BIOCHIPS 2001 - Technology Development & ApplicationMarch 12 - 13, 2001 • Polytechnic University, Brooklyn, NY • Brooklyn, NY USA [ Overview | Agenda | Call for Posters | Register ] View Electronic Brochure (PDF)OverviewPresented in conjunction with Polytechnic UniversityBiochip and biosensor technology development today secures the new advanced level of medicine and pharmacology of tomorrow. Introduction of new precise and early diagnostic techniques, turning upside down the current understanding of untreatable diseases, complex application of the novel methods of diagnoses and localization, drug delivery techniques and treatment control will be at a large extent based on success in development, fabrication and implementation of novel materials and technologies towards creating state-of-the-art biochips and biosensors. The conference will provide a balanced review of both crucial materials R&D, technology development and commercial application prospects of this revolutionary class of bioelectronic systems. Numerous medical, as well as some prospective non-medical applications of biochips and biosensors will be presented. Special emphasis will be given to bioMEMS as biomaterials for different applications. In addition, this program will also look at biochips' and biosensors' effect on the latest developments in Bioinformatics, enabling more accurate predictions in the medical research and diagnoses. Don't miss this opportunity to participate in this important gathering with the most comprehensive coverage of this emerging technology. Program features Include:• DNA-, RNA-, gene- and protein microchips development and application • Novel nanoscale materials for biochips and biosensors development • Nanofabrication and self assembly technology for biochips • High throughput screening and analysis automation concepts • Therapeutic microchip technologies and bioMEMS • Bioinformatics - intelligent data collection, handling and analysis • Hetero-functional biochip platform for applications in proteomics and genomics • Implantable microchips for drug delivery • Bioelectronic detection of DNA hybridization: Toward point-of-concern DNA diagnostics • Integration of genomics and biochip technology for drug discovery from traditional Chinese medicine • Impedimetric, reagentless affinity sensors • Microarray technology: From research lab to "real life" applications • Microelectronic array devices and systems for DNA diagnostic, pharmacogenomic and drug discovery applications • Development of high density antibody mimic microarrays • Novel electrochemical biosensor using synthetic ion channels • Miniaturization of the array biosensor • Advanced diagnostics and cell based biosensors • Microanalytical system for blood analysis SCIENTIFIC ADVISORSTauseef R. Butt, LifeSensors, Inc. Anthony Guiseppi-Elie, Center for Bioelectronics, Biosensors and Biochips, Virginia Commonwealth University Kalle Levon, Professor, Director of Herman F. Mark Polymer Research Institute, Polytechnic University, Brooklyn John T. Santini, Jr., MicroCHIPS, Inc. Pankaj Vadgama, Interdisciplinary Research Centre in Biomedical Materials, Queen Mary & Westfield College, University of London, United Kingdom Tuan Vo-Dinh, Advanced Monitoring Development Group, Oak Ridge National Laboratory Michael M. Yang, Applied Research Centre for Genomics Technology, City University of Hong Kong DISTINGUISHED FACULTYDietmar H. Blohm, Universität Bremen, Biotechnologie und Molekulare Genetik, Germany Mauro Ferrari, Biomedical Engineering Center, The Ohio State University Michael J. Heller, Nanogen, Inc. Markus Kurz, Senior Research Scientist, Phylos, Inc. R. Bruce Lennox, Department of Chemistry, McGill University, Canada Frances S. Ligler, Laboratory for Biosensors and Biomaterials, Center for Bio/Molecular Science and Engineering, Naval Research Laboratory Abhijit "Ron" Mazumder, Motorola Life Sciences Rich Meyer, Vice President of R&D, Protogene Laboratories Andrei D. Mirzabekov, BioChip Technology Center, Argonne National Laboratory Alan S. Rudolph, DSO / DARPA Anca R. Varlan, iSTAT Canada John N. Weinstein, Laboratory of Molecular Pharmacology, National Cancer Institute, NIH AgendaMonday, March 12, 20018:15 Registration, Exhibit and Poster Set Up, Coffee and Danish 9:00 Conference Opening and Chairperson’s Remarks Biochip and Biosensor Technology Development9:05 Bioelectronic Detection of DNA Hybridization: Toward Point-of-Concern DNA Diagnostics A whole new class of DNA diagnostic devices is being enabled by the development of non-flourescence detection techniques. Three approaches are being developed and compared. The first is label-free impedimetric detection of DNA hybridization using microlithographically fabricated arrays of interdigitated electrodes on oxidized silicon. In a second approach, this detection is enhanced by the use of colloidal gold nanoparticles that serve as labels of target DNA. The third approach uses an electroactive layer of inherently conductive polypyrrole to provide for covalent attachment of DNA probes as well as provide enhanced redox detection sensitivity to labels such as ferrocene. 