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Conference Topics Tuesday, March 30, 2004 8:55 Chairperson's Opening Remarks John T. Santini, Jr., Ph.D., President & Chief Scientific Officer, MicroCHIPS, Inc. Medical Therapeutics 9:00 Implantable BioMEMS for Drug Delivery John T. Santini, Jr., Ph.D., President & Chief Scientific Officer, MicroCHIPS, Inc. BioMEMS technology is enabling the creation of intelligent drug delivery systems. The first such system contains an array of sealed, drug-filled reservoirs in a silicon microchip that can be implanted in the body. Release of drug from the microchip's reservoirs can be controlled by pre-programmed microprocessors, wireless telemetry, or biosensors. This presentation will review recent progress and future challenges in commercializing implantable bioMEMS for drug delivery applications. 9:35 Microstructured Dermabraders Shuvo Roy, Ph.D., Co-Director, BioMEMS Laboratory, Department of Biomedical Engineering, The Cleveland Clinic Foundation Miniature abrasion tools have been investigated for potential skin resurfacing applications. Fabrication of micromachined silicon and microreplicated acrylic dermabraders as well as their subsequent performance evaluation using cadaveric skin will be presented. 10:10 A MEMS Based Retinal Implant - For the DOE Artificial Retina Project Kurt O. Wessendorf, Distiguished Member of the Technical Staff, 1700 Microsystems Science, Technology and Components, Sandia National Laboratories Sandia National Laboratories in conjunction with other DOE National Laboratories, the Doheny Eye Institue and Second Sight Corp. are developing technologies to enable a conforming high-density electrode array for use in an implantable artificial retina. The project goal is to provide useful vision to patients with diseases like macular degeneration and retinitis pigmentosa. There are currently many implant designs being developed in the US and abroad but there are many challenging design problems to be solved before an implant is commercially available. Currently Second-Sight and The Doheny Eye Institute are performing clinical studies with a low-resolution implant of their own design. MEMS technologies offer features that are beneficial to an artificial implant and are truly unique to this technology. I will discuss the general requirements, design trade-offs and obstacles that Sandia and others face in this area and present how Sandia's MEMS based design addresses many key design issues. MEMS in BIOResearch I 11:15 A CMOS Imager Chip for Extracellular Monitoring of Nerve Cells and Neural Tissue with 16 k Pixels on 1 mm2 Roland Thewes, Ph.D., Senior Director, Corporate Research, Infineon Technologies, Germany In this talk, a high-density sensor chip is presented for extracellular in-vitro recording of the electrical signals from nerve cells and neural tissue. The chip is based on an extended CMOS process and provides 128x128 sensor sites within an area of 1x1 mm2. The capacitively working sensors scan the surface potential at a full-frame rate of 2 kHz. A specifically developed self-calibration circuitry is used to compensate for intrinsic parameter variations of the small pixel circuits. Measured data will be shown from cultured snail neurons demonstrating the system functionality. 11:50 Chiral and Achiral Biosensing Using Nanostructured Microcantilevers Michael Sepaniak, Professor, Department of Chemistry, University of Tennessee The magnitude, kinetics, and reversibility of surface stresses caused when common Bioaffinity agents interact with microcantilevers (MCs) with nanostructured (roughened) gold surfaces on one side will be reported. Exposure of nanostructured, unfunctionalized MCs to the proteins immunoglobulin G and bovine serum albumin (BSA) resulted in reversible large tensile stresses, whereas MCs with smooth gold surfaces on one side produced reversible responses that were considerably smaller and compressive. The response magnitude for nanostructured MCs exposed to BSA is shown to be concentration dependent and linear calibration over the range of 1-200 mg/L is demonstrated. Stable, reusable protein bioaffinity phases based on nantioselective antibodies are created by covalently linking monoclonal antibodies to nanostructured MC surfaces. The direct (label-free) stereoselective detection of trace amounts of a-amino acids is achieved based on immuno-mechanical responses involving nanoscale bending of the cantilever. A survey and of other bioaffinity measurements on nanostructured MCs will also be presented. In collaboration with Pampa Dutta,1 OliverHofstetter,2 Nickolay Lavrik,3 and Pampa Datskos3 ; (1) Department of Chemistry, University of Tennessee (2) Department of Chemistry and Biochemistry, Northern Illinois University (3) Oak Ridge National Laboratory 12:25 Technologies for High Throughput Microinjection of Fruit-Fly Embryos Ralph W. Bernstein, SINTEF Electronics and Cybernetics, Department Of Microsystems, Norway The results from the genome projects open new opportunities for determination of gene functions important for development and disease. To investigate the functions of the genes or the effect of drugs a rapid screening method is required. One powerful method is to inject embryos with double-stranded RNA, DNA or other biologically active materials. Today such microinjection is carried out at single embryos; a