LAB-ON-A-CHIP MICROARRAYS FOR POST GENOMIC APPLICATIONS

Miniaturized platform technologies are no longer new concepts. Chips and microarrays are becoming standard tools for the high-throughput analysis of gene expression and continue to grow in information quality and to discover new applications. The power of microarray analysis lies in the ability to compare large sets of genes in different tissues or conditions to identify pathways and regulatory networks. Building upon the successful foundation of Cambridge Healthtech Institute's Fifth Annual Lab-on-a-Chip and Microarrays, the critical topic of Informatics and Microarray Data Analysis completes the picture. The meetings are a must-attend event for biological researchers, drug developers, diagnosticians, engineers, statisticians, bioinformaticists, database developers, and computer software designers. Each discipline (topic) contributes to a successful team effort and like the microarray must be measured as a whole.

Advances in Hybridization and Reliability
Dr. Binita Dutta, Flanders Institute for Biotechnology
Dr. Achim Wixforth, Advalytix AG
Dr. Vladimir Lazar, Institut Gustave Roussy

Improvements in Array Content and Labeling
Dr. Søren M. Echwald, Exiqon A/S
Dr. Jim Collins, Agilent Technologies, Inc.
Dr. Michael Lässle, PerkinElmer Life Sciences
Dr. Tito Bacarese-Hamilton, Imperial College of Science, Technology and Medicine

Novel Concepts in Chip Design
Dr. Jacques Jonsmann, Scandinavian Micro Biodevices A/S
Dr. Nir Dotan, Glycominds Ltd.
Dr. Roland Wicki, Applied Biosystems
Dr. Riet Hilhorst, PamGene BV
Dr. Theresa L. Giesler, Amersham Biosciences

Microarrays for Molecular Diagnosis
Dr. Cor D. Schoen, Plant Research International B.V.
Dr. Linda E Cammish, NextGen Sciences Ltd.
Dr. Andreas Schütz, IMNT
Dr. Guido Sauter, University of Basel
Dr. Daniela Massa, Genescan Europe AG

Scientific Advisors
Dr. Tito Bacarese-Hamilton, Imperial College of Science, Technology and Medicine
Dr. Jutta Bachman, Bachman Consulting, BioChipNet
Dr. Elaine Broomfield, Agilent Technologies, Inc.

7.30 Conference Registration, Poster and Exhibit Viewing, and Light Continental Breakfast

8.30 Chair's Opening Remarks
Dr. Jutta Bachman, Bachman Consulting, BioChipNet

8.40 Keynote Presentation: The Saga of Expression Profiling:
The Past 25 Years - The Next 25 Years
Dr. Charles Auffray, Director, Department of Molecular Genetics and Developmental Biology, CNRS
Expression profiling has developed over a quarter century, since the advent of cDNA cloning. Despite many advances introduced ranging from robotics to information technology, it is still an immature technology compared to DNA sequencing. Academic and industrial scientists need to work together to establish the common standards and quality assurance plans required to enable sharing, comparison and integration of large data sets. The development of a Transcriptome Annotation Database and of an Expression Profile International Consortium are initial efforts in this direction. Novel technologies for quantitative expression profiling at the single protein and RNA molecule level will pave the way for system-level understanding in molecular medicine during the next quarter century.

9.30 Shear-Driven Microarray Hybridization: Development of Fast DNA and Protein Screening Systems
Dr. Binita Dutta, Postdoctorate, MicroArrayFacility Lab, Flanders Institute for Biotechnology
As the Human Genome Project heads towards completion, the scientific world is looking towards new ways to translate sequence data to the functional knowledge of genes in a biological system. Microarray technology can potentially be exploited to study genome complexity in plants and animals. To elevate diffusion limitation in the hybridization step of microarray experiments, we used shear-driven flows to generate a rapid lateral convective transport across the microarray surface. The shear-driven concept would yield reductions in the sample amount and the time of hybridization. Hence, small arrays can be developed for rapid diagnosis of cancer, mutations, or other genetic diseases.

10.45 Acoustic Wave-Driven Biochips for in Situ Monitoring of Hybridization Assays
Dr. Achim Wixforth, Chief Technology Officer, Advalytix AG
We present a novel microfluidic platform allowing for the in situ monitoring of DNA, SNP, and proteomic hybridization events. The fluid in this case is actuated by surface acoustic waves, propagating on the planar surface of our microfluidic biochip. The chips are completely computer controlled, aiming towards the realization of programmable bioprocessors for smallest liquid volumes. Apart from a demonstration of the unique capabilities of our novel microfluidic platform, we present a first commercially available device for the hybridization of microarrays, the ArrayBooster. We demonstrate the applicability of such devices for enormously enhanced homogeneity, signal intensity, and selectivity for hybridization assays if compared to diffusion limited experiments. The reduced time scale enables us to directly observe the dynamics of hybridization events of any kind, opening up a wide field of different applications both in research and in diagnostics.

11.15 A New Approach to Perform Quality Control Using Microarray Technologies
Dr. Vladimir Lazar, Head of Functional Genomics Unit, Institut Gustave Roussy
Translational research, from bench top to clinical applications, becomes the cornerstone of the strategy at Institut Gustave Roussy. The use of new technology approaches always starts by a validation step before entering the production line for research and clinical purposes. Recently we developed a microarray facility based on technologies that use cDNA as well as oligonucleotide microarrays to analyze the gene's steady state level on the whole transcriptome level. The topics will present a new concept to perform quality control of RNA specimens and of labeled targets, prior to any hybridization. Surprisingly, important correction can be done prior to performing hybridization. These protocols dramatically improved the quality of our experiments.

