Joao Pedro Conde Instituto Superior Tecnico
(and INESC Microsistemas e Nanotecnologias)
Barclay Morrison Columbia University
Stéphanie P. Lacour University of Cambridge
CC1: Electrode Coating - Electrical Transfer I
Tuesday PM, April 18, 2006
Room 2005 (Moscone West)
9:30 AM - **CC1.1
Polymer Implantable Microscale Neural Probes for Interfacing with the Brain
Daryl Kipke 1 Show Abstract
1 Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, United States
Our group is developing neural probe platform technologies to provide combined electrical and chemical interfaces at the cellular level to selective areas of the brain. Our long-term goal is to develop multifunctional neural probe systems for sensing and actuation in both the electrical and chemical domains. We have developed parylene-based microfabricated multi-channel implantable devices to stimulate and/or record from populations of neurons for long periods of time. While current studies are directed at establishing performance benchmarks for the base probe technology, long-term reliability and sensitivity remain issues as we work towards neural implants that are intended to remain functional for years. Successful recording of chronic neural activity is greatly affected by the tissue reaction in the microenvironment surrounding the implant site. We are developing and investigating methods for in vivo monitoring of the tissue reaction and specific intervention strategies, including drug-eluting polymer coatings and site rejuvenation. We have developed polymer-based probe substrates with integrated ribbon cables and specially designed microarchitectures in an effort to improve the mechanical interface. We are also extending our neural probe technology to include chemical delivery and sensing. Together, these advances in bioMEMS technologies for interfacing with the brain will help to enable important new advances in research and medicine.
10:00 AM - CC1.2
Templated Conductive Polymer Networks to Stabilize Electrode-Neural Interfaces
Matthew Meier 1 , Sarah Richardson-Burns 2 , Jeff Hendricks 1 , David Martin 3 2 1 Show Abstract
1 Biomedical Engineering, University of Michigan Ann Arbor, Ann Arbor, Michigan, United States, 2 Department of Material Science and Engineering, University of Michigan, Ann Arbor, Ann Arbor, Michigan, United States, 3 Macromolecular Science and Engineering Center, University of Michigan, Ann Arbor, Ann Arbor, Michigan, United States
Microporous films of the conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT) were polymerized on the surface of gold coated silicon electrodes and ITO glass using polystyrene latex microspheres as a template. Monodisperse microspheres were suspended in water and deposited on the surface of the bare gold electrodes before electricochemical polymerization of the PEDOT through the microsphere templates. After removing the microspheres, the electrical properties of the PEDOT thin films were investigated using cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The interconnected channels of the microporous networks were confirmed by the use of scanning electron microscopy, and focused ion beam milling. SH-SY5Y neuroblastoma-derived neural cell lines were cultured in DMEM according to ATCC protocols and primary cultures of neurons and glia were prepared from the cortex of neonatal mice. The cultures were put on the templated networks of various sizes and experiments addressing the effects of pore size on the biological response are underway. It was found that deposition of the PEDOT films reduced the electrode’s impedance. This coupled with its interconnected structure makes it better suited for direct electrical connections with neurons. The drop in impedance can be explained by the increased surface area of the electrode due to the templated conductive polymer network’s increased surface area. In addition to the improved electrical properties, it was also found that various sphere sizes, and high concentrations of spheres provided a more ordered template further increasing the net surface area of the electrode. Investigation of PEDOT films using ellipsometery, and atomic force microscopy, as well as biological data will be reported.
10:15 AM - CC1.3
Generation of a Functional Biointegrated Electrode by Polymerization of Conductive Polymer Networks Within Brain Tissue.
Sarah Richardson-Burns 1 , Jeffrey Hendricks 2 , Dong-Hwan Kim 2 , Mohammad Abidian 2 , David Martin 1 2 3 Show Abstract
1 Materials Science and Engineering, University of Michigan, Ann Arbor, Michigan, United States, 2 Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, United States, 3 Macromolecular Science and Engineering Program, University of Michigan, Ann Arbor, Michigan, United States
We are investigating interactions between central nervous system (CNS)-derived cells and inherently conductive polymers towards the development of novel electroactive biomaterials for use in the next generation of biomedical devices and biosensors. Prosthetic devices for chronic electrical stimulation and recording in the CNS are finding widespread applications in deep brain stimulation and are currently being developed for visual, auditory, and cortical prostheses. However, one of the most important problems with all of these devices is their limited and unpredictable long-term performance primarily due to poor integration at the device-tissue interface. This results in cell loss and formation of electrically insulating scar tissue that encapsulates the device. Significant improvements in the performance of all electrode-based biomedical devices would be achieved by increasing interfacial compatibility or by having the ability to maintain communication with target cells despite the immunoreaction.Our materials research strategies are aimed at improving device biointegration and stabilizing electrical communication. Here we describe a novel conductive polymer 3-dimensional electrode network that can be polymerization directly into the surrounding brain tissue from electrode sites of implanted neural prosthetic devices. The conductive polymer networks (CPN) are comprised of electrochemically in situ polymerized poly(3,4-ethylenedioxythiophene) (PEDOT) that are essentially nano-wire extensions of the electrode. This represents a novel way of bringing the electrode sites into direct contact with surrounding neurons, dramatically increasing the electrode surface area, and facilitating ionic to electronic carrier transport.Previous studies from our laboratory described methods for depositing PEDOT directly onto electrode sites of neural prosthetic devices, polymerizing CPN within hydrogel coatings, and for tailoring porous and fibrous micrometer and nanometer scale PEDOT features. We have extended these methods to make possible deposition of PEDOT networks directly within murine brain tissue and in the presence of cultured neurons with little toxicity to the cells. Cells adhered to or within the CPN can be electrically stimulated via the CPN as indicated by markers of synaptic activity and electrophysiological studies. We have found these novel electrodes to be functional after implementation within brain tissue as indicated by electrical stimulation, impedance spectroscopy and cyclic voltammetry. This work is supported by the NSF DMR-0084304, NIH NINDS NO1-NS-1-2338.
10:30 AM - CC1.4
Vertically Aligned Carbon Nanofiber in a versatile 3-D Electro-Biological Array.
T.D. Barbara Nguyen-Vu 1 , Hua Chen 1 , Alan Cassell 1 , Meyya Meyyappan 1 , Russell Andrews 1 , Jun Li 1 Show Abstract
1 Center for Nanotechnology, NASA Ames Research Center, Moffett Field, California, United States
It has been demonstrated that vertically aligned carbon nanofibers (CNFs) can be grown from pre-fabricated microcircuits using plasma enhanced chemical vapor deposition (PECVD) and standard semiconductor processes to form nanoelectrode arrays. Such fabrication methods enable the CNFs to be directly integrated into electronic devices, thereby providing the added benefit of having a three-dimensional (3-D) structure for enhanced biological interaction over traditional two-dimensional electro-biological interfaces. Due to its 3-D nanostructure and large effective surface area, CNF arrays possess desirable electrical properties, such as large capacitance, for less harmful stimulation of biological tissues. In addition to exhibiting excellent electrical properties, the CNF arrays provide a versatile template for modification with electronic-conducting polymers such as polypyrrole (PPy) to further improve the interface. First, the PPy enhances the electrical quality of the surface by adding an element of pseudo-capacitance to the substrate. Secondly, a thin conformal coating of PPy helps to increase the mechanical strength of the CNFs to provide an assembly of free-standing CNFs that are soft and flexible yet resilient enough to withstanding multiple wetting and drying cycles. The combined structure helps to maintain the integrity of both the CNFs and polymer film in the challenging aqueous environment of biological systems. We have also shown that the PPy film can be tuned with various anionic dopants to promote or prevent adhesion of PC12 cells, a model neuronal cell type derived from the rat pheochromocytoma. The cells demonstrate monolayer growth and normal morphology when grown on the CNF arrays establishing suitable biocompatibility of the material. Examination of cytotoxicity revealed no acute toxicity from either the CNF or the PPy films. When provided with nerve growth factor (NGF) in the medium, the PC12 cells were induced to differentiate and extend neurites and form a neural network. Results show that the 3-D CNF arrays facilitate the growth of neurites and further work is underway to elucidate the exact interaction between the neurites and the vertically aligned CNFs.
10:45 AM - CC1.5
Highly-Aligned Conducting Polymer Nanotubes for the Precisely Controlled Release of Drugs at the Electrode-Tissue Interface of Neural Prosthetic Devices
Mohammad Reza Abidian 1 , David Martin 2 Show Abstract
1 Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, United States, 2 Materials Science and Engineering, Biomedical Engineering, and Macromolecular Science and Engineering, University of Michigan, Ann Arbor, Michigan, United States
The interface between microfabricated neural microelectrodes and neural tissue plays a significant role in the long term performance of these devices. It is thought that biocompatible polymer coatings can stabilize the interface between microelectrode and living tissue at the site of implantation. The ability of neural electrodes to record high signals over extended periods of time remains a significant problem. The engineering of bioactive electrode coatings has been investigated for its potential to promote in-growth of neural tissue, reduce shear stress, and enhance signal transport from electrons to ions at the electrode-host interface. The precisely controlled local release of anti-inflammatory drugs at desired points in time is important for treating the inflammatory response to neural prosthetic devices in the central and peripheral nervous systemsWe have developed a new approach for preparing anti-inflammatory drug loaded conducting polymer nanofibers. The fabrication process includes the electrospinning of a biodegradable polymer (here poly(lactide-co-glycolide) or PLGA) into which a drug has been incorporated (here the anti-inflammatory agent dexamethasone) followed by electrochemical deposition of a conducting polymer (here poly(3,4-ethylenedioxythiophene or PEDOT). The wall thickness of the PEDOT nanotubes varied from 50-100 nm, and the nanotube diameter ranged from 100-600 nm. By controlling the polymerization time, we could reproducibly prepare tubular structures with thin walls (shorter deposition time) or thick walls (longer deposition time).The conducting polymer nanotubes significantly decrease the impedance and increase the charge capacity of recording electrode sites on microfabricated neural probes. The drugs can be released from the nanotubes in a desired fashion by electrical stimulation of the nanotubes, presumably either through the ends of PEDOT nanotubes or though openings or cracks on the surface of nanotubes created by actuation. The impedance spectroscopy revealed that the impedance of gold electrode sites significantly decreased from 800 kΩ to 8 kΩ after PEDOT deposition on the electrode sites and around the PLGA fibers. The charge transfer capacity of the electrode site increased from 0.001 µC to 2.8 µC by growing PEDOT around the PLLA/PLGA nanofibers. This value was increased significantly to 4.9 µC after making the PEDOT nanotubes. By using external electrical stimulation of the nanotubes we can precisely release drugs at desired points in time. After the electrical excitation we observed a significant increase in the amount of dexamethasone released. The surface morphology of the coated electrodes was assessed by optical microscopy and scanning electron microscopy. Scanning electron microscopy (SEM) and focused ion beam (FIB) showed the nanotubular structure of conducting polymers on the electrode sites.