very tedious process. The main goal of the presented work is to develop tools that enable eliable and precise injection of biological material into a large number of embryos within a short time frame. In collaboration with Xiaojing Zhang2, Stefan Zappe2, Matt Fish3, Matthew Scott3, and Olav Solgaard2, Department of Electrical Engineering (2) and Department of Developmental Biology (3) , Stanford University 2:25 Chairperson's Remarks Kurt O. Wessendorf, Distiguished Member of the Technical Staff, 1700 Microsystems Science, Technology and Components, Sandia National Laboratories MEMS in BioResearch II 2:30 Micromachined Cytoadhesive Drug Delivery Devices: Ingestible, Implantable, and Beyond Tejal A. Desai, Associate Professor, ENG Biomedical Engineering, Boston University This talk will focus on micro and nanofabrication approaches to create multifunctional drug delivery platforms, which interact specifically with in vivo cells and tissues Examples include bioadhesive reservoir-containing microparticles for oral delivery and nanoporous capsules for cellular immunoisolation. 3:05 Multiplexed Gene and Protein Analysis for Macro-Scale Drug Discovery and Miniaturized Diagnostics Travis D. Boone, Ph.D., Director, Business Coordination, ACLARA BioSciences, Inc. Abstract not available at time of print. 3:40 MGX™ 4D Array Platform: A Streamlined System for Research of Cancer, Immune Response and Infectious Diseases Mridula Iyer Ph.D, Product Manager, Metrigenix, Inc. Molecular profiling by DNA microarray technology has made significant contributions to the understanding of many diseases, especially cancer. Cancer-specific gene sets, or disease signatures, generated from microarray studies need to be validated using independent cancer samples and sophisticated analytical tools. The MetriGenix 4D™ array system lends itself well to serve these needs. The MGX 4D™ System consists of a patented Flow-thru Chip™ contained within a microfluidic cartridge, automated hybridization and chemiluminescence detection stations, and data analysis software. Disease-relevant gene sets are identified through extensive data mining of comprehensive gene expression databases followed by sophisticated data analysis. Gene selection is based on expression signatures and fold changes between normal and diseased sample groups. In studies with our arrays, our goal is to determine biological markers for potential early detection and clinical diagnostics in the general population using a well defined data mining strategy and an easy-to-use validation platform. Data will be presented that describes the gene selection process including data from the patent pending genes selected that mark the signature for the diseases will be presented. Data will also be presented on expression pattern of the important signature genes using patient samples. Commercialization Experience 4:45 Hybrid Solutions: BioMEMS that Meet Typical Market Demands Dr. Hans-Joachim Hartmann, General Manager, thinXXS GmbH, Germany Customers from the life sciences hardly ever show an interest in the mysteries of MEMS technology. What they expect, instead, is a solution to their product idea. Unfortunately, one might say, these ideas rarely fit with the way micro systems are manufactured. Or differently put: their notions as to functionality and price are difficult to reconcile. In this situation, we have looked for new approaches and found that hybrid micro systems, which combine different materials and hence techniques, often meet the requirements best. 5:20 Lessons Learned from a MEMS Manufacturing Company Sandra Katz, Vice President, Marketing and Business Development Biosystems, Micralyne, Inc., Canada Companies developing BioMEMS products eventually get to the stage where they must focus their efforts on evaluation of a foundry. Very little has been written regarding the questions that should be asked by MEMS foundries of the MEMS companies that approach them for product development. While it is difficult to turn away paying customers, it is often a prudent business decision to do so as the wrong match between customer and supplier can often mean the difference between project success and failure. Micralyne has a proactive approach to assess the prospective customers that approach them. Effective "selection" by a foundry of its customers can have a profound effect on the success of the product development. The new question is, "What makes a customer strong in the eyes of a foundry?" Wednesday, March 31, 2004 8:15 Chairperson's Remarks Shuvo Roy, Ph.D., Co-Director, BioMEMS Laboratory, Department of Biomedical Engineering, The Cleveland Clinic Foundation Micro/Nanofabrication Approaches 9:00 Development of a Flagellar Motor Based Microfluidic System Steve Tung, Assistant Professor, Department of Mechanical Engineering, University of Arkansas Bacterial flagellar motors have the highest power and torque output when compared to other forms of molecular motors. For some bacteria, the cell body, after genetic modification, can be tethered down to a smooth substrate through a single flagellar filament. When this occurs, the rotary motor at the base of the filament turns the cell body at a high speed of rotation. We are in the process of developing a hybrid microfluidic system that uses tethered flagellar motors as rotary actuators. In this system, the biological motors are