9:40 Microarrays of Gel Immobilized Compounds: Massive Parallel Analyses of Specific Interactions and Chemical and Enzymatic Reactions MicroArrays of Gel Immobilized Compounds on a Chip (MAGIChipsTM) are produced by immobilizing oligonucleotides, DNA, enzymes, antibodies, and other compounds on a photopolymerized micromatrix of polyacrylamide gel pads 100x100x20 µm and smaller in size. Alternatively, allyl-modified compounds can be embedded within polyacrylamide gel pads by copolymerization. MAGIChips have been shown to be efficient for analysis of nucleic acid hybridization, specific binding of DNA with proteins, and low-molecular-weight compounds, and protein-protein interactions. The three-dimensional gel pads of the microarrays can be used as nanoliter-sized microtest tubes to perform ligation, single-base extension, PCR amplification of DNA, and other reactions. The fluorescence microscope has been devised for analyzing reactions on MAGIChips, including quantitative and real-time monitoring of hybridization, measuring the thermodynamic parameters of DNA duplexes containing different modified nucleotides, and measuring the kinetics of enzymatic reaction. On-chip MALDI-TOF mass spectrometry was successfully tested for analysis of DNA and protein interactions. Application of these biochips for detection of human polymorphism and mutations, identification of microorganisms and their drug resistant and toxin-bearing strains, and in different fields of biotechnology and medicine will be described. 10:15 Color-Coded Clustered Image Maps (CIMs) for Gene Expression Fingerprinting and Cancer Drug Discovery It has proved easier to use gene expression profiles for classification of tumors and for prognosis than it has been to integrate such profiles into the drug discovery process. We and our collaborators have used both cDNA microarrays and oligonucleotide chips to characterize patterns of gene expression in 60 human cancer cell lines used by the National Cancer Institutes drug discovery program. Since those cells have also been characterized by their patterns of sensitivity to >70,000 chemical agents, we are afforded a unique opportunity to relate the genomics to the pharmacology. Databases and tools of analysis can be found at http://discover.nci.nih.gov. For background, see Weinstein, et al., Science 275:343, 1997 and Scherf, et al., Nature Genetics 24:236, 2000. 10:50 Refreshment Break and Exhibit/Poster Viewing, 11:15 Miniaturization of the Array Biosensor The array biosensor was developed for simultaneous analysis of multiple samples for multiple analytes. A patterned array of capture antibodies is immobilized on the surface of a planar waveguide and a sandwich immunoassay conducted using a cocktail of fluorescent tracer antibodies. Upon excitation of the fluorescent label by a small diode laser, a CCD camera detects the pattern of fluorescent antigen:antibody complexes on the sensor surface. Image analysis software correlates the position of fluorescent signals with the identity of the analyte. The assays are fast, sensitive, and specific. A sensor prototype has been tested which includes a flow cell permanently mounted on the waveguide and a novel fluidics component milled in a plastic cube. With the miniaturization of the fluidics and electronics, the biosensor fits in a 1.5 cubic foot case. Replacement of the peltier-cooled CCD will make a handheld instrument a reality. 11:50 Hetero-Functional Biochip Platform for Applications in Proteomics and Genomics An integrated hetero-functional biochip based on an integrated circuit photodiode array for use in genomics and proteomics is described. The biochip is a self-contained device which allows simultaneous detection of various types of biotargets using different bioreceptors (e.g., antibodies, nucleic acids, enzymes, cellular probes) on a single system. The biochip sensor array device, which is based on an integrated circuit (IC), is designed using complementary metal oxide silicon (CMOS) technology and includes photosensors, amplifiers, discriminators and logic circuitry on board. The highly integrated biochip is produced using the capability of fabricating multiple optical sensing elements and microelectronics for up to 100 sensing channels on a single IC. The capability of large-scale production using low-cost IC technology is an important advantage. The assembly process of various components is made simple by cost-effective integration of multiple elements on a single chip. The usefulness and potential of the biochip technology for proteomics and genomics applications will be discussed. Rapid, simple, cost-effective medical devices for screening multiple medical diseases and infectious pathogens are essential for early diagnosis and improved treatments of many illnesses. An important factor in medical diagnostics is rapid, selective, and sensitive detection of biochemical substances (proteins, metabolites, nucleic acids), biological species or living systems (bacteria, virus or related components) at ultratrace levels in biological samples (e.g., tissues, blood and other bodily fluids). The performance of the biochip device is illustrated with fluorescence detection of both DNA probes specific to gene fragments of the Mycobacterium Tuberculosis (TB) and the human immuno-deficiency virus (HIV) systems, and of antibody probes targeted to the cancer suppressor gene p53. 