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Overview

MAIN CONFERENCE

In it's 2nd year, this internationally recognized conference addresses the most recent achievements in biochip, biosensor, microarray, and bioinformatics technologies. BioChips 2002 meets the demands of academia, government, and industry with emphasis on the major challenges faced by biochip developers bringing their technologies to the marketplace.

This conference will provide a balanced review of medical, biological and biodetection applications of biochip related instruments as well as examine the state-of-the-art technology R&D issues including:

• Biochips in Perspective: Technology, Biology, Informatics
• DNA and Protein Biochips
• Multi-Functional Biochips for Biological and Medical Diagnostics
• Advanced Detection and Sampling
• On-Chip Monitoring of Cell Based Reactions
• Biosensing - Silicon-Based Biosensors
• Membranes, Microflows and In Vivo Monitoring
• Microchip Platform for DNA Hybridization
• Microelectronic DNA Array Devices for Molecular Diagnostics
• Implantable Microchips for Drug Delivery
• Microfluidic Systems - A Practical Perspective
• Advanced Microarray Technologies for Genomics and Proteomics
• Dissecting Gene Regulatory Networks
• Oligonucleotide Arrays for Functional Genomics
• Novel Automated Microarray Systems and Devices

RELATED LINKS
ACLARA BioSciences, Inc.
Affymetrix, Inc.
American Institute of Physics Journal – Applied Physics Letters
Lab-on-a-Chip.com
MicroCHIPS, Inc.
Packard BioScience
PharmaGenomics Magazine
Royal Society of Chemistry Publication - Lab on a Chip
VCU C3B
Zyomyx, Inc.

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Biochips 2002 Hands-on Workshop
Technologies for Producing and Analyzing High Density DNA Microarrays

Wednesday, March 20, 2002, Virginia Commonwealth University Richmond, VA, USA

Organized by Virginia Commonwealth University's Center for Bioelectronics, Biosensors and Biochips (C3B) and Virginia Microelectronics Center (VMC)

This workshop aims to present principles, current best practices and methodologies for DNA Microarray fabrication with emphasis on differential gene expression in cancer genomics. This workshop is scheduled for the third day following the two-day Knowledge Foundation's BioChips 2002 International Conference (March 18-19) to be held in Richmond, Virginia. The workshop will include targeted lectures as well as direct hands-on training in the C3B's Advanced Microarraying Facility.

For more information please visit Workshop web site

Who Should Attend

- ­­Industrial scientists and engineers who are interested in developing and applying DNA microarraying techniques to issues in protein engineering, metabolic engineering, bioprocess monitoring and optimization, and biocatalysis screening.
- Academic researchers who are preparing to establish their own facility and who seek direct evaluation of a complete facility.
- Research managers responsible for R&D strategic planning who are interested in exploring the role and value of microarraying technologies in their development programs.

Lecture Tips and Hands-on Laboratory Sessions:
- Microarray printing using a Cartesian Technologies PixSys 5500 SQ
- Data Analysis using GeneSpring's Expression Analysis Software
- Microarray Imaging using Packard BioChips Scan Array 5000
- Liquid handling using a Packard Biochips MultiProbe II
- Clean room protocol for biochips and DNA microarrays

Number of seats is limited. Please register early!

Agenda

Monday, March 18, 2002
MORNING SESSION

8:00 Registration, Poster/Exhibit Set-Up, Coffee and Pastries

8:50 Chairperson's Opening Remarks
Michael J. Heller, PhD, Professor, Depts Bioengineering/ Electronic and Computer Engineering, University of California San Diego; Consultant, Nanogen Inc.

9:00 Keynote Address
BioChips in Perspective: Technology, Biology and Informatics
John N. Weinstein, MD, PhD, Senior Investigator, Laboratory of Molecular Pharmacology, National Cancer Institute, NIH
BioChips will revolutionize the biomedical sciences. That much is a universal assumption - or at least an urban legend. But the lofty expectations will be met only if we can overcome a number of major challenges - at the levels of technology, statistical analysis, and biological interpretation. In no context are those challenges as fully evident as in the application of BioChips to molecular pharmacology and drug discovery.