integrated with microfabricated devices to perform the three basic functions of a microfluidic system: pumping, valving, and mixing. Development of such hybrid system requires a significant convergence of cellular biology and MEMS. This presentation will discuss the technical difficulties and potential solutions in the integration of flagellar motors and MEMS. 9:35 Thermoelectric Microdevice Fabricated by Electrochemical MEMS Process G. Jeffrey Snyder, Jet Propulsion Laboratory/California Institute of Technology An inexpensive, electrochemical technique is described which can build MEMS-like structures that contain several different metals and semiconductors with three dimensional bridging structures. This novel technique is demonstrated by building a working micro-thermoelectric device. Such a device can revolutionize the technology for precise thermal control for lab-on-a-chip applications when operating as a cooler/heater. 10:30 Ultra-High-Speed Cell Sorting Using MEMS John S. Foster, CEO, Innovative Micro Technology We describe a MEMS (micro-electro-mechanical system) chip technology, which uses 32 parallel channels to sort cells in a fluid mixture. Laser-driven fluorescence of appropriately tagged cells is used for the detection mechanism. The chip integrates optical components, fluid manifolds, and electromagnetic valves. The goal for this project includes high performance, ease of use, and disposability, which can enable eventual clinical use. Clinical Diagnostics 11:05 Experiences with Microfluidics Chips in Molecular Biology and Bionanotechnology Applications Leo Kretzner, Ph.D., Research Scientist, Urologic Oncology/Surgical Research, City of Hope National Medical Center Our lab has now had over three years of microfluidics experience using the Agilent 2100 Bioanalyzer© for a variety of applications. These range from "standard usage", such as detection and sizing of RT-PCR products in basic science and clinical diagnostics, to novel applications with unusual DNA structures and other experimental permutations. Using representative data from these studies, the strengths as well as current limitations of the technology in our hands will be reviewed and discussed. 1:00 Chairperson's Remarks Dr. Holger Bartos, STEAG microParts GmbH, Germany Clinical Diagnostics II 1:05 Novel Biochips with Integrated Fluidic Functions for Medical Applications Dr. Holger Bartos, STEAG microParts GmbH, Germany* Microfluidic devices are currently established in laboratory equipment for biomedical research and start to penetrate the diagnostic market for point-of-care and lab automation applications. For an effective development of such products STEAG microParts has created various microfluidic design elements, which allow the integration of fluidic functions on microfluidic reaction platforms, like blood plasma separation, resuspension of dried chemicals, a defined i ncubation time and transport to a detection zone. These features, together with the high precision and reproducibility of micro injection molding, surface modification and bonding of the platforms enable the design of quantitative assays, e.g. for point of care immunoassays. Results concerning the development of microfluidic devices, design elements, fabrication and performance of these biochips will be presented. * In collaboration with Dr. Ralf-Peter Peters, STEAG microParts GmbH 1:40 High-Throughput Genotyping by Microchip Electrophoresis András Guttman, DIVERSA Co. Large-scale genotyping, mapping and expression profiling require affordable, fully automated high throughput devices enabling rapid, high performance analysis using minute quantities of reagents. This presentation reports on a novel combination of miniaturized PCR based DNA amplification and restriction digestion followed by microchip or micro-gel electrophoresis analysis of the resulting products. This approach decreases reagent consumption (total reaction volume 0.75 - 1 ml) as well as the amplification 15-20 minutes), digestion (3-10 min) and electrophoresis times (90-300 seconds) by automating the current manual procedures and reducing human intervention by using sample loading robots and computerized real time data analysis. 2:35 Micro Sensors For Vascular Intervention Procedures William Suh, Verimetra, Inc. Useful information from the tip of catheters helps surgeons improve vascular intervention procedures because it allows them to make intra-operative decisions. Extraction of such information is realized by embedding micro sensors directly onto the distal end of catheters. A few examples of catheter sensors will be discussed. 3:10 An Implantable, Wireless, Batteryless, MEMS Pressure Sensor for Tailored Treatment of Cardiovascular Diseases Nader Najafi, Ph.D., President and CEO, Integrated Sensing Systems Incorporated (ISSYS) This talk reports the results of the initial animal studies of a wireless, batteryless, implantable pressure sensor using MEMS (MicroElectroMechanical Systems) technology. The animal studies were acute and proved the functional feasibility of using MEMS technology for wireless bio sensing. The results are very encouraging and surpassed the majority of the application's requirements, including high sampling speed and high resolution. Based on the lessons learned, second generation wireless sensors are being developed that will provide total system solution.