CC2: Electrode Coating - Mechanical Integration
Tuesday PM, April 18, 2006
Room 2005 (Moscone West)
11:30 AM - **CC2.1
Stimulus-responsive, Mechanically-dynamic Nanocomposite for Cortical Electrodes
Dustin Tyler 1 2 , Christoph Weder 3 2 , Stuart Rowan 3 2 , Jeffrey Capadona 2 Show Abstract
1 Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio, United States, 2 Research, Cleveland Louis-Stokes VA Medical Center, Cleveland, Ohio, United States, 3 Macromolecular Sc. & Eng, Case Western Reserve University, Cleveland, Ohio, United States
Cortical electrodes offer an intimate interface to the complex activity of the brain. A limiting factors of current technology is the mechanical mismatch with the cortical tissue. While a stiff electrode is advantageous during insertion, a chronically stiff electrode causes micro-motion, micro-damage, and chronic astrocytic response in the brain tissue. An ideal electrode would have a high modulus (>= 100 GPa) during insertion and a low modulus (<= 100 MPa) thereafter. We present a novel nanocomposite polymer material, inspired by the mechanically dynamic tissues of echinoderms, that changes mechanical properties in response to a stimulus, such as divalent ion concentration or pH. We have performed a series of proof-of-concept experiments demonstrating stimulus-responsive, mechanically-dynamic behavior in films. Using dynamic mechanical thermal analysis (DMTA), we studied the effect the addition of cellulose whiskers with and without Mg2+ ions present has on the mechanical properties of 50:50 EO/EPI matrix copolymer films (see Table). A moderate water swelling of approximately 24% w/w was observed regardless of percentage whisker filler content. The swelling did not affect the mechanical properties of the neat matrix polymer without whiskers. The addition of 10% whiskers increases the modulus of the neat film by approximately 6-fold due to whisker-whisker interactions. Swelling reduces the film modulus by one-half. It is believed that this is caused by solvation which shields the interactions between whiskers. The addition of 1% MgSO4 in the film increases the modulus by another factor of 2 compared to the whiskers alone as the Mg2+ induces greater whisker-whisker cross-linking. When swollen, solvation shields the Mg2+ and decouples the whiskers, resulting in a decrease of modulus back to the same level as solvation of 10% whiskers only. The mechanism of modulus change in the nanocomposite is related to coupling and decoupling of a whisker matrix and differs from a hydrogel which expands the polymer matrix. The nanocomposite approach provides greater opportunity for engineering the modulus range and the switching mechanisms. These results do not represent the full potential of the optimized nanocomposite system. We expect controlling the pH of the whiskers to maximize ion/whisker interactions and addition of acid groups will to further facilitate whisker coupling and coordination with the Mg2+. We expect an increase of two to four orders of magnitude is possible.
12:00 PM - CC2.2
Stretchable Dielectric Material for Conformable Bioelectronic Devices.
Candice Tsay 1 , Stephanie Lacour 1 , Sigurd Wagner 1 , Zhe Yu 2 , Barclay Morrison 2 Show Abstract
1 Department of Electrical Engineering, Princeton University, Princeton, New Jersey, United States, 2 Department of Biomedical Engineering, Columbia University, New York, New York, United States
12:15 PM - CC2.3
Polymerization of Conductive Polymer Networks in Neural Cell-Seeded Hydrogel Intracortical Electrode Coatings.
Jeffrey Hendricks 1 , Sarah Richardson-Burns 2 , David Martin 2 1 Show Abstract
1 Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, United States, 2 Materials Science & Engineering, University of Michigan, Ann Arbor, Michigan, United States
12:30 PM - CC2.4
Open-architecture Neural Probes Reduce Cellular Encapsulation.
John Seymour 1 , Daryl Kipke 1 Show Abstract
1 Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, United States
12:45 PM - CC2.5
Chronic Tissue Response Induced By Flexible Polymer Interconnects at The Electrode-Tissue Interface.
Jeyakumar Subbaroyan 1 , Keith Pennington 1 , Daryl Kipke 1 2 Show Abstract
1 Department of Biomedical Engineering, University of Michigan, Ann Arbor, Ann Arbor, Michigan, United States, 2 Department of Electrical Engineering, University of Michigan, Ann Arbor, Ann Arbor, Michigan, United States
Among several factors, chronic tissue response to implanted neural microelectrodes could be caused due to the presence of a foreign body and/or mechanical shear induced damage at the electrode-tissue interface. Reducing tethering forces could reduce shear induced damage and hence could maintain a healthy neuronal interface at the implant site. This can be achieved by changing cabling forces (normal vs. transverse), reducing the stiffness of the implanted substrate or by reducing the stiffness of the interconnect material. Since flexible substrates pose insertion problems, flexible interconnects could provide a more feasible solution in reducing the effect of tethering forces on the tissue. We have developed a 3-D finite element model to simulate the effect of interconnect stiffness on the strain induced at the electrode-tissue interface for two different tethering forces. The simulation results indicate that flexible interconnects reduce the interfacial strains by two orders of magnitude compared to their stiff counterparts. Based on the simulation results, we posit that the reduced interfacial strains from using a flexible interconnect could possibly result in reduced chronic tissue response surrounding the implant site. Flexible PDMS (Poly dimethyl siloxane) interconnects were microfabricated, assembled with silicon microelectrodes, and implanted in adult, male sprague-dawley rats. Immunohistochemical results from chronic implants (defined as post-implant period of 4 weeks) indicate that a compact glial sheath of less than 100 μm encapsulated the implants without appreciable neuronal cell loss at the electrode-tissue interface. A pixel extraction algorithm and a cell counting algorithm were developed in Matlab to quantify the results and compare the same with the control tissue.
CC3: Surface Functionalization
Tuesday PM, April 18, 2006
Room 2005 (Moscone West)
2:30 PM - **CC3.1
Direct Integration of Biomedical Devices with Living Tissue by the In-Situ Electrochemical Polymerization of Conducting Polymers
David Martin 1 3 2 , Jeffrey Hendricks 2 , Mohammad Abidian 2 , Matt Meier 2 , Ming Guang Yong 1 , Sarah Richardson-Burns 1 Show Abstract
1 Materials Science and Engineering, The University of Michigan, Ann Arbor, Michigan, United States, 3 Macromolecular Science and Engineering, The University of Michigan, Ann Arbor, Michigan, United States, 2 Biomedical Engineering, The University of Michigan, Ann Arbor, Michigan, United States
We have been investigating the use of electrochemically deposited conducting polymers such as poly(3,4-ethylenedioxythiophene) (PEDOT) and its derivatives for creating stable, biocompatible interfaces between microfabricated neural probes and cortical tissue. The conducting polymer coatings develop a fuzzy surface structure that significantly reduces the electrode impedance and provide a compliant, mechanical buffer layer. They also make it possible to control the local delivery of pharamacological agents such as anti-inflammatory and neurotrophic factors. Recently, we have developed methods for the in-situ polymerization of PEDOT around living cells both in-vitro and in-vivo. These methods result in an interconnected polymer network that creates an intimate interface between the electrode and the tissue. These coatings are expected to be of interest not just for neural prosthetics but for a variety of other biomedical devices where sustained electrical contact is important such as deep brain stimulators, cochlear implants, retinal implants, pacemakers, and glucose sensors.
3:00 PM - CC3.2
Nano Monitors for Identification of Vulnerable Cardio-vascular Plaque.
Shalini Prasad 1 Show Abstract
1 ECE, Portland State University, Portland, Oregon, United States
The development of new, affordable, disposable analytic microchips are changing diagnostics. We have developed a diagnostic assay system for determining the indicators for development of vulnerable plaque that cause fatalities. Nano porous alumina and silicon substrates are fabricated by the principles of wet etching and electro chemistry. These substrates were embedded in silicon based micro fluidic devices to develop a monitor for detecting markers for vulnerable plaque resulting in fatal cardiac outcomes. The surface of the nano porous template was selectively functionalized to detect specific pro-inflammatory markers. Size and enzyme-substrate mechanisms were simultaneously adopted to bind the pro-inflammatory proteins from serum samples on to the sensitized substrate. The binding event resulted in surface charge variations that were measured by variations to resonance binding frequency. Unique identifiers for each pro-inflammator protein were developed. The identifiers were used to determine the capability of formation of vulnerable plaque. The potential application of this technique is lab bench based health care systems for improving post surgical outcomes. These systems will eventually perform diagnostic procedures in a multiplexed format that incorporates multiple complementary methods. Ultimately, these systems will be combined with other devices to create completely integrated analysis and treatment systems
3:15 PM - CC3.3
Reversible Electrochemical Patterning of Antibodies in β-Cyclodextrin SAMs.