9:45 A Multi-Functional Biochip for Biological and Medical Diagnostics
Tuan Vo-Dinh, PhD, Group Leader, Corporate Fellow, Advanced Monitoring Development Group, Oak Ridge National Laboratory
We describe an integrated Multi-Functional Biochip (MFB), which allows simultaneous detection of several disease end-points using different bioreceptors such as DNA, antibodies, and enzymes on a single platform. The MFB includes an integrated circuit (IC) electro-optic system for the microchip detection elements based on the complementary metal oxide silicon (CMOS) technology. With this technology, highly integrated biochips are made possible partly through the capability of fabricating multiple optical sensing elements and microelectronics on a single system. The MFB device is a self-contained system based on an integrated circuit including photodiode sensor arrays, electronics, amplifiers, discriminators and logic circuitry on board. The highly integrated biochip is produced using the capability of fabricating multiple optical sensing elements and microelectronics on a single IC. The capability and potential of the biochip technology in medical diagnostics and biological pathogen monitoring will be discussed.

10:20 Refreshment Break, Exhibit/Poster Viewing

11:00 Dissecting Gene Regulatory Networks: A Two-Sided Approach
Thomas L. Volkert, Director, Whitehead Institute Center for Microarray Technology, Whitehead Institute
Much has been learned from microarray technology about how cells respond to environmental stimuli by regulating the expression of various genes. While this expression information is extremely useful for many purposes, it tells us very little about the underlying mechanisms that regulate gene expression. A global view of transcriptional regulation can only be obtained by integrating expression data with assays that directly monitor the activity of the transcription factors that regulate expression. Our goal is to create a network map for transcriptional regulation in yeast by combining expression analysis with transcription factor binding information from Genome-Wide Location Analysis. This talk will present the technique of Genome-Wide Location Analysis and show how it can be used to create network maps for transcriptional regulation.

11:35 A Microchip Platform for DNA Hybridization in Point-of-Concern DNA Diagnostics
Anthony Guiseppi-Elie, ScD, President and Scientific Director, ABTECH Scientific Inc.; Professor, Dept Chemical Engineering; Director, Center for Bioelectronics, Biosensors and Biochips, Virginia Commonwealth University
A microlithographically fabricated device or biochip platform has been developed for impedimetric and / or amperometric detection of DNA hybridization reactions. The microchip platform consists of a 32-element array of interdigitated electrodes or a 64-element array of microbore electrodes on oxidized silicon or glass. With 5 micron critical dimensions, this platform allows bioelectronic detection of DNA hybridization reactions performed on sensory elements. These elements allow:
1) label-free impedimetric detection of DNA hybridization,
2) enhanced impedimetric detection using colloidal gold nanoparticles that serve as labels of target DNA, and
3) the use of an electroactive layer of inherently conductive polypyrrole to provide for covalent attachment of DNA probes as well as to provide enhanced redox detection sensitivity with electroactive labels such as ferrocene.
This biochip platform has enabled a whole new class of DNA diagnostic devices that are independent of fluorescence and have the potential for clinical diagnostics of targeted genetically-based conditions.

12:10 Implantable Microchips for Drug Delivery
Norman Sheppard, PhD, Director of Basic Research, MicroCHIPS, Inc.
Microfabrication technology is enabling the creation of intelligent drug delivery systems. Typical microchip systems include an array of sealed micro-reservoirs, where each reservoir is filled with a chemical and can be released on demand. Our group was the first to demonstrate the storage and in vitro release of multiple chemicals from a microchip, and recently, we achieved in vivo chemical release from subcutaneously implanted microchip devices. This talk will cover recent progress in the development of implantable microchips for drug delivery applications.