12:25 Luncheon Sponsored by The Knowledge Foundation 1:40 Chairperson’s remarks 1:45 Key Note Address: Abstract to be provided Microarray Biosensor Technologies2:20 Applications and Features of Custom Designed Oligonucleotide Microarrays The need for customizable, affordable DNA microarrays is not well served in the current marketplace. We have developed a novel microarray technology platform that combines inkjet printing, in situ oligo synthesis and a proprietary differential surface tension chemistry. This platform offers the ability to create custom microarrays at the time of synthesis, and yields arrays with superior feature morphology, reproducibility, and design flexibility. Through an integrated on-line design tool that automates the bioinformatics and array design process, oligos are chosen to provide optimal signal, minimal cross-hybridization and matched Tm. Importantly, these customized arrays can be manufactured within days. The ability to rapidly generate microarrays with customized content represents an unprecedented tool that allows the rapid iterative design and optimization of probes for a variety of applications, such as gene expression profiling and genotyping, and data from these applications will be presented. 2:55 Microarray Technology: From Research Lab to "Real Life" Applications At present microarray technology is a pure research method with great promise for being also applicable in routine applications e.g. in the clinic or industry. But it’s sensitivity, specificity, hybridization efficiency, and other quality parameters depend on the design of the oligonucleotide libraries or cDNA-probes and high tech systems not underlying quality standards or generally accepted protocols. Second generation microarrays are necessary, being part of robust, fully integrated, automatable stand-alone equipment, which should be able to measure real-time hybridization in a flow-through system with a label-free read-out. Progress in these directions will be discussed. 3:30 Refreshment Break and Exhibits/Poster Viewing 3:55 Gene Expression Profiling with Oligonucleotide Arrays on Three Dimensional Substrates Abstract to be provided 4:30 Development of High Density Antibody Mimic Microarrays Using our PROfusionTM protein in vitro selection platform, we have generated novel high-affinity capture proteins that were spotted onto glass chip surfaces to form high-density protein arrays. Our new class of antibody-like capture probes are based on a proprietary protein scaffold and exhibit remarkably high binding affinities combined with excellent target specificity. Target proteins can be detected with high sensitivity using fluorescence or radioactive labeling, mass spectroscopy or enzyme-linked signal amplification methods. We expect our microarrays to find broad application in protein expression profiling and for diagnostic use. 5:05 Protein Biochips for Direct Binding Assays: Applications in the Drug Discovery Process The completion of the human genome project will yield several thousand new potential drug targets. Initially, little information about the function and natural ligand(s) of these orphan proteins will be known. High-sensitivity, direct binding assays using an interferometric protein biochip with integrated reference allow the characterization of these proteins without the development of an assay using e.g. a fluorescent label. 5:40 General Discussion and Close of Day One Tuesday, March 13, 2001,8:00 Exhibit/Poster Viewing, Coffee and Danish 8:30 Selected Oral Poster Presentations Biochip and Biosensor Technology and Application9:00 Chairperson’s Remarks 9:05 Impedimetric, Reagentless Affinity Sensors Biosensors offer the prospect of rapid de-skilled analysis coupled with easy, cheap manufacture. The construct described utilises the intimate association between a conducting polymer (poly(pyrrole)) and entrapped affinity elements to produce reagentless recognition/transduction devices. Monomer electropolymerised across gold interdigitated electrodes on silicon allow impedimetric analysis of bioaffinity interactions that occur at the polymer/entrapped ligand surface. The system is versatile with antigen-antibody, avidin-biotin and DNA hybridisation having been demonstrated. 9:40 A Biotransistor Sensor Based on Immobilized Lipid Membrane Analogues There have been many approaches to coupling biological receptors to electrode surfaces as a menas to produce biosensors. Transduction of receptor-ligand events into an electrochemical signal has been effected using a number of clever schemes involving secondary mediators, redox catalysis, 'wiring' the receptor with electron transfer reagents, etc. These approaches tend to lack generality however, and require adaptation from system to system. Moreover, most of these schemes require immobilization procedures in order to ensure close proximity between receptor and the electrode. We have focused on approaches where the immobilization layer on the electrode surface is also the transducer. Studies will be described where highly resistive self assembled monolayers act as both the immobilization matrix for receptors as well as the transduction element. This system appears to be highly general as a biosensor platform and is amenable to parallel array configurations.