Matthew Farrow 1 , Kevin Zavadil 1 , Donald Pile 1 , W. Yelton 1 , Bruce Bunker 1 Show Abstract
1 , Sandia National Laboratories, Albuquerque, New Mexico, United States
Self assembled monolayers (SAMs) of cyclodextrin can be used as a template for the reversible electrochemical patterning of biomaterials. This work describes electrochemical means of controlling the formation of complexes between a variety of host molecule SAMs (comprised of derivatives of β-cyclodextrin) and analyte guest molecules based on ferrocene. Interaction between the host and guest molecule is controlled by preferential association of the neutral, hydrophobic form of ferrocene with the cyclodextrin pocket. Subsequent oxidation of ferrocene to the positively charged Fe(III) form drives dissociation of the guest molecule from the hydrophobic pocket of cyclodextrin. Biological species can be reversibly patterned to the surface in this manner by linking them to ferrocene. To accomplish this we employ a linking strategy of ferrocene-biotin-streptavidin-biotin-antibody. Electrochemically controlled complexation between ferrocene derivatives and the cyclodextrin host molecules is demonstrated in aqueous electrolytes. Biotin is linked to ferrocene via an ethylene glycol bridge. This tethered biotin is active towards the adsorption of streptavidin and shows excellent inhibition of non-specific biological adsorption. These streptavidin surfaces can be used to create patterns with a wide range of biotinylated biological species, such as antibodies. A combination of electrochemical stripping, cyclic voltammetry, secondary ion mass spectroscopy, atomic force microscopy, and quartz crystal microbalance measurements are presented. These results show that binding functionality can be maintained, monitored, and controlled in aqueous electrolytes over a practical range of potentials for sensing. The use of such switchable films for the creation of electrochemically programmable patterns of antibodies is described. This system is an important step in the creation of tunable, reusable biosensor arrays.
3:30 PM - CC3.4
Bio-Sensor Arrays on Flexible Polyimide Substrates for Drug Discovery Applications.
Michal Wolkin 1 , Dirk De Bruyker 1 , Gregory Anderson 1 , Eric Peeters 1 , Francisco Torres 1 , Michael Recht 1 , Alan Bell 1 , Richard Bruce 1 Show Abstract
1 , Palo Alto Research Center and Scripps-PARC Institute for Advanced Biomedical Sciences, Palo Alto, California, United States
AbstractPARC’s enthalpy arrays are designed to provide a high-throughput, label-less assay methodology for screening and thermodynamically analyzing molecular interactions while effectively eliminating need for specific assay development. The enthalpy arrays are used to detect molecular interactions involving proteins, ligands, RNA, DNA and other bio molecules for proteomic research and drug discovery. Each enthalpy array consists of 96 individual bio sensors and is fabricated on thin flexible kapton substrates using micro scale technologies to reduce the device cost. In this talk we will discuss the sensor design, architecture, and materials selection. We will describe the device optimization and show how we can detect reactions with sub-milidegree temperature variation using reagent sample sizes of 250nl at concentrations in the low tens of micromolar. The reduced sample quantity and measurement time offer major improvement over conventional microcalorimetry.
3:45 PM - CC3.5
Dexamethasone-Triblock Copolymer Composites as Immune Response-Suppressing Materials for Enhancement of Implant Biocompatiblity.
Dean Ho 1 2 , Yu-Chong Tai 1 Show Abstract
1 Electrical Engineering, California Institute of Technology, Pasadena, California, United States, 2 Mechanical and Aerospace Engineering, University of California at Los Angeles, Los Angeles, California, United States
Fabrication of next-generation biologically active materials will involve the integration of proteins with synthetic membrane materials towards a wide spectrum of applications in nanoscale medicine including high-throughput drug-testing, energy conversion for powering medical devices, and bio-cloaking films for mimicry of cellular membrane surfaces towards the enhancement of implant biocompatibility, etc. Here we report the integration of dexamethasone, an anti-inflammatory corticosteroid that interacts with nuclear receptors, with a copolymeric membrane as a potential coating that will enhance implant biocompatibility. Preliminary studies have indicated that both ethanol-soluble as well as dexamethasone-cyclodextrin complexes that are water soluble may be tethered at the air-water interface for the deposition of copolymer-dexamethasone hybrid materials onto solid substrates (e.g. electrodes). To facilitate the interfacial presence of dexamethasone, both a diblock copolymer (PEO-PMMA) as well as triblock copolymer (PMOXA-PDMS-PMOXA) were explored as amphiphilic substrates/matrices for corticosteroid hybridization. Langmuir compression isotherms of varying dexamethasone concentrations revealed altered phase behaviors indicating the possible intercalation of the anti-inflammatory in between the amphiphilic molecules. Furthermore, the maximum collapse pressures were observed to be dependent upon the starting concentration of dexamethasone. Confirmation of copolymer-dexamethasone deposition was confirmed using a dexamethasone-fluorescein complex as well as imaging using atomic force microscopy. Dexamethasone is known to regulate a wide variety of cellular processes including nitric oxide production from cultured astrocytes as well as cytokine production pathways in inflamed cells. Future work will interface a variety of these cellular systems with these copolymer-dexamethasone complexes to investigate biotic-abiotic interactions that mitigate inflammatory conditions towards potential bioimplant cloaking applications.
CC4: Electrode Coating - Electrical Transfer II
Tuesday PM, April 18, 2006
Room 2005 (Moscone West)
4:30 PM - CC4.1
Carbon Nanotube Based Electrodes for Neuroprosthetic Applications.
Thomas Phely-Bobin 1 , Thomas Tiano 1 , Brian Farrell 1 , Lois Robblee 2 , David Edell 3 , Richard Czerw 4 Show Abstract
1 Materials Technology Group, Foster-Miller Inc., Waltham, Massachusetts, United States, 2 , LSR Consulting, Peabody, Massachusetts, United States, 3 , InnerSea Technology, Bedford, Massachusetts, United States, 4 , NanoTechLabs Inc., Yadkinville, North Carolina, United States
4:45 PM - CC4.2
Initiated Chemical Vapor Deposition of Biopassivation Coatings
William O'Shaughnessy 1 , David Edell 2 , Karen Gleason 1 Show Abstract
1 Chemical Engineering, M.I.T., Cambridge, Massachusetts, United States, 2 , Innersea Technology Inc., Bedford, Massachusetts, United States
Recent advances in the field of neuroprosthetics have brought the possibility of human utilization into the near term. One major barrier to this remains the encapsulation and biopassivation of the implants. Current implant technology still suffers from loss of functionality due to scar tissue buildup at the implant site. In addition, implant coating methodologies currently in use require coating thicknesses of 10-25 microns in order to provide the required electrical insulation. This requirement significantly increases the diameter of the neural probe shanks (often only 25-100 microns when uncoated) and consequently the amount of neural damage upon implantation.In this work, a novel biopassivation coating is created using initiated chemical vapor deposition (iCVD). Trivinyl-Trimethyl-Cyclotrisiloxane is utilized as a self crosslinking monomer, initiated by radical fragments generated from the thermal breakdown of Tert-Butyl Peroxide. Due to the three vinyl moieties present on the monomer, the resulting coating is a highly crosslinked organosilicon polymer matrix which is synthesized directly on the surface of the substrate. Deposition rates on the order of 25nm/min have been observed for this process. This novel material possesses a resistivity on the order of 5 X 1015 Ohm-cm, allowing for a coating thickness on the order of only 5 microns to provide the required electrical protection. In addition, the material is insoluble, flexible, and extremely adherent to silicon substrates. This novel polymer coating has also been demonstrated to retain its electrical properties in a simulated biological environment for over 1 year.Material samples are prepared in a custom built vacuum reactor. Monomer and initiator species are fed as gases to the reactor where the initiator is then broken down by a resistively heated filament at a temperature of between 300°C and 500°C. The radical species generated then react with the monomer to begin polymerization. An activation energy of 29 KJ/mol K was observed for the deposition process with respect to the filament temperature. In addition, the substrate temperature is independently controlled between 50°C and 80°C, allowing deposition on very heat sensitive substrates. This approach to thin film formulation allows greater control of film chemistry than traditional plasma or thermal CVD as the reaction pathways available for the monomer are severely limited by the benign reaction conditions at the surface. Common problems of liquid phase coating techniques such as non-uniform wetting of the substrate and entrainment of solvent are also avoided. Additionally, this methodology allows for easy copolymerization and the deposition of coatings of graded composition, due to the use of vinyl moieties for monomer reaction. As a result, this approach gives maximum flexibility for optimization of both bulk and surface material properties.
5:00 PM - CC4.3
Enabling Protein-based Single Molecule Sensors.
Noah Malmstadt 1 , Tae-Joon Jeon 1 , Jacob Schmidt 1 Show Abstract
1 Bioengineering, UCLA, Los Angeles, California, United States
Membrane channel proteins play crucial roles in governing the transport of material and energy across every cellular membrane. Accordingly, they are the subjects of interest for science, medicine, and engineering as well as major targets of drug discovery efforts. Recent work has also shown their potential as highly rapid and sensitive single molecule sensors. However, techniques conventionally used to create the freestanding lipid membranes for measurement of the electrical transport through these proteins have major shortcomings. These membranes can be problematic to form and are extremely fragile, limiting the range and scope of possible studies. We have developed two new technologies which have addressed these problems: in situ encapsulation of lipid membranes in hydrogels and automated microfluidic formation. The hydrogel encapsulated membranes are mechanically robust and long-lived as a result of the intimate contact between the hydrogel and the membrane, enabling measurements of single channel currents for a week or longer. Our preliminary work has also shown that this gel slows the translocation of single-stranded DNA through the incorporated protein, possibly reducing the required measurement bandwidths sufficiently to enable sequencing. The automated microfluidic formation apparatus enables the creation and manipulation of lipid membranes and the incorporation and measurement of channel proteins in these membranes through an entirely computer controlled process. This device geometry is particularly amenable to scaling and automation. I will report our initial development and results of these technologies as well as progress toward exploiting them to DNA sequencing, drug discovery, and single molecule experiments.
5:15 PM - CC4.4
Ion Implanted LPCVD Polysilicon Thin Films for Neuroelectronic Devices.
Rajarshi Saha 1 , Jit Muthuswamy 1 Show Abstract
1 Harrington department of Bioengineering, Arizona State University, tempe, Arizona, United States
5:30 PM - CC4.5
Electron Transport Study on Viruses Functionalized with Metallic Nanoparticles.
