomposite, the TW reinforcing network can be mechanically decoupled, reducing the modulus to a fraction of its initial value. The mechanism for dynamic modulus change is the mediation of the whisker-whisker interactions, not the swelling of the polymer system, contrasting the “hydrogel approach”. These interactions can be varied between a rigid and a compliant state through the control of water uptake and the system can be cycled without appreciable hysteresis. The extension of the general design principles established thus far may result in an entirely new class of bio-inspired adaptive nanocomposites.This work was funded by the Advanced Platform Technology (APT) Center of the US Department of Veterans Affairs, and NIH grant number R21NS053798-01.
4:45 PM - U4.2
Advances in Encapsulating Elastically Stretchable Microelectrode Arrays.
Oliver Graudejus 1 , Candice Tsay 1 , Zhe Yu 2 , Barclay Morrison 2 , Stephanie Lacour 3 , Sigurd Wagner 1 Show Abstract
1 Electrical Engineering, Princeton University, Princeton, New Jersey, United States, 2 Department of Biomedical Engineering, Columbia University, New York, New York, United States, 3 Department of Materials Science, University of Cambridge, Cambridge United Kingdom
Stretchable thin-film metallization is showing great potential for elastically stretchable micro-electrode arrays for interfacing with neural tissue and for the study of traumatic brain injury. In addition, stretchable metallization may enable elastically stretchable metal interconnects for implants such as electronic skin. The basic structure of elastic thin-film metallization is (i) an elastomeric substrate, (ii) a thin-film metallization patterned as needed by the application, (iii) an overlayer of stretchable encapsulation and electrical insulation, and (iv) vias made in the encapsulation for contacts and electrical interconnects. Encapsulating the electrodes and opening contact areas are critical steps in building the devices. We report the successful use of a photopatternable silicone for electrode encapsulation. Significant process optimization was required to accommodate the flexible and stretchable nature of the poly dimethyl siloxane (PDMS) substrate. The optimization included exposure, bake, and development. A stretchable microelectrode array fabricated in this way has been used to detect spontaneous electrical signals and evoked potentials from hippocampal cultures. We will report this work and summarize the status of elastically stretchable microelectrode technology.This research is supported by the NIH (NINDS R21 052794) and the New Jersey Commission for Science and Technology.
5:00 PM - U4.3
PECVD Silicon Carbide as a Thin Film Packaging Material for Microfabricated Neural Electrodes
Allison Hess 1 , Jiangang Du 1 , Christian Zorman 1 Show Abstract
1 Electrical Engineering and Computer Science, Case Western Reserve University, Cleveland, Ohio, United States
SiC is an attractive material for microsystems due to its outstanding mechanical, chemical and electrical properties. The preponderance of work in the development of SiC for such applications has focused on SiC thin films deposited by APCVD and LPCVD at high substrate temperatures (800C to 1350C). Recently, however, interest in using SiC on temperature-sensitive substrates has motivated the development of PECVD-based processes for hydrogen-terminated, amorphous SiC (a-SiC:H). The PECVD approach has permitted the lowering of substrate temperatures to below 400C, thus enabling the incorporation of buried metal electrode structures, the use of non-conventional substrates (i.e., polyimide) and furthering the integration of SiC with Si microelectronics, all potential attributes of next generation neural electrodes.This paper reports our effort to develop a-SiC:H films suitable for thin film packaging of moisture-sensitive microsystems. The SiC films are deposited by PECVD using trimethylsilane (3MS) as the precursor. Trimethylsilane is an attractive precursor since it is currently being used in advanced Si microelectronics to produce low-k dielectric, diffusion barrier SiC thin films. In our work, the SiC films were deposited in a GSI UltradepTM PECVD system using Dow Corning Z3MS metalorganic precursor diluted in He. Films were deposited at a substrate temperature of 350C. The films deposited on Si substrates exhibited compressive residual stresses as determined using the wafer curvature measurement technique. These films would, upon a short (< 10 min) anneal at 450C, exhibit modest tensile stresses (<100MPa), which in some cases could be reduced to nearly zero. The chemical composition of the films was examined by using X-ray Energy Dispersive Spectrum (EDS), Rutherford backscattering spectroscopy (RBS) and elastic recoil detection (ERD). Films with a Si-to-C ratio near 1:1 were achieved by carefully choosing the trimethylsilane/He ratio and deposition pressure. Chemical resistance to acids and bases commonly used in Si micromachining as well as the mechanical stability of the films exhibiting moderate tensile stresses were evaluated using bulk micromachined membranes. Free-standing, 2 μm-thick, membranes with a nominal surface area of 1 x 1 mm2 and fabricated by Si anisotropic etching in a KOH/H2O solution at 55C could be pressurized to over 100 PSI and over 20 microns of deflection without breakage, delamination or leakage. To determine the hermetic properties of the films, interdigitated electrode (IDE) test structures consisting of 200, 100 micron-wide fingers each spaced 50 microns apart were designed, fabricated and encased in SiC. The extended paper will detail recipe development, material characterization, IDE testing, and the characterization of SiC-coated polymer substrates including those fashioned into flexible neural electrodes.
5:15 PM - U4.4
Assessment of Biocompatibility of Photosensitive Polyimide for Implantable Medical Device Use
Yun Sun 1 , Roger Brooks 2 , Stephanie Lacour 1 , Ruth Cameron 1 Show Abstract
1 Materials Science and Metallurgy, University of Cambridge, Cambridge United Kingdom, 2 Orthopaedic Research Unit, University of Cambridge, Cambridge United Kingdom
Polyimides (PIs) that have been interfaced with nerves as neural conduits have showed excellent properties as implant material. Recently, photosensitive polyimides (PSPIs) have attracted great attention because they are easily processed owing to their direct patternability, in addition to having excellent thermal stability, good mechanical properties and high chemical resistance. To date little biocompatibility data for PSPIs has been reported. Five candidate materials were tested: Dupont Kapton HN, Kapton E, HD Microsystem PI2611, PI2525 and Fujifilm Durimide 7020 (PSPI). PI2611, PI2525 and PSPI were fabricated using typical spin-coating techniques and sterilized by autoclave. They were evaluated using ISO 10993 standard on biocompatibility testing. In addition, cell growth on these materials were evaluated using a scanning electron microscope (SEM). The mechanical properties during cell culture as a function of time and environment were investigated by nanoindentation.Results on cytotoxicity measured by MTS show that PSPI is non cytotoxic compared to negative control of polyethylene and PIs, and cells grow even better on PSPI substrate than some of PIs. We conclude that PSPI performs better than PI2611, suggesting that PSPIs may have potential use for biological microsystems and neuroprosthetic applications.