This talk reviews current programs in the fields, highlights opportunities, and focuses on the work we have done over several years at OSU and Berkeley. In particular, we will discuss recent advances in the controlled release of biotechnological molecules from implants, and the development of injectable antiangiogenesis microfabrocated particles for the treatment of metastatic neoplastic disease. 10:50 Refreshment Break and Exhibit/Poster Viewing Therapeutic and Analytical Biochip and Microchip Technologies11:15 Integration of Functional Genomics and Biochip Technology for Drug Discovery from Traditional Chinese Medicine Current drug discovery pipeline relies upon two critical aspects - combinatorial chemical library and high-throughput screening. The output of the pipeline is limited by the availability of gene targets for screening, and the diversity of the compounds to be screened. By integrating state-of-the-art technologies such as biochips, cell-based assays and bioinformatics, in combination with traditional Chinese medicine (TCM), we have established a functional genomics platform for disease gene identification and drug discovery. Our technology platform performs comprehensive biochip-based gene expression profiling and cell function profiling to identify disease pathways and genes that are targeted by effective TCM. The combination of these technologies will greatly accelerate the identification of disease-related genes as potential drug targets, the understanding of action mechanisms and toxicology of TCM, and the discovery of new drug leads from TCM. 11:50 Implantable Microchips for Drug Delivery There is growing interest in the use of microchips as delivery systems for pharmaceuticals, diagnostic reagents, and other chemicals. Our prototype microchips contain an array of sealed micro-reservoirs, each of which is filled with a chemical to be delivered. We were the first to demonstrate the storage and in vitro release of multiple chemicals from a microchip. Recently, our technology has advanced to allow controlled chemical release from subcutaneously implanted microchip devices. This in vivo demonstration of chemical release from a microchip represents a significant step toward the development of "smart" drug delivery systems. 12:25 Biosensors Encapsulating Human Gene Functions: Applications in Drug Discovery and Diagnostics Human receptors that are important therapeutic and diagnostic targets are complexes of many proteins. Ligand dependent function for most of the receptors cannot be established in vitro due to complexity and lack of ligand mediated sensitivity and selectivity. To circumvent this problem ligand dependent functions for many of the human nuclear receptors have been established in yeast. These highly sensitive LiveSensors are robust and amenable to miniaturization on chip-based format. The need for such a nanoscale Functional Microarray in post-genomic era will be discussed. 1:00 Microanalytical System for Blood Analysis 1:35 Lunch on your own
Chairperson - R. Bruce Lennox, Ph.D., Professor, Dept of Chemistry, McGill University, Canada 2:30 Microelectronic Array Devices and Systems for DNA Diagnostic, Pharmacogenomic and Drug Discovery Applications Active microelectronic array systems are being developed for applications in DNA diagnostics, pharmacogenomic research and drug discovery. These microarray devices allow charged reagent and analyte molecules, including DNA, RNA, oligonucleotide probes, amplicons antibodies, proteins, enzymes, nanostructures, cells, and even semiconductor structures to be moved to or from any of the microscopic test sites on the device surface. A research laboratory system (Molecular Biology Workstation and NanoChipTM) has been designed to provide the end-user with "make your own chip" capabilities. Applications include SNP and STR analysis, infectious disease diagnostics, gene expression analysis, and ultimately on-chip amplification capabilities. This system allows assays to be carried out rapidly and with high selectivity. Nanogen’s electronic hybridization technology has been shown to provide highly reliable results for "problematic" genotyping. Nanogen is now also developing other versions of its electronic hybridization technology for general laboratory and high throughput applications. Additionally, in collaboration with Aventis/Selectide R&D groups, Nanogen is investigating the use of active electronic devices for the development of high throughput screening systems for carrying out kinase, phosphatase, and protease enzyme inhibitor assays. This technology may prove useful for drug discovery applications.
3:40 Microarrays - Past, Present and Future The field of microarray technology is revolutionizing biological research. The various applications of microarrays include gene discovery and expression, human disease diagnosis and treatment, forensics, drug discovery and development, and agricultural diagnostics (such as detection of plant and animal pathogens). The future of microarray technology is in its ability to provide protein expression profiles using protein arrays while validating the information using cDNA based arrays that can measure expression levels indirectly at mRNA levels. Some of the challenges facing the protein array development will be iscussed while comparing its similarity with gene arrays. A successful platform for protein arrays has to be reliable, flexible, and cost effective in terms meeting the expectations of end users. 4:15 General Discussion 4:30 Chairperson’s Remarks and Close of Conference Call for PostersCall for Posters Sponsorship & Exhibit Opportunities Conference Sponsorships Networking Event Sponsorships • Cocktail Receptions Workshop Sponsorships Register
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