Cengiz Ozkan 1 , Chunglin Tsai 2 , Yang Yang 3 , Ricky Jia-hung Tseng 3 Show Abstract
1 Mechanical Engineering, University of California at Riverside, Riverside, California, United States, 2 Electrical Engineering, University of California, Riverside, California, United States, 3 Materials Science and Engineering, University of California, Los Angeles, California, United States
The combinations of organic biomolecules with inorganic nanoparticles provide immeasurable possibilities to create bottom up assembled functional building-block for nanoelectronics. Among the varieties of biomaterials, unenveloped viruses such as rod-shape tobacco mosaic virus (TMV) and icosahedral satellite tobacco mosaic virus were chosen in our self-assembled hybrid nanostructures owing to their different geometric options for heterostructure assembly along with their well characterized surface properties and nanoscale dimensions. The virions were metallized with platinum nanoparticles using electrodeless deposition. The platinum ion solution (K2PtCl4) first activated the virus coat protein to form nucleation centers. After activation, a reduction bath was provided by adding dimethylamine borane. Scanning and transmission electron microscopies were used to characterize the nanostructures showing the metal clusters dispersed uniformly with size ranging from 10 to 15 nm. X-ray photoelectron spectroscopy (XPS) study of the hybrid nanostructures indicated the metallic Pt clusters mainly attach to the carboxyl and hydroxyl groups on the virus surface. Moreover, the electron transport phenomenon of the thin film containing the metallized biomaterials was observed using a semiconductor parameter analyzer.
5:45 PM - CC4.6
Nanocomposites for Neural Interfaces
Tanja Kmecko 1 , Gareth Hughes 1 , Larry Cauller 2 , Hong Lu 3 , Jeong-Bong Lee 3 , Mario Romero-Ortega 4 Show Abstract
1 , Zyvex Corporation, Richardson, Texas, United States, 2 School of Behavioral and Brain Sciences, University of Texas at Dallas, Richardson, Texas, United States, 3 Department of Electrical Engineering, University of Texas at Dallas, Richardson, Texas, United States, 4 , Texas Scottish Rite Hospital for Children, Dallas, Texas, United States
We have fabricated micro-probes consisting of gold microelectrode sites (500 μm long and 12 μm wide) modified with conductive polymers and carbon nanotubes to achieve intimate contact with the nervous system. The fabrication process includes photolithography, electroplating and micromachining techniques. In order to obtain a high quality neural contact, we have investigated the preparation and characterization of neural interface materials. Electrochemical polymerization using potentiostatic and galvanostatic methods was used to optimize the surface of the metal electrode sites. Scanning electron microscopy (SEM), atomic force microscopy (AFM), cyclic voltammetry (CV), and electrochemical impedance spectroscopy (EIS) were used to study the surface morphology, and electrochemical properties and stability of electrodeposited polymers. Cytotoxicity tests using fibroblasts and Schwann cells were performed to evaluate biocompatibility and cell adhesion capability of the neural interface materials. Polypyrrole (PPy) and poly(3,4-ethylendioxythiophene) (PEDOT) with various thicknesses and dopant anions were deposited onto microelectrode sites from aqueous solution. Our results demonstrate that we can control the morphology, size and electrical properties of PPy and PEDOT by changing the polymerization conditions and adding dopant structures, such as chloride and carbon nanotubes. It was observed that the addition of carbon nanotubes favors the formation of nodules and increases the surface roughness. Also, electrochemical impedance spectroscopy revealed that conductive polymers lower the impedance of gold microelectrodes at the neural interface by three orders of magnitude. To induce selected neurons to attach onto the micro-probe we incorporated into PPy and PEDOT bioactive dopant, such as laminin, saccharin sodium salt and dextran. We compared different deposition parameters and material formulations with resulting morphologies, electrical and electrochemical properties, in addition to neural recording and stimulation. We found that conductive polymer/biomolecule blends and conductive polymer/carbon nanotube composites coated on electrodes maintain intimate contact with axons. Using these conductive polymer composites, high quality nerve spike signals can be detected and electrical stimulation of axons can be achieved.
Joao Pedro Conde Instituto Superior Tecnico
(and INESC Microsistemas e Nanotecnologias)
Barclay Morrison Columbia University
Stéphanie P. Lacour University of Cambridge
Wednesday AM, April 19, 2006
Room 2005 (Moscone West)
9:30 AM - **CC5.1
Soft-state Biofluidic ASIC and Nanocrescents for Systems Biology.
Luke Lee 1 Show Abstract
1 Department of Bioengineering, University of California-Berkeley, Berkeley, California, United States
Cellular Biofluidic Application Specific Integrated Circuits (BASICs)[1-7] are developed for quantitative systems biology and molecular medicine. Soft-state BASICs are created by connecting existing and novel nano- or microfluidic circuits for biological analysis in new ways. We are creating a library of these "building blocks" to develop multifunctional biochip systems. In order to build a solid foundation of future quantitative biology and systematic bioinformatics, we are currently establishing critical modules of BASIC such as Integrated Multiple Patch-clamp Array Chip Technology (IMPACT)[1,2], integrated cell culture chip, cell lysing chip, sample preparation chip, cell separation, single cell array chip, and cell-cell communication biochip. Gold-based nanophotonic crescents have structures with a sub-10 nm sharp edge, which can enhance local electromagnetic field at the edge area. Metallic quantum plasmonic nanocrescents are ideal for nanoscale spectroscopic molecular imaging and photothermal therapeutic applications. The formation of unconventional nanophotonic crescent structure is accomplished by the interfacing both bottom-up and top-down methods, which allows an effective batch nanofabrication and precise controls of surface enhanced Raman scattering (SERS) hot spot coupling nanogap. The nanocrescent SERS probes can be used for sensitive molecular detection and electron transfers of biomolecules, which has enormous benefits in early disease detection, and drug discovery.J. Seo, C. Ionescu-Zanetti, J. Diamond, R. Lal, and L. P. Lee, “Integrated Multiple Patch-clamp Array Chip via Lateral Cell Trapping Junctions” Appl. Phys. Lett., Vol. 84, No. 11, 1973-75(2004). C. Ionescu-Zanetti, R. M. Shaw, J. Seo, Yuh-Nung Jan, L. Y. Jan, and L. P. Lee, “Mammalian Electrophysiology on a Microfluidic Platform” PNAS(2005). P. Hung, P. Lee, and L. P. Lee, “A Continuous Perfusion Microfluidic Cell Culture Array for High Throughput Cell-based Assays” Biotechnology & Bioengineering, 89, 1-8(2005). D. Di Carlo, C. Ionescu-Zanetti, Y. Zhang, P. Hung and L. P. Lee, “On-Chip Cell Lysis by Local Hydroxide Generation” Lab on a Chip 5 (1)(2005). W. C. Chang, L. P. Lee and D. Liepmann, “Biomimetic Technique for Adhesion-based Collection and Separation of Cells in a Microfluidic Channel” Lab on a Chip, 5 (1), 64-73(2005).M. Khine, A. Lau, C. Ionescu-Zanetti, J. Seo, and L. P. Lee, “A Single Cell Electroporation Chip” Lab on a Chip, 5 (1), 38-43(2005). P. J. Lee, P. J. Hung, R. Shaw, L. Jan, and L. P. Lee, “Microfluidic Application Integrated Device for Monitoring Direct Cell-Cell Communication via Gap Junctions Between Individual Cell Pairs” Appl. Phys. Lett. 86, 223902(2005). Y. Lu, G. L. Liu, J. Kim, Y. X. Mejia, and L. P. Lee, “Nanophotonic Crescent Moon Structures with Sharp Edge for Ultrasensitive Biomolecular Detections by Local Electromagnetic Field Enhancement Effect” Nano Letters, 5(1), 119-124(2005).
10:00 AM - CC5.2
Electrochemical Characterization of Protein Superstructures Encapsulated Within Silica Aerogel Nanoarchitectures.
Amanda Harper 1 , Katherine Pettigrew 1 , Christopher Rhodes 1 , Rhonda Stroud 2 , Jeffrey Long 1 , Debra Rolison 1 Show Abstract
1 Surface Chemistry Branch, Code 6171, Naval Research Laboratory, Washington, District of Columbia, United States, 2 Materials and Sensors Branch, Code 6360, Naval Research Laboratory, Washington, District of Columbia, United States
The electron-transfer protein, cytochrome c (cyt. c), can be stabilized within silica gels and supercritically processed to form biofunctional aerogels. Stabilization occurs in buffer through an initial nucleation step in which the protein specifically adsorbs to metal (Au or Ag) nanoparticle, followed by protein-protein electrostatic bonding. The resulting multilayered superstructure is captured within the monolithic gel upon the silica sol-to-gel transition. This nanoarchitecture lends itself to applications such as gas-phase sensing, and biomimetic energy transport through protein-based electron-transfer chains. Towards the latter goal, we are studying the electrochemical characteristics of cyt. c and another electron-transfer protein, azurin, within the gel matrix through the use of mobile, electron-transfer mediators. The results will be compared to UV-visible spectroscopy, Raman spectroscopy, porosimetry, and transmission electron microscopy results.
10:15 AM - CC5.3
Electrically Conductive Polymer Composites Comprised of Poly(ε-caprolactone), Polyaniline, and Bioactive Mesoporous Silicon
Jeffery Coffer 1 , Melanie Whitehead 1 , Leigh Canham 2 Show Abstract
1 Chemistry, Texas Christian University, Fort Worth, Texas, United States, 2 , PSiMedica Ltd, Malvern United Kingdom
To produce electrically-responsive biomaterials whose biological impact can be altered with bias is a long-sought goal. Electroactive materials are especially desirable in tissue engineering because of their ability in principle to control useful biological functions, such as the modification of cellular migration, adhesion, and protein secretion in a synthetic scaffold. We have previously described the fabrication of highly porous composite materials comprised of the bioerodible, bioactive semiconductor mesoporous silicon (BioSilicon™) and the well-established biopolymer polycaprolactone. Yet remaining to be demonstrated in this type of composite scaffold is a framework whereby the semiconducting character of the Si can be exploited. Scaffolds fabricated of this composition to date have involved relatively low loadings of Si (1-10%) in a non-continuous network, with the Si embedded in an insulating PCL sponge. Therefore, it is necessary to develop an architecture that can essentially allow the semiconductor-containing scaffold to be connected to an external bias.One strategy to achieve the above is to employ electrically conductive polymers (ECPs) as an interfacial contact layer with silicon. While most ECPs do not possess the necessary mechanical properties and degradability for tissue engineering purposes, they do provide a facile processibility with BioSilicon™ and PCL, along with necessary conductivity, to permit proof-of-concept with regard to demonstrating electrically-responsive behavior directed by the Si. Previous in vivo studies have also demonstrated that PANi is of sufficient biocompatibility to be useful as a biomaterial. Therefore, a combination of mechanical and electronic properties of conductive polymers (e.g. PANi) and conventional biodegradable polymers (e.g. PCL), along with semiconducting mesoporous Si, has potential merit for use in orthopedic-relevant applications. In this study the fabrication and characterization of an electrically conductive composite material comprised of poly(ε-caprolactone) (PCL), polyaniline (PANi), and bioactive mesoporous silicon (BioSi™) are discussed. The goals of this study are: (1) to develop a device platform stable to extended bias; (2) demonstrate bias-induced biorelevant phenomena in these scaffolds; (3) explicitly evaluate the cytocompatibility of this PCL/PANi/BioSi™ composite. Given the demonstrated ability of BioSi™ to undergo calcification in simulated blood plasma at zero bias, we selected this assay of biorelevance as an initial protocol for evaluating bias-induced effects. This property can be assessed in vitro by exposing an appropriate material to an acellular simulated body fluid (SBF) under the influence of electrical bias.