5:30 PM - *U4.5
Parylene-enabled Flexible Technologies for Neural Prostheses
Yu-Chong Tai 1 , Damien Rodger 1 , Wen Li 1 Show Abstract
1 EE and BE, Caltech, Pasadea, California, United States
We are developing a new series of parylene-enabled flexible technologies for retinal, cortical, and spinal cord prosthesis applications, where parylene is used as the main structural material rather than simply as a final coating. These technologies include high-density stimulating and recording electrode arrays, flexible cables for routing electrodes to their point of application, scalable packaging technologies for interconnection of large numbers of electrodes with driving circuitry, and flexible radiofrequency coils for inductive power and data coupling. The advantages of the use of parylene C stem from its chemical inertness, its biocompatibility, its low moisture permeability, its low dielectric constant, its high breakdown voltage, its transparency, its ability to form pinhole-free conformal coatings, and its ideal Young’s modulus (~4 GPa) and flexibility for biomedical implant purposes. Much consideration has been placed on the different requirements of these unique environments of implantation and we have developed an ability to tailor devices so as to optimize the biotic/abiotic interface in each application. As a start, high-density flexible electrode arrays, typically comprising exposed platinum electrodes, have been developed for the retinal and spinal cord prostheses, whereas for cortical applications we have developed more rigid penetrating electrodes with flexible parylene-based cabling. Additionally, a novel packaging paradigm whereby electrodes are directly integrated with prefabricated driver circuitry and discrete components in a fully scalable, standard photolithography-limited manner, has been developed. This technology is critical, for without it electrode densities would be severely limited. Finally, flexible parylene-based radiofrequency coils that are compatible with the microfabrication processes of these other technologies are under investigation to enable wireless telecommunication with the implanted devices. Biological, electrochemical, and accelerated-lifetime saline soak testing has been performed on these devices with excellent results, and, furthermore, has demonstrated the efficacy of a novel high-temperature annealing process to improve parylene-to-parylene adhesion that has been shown to convert devices that would typically fail into highly reliable ones.
U5: Poster Session
Wednesday PM, April 11, 2007
Salon Level (Marriott)
9:00 PM - U5.1
Functionalized Poly(3,4-ethylenedioxythiophene) for Bio-electrode Coatings.
Laura Povlich 1 , Jae Cheol Cho 2 , Jinsang Kim 1 2 3 , David Martin 1 2 3 Show Abstract
1 Macromolecular Science and Engineering, University of Michigan, Ann Arbor, Michigan, United States, 2 Materials Science and Engineering, University of Michigan, Ann Arbor, Michigan, United States, 3 Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, United States
By synthesizing carboxylic acid-functionalized 3,4-ethylenedioxythiophene (EDOT) we have demonstrated the potential to create peptide-functionalized conjugated polymer poly(3,4-ethylenedioxythiophene) (PEDOT). The synthesis of the carboxylic acid derivative consisted of seven steps and resulted in a 12% overall yield of the product. The purity of the product was confirmed by NMR spectroscopy and electron impact ionization mass spectroscopy. Electrochemical co-polymerization of the carboxylic acid functionalized EDOT with non-functionalized EDOT has shown that it may be possible to produce bioactive, electrically conductive polymer films. To develop this idea further, the carboxylic acid functional group has been coupled to a peptide containing the amino acid sequence RGD using DCC/NHS chemistry. This peptide-functionalized EDOT could be used to create coatings on bio-electrodes for applications in which improved non-specific cell adherence is desired. To demonstrate the potential usefulness of the coatings, electrical characterization and in vitro cell experiments will be performed after the peptide-functionalized EDOT has been polymerized. In order to target neural cells, the IKVAV peptide will also be conjugated to the EDOT monomer. A coating containing IKVAV should selectively improve the adherence of neurons and, therefore, is potentially useful in neural probe applications. Based on the experiments performed thus far, it should be possible to make PEDOT coatings with a wide variety of biological functions by coupling peptides or biomolecules to carboxylic acid-functionalized EDOT.
9:00 PM - U5.10
Induction of Presynaptic Complexes by Microscale Patterns of Neuroligin
Peng Shi 1 , Lance Kam 1 Show Abstract
1 Biomedical Engineering, Columbia University, New York, New York, United States
Neurons are connected through synapses to form functional networks. Towards the development of biomimetic interfaces, we report the use of markers based on Neuroligin-1 (NL1), a post-synaptic protein which is involved in early synaptogenesis, to promote interaction between neurons and engineered substrates. Previous studies have demonstrated the ability of Neuroligin-1, either expressed in non-neuronal cells or tethered to lipid bilayers, to promote presynaptic differentiation in contacting axons. In the current study, we explore the application of a multi-component patterning technique to present microscale patterns of NL1 directly to neurons, in order to control where synapses form in vitro.Three variants of NL1 were investigated, each consisting of the extracellular domain of NL1 appended with a different C-terminal moiety: GPI-modified NL1 (NLG), Poly-His-tagged NL1 (NL6H), and cMyc-tagged NL1 (NLmyc). Glass substrates were micropatterned with arrays of 25 to 50 micrometer-wide islands of polylysine (PLL) using a directed plasma ablation technique. Patterns of NLG, NL6H or anti-cMyc antibodies were then directly microcontact printed onto the substrates, defining a network of 5 micrometer-wide lines of each protein connecting the PLL islands. The anti-cMyc patterned substrates were subsequently used to capture NLmyc by soaking in NLmyc solution for 30 minutes.Embryonic rat hippocampal neurons selectively attached to the islands of PLL on all surfaces. On the NLG surfaces, but not those modified with NL6H or NLmyc, neurons extended processes off the polylysine islands, which followed the NLG lines. This growth pattern was maintained throughout the culture period up to 10 days, the extent of these experiments. At select time points, cells were stained for synapsin I and PSD-95. Processes following the NLG lines exhibited “spine-like” morphologies, along with a density of synapsin puncta that was dramatically higher than those of neurons on polylysine control surfaces, suggesting activity associated with formation of synaptic complexes. Moreover, there were no PSD-95 puncta colocalized with the synapsin puncta on NLG lines, confirming that these synapsin clusters were actually induced by substrate-immobilized NLG, and not by interneuron contacts.In summary, this report demonstrates the successful patterning of neuroligin in a manner that maintains biological activity. Interestingly, the presence of a hydrophobic GPI moiety, but not the more traditional tags, promoted NL’s biological activity. In previous efforts, we created well-defined neuron networks by patterning NCAM-L1, N-cadherin, and PLL onto a single surface, providing control over neuron location and polarity. Future work will focus on incorporating NLG into these substrates in order to capture more complex aspects of neuron function, such as synapse modulation along guided axons or dendrites.
9:00 PM - U5.2
PEDOT-coated, BDNF-secreting Cochlear Implants for Improved Spiral Ganglion Stimulation.