12:45 Speaker Power Luncheon Sponsored by The Knowledge Foundation
Don't miss an opportunity to meet one-on-one with our conference faculty. Delegates are invited to join participating speakers over luncheon to discuss today's "hot topic" biochip issues.

AFTERNOON SESSION

2:00 Chairperson's Remarks
Tuan Vo-Dinh, PhD, Group Leader, Corporate Fellow, Advanced Monitoring Development Group, Oak Ridge National Laboratory

2:05 Advanced Detection Technologies
Alan S. Rudolph, PhD, MBA, Program Manager, Defense Sciences Office, DARPA
The Defense Advanced Research Projects Agency has explored innovative detection technologies for evaluating chemical and biological agent threats in environmental or medical diagnostic applications. These efforts include interfacing with biomolecular, cellular, tissue, and organismal-based systems in order to create technologies, which can rapidly assess threats, present correlative data on human health risk assessments. Specific examples of projects from the portfolio will be presented with the purpose of demonstrating both near term and next generation capability for enhancing our response to national security threats.

2:40 BioChips - Sampling and Detection in the Field
William Ragland, PhD, MBA, PE, Senior Account Manager, Life Sciences, Argonne National Laboratory
Many BioChip systems developed to date have been designed for use in "clean" industries: pharmaceutical screening, medical applications, and basic research. As applications of BioChips in field settings develop, BioChips systems will not only be used in a controlled laboratory environment but against the background noise of the biosphere. Such uses will require low cost, rugged systems with high discrimination than can be used either by operators with limited training or in an automated mode. Argonne National Laboratory, working with DOE, DARPA, other defense agencies, and several commercial partners, has been working for a number of years to develop a low cost, portable system to meet such these requirements. In optical detection, Argonne has already moved from the paradigm of putting the camera on the microscope to putting the microscope on the camera and, finally, to replacing the camera with CCD detection. Argonne's most recent hand-held microscope eliminates costly stages and focusing requirements. Argonne is testing its hand-held microscope for cross-platform compatibility with BioChips in addition to Argonne's MagicChip®. In developing cross-platform compatibility it is Argonne's goal to enable the use of BioChips from multiple sources for field use in areas such as environmental monitoring, food safety testing, and biodiversity research.

3:15 Microelectronic DNA Array Devices for Molecular Diagnostic, Pharmacogenomic and Other Applications
Michael J. Heller, PhD, Professor, Depts Bioengineering/ Electronic and Computer Engineering, University of California San Diego; Consultant, Nanogen Inc.
Active microelectronic array devices have been developed for applications in DNA diagnostics and pharmacogenomics research. Electronic hybridization formats provide considerable advantages for carrying out rapid SNP, point mutation and STR analysis with extremely high accuracy and reliability. Results from many thousands of test samples show that electronic hybridization provides higher reliability for homozygous and heterozygous calls than conventional "gold standard" methods (DNA sequencing, passive array, RFLP, etc.). Electronic hybridization allows highly reliable results to be obtained for problematic or difficult SNP's, which include SNP's with associated secondary structure, SNP's within high G/C sequences and multiple SNP's in close proximity. High reliability minimizes the potential for false positives or false negatives, which will be an important performance criterion for any genotype panel that would be used for actual clinical diagnostic applications. In other areas, prototype integrated "sample to answer" systems are being developed for potential point of care and biohazard detection applications. These integrated systems can carry out cell separation, lysis, DNA/RNA extraction, amplification and genotyping (via electronic array hybridization).