10:30 AM - CC5.4
The Electric-Protein Interface: New Functionality with Nanoscale Molecular Photovoltaic Structures.
Elias Greenbaum 1 , Barbara Evans 1 , Hugh O'Neill 1 , Ida Lee 2 , Tanya Kuritz 1 Show Abstract
1 Chemical Sciences Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee, United States, 2 Electrical Engineering and Computer Science, The University of Tennessee, Knoxville, Tennessee, United States
The focus of this talk is the presentation of data with novel electronic devices that are comprised of biological components. We have extracted Photosystem I reaction centers from spinach leaves. Using the combined techniques of tapping-mode atomic force and scanning surface probe microscopies, we have demonstrated that PSI retains its molecular photovoltaic properties. PSI has been used to impart photoactivity to tissue cultures of retinoblastoma cells. Photoactive mammalian cells are novel hybrid biological structures that may have application in the field of artificial sight(1). We are also interested in the general problems of biomimetic photosynthesis, molecular “wiring” and the interfacial properties of protein-metal interfaces. Metallic platinum can be photoprecipitated at the point of electron emergence from the PSI reaction center in such a way that electric contact is made between protein and metal nanocatalyst. If platinization is performed on the stromal side of thylakoid membranes, it’s possible to observe the simultaneous photoevolution of hydrogen and oxygen. This biomimetic reaction is a direct analog of natural photosynthesis in which the energy-rich product is molecular hydrogen rather than a carbon dioxide fixation compound. We have demonstrated that plastocyanin and PSI can be molecularly wired to enhance electron transfer between these two biomolecular electron transport proteins (2). In addition, we have performed spectroscopy and photochemistry of spinach PSI entrapped and stabilized in a hybrid organosilicate glass (3) and that cross-linked plastocyanin-platinized PSI possesses remarkable operational stability (4).1. T. Kuritz, I. Lee, E. T. Owens, M. S. Humayun, and E. Greenbaum, “Molecular Photovoltaics and the Photoactivation of Mammalian Cells,” IEEE Trans. Nanobiosci. 4, 196-200 (2005).2. B. R. Evans, H. M. O’Neill, S. A. Hutchens, B. Bruce and E. Greenbaum, “Enhanced Photocatalytic Hydrogen Evolution by Covalent Attachment of Plastocyanin to Photosystem I” Nano Letters 10, 1815-1819 (2004).3. H. M. O’Neill and E. Greenbaum, “Spectroscopy and Photochemistry of Spinach Photosystem I Entrapped and Stabilized in a Hybrid Organosilicate Glass,” Chem. Mater. 17, 2654-2661 (2005).4. B. R. Evans, H. M. O'Neill, J. Y. Howe, E. Greenbaum, “Photocatalyzed Electron Transfer From Spinach PSI to Metal Nanoparticles,” Preprint, Fuels Division, 230th National Meeting of the American Chemical Society (2005).
10:45 AM - CC5.5
In vitro Analysis of Glial Scar Formation around Model CNS Recording Microelectrodes.
Vadim Polikov 1 , Michelle Block 2 , Cen Zhang 1 , Jau-Shyong Hong 2 , W. Reichert 1 Show Abstract
1 Biomedical Engineering, Duke University, Durham, North Carolina, United States, 2 Neuropharmacology Section, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, United States
Chronically implanted recording electrode arrays linked to prosthetics have the potential to make extraordinary positive impacts on patients suffering from full or partial paralysis. While such systems perform well during acute recordings, they fail to function reliably in clinically relevant chronic settings due to the tissue reaction against these implants. In order to explore the biological mechanisms involved in this tissue reaction, we have developed an in-vitro neuron-glia cell culture model from E14 embryonic rat midbrains. Cultures were grown in 24 well plates for 1 week and then treated with no treatment, 10 ng/ml LPS, a scrape wound, or a foreign body (50 um stainless steel microwires). Supernatant was collected for soluble factor analysis, RNA was isolated from the cell cultures, and cultures were fixed at 0, 3, 6, 12, 24, 48 hours, and 7 days after treatment for immunocytochemical (ICC) analysis. ICC showed microglia responding to treatment by chemotaxis to the injury site beginning at 3 hours after treatment while astrocytes responded by extending processes towards the injury and forming a glial scar around the foreign body characterized by upregulated GFAP and Vimentin. Inflammatory and wound healing genes such as those for TNF-a, IL-1b, MCP-1 and TGF-b were found to be upregulated and inflammatory factors including IL-1b and TNF-a were detected in the supernatant at both early and late time points. Double staining showed a layer of microglia sitting atop the wire surrounded by a thick layer of astrocyte processes. These results point to the validity of this cell culture system as an accurate model for the in vivo tissue reaction to chronically implanted cortical electrodes and the presence of inflammatory processes within this reaction.
CC6: Electrode Array
Wednesday PM, April 19, 2006
Room 2005 (Moscone West)
11:30 AM - **CC6.1
Polymer Based Implantable Electrodes: State of the Art and Future Prospects.
Klaus Koch 1 Show Abstract
1 Medical Technology and Neuroprosthetics, Fraunhofer-IBMT, Sankt Ingbert, Saarland, Germany
Electrical interfaces between technical system and the biological system differs with respect to material and shape depending on their intended application. Although there are different approaches using silicon as basic material for sieve or needle like electrodes interfacing the nerve tissue. This abstract will focus on polymer-based flexible implantable electrodes. Mechanical interaction between the electrode and tender nerve tissues can induce adverse body reaction such as fibrous tissue encapsulation. Using flexible materials to design the electro-biological interface might reduce this effect. Different designs of such flexible electrodes were proposed for contacting the nerve or as platform for sensors. For example, Cuff like electrodes can be elastically wrapped around the nerve for recording or stimulation of neural signals. Using microtechnology for the structuring of polymer substrates new fiber like electrodes with multiple electrode sites were developed that can be sewed into the nerve. Thereby the possibility of selective nerve recording and stimulation was improved. One major problem of these tiny and flexible electrodes is the connection to recording and stimulation system. Incorporating electronics such as multiplexer or amplifier directly on the flexible substrate could reduce the number of connection lines or improve the sensor capabilities. Further, the integration of flexible organic electronics on the implant allows the design of more flexible and intelligent electrodes. Additionally the electrodes and sensors can be designed using conductive polymers to create a new generation of “All Polymer ” active implants. Not only the chemical and mechanical properties of the materials employed can influence the biocompatibility of an implant but also the surface topography in the nanometer range plays a key role such as the growth of cells on the implants. Selective adhesion of different type of cells to different parts of the implant is a challenge for the interdisciplinary research. Finally the combination of surface nanostructuring, for example the interference laser beam structuring, and organic electronics with microstructured polymer implants offers interesting potentials for new active implants of the next decades.
12:00 PM - CC6.2
Polymer-Based Microelectrode Arrays
Scott Corbett 1 2 , Tim Johnson 2 , Joe Ketterl 1 Show Abstract
1 , MicroConnex, Snoqualmie, Washington, United States, 2 , Advanced Cochlear Systems, Snoqualmie, Washington, United States
We are developing polymer-based arrays for a variety of implantable applications and have recently fabricated a high-density cochlear electrode array with significantly greater channel density over current generation devices. The polymer-based electrode utilizes liquid crystal polymer (LCP) as the base dielectric. LCP has many desirable properties for medical implants, including biocompatibility, high dielectric constant and high bulk resistivity. The material is also readily processed by injection molding and thermoforming. The array as currently developed utilizes traces formed by thin-film metallization and laser-based lithography and utilizes iridium oxide metallization on the stimulation sites to promote maximum charge transfer while minimizing stimulation voltage.To date we have fabricated high-density arrays (100 micron wide array elements with 100 micron space separating elements) in a small footprint suitable for acute auditory stimulation in animals. We have successfully stimulated cat cochleae with the LCP array and demonstrated improved auditory perception through recordings in the cat inferior colliculus. These results confirm the potential performance improvements possible using high-density arrays for cochlear implants. Testing of the array in a variety of long term soaking and other tests, indicate that while the array functions successfully in acute applications, further improvements are needed before the electrodes are suitable for chronic stimulation. Specifically, interfaces between LCP layers in the array are susceptible to ion leakage, degrading channel isolation. The thin-film stimulation interface also requires further characterization under chronic stimulus demands. We are working on methods to improve the array and continue to explore new and traditional polymer materials in combination with advanced fabrication techniques to advance the art of polymer-based arrays. We are also exploring other uses for the array technology including retinal, deep brain stimulation and neural recording applications. This work was funded by NIH Phase II SBIR Grant, 5 R44 DC004614-03
12:15 PM - CC6.3
A polymer-based Chronic Nerve Interface Microelectrode Array.