Jeffrey Hendricks 1 , Jennifer Chikar 2 , Sarah Richardson-Burns 3 , Yehoash Raphael 4 , Bryan Pfingst 5 , David Martin 1 3 6 Show Abstract
1 Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, United States, 2 Neuroscience, University of Michigan, Ann Arbor, Michigan, United States, 3 Materials Science & Engineering, University of Michigan, Ann Arbor, Michigan, United States, 4 Otolaryngology, University of Michigan, Ann Arbor, Michigan, United States, 5 Otorhinolaryngology, University of Michigan, Ann Arbor, Michigan, United States, 6 Macromolecular Science & Engineering, University of Michigan, Ann Arbor, Michigan, United States
9:00 PM - U5.3
A PDMS-based Elastic Multi-Electrode Array for Spinal Cord Surface Stimulation and Its Electrode Modification to Enhance Performance.
Liang Guo 1 , Kathleen Williams 1 , Rick Giuly 1 , Stephen DeWeerth 1 Show Abstract
1 Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia, United States
For our ongoing research involving electrical stimulation of rat spinal cord axonal tracts, it is desirable to use a microelectrode array which highly conforms to the surface of the spinal cord. The elastic polymer, polymethylsiloxane (PDMS, known commercially as Sylgard), possesses properties which make it suitable to meet this demand by serving as the electrode substrate. In addition to elasticity, cured PDMS is also gas permeable and biocompatible, and the surface multi-electrode array (MEA) fabricated on such a substrate would cause minimal damage to the cord in that the electrodes do not penetrate spinal tissue. Using standard microfabrication technology, we have previously implemented such an elastic MEA on the PDMS substrate. Our fabrication process involves patterning gold traces onto a PDMS substrate cured on a glass slide, covering the traces with another thinner PDMS layer for insulation, and then exposing the sites of electrodes and contact pads. The advantages of fabrication of this type of MEA include achievement of high electrode spatial density, high geometrical precision, and ability to be fabricated easily in batches with little geometrical and electrical difference between each other. These advantages in turn enable high spatiotemporal stimulation selectivity and parallel stimulation capabilities, as well as reliable data reproducibility.To enhance the performance of this PDMS-based Multi-Electrode array, we have recently implemented volcano-like conical PDMS electrode shells around each electrode on the MEA with the help of microfabrication techniques. We then electroplate platinum-black in the central vent of the conical shell, at the bottom of which the electrode sits. The volcano-like conical PDMS shell potentially provides improved contact between the electroplated electrode and the spinal cord surface as well as a more isolated micro-environment for current exchange between the electrode and spinal cord. This technique also serves to protect the electroplated platinum-black from being rubbed off. The electroplated platinum-black in the central vent of the conical PDMS shell also lowers the electrode impedance, thus providing better electrical performance.We present in vitro performance evaluation of this new MEA design architecture using the isolated young rat spinal cord preparation. Both the physical and electrical performances are excellent. Therefore, our MEA provides a powerful tool for researchers to study spinal cord systems via multi-site surface stimulation.
9:00 PM - U5.4
Thin TiO2 Coatings for Neural Cell Growth.
Nieves Casan-Pastor 1 , Jorge Eduardo Collazos-Castro 2 , Monica Carballo 2 , Monica Lira-Cantu 1 , Angel Perez 1 , Josep Bassas 3 Show Abstract
1 Solid State Chemistry and Cristalography, Institut de Ciencia de Materials de Barcelona, CSIC, Bellaterra, Barcelona, Spain, 2 , Hospital Nacional de Paraplejicos, Toledo, Castilla La Mancha, Spain, 3 Serveis Cientifico tecnics, University of Barcelona, Barcelona, Barcelona, Spain
9:00 PM - U5.5
Rutile Substrata for Neural Cell Growth
Jorge Collazos-Castro 1 , Berta Moreno-Burriel 1 , Monica Carballo-Vila 1 , Eva Chinarro 2 , Nieves Casañ-Pastor 2 , Jose Jurado-Egea 2 Show Abstract
1 Neural Repair Laboratory, Hospital Nacional de Paraplejicos, Toledo Spain, 2 Ceramics and Glasses Institute, CSIC, Madrid Spain
Titanium oxide shows anti-inflammatory activity and highly tunable electrochemical properties that make it an attractive material for the fabrication of implantable devices. Here we report the preparation of TiO2 (rutile) surfaces that permit excellent adherence and growth of mammalian neurons in vitro. Rutile discs were obtained by sinterization of TiO2 powders of commercial origin or precipitated from Ti(IV)-isopropoxide, and were used for culturing rat cerebral cortex neurons. Sinterization of commercial TiO2 powders at 1300 οC – 1600 οC produced rutile surfaces on which neurons adhered in variable amount. However, the surfaces had abnormal grain growth, probably due to impurities of the powders, and neurons cultured on them showed less neurites than on control materials. In contrast, rutile sintered from chemically precipitated powders showed homogenous grain growth and no contaminating elements. By adjusting the time of sinterization, it was possible to produce surfaces with micro/nano-topography that performed very well as neuron substrate. These findings support a potential use of titanium oxide in neuroprostheses and other devices demanding materials with enhanced properties in terms of biocompatibility and promotion of neural cell growth.
9:00 PM - U5.6
A Combinatorial Approach Towards Functionalizing Copolymers with Effector Molecules that Attenuate Cyto-inflammatory Responses at the Biotic-abiotic Interface.
Erik Pierstorff 1 , Dean Ho 1 Show Abstract
1 Departments of Biomedical and Mechanical Engineering, Northwestern University, Evanston, Illinois, United States
9:00 PM - U5.7
Electrostatic Potential Mapping and Spatial Resolution at the Visual Prosthesis/Vitreous Humor Interface.