3:50 Refreshment Break, Exhibit/Poster Viewing

4:30 Demonstration of a Single-Color Expression Profiling Assay Based on Oligonucleotide Microarrays with a Three-Dimensional Polymeric Surface
Abhijit "Ron" Mazumder, PhD, Senior Manager, Expression Profiling, Motorola Life Sciences
The use of a three-dimensional, branched polymeric substrate, an integrated hybridization chamber which permits efficient mixing, and piezoelectric printing has generated a highly sensitive, specific, and reproducible expression profiling platform. The attachment chemistry permits the assay to be performed in probe excess, generating a linear dynamic range of 2.5 logs. A linear, sensitive, and reproducible detection method has generated a sensitivity of one copy per cell and CVs in the hybridization signals in the 7-12% range. The use of 30mer oligonucleotides permits the discrimination of sequences which are up to 90% homologous. Lastly, automation of the target preparation and batch processing of the slides generates low target preparation variability and high throughputs.

5:05 Development of Oligonucleotide Arrays for Functional Genomics
Viktor Stolc, PhD, Research Scientist, Center for Nanotechnology, NASA Ames Research Center
NASA Ames Research Center, Center for Nanotechnology (Moffett Field, CA) is developing functional genomics assays using high-density oligonucleotide arrays synthesized with electrochemistry. A high-density DNA-chip based method called quantitative phenotypic analysis is used to investigate the biological functions of all genes in yeast Saccharomyces cerevisiae under any growth condition. Yeast is used as a model system because it is one of the most genetically and genomically tractable organisms and because it has proven itself a model for the study of human physiology and genetics. http://ipt.arc.nasa.gov/stolc.html

5:40 SNP Analysis Using Surface Invasive Cleavage Reactions on Addressed Arrays
Michael R. Shortreed, PhD, Assistant Scientist, Dept Chemistry, University of Wisconsin-Madison*
The structure-specific invasive cleavage of single-stranded DNA by 5' nucleases is a useful means for sensitive detection of single-nucleotide polymorphisms or SNPs. The solution-phase invasive cleavage reaction has sufficient sensitivity for direct detection of as few as 600 target molecules with no prior target amplification. Our approach to the parallelization of SNP analysis is to adapt the invasive cleavage reaction to an addressed array format. Reverse fluorescence resonance energy transfer (FRET) was utilized for detection on first generation arrays. The second generation arrays, now in development, will employ label-free probes and use surface plasmon resonance (SPR) imaging for array readout.
*In collaboration with: T. Berggren, R. Corn, M. Lu, L.M. Smith, and L. Wang, University of Wisconsin-Madison; J.G. Hall, V. Lyamichev, and B. Neri, Third Wave Technologies; P.W. Stevens and D.M. Kelso, Northwestern University

6:15 End of Day One

Tuesday, March 19, 2002
MORNING SESSION

8:00 Exhibit/Poster Viewing, Coffee and Pastries

8:55 Chairperson's Remarks
Norman Sheppard, PhD, Director of Basic Research, MicroCHIPS, Inc.

9:00 Membranes, Microflows and In Vivo Monitoring
Pankaj Vadgama, PhD, Professor, Director IRC in Biomedical Materials, Queen Mary & Westfield College, United Kingdom
Any interfacing biosensor requires surface modification or membrane materials that create an interphase to modify the biomatrix compatibility of a device and control solute transport. Our work on solute selective thin and thick films will be described, capable of selective transport. Also work on porous membrane structures modified with pre-absorbed protein will be presented to assess their ability to permit lateral transport of indicator and binding proteins for electrochemical immuno detection. Thus description of solute flows will extend to flow in linear channels, where parallel, but non-mixed, electrolyte streams are shown to present a mobile barrier interphase serving to protect electrode surfaces. The concept of fluid flows to reduce electrode fouling will be extended to the case of percutaneously implanted metabolite sensors to permit reliable operation in a complex tissue environment.

9:35 Silicon-Based Biosensors
Philippe M. Fauchet, PhD, Professor, Director, Center for Future Health, University of Rochester
Silicon technology is very mature but it is only recently that biosensors made in and of silicon have been proposed. This presentation will review progress toward making optical and electrical silicon biosensors, including DNA sensors, protein sensors and bacteria sensors. These sensors rely on the simultaneous control of multiple length scales, from the nanometer to the micrometer level. The integration of these biosensors with silicon microelectronics will be discussed.