Brian Farrell 1 , Dave Edell 2 Show Abstract
1 , Foster-Miller, Inc., Waltham, Massachusetts, United States, 2 , InnerSea Technology, Bedford, Massachusetts, United States
Neural electrodes are essential laboratory tools for neurophysiologists studying the behavior of single neurons and populations of neurons in brain, spinal cord and peripheral nerve. Neurophysiologists are moving beyond single electrode recordings in anesthetized animals to multichannel recordings in awake, behaving animals to continue learning how the nervous system works. Neural electrodes are also useful clinical tools. Intra-cochlear stimulating electrodes are frequently used to produce prosthetic sound for deafness caused by hair cell damage. Implanted surface and penetrating brain electrodes are commonly used in mapping foci of epilepsy. Epidural stimulation electrode arrays over the motor cortex or spinal cord are used for suppression of chronic pain. Deep brain stimulation electrode arrays are used for long-term suppression of the tremors of Parkinson’s disease. Neural electrodes are currently fabricated from small, insulated wires or are micromachined from silicon. Wire and micromachined electrode technologies have shortcomings that the proposed work may address. Wire based electrodes are reliable, but are difficult to place with precision. Further, the large number of wires necessary for some applications can cause excessive neural damage. Micromachined silicon arrays can be used to precisely locate micro-contacts in neural tissue relative to each other but they are stiff. Stiffness allows silicon arrays to be readily inserted into neural tissue, but stiffness does not allow movement with the tissues as the tissue expands or contracts. The result is either the electrode migrates, or there is a proliferation of glial scar about the microelectrode shafts. Also, both metal wires and silicon substrates are much denser than brain which creates the potential for differential acceleration during sneezing or trauma which could destroy local neuron thereby eliminating the signals of interest. In fragile structures such as the cochlea, the process of insertion of the wire arrays currently in use can cause considerable damage, and is limited to the basal turns.This paper will present ongoing work in the development of a thin, flexible, photolithographically-defined polymer-based electrode array based on Liquid Crystal Polymer films and substrates. The goal of the effort is to develop and qualify a new platform technology that would allow accurate positioning of large numbers of electrode contacts in neural tissue for chronic applications. LCP films are a far greater match to the density of neural tissue than the competing wire and silicon arrays and thus will match the bending and flexing as the neural tissues change dimension. This flexibility would cause less neural damage and will maintain a more constant relationship with local neurons. Technology development activities include thin film metallization, interconnect insulation and device microfabrication. In-vitro and in-vivo results will also be presented.
12:30 PM - CC6.4
Fabrication and Characterization of Flexible, Microfabricated Neural Electrode Arrays Made from Liquid Crystal Polymers and Polynorbornene.
Varun Vardhan Keesara 1 , Dominique Durand 2 , Christian Zorman 1 Show Abstract
1 Department of Electrical Engineering and Computer Science, Case Western Reserve University, Cleveland , Ohio, United States, 2 Department of Biomedical Engineering, Case Western Reserve University, Cleveland , Ohio, United States
Microfabrication techniques are being developed for advanced neural electrode arrays to create minimally invasive structures that incorporate a large number of electrical contacts. One common approach utilizes Si as the structural support; however, the rigidity and brittleness of Si restrict the use of these devices. Alternatively, flexible structures based on polyimide have been developed, but these suffer from high water absorption rates which can lead to electrode corrosion and device failure in long-term implants. Liquid crystal polymers (LCP) and polynorbornene (PNB) based polymers, recently developed for electronic packaging, exhibit favorable properties for neural electrode applications. Aside from being flexible and electrically insulating, these polymers provide an efficient barrier against moisture penetration, with absorption rates for LCP and PNB being factors of 50 and 28 better that polyimide, respectively. LCP has been used in neural electrode arrays; but only as a structural base supporting unprotected conductors. To the best of our knowledge, PNB has not yet been used in such devices.This paper reports the development of implantable flexible neural electrode arrays designed to accommodate Si electronics, made from LCP and a PNB known by its trade name AvatrelTM. Each array consists of a single flexible structure composed of an 8 mm-wide pad supporting eight Pt contacts connected to an ASIC mounting pad by a 5 cm-long, 2 mm-wide shaft carrying eight, 50 μm-wide Pt interconnect lines. The Pt conductors sit atop a 50 μm-thick base layer and are isolated from the environment except at the contacts by a capping layer of the same material as the base. In both cases, the devices were fabricated using conventional microfabrication techniques adapted for the particular polymeric material. In the case of LCP, the base structure was fabricated on 50 μm-thick sheets that were mounted to Si wafers with photoresist. Pt conductors were deposited on the sheets and patterned by lift-off. A second LCP sheet was then laminated onto the first sheet. Al or Cu films were deposited and photolithographically patterned into an etch mask to delineate the contact pads as well as the overall structure. CF4/O2 plasmas and KOH solutions were used to etch the structures. In contrast to LCP, PNB is photodefinable which greatly simplifies the fabrication process. Fabrication began by spin coating a 50 μm-thick PNB film on SiO2-coated Si wafers after which the film was photolithographically patterned and cured. Pt conductors were fabricated on top of the film using lift-off. A 10 μm-thick coating was then applied and patterned to expose the Pt contacts. The resulting structures were then released in HF. The extended paper will detail the fabrication sequences comparing the various processing techniques and present the results from mechanical flex, electrical conductivity and moisture resistance testing of both the array and encapsulated electronic chips.
12:45 PM - CC6.5
Flexible Parylene-based Technologies for the Biotic-Abiotic Interface in Retinal Prostheses.
Damien Rodger 1 2 , Wen Li 3 , Hossein Ameri 2 , James Weiland 2 , Mark Humayun 2 , Yu-Chong Tai 1 3 Show Abstract
1 Bioengineering, California Institute of Technology, Pasadena, California, United States, 2 Doheny Eye Institute, Keck School of Medicine of the University of Southern California, Los Angeles, California, United States, 3 Electrical Engineering, California Institute of Technology, Pasadena, California, United States
We are developing flexible radio-frequency coil, chip packaging, and high-density microelectrode array technologies according to a novel paradigm whereby parylene C, a USP Class VI biocompatible, polycrystalline polymer that is vapor-deposited at room temperature, is used as the bulk substrate for a monolithically fabricated retinal prosthesis. Parylene C has been used as an encapsulation material in biomedical implants for many years in particular because of its low moisture permeability and biocompatibility. In light of this, others are attempting to use parylene C in a similar manner as a coating for retinal prostheses typically fabricated mostly of PDMS (a silicone) or polyimide. However, because of the specialized mechanical, electrical, and water permeability requirements for the biotic-abiotic interface in intraocular retinal prostheses, this approach of utilizing traditional bulk materials with a parylene C coating is not favorable. We are applying the knowledge gained from our previous parylene MEMS experience to the fabrication of parylene-based retinal prostheses.Parylene C is an optimal structural material for retinal prostheses when compared with traditional materials in large part because its Young’s modulus (~ 3-4 GPa) gives it flexibility properties that lie between those of PDMS (often reported by surgeons as too flexible at ~ 0.8-1 MPa) and the often-used PI-2611 polyimide (often considered too inflexible at ~ 8.5-9 GPa). Furthermore, parylene C has an elongation to break (~ 270%) that is much higher than that of PI-2611 (100%), and, as such, tears less easily under surgical conditions. We have implanted parylene-based prototypes of intraocular retinal prostheses in enucleated porcine eyes with positive results, and are currently undertaking acute and chronic experiments in canine eyes to study the surgical feasibility of a complete intraocular system and to compare the mechanical effects of parylene C on the retina with the more traditional polyimide.Electrically, parylene C is also well-suited as the substrate for a retinal prosthesis. It has a dielectric constant of approximately 3, enabling low capacitive crosstalk between adjacent metal lines embedded within it, and a dielectric strength better than that of Teflon. Our electrochemical tests have verified that its pinhole-free conformal coating is stable under pulsing in PBS electrolyte.Parylene has one of the lowest water absorption rates (< 0.1% after 24 hours) of any polymer. We have recently developed a new annealing process to enhance chemical adhesion at parylene-parylene and parylene-metal interfaces under accelerated-lifetime saline soak conditions that can convert water-trapping samples to samples that demonstrate no evidence of delamination at these crucial interfaces after months of continuous soaking. Taken together, these experiments and properties suggest that parylene C is ultimately the best structural material for multielectrode retinal prostheses.
Wednesday PM, April 19, 2006
Room 2005 (Moscone West)
2:30 PM - **CC7.1
Development of an On-Chip Micro/Optoelectronic Interface for Brain Implantable Neuroengineering Applications
Arto Nurmikko 1 , Yoon-Kyu Song 1 , William Patterson 1 , Kristina Davitt 1 , John Donoghue 1 Show Abstract
1 Division of Engineering, Brown University, Providence, Rhode Island, United States
Using a silicon based microelectrode array as the cortical neural recording platform, micro- and optoelectronic components have been integrated onto a flexible substrate to create a versatile brain implantable system which has been used to record neural activity in the motor cortex of a rat. The ultralow power system integrates an ultra-low power analog CMOS chip directly to the Si-based neural probe array for amplifying and multiplexing the cortical spikes. Additionally, a low power A/D converter, command and control chip, and optoelectronic components for enabling a fiber optic interface have been fully integrated into a microminiaturized flexible neural chip interface for future brain implantable neuroengineering applications. The flexible platform onto which the discrete components are mounted is based on material choices such as liquid crystal polymer which enables the spatial distribution of the rigid small microlectronic components on two interconnected islands interconnected by imbedded gold microwires. This “dogbone” geometry has been designed by considering surgical insert and physiological constraints of the brain. The CMOS IC includes preamplifier and multiplexing circuitry, and a hybrid flip-chip bonding technique was developed to fabricate a functional, encapsulated microminiaturized neuroprobe device. Our neural interface unit has been tested and evaluated by various methods, including pseudo-spike detection and local excitation measurement, and showed suitable characteristics for recording neural activities. In in-vivo testbed demonstrations we have measured neural activity from the motor cortex of rats, suggesting that the new neural interface chip can form a prime platform for the development of a microminiaturized neural interface to the brain in a single implantable unit. Extraction of the digitized neural signals from the neuroport is performed via a fiber optic coupled, on-chip optoelectronic interface utilizing a low threshold current semiconductor laser. The fiber optical access has also enabled a power delivery scheme to the microelectronic components via a chipscale photovoltaic power converter. We have also been developing an encapsulation strategy for chronic implantation of active devices, including diagnostic measurements.