Charlene Sanders 1 , James Weiland 2 , Mark Humayun 2 , Elias Greenbaum 1 Show Abstract
1 , Oak Ridge National Laboratory, Oak Ridge, Tennessee, United States, 2 , Doheny Eye Institute, Los Angeles, California, United States
Visual prosthesis microelectrode arrays, implanted on the retinas of photoreceptor impaired patients, transfer patterned electrical stimuli across the electrode/vitreous humor interface to the visual neural pathway. To be effective, electrodes must transfer enough charge through the vitreous to exceed neuronal depolarization threshold potentials. However, physiological considerations of safe stimulation restrict the maximum charge density that may be applied to individual electrodes in the array. Decreasing electrode areas and increasing electrode numbers in the newer designs of multipixel prosthesis arrays necessitate investigation of the distribution of interfacial potentials over the active surface of individual and clustered, energized electrodes.Electric field potentials were mapped above single Pt electrodes and multiple (16X Pt and 60X gold) electrode arrays. Test electrodes were immersed in physiological electrolyte medium. The three-electrode test circuit configuration consisted of a stimulating electrode, a 10 micron recording electrode, and a counter electrode, energized by a stimulus from a pulse generator. The recording electrode was mounted on a xyz translation stage and moved incrementally vertically and horizontally over the stimulating electrode. Pulses were monophasic or symmetrical biphasic, applied at a maximum charge density of 1 mC/cm2. Voltage between the stimulating and counter electrode (compliance V) and between the recording electrode and counter electrode was monitored on a digital oscilloscope. Three-dimensional potential maps were generated over the single stimulating electrode as the recording electrode was moved in xyz coordinates over its surface. Voltages in the horizontal plane decreased on either side of the center of the stimulation electrode. Voltages decreased as the vertical distance between the stimulation and recording electrode increased. Potential profiles over multielectrode arrays were obtained by fixing the position of the recording electrode over an electrode in the center of the array while individually stimulating other electrodes in its vicinity. Potentials from active nearest neighbor electrodes propagated a potential over the center electrode half as high as the voltage from the active electrode. Activation of the next concentric layer of closest electrodes dropped the potential over the center electrode to a third. Cross-talk was higher when track lines of distant activated disks ran next to the center recording electrode. Potential mapping above single prosthesis electrodes is useful for quantifying the charge from a point source and its propagation through a conductive medium. In multielectrode arrays, the spatial arrangement of electrode disks, their size and pitch, and the metal tracks running between the disks determine the potential profile over the surface of individual electrodes.Supported by DOE Office of Biological and Environmental Research.
9:00 PM - U5.8
Characterization of Degradation Mechanisms in Neural Recording Electrodes.
Jennifer Anton 1 , Stephanie Hooker 1 Show Abstract
1 Materials Reliability Division, National Institute of Standards and Technology, Boulder, Colorado, United States
Understanding the nature of specific neural activity is essential to the progression of research in the field of brain disorders and diseases, as well as neuroprosthetics. Microelectrodes are the primary measurement devices used to transduce neural activity into electrical signals to help neuroscientists study dynamic brain function. Advances in signal processing and packaging currently allow neural recording with chronically implanted electrodes from freely behaving animals for periods as long as a year. Stability of the electrode impedance is required for optimum signal recording over the length of the recording interval. While electrode–tissue interaction plays a major role in the recorded signal, it is also useful to understand how the electrode design and component materials affect the signal over the course of time. This study investigates the reliability of commercially available electrodes in a controlled in vitro environment where electrode performance was monitored over time periods up to three weeks and failure was induced by both chemical and mechanical means. Electrode impedance shifts due to degradation of the insulating coating were monitored using electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). Optical microscope and SEM analysis provided visual information on the physical state of the electrodes before and after electrochemical testing in regards to coating adhesion and continuity. Combining this set of failure analysis tools has facilitated isolation of the sources of degradation in commercially available electrodes.
9:00 PM - U5.9
Mechanisms of Mass Transport During Actuation of Poly(3, 4-ethylene dioxythiophene) (PEDOT) using a Quartz Crystal Microbalance for Neural Drug Delivery Devices
Rickard Axelsson 1 , Mohammad Abidian 2 , Peter Keshtkar 3 , David Martin 2 4 5 Show Abstract
1 Department for Applied Physics, University of Linköping, Linköping Sweden, 2 Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, United States, 3 , Green Hills School, Ann Arbor, Michigan, United States, 4 Materials Science & Engineering, University of Michigan, Ann Arbor, Michigan, United States, 5 Macromolecular Sciences & Engineering, University of Michigan, Ann Arbor, Michigan, United States
This investigation was done in order to get more fundamental understanding of the mechanisms of mass transport that lies behind actuation of a conducting polymer. Our group has shown that nanotubes of the conducting polymer poly(3, 4-ethylene dioxythiophene) (PEDOT) containing drugs such as NGF or dexamethasone can be used for drug delivery to promote neuronal extension and decrease the impedance of implanted neural electrodes. Application of a voltage on the tubes makes them expand and contract depending on the counter ion incorporated during polymerization and the sign of the applied voltage.In this study the mechanism was investigated for PEDOT films as well for tubes with PSS and LiClO4 as counter ions using a quartz crystal microbalance. This technique offers an accurate way of measure changes in mass (e.g. in polymer films) down to the nano gram range.Measurements of the mass of the film as a function of external bias show that ions are moving in and out of the polymer film during voltage cycling. The behavior of the film is strongly dependent of the counter ion used and the frequency of cycling. The results also show that PSS and LiClO4 give PEDOT films with different mechanical and mass changing properties, a PEDOT-PSS film appears to be more flexible and show expansion for negative voltage while a PEDOT-LiClO4 film is contracting for negative voltage and seem to be more rigid.Ongoing research will also investigate the possibility of using the quartz crystal microbalance to measure the mass of biologically-active drugs delivered from PEDOT nanotubes.
Daryl R. Kipke University of Michigan
Stephanie P. Lacour University of Cambridge
Barclay Morrison Columbia University
Dustin Tyler Case Western Reserve University
U6: Compliant Neural Devices: New Process Fabrication
Thursday AM, April 12, 2007
Room 2010 (Moscone West)
9:00 AM - **U6.1
Neuro-technical Interfaces based on Biocompatible Polymeric Substrates.
Thomas Stieglitz 1 Show Abstract
1 Department of Microsystems Engineering, University of Freiburg - IMTEK, Freiburg Germany
Multielectrode arrays create the interfaces between nerves and technical systems in neuroprosthetic devices. MEMS (microelectromechanical systems) technologies offers opportunities to develop high density arrays with large numbers of electrodes and smallest dimensions of electrode site area and pitch. Polymers are promising candidates for flexible substrates of these electrode arrays to meet the requirements of structural biocompatibility. In addition, these substrates must be biostable and should be non-toxic. From an engineering point of view, material processing should be feasible with standard MEMS process technology. Fail-safe integration of electronic circuitry, encapsulation of the systems with substrate-integrated electrodes and connection to cables and connectors is of great importance for reliable (micro-) implants.A comprehensive overview of the application of polymers like polyimide and parylene C as substrate, insulation and encapsulation material for multielectrode arrays will be given. Assembling techniques for system integration and encapsulation concepts will be discussed with a special attention on the adhesion properties between substrate, interconnects and insulation and possible failure mechanisms. Application scenarios include peripheral nerve interfaces like cuff and sieve electrodes as well as multielectrode arrays for retinal vision prostheses and shaft and grid arrays for the central nervous system interfaces.
9:30 AM - U6.2
Transformation of Silicone Rubber under YAG Laser Irradiation : First Step towards a New Miniaturized Nerve Electrode Fabrication Process.