10:10 Refreshment Break, Exhibit/Poster Viewing

10:45 Development of Microfluidic Systems - A Practical Perspective
Phil Belgrader, PhD, Vice President, Microfluidic Systems Inc.
In this presentation, we will present the practical view of microfluidic systems development, implementation and commercial opportunities. Examples will be given for automated sample processing for nucleic-acid-based pathogen detection. Included will be results from actual field trials and large volume water sample processing. As well, we will discuss the extension of these results and designs into system concepts and developments for applications such as oligonucleotide hybridization arrays. Issues concerning fluid handling, volumes, processing steps, and analytical methodologies will be presented. The perspective presented in this talk includes an analysis of existing commercial approaches and new research and development opportunities in the area of microfluidics.

11:20 On-Chip Monitoring of Cell-Based Reaction by Controlled Concentration Gradients
Michael M. Yang, PhD, Director, Applied Research Centre for Genomics Technology, City University of Hong Kong*
This presentation describes a passive microfluidics with simple planar geometry for mammalian cell-based reaction analysis. In order to reduce fabrication complexity, all functions were performed with a 2D main feature design with no moving parts employed. Fluidic flow is generated from liquid level difference among vials without the need for mechanical or electrical fluidic driving force. Difference liquid level programs (LLP) can be assigned for different flow patterns. Cell docking, where mammalian cells were driven and aligned on a dam structure was performed by carefully controlled LLP. Dilution of interested analyte is performed with different LLP such that an on-chip analyte concentration gradient is established. An ATP-dependent calcium uptake reaction is utilized as a model to demonstrate the ability of this micro-device in looking for threshold ATP concentration of this reaction.
*In collaboration with: Li Cheuk Wing, Yang Jun, City University of Hong Kong

11:55 Advances in Using GeneChip® Technology for Expression Studies
Raji Pillai, PhD, Genomics Collaborations Scientist, Affymetrix, Inc.

(Abstract not available at time of posting. Visit this page later.)

12:30 Lunch on Your Own

AFTERNOON SESSION

2:00 Chairperson's Remarks
Anthony Guiseppi-Elie, ScD, President and Scientific Director, ABTECH Scientific Inc.; Professor, Dept Chemical Engineering; Director, Center for Bioelectronics, Biosensors and Biochips, Virginia Commonwealth University

2:05 The Development of Protein BioChips
Jens R. Sydor, PhD, Manager Assay Development, Zyomyx, Inc.
While technological innovation has adapted the analysis of genetic material to a miniaturized format, the more delicate nature of protein structures has precluded the development of analogous devices for proteins. Protein microarrays have started to emerge recently based on new developments and integration efforts in advanced materials, protein engineering, and detection physics. (i) High-density protein microarrays for quantification of multiple proteins in complex mixtures, (ii) implementation of new surface chemistries for immobilization of exactly defined quantities of proteins on each spot while retaining the full activity of the protein, and (iii) using this platform for developing the multiplexed, microchip-based immunoassay to analyze expression levels of serum proteins will be discussed. Detection limits on this microassay are equal to commercial ELISA tests and reduce the sample volume by many orders of magnitude.

2:40 HydroGel™ Substrate as a Platform for Protein Microarray Applications
Martin Sommer, PhD, Research Scientist, PerkinElmer Life Sciences
Microarrays will revolutionize proteomics as they have the field of genomics. Because proteins are more sensitive to their environment than nucleic acids, substrate requirements are heightened for protein microarray applications. At Packard BioChip Technologies, we have developed HydroGel™ coated slides, featuring a 3-D substrate that offers several advantages over other substrates, including a high probe loading capacity, low background and a 3-D environment that seems to preserve protein functionality and accessibility. This platform has been used to develop fluorescence-based multiplexed assays.