3:00 PM - CC7.2
Monitoring of Traumatically Injured Organotypic Hippocampal Cultures with Stretchable Microelectrode Arrays
Zhe Yu 1 , Candice Tsay 2 , Stephanie Lacour 2 , 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
Traumatic brain injury (TBI) can be caused by motor vehicle accidents, falls and firearms, and approximately 2% of the US population lives with disabilities cause by TBI. We have developed a TBI model for the precise and reproducible injury of hippocampal cultures to study the injury pathology, as well as, strategies to restore lost function with neural interfaces. The hippocampal cultures are grown on silicone membranes and injured by bi-axialy stretching the membranes. The effect of the mechanical injury on hippocampal function can be studied by measuring the extracellular field potentials of neuronal populations within the cultures. Microelectrode arrays (MEA), are a tool for long-term and simultaneous multi-site recording of extracellular signals from neural circuits which enable the investigation of electrophysiological activity of normal and injured hippocampal slice cultures. However, the traditional MEAs are rigid and are not compatible with in vitro TBI models. We have set-out to create a stretchable microelectrode array (SMEA) with the novel ability to deform with the tissue during injury allowing for continuous recording of neuronal function, pre-, during, and post-stretch.Our SMEAs are fabricated on elastomeric substrates, which are compatible with our TBI model and will allow for long-term and simultaneous multi-site recording of extracellular activity from hippocampal cultures, before and after injury. The SMEAs consist of stretchable 100µm wide, 25nm thick gold electrodes patterned on a polydimethylsiloxane (PDMS) substrate, and encapsulated with a 20μm thick, photo-patternable silicone (WL-5150, Dow Corning) insulation layer. Vias were opened in the encapsulation layer to expose recording/stimulating sites and electrical contact pads. Finally, the SMEA was packaged between two printed circuit boards and mounted in a commercial Multi Channel Systems amplifier. Biocompatibility test show no overt necrosis or cell death after 2 weeks in culture. Therefore, long-term monitoring of hippocampal slices on the SMEA is possible.We report on the electrical performance of the micro-electrodes in electrophysiological saline before, during and after biaxial stretching. The initial electrode impedance at 1kHz was ~2kΩ, and the working noise level was ~8µVpp. The SMEA was stretched to 8.5% biaxial strain. The micro-electrode impedance increased with the strain to reach 800kΩ at 8.5% strain. Upon relaxation, the impedance recovered to 10kΩ. The working noise level of the sMEA remained at ~8 µVpp for strain < 8%, increased to more than 200µVpp at 8.5% strain, and recovered after relaxation. Compared to commercial MEAs, the impedance and working noise level of our SMEA are well adapted to extracellular recording from neuronal cultures.
3:15 PM - CC7.3
A Biomimetic Retinal Interface Based on Localized Neurotransmitter Stimulation.
Neville Mehenti 1 , Harvey Fishman 2 , Stacey Bent 1 Show Abstract
1 Chemical Engineering, Stanford University, Stanford, California, United States, 2 , Plager Vision Center, Santa Cruz, California, United States
Current retinal prostheses primarily use silicon-based microelectrode arrays to locally depolarize groups of neurons in a field-effect manner. There is great concern, however, over both the immune response to chronic electrical stimulation as well as the ability of such a device to maintain intimate contact with excitable cells and harness the biological specificity of retinal circuitry. Since retinal cells communicate primarily through synaptic transmission, we are investigating the feasibility of a flexible retinal interface that mimics this physiological process through localized neurotransmitter delivery. Our flexible neurotransmitter delivery device for physiological stimulation requires the following integrated components: (1) a thin polymeric membrane containing a microchannel network underlying a microaperture through which chemicals are delivered, (2) patterned electrodes within the microchannel network to electrokinetically control fluid flow underneath the microaperture, and (3) an “on/off” switching mechanism to selectively gate neurotransmitter delivery through the microaperture. Soft materials microfabrication methods were applied to mold thin poly(dimethylsiloxane) (PDMS) membranes with a microaperture precisely aligned within a microchannel network using a two-layer photolithography mold. Using pressure-driven flow through the microchannels, fluidic release profiles through the microapertures were observed in real time using fluorescence microscopy. Primary culture retinal ganglion cells were cultured on these microdevices, and subsequent stimulation by glutamate delivery through the microapertures was monitored using calcium imaging techniques.For precise electrokinetic control of the fluid dynamics and contents within the microchannel network, platinum electrodes were patterned on PDMS and glass substrates using standard liftoff techniques. The patterned substrates were bonded to microchannel networks (without an aperture) in order to evaluate different electrokinetic fluid switching schemes. Microfluidic plug injection methods were employed to create and move discrete fluidic plugs of neurotransmitter through the microchannels at a frequency comparable to those achieved by physiological neuronal communication. The integration of the micromolded membranes, patterned electrodes, and plug injection methods will allow for the fabrication and testing of a model retinal prosthetic interface capable of electrically-actuated, high-frequency neurotransmitter delivery.Neurotransmitter-based retinal prosthetic chips are feasible and would not only allow for more physiological stimulation, but may also provide higher resolution stimulation with lower power requirements than current electrically-based devices. This biomimetic approach for prosthetic interfacing could potentially be applied to other neurological disorders in which neurochemical specificity is required to restore physiological function.
3:30 PM - CC7.4
A Neural Stem Cell-Seeded Open-Channel Neural Probe.
Erin Purcell 1 , John Seymour 1 , Daryl Kipke 1 Show Abstract
1 , University of Michigan, Ann Arbor, Michigan, United States
3:45 PM - CC7.5
Biocompatible Parylene Neurocages for Action Potential Recording and Stimulation
Angela Tooker 1 , Jon Erickson 2 , Yu-Chong Tai 1 , Jerry Pine 3 Show Abstract
1 Electrical Engineering, California Institute of Technology, Pasadena, California, United States, 2 Bioengineering, California Institute of Technology, Pasadena, California, United States, 3 Physics, California Institute of Technology, Pasadena, California, United States
Traditional in vitro techniques for studying neural networks use multi-electrode arrays [1,2]. While furthering the study of neural networks, the inherent mobility of the neurons, and the lack of neuron-electrode specificity, can limit the use of these arrays.Parylene neurocages counteract these difficulties by using micromachined structures to trap neurons in close proximity to electrodes, without inhibiting their growth. The neurocages consist of a chimney, tunnels, and anchors. The chimney, in which the neuron resides, is 30μm in diameter and 4μm tall, with a 15μm diameter hole in the top for loading the neuron. 6 tunnels, 25μm long, 10μm wide, and 1μm high, are connected to the chimney, to allow neurite outgrowth. Also connected to the chimney are 6 anchors to lock the parylene neurocage to the substrate. 4 x 4 arrays of parylene neurocages were used. The electrodes are made of Au and insulated with 2μm of parylene. Each neurocage has its own electrode, which is platinized to increase its capacitance. The neurocages can be fabricated on either glass or silicon substrates.Parylene is a biocompatible polymer that is non-toxic, extremely inert, and resistant to moisture and most chemicals. Its conformal deposition makes it easy to fabricate 3D structures like the neurocage. Parylene is transparent, allowing the neurons to be easily seen.The fabrication process begins by evaporating the Au metal for the electrodes. Anchors for the parylene insulation layer are etched into the silicon using a DRIE process  to create an inverted mushroom structure that locks the parylene to the surface. The parylene insulation is deposited and openings for the electrodes are etched with O2 plasma. 1μm of Al is evaporated to form the tunnels. Anchors are etched into the silicon substrate to create anchors for the second parylene layer. A thin layer of Al is evaporated covering the parylene insulation to form an etch stop. 4μm of photoresist are patterned to form the chimneys and the second layer of parylene is deposited to form the neurocage. The opening in the chimney is etched and the chimney photoresist is removed. The tunnels are etched open and the Al is removed. Finally, the electrodes are platinized.Successful growth of neural networks has been achieved using arrays of neurocages with parylene insulation. Since parylene is transparent, the neurites in the tunnels are easily seen. The next step is to stimulate and record from the neurons inside the neurocages. J. Pine, "Recording action potentials from cultured neurons with extracellular microcircuit electrodes," J. Neurosci. Meth. 2, pp. 19-31, 1980. Y. Jimbo, T. Tateno, and H.P.C. Robinson, "Simultaneous induction of pathway-specific potentiation and depression in networks of cortical neurons," Biophys. J., vol. 76, pp. 670-8, Feb. 1999. M. Liger, D.C. Rodger, and Y.C. Tai, "Robust parylene-to-silicon mechanical anchoring," MEMS '03, pp. 602-5, Jan. 2003.
CC8: Electro-biological Systems on Soft Substrates
Wednesday PM, April 19, 2006
Room 2005 (Moscone West)
4:30 PM - **CC8.1
Conformable Electronic Artificial Skins with Organic Transistor Integrated Circuits.