Catherine Dupas-Bruzek 1 , Odile Robbe 2 , Ahmed Addad 3 , Sylvia Turrell 2 , Dominique Derozier 1 Show Abstract
1 Centre d'Etudes et de Recherches Lasers et Applications, Universite des Sciences et Technologies de Lille, Villeneuve d'Ascq France, 2 Laboratoire de Spectroscopie Infrarouge et Raman, Universite des Sciences et technologies de Lille, Villeneuve d'Ascq France, 3 Laboratoire de Structures et Proprietes de l'Etat solide, Universite des Sciences et technologies de Lille, Villeneuve d'Ascq France
One important challenge in nerve electrode fabrication is miniaturization so as to increase the number of tracks and contacts (thus increasing nerve selectivity) via materials which have to be biocompatible and able to adhere to each other.Lasers are convenient tools for reaching the goal of electrode miniaturization because 1) small beam sizes can be used thus allowing etching of small track widths, 2) photons do not contaminate the polymer surface.Silicone rubber, also called poly-dimethyl siloxane (PDMS), with a (-Si(CH3)2-O-) repeat unit has been chosen as the major material of the electrode because it is biocompatible and it has large elastic properties convenient for rolling the polymer around nerves and which prevent damaging of the surrounding living tissues. Platinum, one of the few biocompatible metals, has been chosen as the metal for the tracks and contacts.Our electrode fabrication process is decomposed into two steps: 1) laser irradiation of PDMS creating engraved activated tracks and contacts and 2) selective Pt metallization of these tracks and contacts when PDMS is immersed in an autocatalytic Pt bath.In order to have a better control of the effect of UV laser irradiation on PDMS, we carried out a series of different irradiation regimes on a medical-grade PDMS using a frequency-quadrupled YAG laser source at 266 nm. Samples have been irradiated at a repetition rate of 10 Hz, with the number of pulses “N” varying from 10 to 100 and at different fluences “Ei” (energy per pulse and per surface unit) from 1 to 3 J/cm2. Samples are irradiated either statically (sample speed under beam = 0) allowing the formation of contacts or dynamically (sample moves under the beam) allowing the formation of tracks. Irradiation products were analyzed using optical microscopy, micro-Raman spectroscopy and the SEM and TEM techniques, both equipped with an EDX microanalysis-system. Optical micrographs show that a minimum fluence “Ei” of 2 J/cm2 and a minimum number of pulses “N” of 20 are required to obtain homogeneous engraving.SEM pictures show a remarkably different morphological structure between virgin non-irradiated PDMS and irradiated ones. Samples are completely transformed except for those irradiated statically at low fluences and/or low pulse numbers, which are partially transformed with untransformed parts being covered by ejectas.Micro-Raman spectroscopy and TEM both show that compared to a virgin PDMS, an irradiated PDMS is constituted of an amorphous matrix depleted with Si in which are embedded mostly Si nano-crystals (10-100 nm) while ejectas are constituted of an amorphous matrix enriched with O in which are embedded mostly Si-C nano-crystals (10-20 nm).We conclude that these different morphologies, roughness, chemical composition and structure which depend on the irradiation conditions will strongly influence the nucleation and growth rates of Pt which govern the adhesion and the thickness of the Pt layer on the electrode.
9:45 AM - U6.3
Morphology and Stretchability of Thin Film Metal Conductors on Elastomeric Substrates.
Candice Tsay 1 , Oliver Graudejus 1 , Sigurd Wagner 1 , Stephanie Lacour 2 , Barclay Morrison 3 Show Abstract
1 Electrical Engineering, Princeton University, Princeton, New Jersey, United States, 2 Materials Science, University of Cambridge, Cambridge United Kingdom, 3 Biomedical Engineering, Columbia University, New York, New York, United States
10:00 AM - U6.4
Metallized Silicone Rubber (PDMS) for Implantable Electrodes.
Stephane Befahy 1 2 , Sami Yunus 1 , Patrick Bertrand 1 , Michel Troosters 2 Show Abstract
1 Physical Chemistry and Physics of Materials (PCPM), Université catholique de Louvain, Louvain-la-Neuve Belgium, 2 , Neurotech SA, Louvain-la-Neuve Belgium
10:15 AM - U6.5
Design and Fabrication of Compliant Neural Implants for Nerve Repair.
Raghied Atta 1 , Edward Tarte 1 , James Fitzgerald 2 , Stephanie Lacour 3 , Mark Blamire 3 , James Fawcett 2 Show Abstract
1 E E &C Engineeirng, The university of Birmingham, Birmingham United Kingdom, 2 Centre for Brain Repair, University of Cambridge, Cambridge United Kingdom, 3 Materials Science, University of Cambridge, Cambridge United Kingdom
10:30 AM - **U6.6
SiC/Parylene C based Encapsulation for Next Generation Chronic Wireless Neural Interfaces.
Florian Solzbacher 1 2 3 , JuiMei Hsu 2 , Loren Reith 1 , Michael Toepper 1 4 , Richard Normann 3 Show Abstract
1 Electrical and Computer Engineering , University of Utah, Salt Lake City , Utah, United States, 2 Materials Science and Engineering, University of Utah , Salt Lake City , Utah, United States, 3 Bioengineering, University of Utah , Salt Lake City , Utah, United States, 4 , Fraunhofer Institute for Reliability and Microintegration IZM, Berlin Germany
Fully integrated wireless neural interfaces potentially allow better performance, lower risk of infection and superior cosmetic appearance compared to conventional wired neural interfaces, rendering them ideal for chronic implantation. Elimination of skin penetrating wires and connector systems requires the integration of signal processing and power supply into the device. We have developed a platform technology that turns the Utah Electrode Array (UEA) into a wireless neural interface. New system integration and packaging concepts were developed that allow the integration of the aforementioned modules on a Silicon platform. To satisfy the long term stability and biocompatibility requirements for the implant, a conformal multi-layer thin film encapsulation consisting of a-SiC:H and Parylene C was developed and tested in-vitro for bare chip-on-chip packaged systems and lid-based systems. Single layer wired UEAs with the new encapsulation layers were also tested in-vivo. The bare-chip systems attach the signal processor, power module and passive SMD components using Au based flip-chip and SMD soldering techniques to the backside of a modified UEA. For the lid-based systems, the signal processor is attached to the UEA, but the coil and passives are attached to or integrated into a Silicon or a ceramic (Low Temperature Co-fired Ceramics) lid, that is soldered onto the UEA. This approach facilitates higher production yield, lower assembly complexity and lower failure rate. The encapsulation materials need to provide hermetic long term protection of the active components and non-changing dielectric insulation of the electrode shafts. Hydrogenated amorphous silicon carbide (a-SiCx:H) films deposited by plasma enhanced chemical vapor deposition (PECVD) using SiH4, CH4, and H2 precursors were investigated as the inner encapsulation layer for such device and compared to Parylene C thin films. Double layer films were deposited with SiC as innermost barrier layer and Parylene C as outer layer. The Si-C bond density was measured by FT-IR and suggests that deposition conditions with increased hydrogen dilution, increased temperature, and low silane flow typically result in increase of Si-C bond density. From variable angle spectroscopic ellipsometry measurements, no dissolution of a-SiCx:H was observed during soaking tests in 90 degree Celsius phosphate buffered saline (PBS); instead, surface oxidation was proposed to explain the small increase in thickness and the change in refractive index during the soaking test. Conformal coating of the a-SiCx:H in Utah electrode array was observed by SEM. Adhesion strength between SiC and Si, Parylene and Si and Parylene and SiC was investigated and optimized. Electrical properties and film stress were studied by impedance spectroscopy and profilometry, respectively, to investigate the performance of a-SiCx:H as an encapsulation layer, and the results showed long term stability of the material for several months.