3:15 Plastic Labcard™ Devices and eTag™ Assay Systems for Genomics and Proteomics
Z. Hugh Fan, PhD, Principal Scientist, ACLARA BioSciences Inc.
Modern genetic analysis and drug discovery depend increasingly on the rapid, parallel, and inexpensive analyses of large numbers of samples. To address these needs, ACLARA is developing low-cost plastic Labcard™ devices that employ modern lab-on-a-chip techniques for highly parallel analyses. In addition, ACLARA's proprietary eTag™ chemistry technology works synergistically with electrophoretic separation methodology to enable rapid and multiplexed detection of both proteomic and genomic targets in each sample. An overview on the capabilities of plastic microfluidic device arrays and the multiplexing power of eTag™ assay systems, as well as recent results and commercial applications, will be presented.

3:50 Refreshment Break, Exhibit/Poster Viewing

4:20 Escape from Flatland of Microarrays - An Introduction to 4D System™
Hongjun Yang, PhD, Vice President of R&D, MetriGenix, Inc.
The 4D™ System consists of a patented Flow-thru Chip™ contained within a microfluidic cartridge, an automated hybridization station, chemiluminescent detection, and data analysis software. The system has been used for gene expression profiling, SNP detection, quantitative protein analysis, and enzymology applications. The 4D™ System has the performance characteristics required to meet the needs of high throughput screening as well as individualized patient care.

4:55 A 3D-Biomaterial for Enablement of Broad-Based Antibody/Enzyme/Protein and Whole Cell BioChips
Charles H. Squires, Senior Technical Leader, Molecular Biology, Biochemistry and Genomics,
The Dow Chemical Company
Modern micro array technology (i.e., DNA and protein micro arrays) enables faster applied discovery of pharmaceutical and biotherapeutic leads. In contrast to DNA micro arrays which are increasingly utilized in many fields of research, the application of protein and whole cell arrays has lagged behind. The main reason for this is the lack of a broadly applicable material or support matrix (biomaterial) for stabilizing protein structures and activities. The given biomaterial itself should be compatible with existing arraying equipment, processes, and detection methods in order to produce quality, high-density arrays. We are currently testing a 3D-biomaterial, a porous modification matrix, that is highly elastic, durable and is a hydrated hydrophilic polymer for its ability to address these needs and enable applications of antibody/enzyme/protein and whole cell BioChips. In initial studies, we have demonstrated incorporation of various proteins, protein systems, and whole cells into the 3-D material. We additionally show stable activity of these systems with the matrix.

5:30 General Discussion
Moderator - Anthony Guiseppi-Elie

6:00 Closing Remarks, End of Conference

Wednesday, March 20, 2002

Organized by Virginia Commonwealth University's Center for Bioelectronics, Biosensors and Biochips (C3B) and Virginia Microelectronics Center (VMC)

Rm. 105, School of Engineering Building,
601 West Main Street, Richmond, VA 23284

Morning Session

7:30 Continental Breakfast
8:15 Welcoming Remarks - Anthony Guiseppi-Elie
8:30 Biochip Fundamentals
9:00 Microarraying Techniques and Principles - Cartesian Technologies
9:45 Array Scanning and Image Generation - Packard BioChips

10:30 Coffee Break

10:45 Bioinformatics For Gene Expression Analysis - Gene Spring

12:00 Lunch Break

Afternoon Session

1:00 Microarray Printing and Hybridization
2:00 Array Scanning and Image Generation
3:00 Date Visualization and Quantification
3:30 Informatics
5:00 Wrap-up

5:30 End of Workshop

Call for Posters

Industry and academic scientists are encouraged to submit poster titles for this event. One-page abstracts (8 1/2" x 11" with 1-inch margins) must be submitted no later than February 15, 2002 for inclusion in conference documentation. Additional poster submissions will be accepted until March 8, 2002 but may not be included in conference documentation.

Note: If you're submitting a poster, you MUST be registered and paid registration fee plus posterboard reservation fee in advance to ensure that a posterboard is reserved for you.

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