Takao Someya 1 , Tsuyoshi Sekitani 1 , Takayasu Sakurai 2 Show Abstract
1 Quantum-Phase Electronics Center, University of Tokyo, Tokyo Japan, 2 Center for Collaborative Research, University of Tokyo, Tokyo Japan
5:00 PM - CC8.2
a-Si:H Electrolyte-Gate Thin Film Devices for Biological Applications
Dina Goncalves 1 2 , Duarte Prazeres 2 3 , Virginia Chu 1 , Joao Conde 1 3 Show Abstract
1 , INESC - Microsystems and Nanotechnologies, Lisbon Portugal, 2 Center of Biological & Chemical Engineering, Instituto Superior Tecnico, Lisbon Portugal, 3 Department of Chemical and Biological Engineering, Instituto Superior Tecnico, Lisbon Portugal
The development of new devices for the detection of small quantities of chemical and biological molecules is currently of great interest for a number of applications. Ion-sensitive field-effect transistors (ISFETs) are one of the most studied structures for biochemical detection. They are analogous to MOSFET devices, but the metal gate is replaced by a conductive electrolyte solution that is in direct contact with the surface of the device. The adsorption of the analytes from the electrolyte on the device surface results in a change of the transverse electric field in the semiconductor active layer of the device that causes a threshold voltage shift. ISFETs are currently mainly fabricated in crystalline silicon (c-Si). However, hydrogenated amorphous silicon (a-Si:H) offers some advantages over c-Si for this purpose. a-Si:H, the active semiconductor material used in thin film transistors (TFT) for applications such as active matrix liquid-crystal displays and imagers, can be deposited at low temperatures and is suitable for applications on polymer substrates.In this work, we describe the use of a-Si:H-based electrolyte-gate (EG) TFTs for biochemical sensing applications. The main device configuration that was studied involved a transistor with a top gate (Top-EG TFTs). Bottom-gate EG TFTs and Floating-EG TFTs were also studied for comparison. In all the devices, a SiNx layer provides the electrical passivation of metal contacts from the conductive electrolyte. This layer can also work as a biochemical sensitive layer. An additional layer, such as SiO2, was also used as an alternative biochemical sensitive layer.The Top-EG TFTs show sensitivity to electrolyte pH and to the presence of charged biomolecules adsorbed onto the surface of the devices. Negatively charged small oligonucleotides (19 nucleotides) and positively charged proteins (horseradish peroxidase, HRP) were used. Sensitivity of the devices to these charged entities resulted in a shift of the transfer curves of the transistors. In the case of the oligonucleotides, the maximum shift observed so far was 125 mV and corresponds to a concentration of 0.4 μM of DNA. In the case of HRP, a shift of -125 mV is achieved for a concentration of 0.1 μM of protein.Besides the EG-TFTs, sensors based on changes of resistance in thin a-Si:H layers are also presented. In these devices, adsorption of molecules is expected to change the band-bending near the surface resulting in a change in resistivity. The device surface upon which the molecules adsorbed was either a SiNx dielectric layer or the a-Si:H semiconductor layer itself (with a thin native or deposited oxide).Covalent immobilization of biomolecules (DNA and proteins) is also performed on the SiNx and SiO2 biochemical sensitive layers. Sensitivity to the covalently immobilized molecules is tested on both transistors and resistivity sensors.
5:15 PM - CC8.3
Elastic Interconnects for Stretchable Electronic Circuits using MID (Moulded Interconnect Device) Technology
Dominique Brosteaux 1 , Fabrice Axisa 1 , Nadine Carchon 1 , Mario Gonzalez 2 , Jan Vanfleteren 1 3 Show Abstract
1 TFCG Microsystems, IMEC, Gent-Zwijnaarde Belgium, 2 MCP/MODL, IMEC, Leuven Belgium, 3 ELIS, University of Ghent, Ghent Belgium
The main challenge in making stretchable electronic circuits consists in the developing of elastic conductors, interconnecting rigid or flexible islands which hold the components.Today metals are the best option to realize this type of interconnection with high performance and at low cost. A few research groups - have recently reported work on the development of stretchable metallic interconnections on or in elastic substrates. In this contribution we propose an approach based on the one of Gray et al. . Stretchability is obtained using tortuous wires. Mechanical simulations have shown that not only the shape of the wires, but mainly the width of the conductors strongly determines the amount of stress in the conductors under deformation. As an example, reduction of the track width from 90 micron to 15 micron of a 4 micron thick Cu conductor under 20% stretching along the conductor axis reduces the maximum stress with of factor of 10 and more. In our process elliptic (“horse-shoe”) shaped tracks have been designed, which have a better distribution of the stress over the tracks, compared to circular or sinusoidal shapes. Using this design highly conductive stretchable interconnection circuits have been built. The process uses cheap flexible sacrificial substrates, pattern plating techniques, casting and curing of the stretchable substrate material and will be explained in detail in the full paper. In this way stretchable interconnects have been realized, consisting of 4 micron thick gold wires, embedded in 250 micron thick silicone material. The Silicones used are Dow Corning materials Sylgard 184 and Silastic MDX-4210, which were selected for their high stretchability (low Young’s modulus) and high degree of biocompatibility (especially Silastic). Two types of horseshoe shaped tortuous wires were realized : (1) five parallel running wires, each of them 10 micron wide and with 10 micron distance between 2 adjacent wires, (2) a single 90 micron wide wire. The structure with parallel wires could be stretched by at least 40%. The 4 micron thick Au has a measured resistance of 3.5mOhm per square or 3.5 Ohm per running cm of interconnection (5 parallel wires case). Besides this interesting technical features the process holds potential for manufacturing on industrial scale : it can be implemented in a reel-to-reel environment and is a low cost process. Au conductors and silicone materials can be replaced by cheaper materials for other applications (e.g. Cu conductors or polyurethane substrates for integration in textiles). Moreover components can be added in a straightforward way, using conventional flexible circuit assembly, and completely embedded circuits can be produced. These processes will also be explained in the full paper. Lacour, S. P. et al. Proc. of the IEEE, Vol. 93, No. 8, 1459 – 1467, (2005). Maghribi, M. N., PhD thesis LLNL, Preprint UCRL-LR-153347, (2003). Gray, D. S. et al. Adv. Mater., 16, 393 - 397, (2004).
5:30 PM - CC8.4
Effects Of Laser Parameters On The Laser Irradiated Micro-Joints For Bioencapsulation.
Ahsan Mian 1 , Tonfiz Mahmood 2 , Greg Auner 3 , Golam Newaz 2 , R. Witte 4 , Hans Herfurth 4 Show Abstract
1 Mechanical and Industrial Eng., Montana State University, Bozeman, Montana, United States, 2 Mechanical Engineering Department, Wayne State University, Detroit, Michigan, United States, 3 Department Electrical Engineering, Wayne State University, Detroit, Michigan, United States, 4 Center for Laser Technology, Fraunhofer USA, Plymouth, Michigan, United States
Novel biomedical products, implantable microsystems in particular, are designed based on the high level of device integration and miniaturization that pose new challenges to their assembly and packaging. Such devices may include various biocompatible materials such as glass, ceramic and polymers that must be reliably joined. Since adhesives often lack long-term stability or do not meet biocompatibility requirements, new joining techniques are needed to address these joining challenges. Localized laser joining provides promising developments in this area. In this paper, we have discussed the laser processing of mirojoints between glass and polyimide. To facilitate bonding between them, a thin titanium film with a thickness of approximately 5 um was deposited on glass wafers using the physical vapor deposition (PVD) process. To bond the materials, a laser beam was applied through the glass wafer that heated the titanium film to the melting temperature of polyimide. Titanium film was selected as a coupling agent due to its excellent biocompatibility. Two sets of laser-bonded samples were processed. One set of the samples was prepared with a 0.8 um cw diode laser (3.0 W), while the other set was processed using a 1.1 um cw fiber laser (1.0 W). For both sets of the samples, the laser head was scanned at a speed of 100 mm/min along the width of the sample to generate a 6 mm long bond. It is mentioned here that the diode and fiber lasers had super-Gaussian and Gaussian type intensity distributions, respectively. First, the samples were subjected to tension using a microtester for bond strength measurements. The failure strengths of the bonds generated fiber laser are quite consistent, while a wide variation of failure strengths are observed for the bonds generated with diode laser. Few untested samples were sectioned and the microstructures near the bond areas were studied using an optical microscope. The images revealed the presence of a sharp crack in the glass substrate near the bond generated with the diode laser. However, no such crack was observed in the samples made using fiber laser. To investigate the reasons behind such discrepancy, three-dimensional uncoupled finite element analysis (FEA) was conducted for both types of samples. The FEA has two parts, namely, thermal and structural to simulate the entire laser process. First, the transient heat diffusion-based FEA model utilizes the laser power intensity distribution as a time dependent heat source to calculate the temperature distribution within the substrates as a function of time. Next, the structural model is cooled from the temperature calculated in the first part to room temperature. This cool down process develops different thermal stresses in the bond area for different lasers. The FEA results confirmed the presence of critical thermal stresses for the diode laser that may have been responsible for generating cracks in the glass substrate.
5:45 PM - CC8.5
Integration of Electrostatic Micro-actuator with Microfluidic Components for Biological Cell Studies.
Jae-Young Kim 1 , Stephen Phillips 1 , Stephen Massia 2 , Gholam Etheshami 2 Show Abstract
1 Electrical Engineering, Arizona State University, Tempe, Arizona, United States, 2 Bioengineering, Arizona State University, Tempe, Arizona, United States
In this paper, we focus on integration of an electrostatic MEMS comb-drive actuator with a novel microfluidic device for a micro analysis system for studying biological cells. Although electrostatic actuators have been integrated into microsystems owing to IC compatible processing and materials, they have yet gained little attention in microfluidic systems because of many potential obstacles such as electrolysis, electrode polarization, and heating problems in the fluidic medium. In order to effectively avoid these detrimental factors, we address a novel microfabrication method to geometrically isolate electrostatic actuator from the functional microfluidic components using a hydrophobic stop-valve architecture implemented by selective flip chip bonding techniques. 2 x 2 packaged device array has two components. The bottom part consists of the comb drive actuator and electrode pads away from the fluidic environment to prevent electrical contact. The top part is composed of a biocompatible SU-8 seal ring and capping silicon layer for containing the fluidic medium. The packaged devices are characterized using electrical capacitance measurements in the fluidic medium, finite element simulations, scanning electron microscopy, and contact angle measurements. These techniques verify the electrostatic actuation and successful stop-valve performance of the devices. As microfluidic devices are increasingly used to perform biological experiments with living cells, this work suggests the possibility of adapting an integrated electrostatic microelectromechanical fluidic device to biomedical applications. Specifically the focus here is on in vitro cellular response to environmental mechanical stimulations. As part of an integrated hybrid device, the MEMS comb drive actuators are capable of applying controlled force and displacement to immobilized single cells or a small group of cells. The cells are localized using biochemically functionalized surfaces in the fluidic portion. This is mechanically coupled through the hydrophobic stop-valve to the electrostatic actuators. The platform will be ultimately used to evaluate cellular changes such as calcium concentration and genetic modification due to mechanical stimulations.