U7: Guiding Neurons
Thursday AM, April 12, 2007
Room 2010 (Moscone West)
11:30 AM - **U7.1
Multicomponent, Biomolecularly-inspired Surfaces for Advanced Guidance of Neurons.
Lance Kam 1 Show Abstract
1 Biomedical Engineering, Columbia University, New York, New York, United States
Proper development, function, and repair of neural tissues rely on the accurate recognition and response of neurons to a spatially complex extracellular environment. Capturing this complexity on engineered surfaces has wide applications in design of prosthesis and interface systems as well as basic neuroscience ranging from the study of individual cells to brain circuitry. In this report, we describe surfaces containing multiple (two and more) different bioactive signals, patterned against an inert background, that provide enhanced control over neuron-substrate interactions; control over the biomolecular identity of these signals and the signaling pathways they engage is a powerful complement to the use of geometry alone to drive cell function. For example, on surfaces containing aligned patterns of 30-micron wide islands of poly-l-lysine connected by a meshwork of 5-micron wide lines of the axonal protein L1, rat hippocampal neurons selectively attach to the adhesive islands, extending axonal processes along the L1 lines. This control over the cell body and process layout is maintained beyond the point where neurons develop interactions with neighboring cells, suggesting a simple, biologically-inspired strategy for establishing directed networks of neurons. Similarly, lines of N-Cadherin direct both axon and dendrite growth between islands of polylysine, maintaining the desired neuron layout. Pattering of additional proteins such as the post-synaptic protein Neurologin-1 selectively promote new neuron interactions on these surfaces; in this case, morphological and protein-expression changes associated with formation of presynaptic complexes. This report explores the considerations that need to be addressed to create multiple biomolecular patterns on a single surface while retaining their biological activity and explore new questions that are made possible using these methods, including the integration of multiple, spatially dispersed cues in fully driving neuron connectivity.
12:00 PM - U7.2
Aligned Conducting Polymer Nanotubes for the Controlled Release of Neurotrophins and Contact Guidance of Regenerating Neurons
Mohammad Reza Abidian 1 , Luis Salas 1 , Timothy Marzullo 2 , Sarah Richardson-Burns 3 , Joseph Corey 6 , Daryl Kipke 1 5 , David Martin 1 3 4 Show Abstract
1 Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, United States, 2 Neuroscience, University of Michigan, Ann Arbor, Michigan, United States, 3 Materials Science & Engineering, University of Michigan, Ann Arbor, Michigan, United States, 6 Neurology, University of Micgigan, Ann Arbor, Michigan, United States, 5 Electrical Engineering & Computer Science, University of Michigan, Ann Arbor, Michigan, United States, 4 Macromolecular Science & Engineering, University of Michigan, Ann Arbor, Michigan, United States
Cortical prosthetics facilitate the recording and stimulation of cerebral cortex using arrays of microelectrodes. Textured implants for neural guidance hold promise approach for controlled neural regeneration. We have developed methods to create oriented conducting polymer nanotubes that can precisely control the local release of neurotrophic proteins, and can provide guidance for directed neurite outgrowth. The fabrication process involves the electrospinning of biodegradable polymer nanofibers into which bioactive proteins have been incorporated followed by electrochemical deposition of conducting polymers around the nanofibers. In order to modify the surfaces of neural electrodes, the conducting polymer nanotubes were electropolymerized on the individual electrode sites. The electrical properties and surface morphologies of nanotube coatings were examined in vitro. These polymer-modified microelectrode arrays were implanted in cerebral cortex of rats and their performance was monitored by impedance spectroscopy, signal amplitude, and noise level over periods of at least 8 weeks. The polymer-coated sites were found to outperform control sites with respect to signal-to-noise ratio and number of viable unit potentials. We also fabricated aligned conducting polymer nanotubes that were loaded with nerve growth factor (NGF). Dorsal root ganglion (DRG) explants, neuroblastoma SH-SY5Y cells and PC12 cells were cultured on these aligned nanotubes. Scanning electron, florescence and confocal microscopy results revealed that cells can be patterned and preferentially guided in the direction of the nanotube orientation. Electrical actuation of nanotubes leads to precise release of NGF at desired points in time, and this is directly correlated with controlled neurite outgrowth.
12:15 PM - U7.3
A Process for Templating Nerve Guidance Scaffolds with Precision, Highly-ordered, High-aspect ratio Architectures.
Jeff Sakamoto 1 , Jim Weiss 1 , Todd Holt 3 , David Welker 3 , Shula Stokols 2 , Tom Gros 2 , Mark Tuszynski 2 Show Abstract
1 , JPL/Caltech, Pasadena, California, United States, 3 , Paradigm Optics Inc., Pullman, Washington, United States, 2 Neuroscience Department, UC San Diego, San Diego, California, United States
A process for fabricating scaffolds to repair spinal cord injuries has been developed through a collaborative effort between the Materials and Device Group at JPL, the Neuroscience Department at UCSD and Paradigm Optics Incorporated. The process is capable of templating, highly-ordered, parallel, high-aspect ratio features (primarily cylinders, ovals and squares) with cross-sectional dimensions ranging from a few hundred nanometers-to hundreds of microns with lengths exceeding 1 centimeter. The process involves the selective etching of two or more constituents using relatively benign chemical solvents (e.g. propylene carbonate, ethanol or pure water) and as such is amenable to materials sensitive to aggressive chemicals to include biopolymers. Although the current emphasis is on templating nerve guidance conduits for spinal cord repair, it is possible that the same process can be used to repair damaged nerves in the peripheral nervous system as well. Comprehensive scaffold characterization and some in vivo data will be presented.
U8: Listening to Neurons
Thursday PM, April 12, 2007
Room 2010 (Moscone West)
2:30 PM - **U8.1
Implantable Biomimetic Electronics as Neural Prostheses for Lost Cognitive Function.
Theodore Berger 1 Show Abstract
1 Department of Biomedical Engineering, University of Southern California, Los Angeles, Pennsylvania, United States
Dr. Berger will present results of a multi-disciplinary project that is developing a microchip-based neural prosthesis for the hippocampus, a region of the brain responsible for the formation of long-term memories. Damage to the hippocampus is frequently associated with epilepsy, stroke, and dementia (Alzheimer's disease), and is considered to underlie the memory deficits related to these neurological conditions. The essential goals of Dr. Berger’s multi-laboratory effort include: (1) experimental study of neuron and neural network function -- how does the hippocampus encode information?, (2) formulation of biologically realistic models of neural system dynamics -- can that encoding process be described mathematically to realize a predictive model of how the hippocampus responds to any event?, (3) microchip implementation of neural system models -- can the mathematical model be realized as a set of electronic circuits to achieve parallel processing, rapid computational speed, and miniaturization?, and (4) creation of hybrid neuron-silicon interfaces -- can structural and functional connections between electronic devices and neural tissue be achieved for long-term, bi-directional communication with the brain? By integrating solutions to these component problems, we are realizing a microchip-based model of hippocampal nonlinear dynamics that can perform the same function as part of the hippocampus. Through bi-directional communication with other neural tissue that normally provides the inputs and outputs to/from a damaged hippocampal area, the biomimetic model could serve as a neural prosthesis for lost memory/cognitive function. A proof-of-concept will be presented in which the CA3 region of the hippocampal slice is surgically removed, and is replaced by a microchip model of CA3 nonlinear dynamics – the “hybrid” hippocampal circuit displays normal physiological properties. How the work in brain slices is being extended to behaving animals also will be described.
3:00 PM - U8.2
Finite Element Modelling of Axonal Amplifiers.
James FitzGerald 1 , Stephanie Lacour 2 , Stephen McMahon 3 , James Fawcett 1 Show Abstract
1 Centre for Brain Repair, Cambridge University, Cambridge, Cambridgeshire, United Kingdom, 2 Department of Materials Science, Cambridge University, Cambridge, Cambridgeshire, United Kingdom, 3 Department of Physiology, King's College London, London, London, United Kingdom
Neuroelectronic interfaces for recording from peripheral nerves must be able to sensitively detect the extracellular signals produced by action potentials as they propagate along axons. This is challenging because the signals are very small (typically a few tens to hundreds of micro-volts), their amplitude decays rapidly with distance from the axon, and in the case of myelinated fibres they are concentrated close to the nodes of Ranvier, which are about 1μm long and spaced several hundred microns apart. Confining axons in microfluidic channels dramatically increases the electrical resistance of the extracellular space. We present here a finite element model of action potential propagation along unmyelinated and myelinated axons encased in a microfluidic channel. Our results show that the microfluidic device works as an axonal amplifier: substantial amplification of the extracellular signal is observed. The exact gain depends on the details of the axon and channel geometry, but for example housing a 10μm myelinated axon in a 1cm long channel with a 1000μm2 cross section is predicted to generate a peak extracellular voltage of almost 11mV, corresponding to a gain of over 100. Radial signal decay is much reduced within the channel, and the dependence of signal amplitude on node of Ranvier location is abolished.
3:15 PM - U8.3
Neural Microcontacts with Wire Electrodes and Woven Logic.
Maria Asplund 1 , Mahiar Hamedi 2 , Olle Inganas 2 , Robert Forchheimer 3 , Hans von Holst 1 Show Abstract
1 School of Technology and Health, Royal Institute of Technology, Huddinge Sweden, 2 Linköping University, Department of Physics, Chemistry and Biology, Linköping Sweden, 3 Linköping University, Department of Electrical Engineering, Linköping Sweden
3:30 PM - U8.4
Towards the Formation of Neuro-transistor Artificial Chemical Synapse.
Shlomo Yitzchaik 1 , Ilya Goykhman 1 , Nina Korbakov 1 , Carmen Bartic 2 , Gustaaf Borghs 2 , Micha Spira 1 , Joseph Sappir 1 Show Abstract
1 Chemistry, Biology and Engineering, The Hebrew University, Jerusalem Israel, 2 Cell Based Sensors & Circuits, IMEC, Lueven Belgium
3:45 PM - U8.5
Fabrication of CMOS Compatible Sub-micron Nails for On-chip Phagocytosis.
Roeland Huys 1 2 , Carmen Bartic 1 , Bart Van Meerbergen 1 3 , S. Yitzchaik 4 , Micha Spira 5 , J. Shappir 6 , Gustaaf Borghs 1 3 Show Abstract
1 MCP, IMEC, Leuven Belgium, 2 Applied sciences, K.U.Leuven, Leuven Belgium, 3 Science, K.U.Leuven, Leuven Belgium, 4 Inorganic & Analytical Chemistry, Hebrew University of Jerusalem, Jerusalem Israel, 5 Neurobiology, Hebrew University of Jerusalem , Jerusalem Israel, 6 School of Applied Physics, Hebrew University of Jerusalem, Jerusalem Israel
U9: Integrated Designs and Devices
Thursday PM, April 12, 2007
Room 2010 (Moscone West)
4:30 PM - **U9.1
Development of Neuroelectronic Interfaces for Repair of Damage to the Peripheral Nervous System.
Stephen McMahon 1 Show Abstract
1 Wolfson CARD, King's College London, London United Kingdom
Prosthetic devices which repair or compensate for damage to the skeleton and other organs have been in use for a number of years. However, the development of neural prostheses poses many special problems, particularly the need to be electrically active. We are developing a set of technologies which will enable a new class of neuroelectronic prosthetic devices to be fabricated, based upon permanently implantable bridging structures which are both biologically and electrically active.When the nervous system is damaged and nerve fibres (axons) are cut, the part still attached to the neuronal cell body survives, but the part distal to the cut degenerates. The tip of the proximal part initiates a vigorous regeneration response, with the formation of a new axon growth cone. If the environment surrounding this axon is permissive to axon regeneration, as in the peripheral nervous system (PNS), the axon will grow, and can continue to grow until it finds a suitable target structure with which it can form a functional connection. However, regeneration over long distances is limited and even when successful, axons often grow to the wrong targets leading to poor muscle control and strength, and inappropriate sensation. One aim of our work is to guide regenerating processes via specific cell and substrate adhesion molecules. A second aim is develop a device that contains multiple electrodes so that signals can be recorded from axons passing through it, as a diagnostic of the progress of regeneration and in order to drive permanently implanted stimulators of individual muscles, if required to help restore limb function. We will describe our regenerating device architecture and fabrication process. The implant consists of thin-film metallic electrodes embedded in biocompatible and flexible polyimide films. We will report on our preliminary data on growing in vitro nerve fibres in your device, and on regenerating in vivo nerve fibres via our guiding implant. This project is a multidisciplinary effort across 4 departments and 3 universities in the UK supported by a Basic Technology RCUK EPSRC initiative. The team of researchers is composed of Mark Blamire and Ruth Cameron, -Materials Science, University of Cambridge, James Fawcett, Centre for Brain Repair, University of Cambridge, Wilhelm Huck, Department of Chemistry, University of Cambridge, Stephen McMahon, Physiology, King’s College London, Edward Tarte, Electrical Engineering, University of Birmingham, project co-ordinator: Stephanie P. Lacour, Materials Science, University of Cambridge.
5:00 PM - U9.2
Stretchable Microelectrode Arrays: Potential for a Highly Compliant Neural Interface.
Zhe Yu 1 , Oliver Graudejus 2 , Candice Tsay 2 , Stéphanie Lacour 3 , Sigurd Wagner 2 , Barclay Morrison 1 Show Abstract
1 Biomedical Engineering, Columbia University, New York, New York, United States, 2 Electrical Engineering, Princeton University, Princeton, New Jersey, United States, 3 Materials Science, University of Cambridge, Cambridge United Kingdom
Neural interfaces are designed to couple neural systems with electronic devices for bidirectional communication between brain and a machine/computer. The development of neural interfaces enables neurophysiologists and clinicians to investigate and treat neurological diseases, such as traumatic brain injury (TBI). Due to the extreme complexity of neural network processing, microelectrode arrays (MEAs), which are designed for long-term and simultaneous multi-site recording of extracellular activity, are widely used for neural interfaces both in vivo and in vitro. However, current MEA technology is based on traditional micro/nano-fabrication techniques, which manufacture electrodes on stiff substrates (glass, silicon or polyimide), which are up to 107 times stiffer than brain tissue. Irreversible tissue damage often occurs at the interface between the stiff array and soft neuronal tissues due to micro-motion. Therefore, we are motivated to develop a ‘soft’ microelectrode array — a stretchable microelectrode array (SMEA) — which will reduce chronic damage from micro-motion and maintain electrical conduction during deformation of both the neural tissue and the SMEA itself.Our SMEAs are fabricated on a polydimethylsiloxane (PDMS) membrane substrate with a patterned stretchable gold layer, and encapsulated with another photo-patternable PDMS insulation layer. The SMEAs are packaged between two printed circuit boards to form a tissue culture well and electrical connections with a bio-amplifier. While maintaining electrode impedance less than 210kΩ during 15% strain biaxial stretch, and in artificial cerebrospinal fluid (aCSF), the SMEA can detect robust spontaneous activity, and bicuculline (50μM) induced epileptiform activity as well, from hippocampal slice cultures. Both spontaneous and induced neuronal activity was eliminated by 1μM tetrodotoxin (TTX), and recovered after washing out the tetrodotoxin. Electrical stimuli applied through the SMEA electrodes evoked measurable population spikes superimposed on excitatory postsynaptic potentials. Our results demonstrate that SMEAs are reliable neural interfaces in vitro capable of both monitoring and controlling (stimulating) neural activity. This work was supported by NIH (NINDS R21 052794) and the New Jersey Commission on Science and Technology.
5:15 PM - U9.3
Neurofluidic System for Neural Cell Experiments to Investigate the Mechanisms of Deep Brain Stimulation.
Michel Decre 1 , Lucia Cinque 1 , Sebastien Popoff 1 , Ger Ramakers 2 , Enrico Marani 3 Show Abstract
1 Healthcare Devices and Instrumentation, Royal Philips n.v., Eindhoven Netherlands, 2 , Netherlands Institute for Neuroscience, Amsterdam Netherlands, 3 , University of Twente, Enschede Netherlands
Deep Brain Stimulation (DBS) has been used for several years as a therapy to treat Parkinson’s disease and is being investigated as a treatment for various other neurological disorders. To date, the underlying mechanisms of DBS that suppress tremor and other symptoms are still debated. In vivo access to the relevant neuronal networks is severely restricted and current in vitro techniques such as organotypic brain slices have so far failed to provide final answers. Using microfluidics and microsystem technologies to construct in vitro models that more accurately reproduce the natural environment of neurons should allow to better study the mechanisms of DBS. We have fabricated a Polydimethylsiloxane (PDMS), multi-compartmented device with soft-lithography techniques that allows neurons to grow for at least several weeks and to form controlled neural networks. Microelectrode arrays (MEAs) are integrated in the device to record and stimulate cultured neuronal networks. We investigated options to grow compartmented cultures of cortical neurons and several neuron types belonging to the basal ganglia motor pathway (involved in Parkinson’s disease), in order to build in vitro models with appropriate connectivities. MEA recordings were used to assess cell viability and network activity. In the future, we envisage to grow neuronal multilayers inside the compartments in order to offer culture environments that more closely reproduce those present in vivo. Three-dimensional recording and stimulation electrodes will be integrated with the cultures. We anticipate that such instrumented, three-dimensional compartmented devices for neuronal culture will greatly contribute to the in vitro study of neuron-device interfaces, neuronal pathways, and neurostimulation.
5:30 PM - **U9.4
New Horizons for Orthotic & Prosthetic Technology.
Hugh Herr 1 Show Abstract
1 Media Lab, MIT, Cambridge, Massachusetts, United States
Rehabilitation technology is at the threshold of a new age when orthotic and prosthetic devices will no longer be separate, lifeless mechanisms, but will instead be intimate extensions of the human body-- structurally, neurologically, and dynamically. Such a merging of body and machine will not only increase the acceptance of the physically challenged into society, but will also enable individuals suffering from limb dysfunction to more readily accept their new artificial appendages as part of their own body. Several scientific and technological advances will accelerate this mergence, including the development of actuator technologies that behave like muscle, control methodologies that exploit principles of biological movement, and device architectures that resemble the body’s own skeletal design.In this talk, I describe research activities in rehabilitation science and engineering currently under development at the Biomechatronics Group within MIT’s Media Lab. I present several computer-controlled devices for leg rehabilitation, including an external knee prosthesis, a powered ankle-foot prosthesis, and a force-controllable ankle-foot orthosis. Patient-adaptive control schemes are discussed in which device impedance and non-conservative motive output are automatically modulated to match patient-specific gait requirements. I discuss the clinical benefits of each assistive device, including improvements in walking economy, biological realism and gait symmetry. Finally, I outline how neural prostheses might be used with these mechanisms to enhance their clinical efficacy.