14.00 Chair's Remarks
Dr. Tito Bacarese-Hamilton, Imperial College of Science, Technology and Medicine

14.05 High Quality Protein Arrays and Assays Produced and Performed Using Microfluidic Capillary Systems
Dr. David Juncker, Post Doc, IBM Zurich Research Laboratory
Diagnostics and analyses routinely performed in central laboratories are quantitative. The use of microarrays for diagnostic purposes would entail an economy of reagents, concurrent testing of different markers, having near-patient diagnostics, and reduced time consumption and overall cost. Yet, the quality of the spots in DNA and protein microarrays is strongly affected by the uncontrolled drying of the spotted solutions, and furthermore the fluorescence readout is often equally subjected to fluctuations. Quantitative, sensitive, and reliable analyses however require each the formation of the array and the assay to be tightly controlled. We have developed microfluidic capillary systems and arraying strategies that provide the necessary control for each step from "spotting" to the final assay readout. We illustrate the possibilities of our technique by (i) patterning proteins as 50 × 50 µm2 highly homogeneous spots, by (ii) performing sandwich immunoassays on such sites, and by (iii) performing immunoassays in a combinatorial format.

14.35 Performance of High-Density 60-mer Oligonucleotide Microarrays in Profiling Global Gene Expression
Dr. Jim Collins, Senior Scientist, BioResearch Solutions, Agilent Technologies, Inc.
Agilent's high-density Human Oligonucleotide Catalog microarrays consist of validated 60-mer probes for precise monitoring of global gene expression. These microarrays, manufactured using Agilent's SurePrint noncontact in situ synthesis process, are provided with high-quality protein function annotation. Data are presented that outline the experimental selection of probes, which are highly specific for each gene represented. The reproducibility and sensitivity of these microarrays allow for extremely accurate differential expression measurements, even when starting material is very limited.

15.05 Unique Properties of LNA in Sample Preparation and Expression Profiling
Dr. Søren M. Echwald, Senior Manager, Business Development, Science and Technology, Exiqon A/S
Due to LNA's superior binding affinity and specificity, LNA spiked Oligo-dT oligonucleotides show severalfold increased and more robust (i.e., automatable) binding of polyA-mRNA. Furthermore, the increased specificity of LNA can also be rendered to expression profiling arrays. Especially for discriminating between highly homologous sequences, such as when designing splicing-specific gene arrays, within the coding regions, LNA can greatly enhance specificity as well as sensitivity. Since LNA is compatible with standard oligonucleotide synthesis and can be used in most standard molecular biology methods, we expect that LNA will become very widely used in enhancing existing technologies in the near future.

16.15 RNA and DNA Direct Chemical Labeling for Unbiased, Accurate, Sensitive, and Precise (ASAP) Differential Gene Expression for Microarrays
Dr. Michael Lässle, Technology Manager, Biomics-Europe, PerkinElmer Life Sciences
Unlike current direct enzymatic protocols incorporating cyanine or amino allyl nucleotides, this novel direct chemical labeling technology, MICROMAX ASAP, provides a faster, less complex procedure that can easily be carried out by first-time users. Unparalleled in combining sensitivity, accuracy, and precision, this new labeling technology allows for reproducible and robust data. Results show that 3' end labeling bias can be completely eliminated with this direct labeling of total RNA, thereby enabling the determination of splice variants.

16.45 Signal Amplification of Protein Arrays as a Means of Enhancing Test Sensitivity
Dr. Tito Bacarese-Hamilton, Imperial College of Science, Technology and Medicine
Indirect fluorescence has been used for the detection of human IgG and IgM in protein microarrays. However, for clinical applications where high test sensitivity is required, an amplification system is required. We have used Tyramide Signal Amplification (TSA) for the detection of allergen-specific IgE in human serum. The development of the test format and the clinical performance of the test will be discussed.

7.30-8.15 Breakfast Technology Workshop

Agilent Technologies
Workshop Presentation

Innovative Informatics Solution Bridging Genomics and Proteomics
Chips and microarrays are becoming standard tools for the high-throughput analysis of gene expression and continue to grow in information quality and to discover new applications. Success in proteomics could continue the progression toward personalized medicine: more precise diagnostics to characterize diseases more accurately for earlier detection and more tailored treatment.

To capture the true value of high-throughput platforms and predictive modeling applications in Genomics and Proteomics, Agilent proposes an innovative bridging informatics solution, Synapsia Informatics Workbench, to allow scientists to correlate and organize heterogeneous data sources rapidly generated in the high-throughput processes by various new technologies, and manage and produce scientific information. In particular, Agilent Synapsia Informatics Workbench provides a framework for scientists to build collaborative project stories by linking key data from Genomic and Proteomic research, annotating the data and documenting experimental design.

8.35 A Novel Chip Platform for Single- and Multiple-Cell Analysis
Dr. Jacuqes Jonsmann, Head of Silicon Microfluidics, Scandinavian Micro Biodevices A/S
The primary motivator for establishing a technology platform for cell-based analysis is the usually long development phase associated with such systems. A technology platform enables fast and more cost-efficient development of new chip systems. The chip contains both silicon and polymer microfluidics, with functions requiring true microfeatures placed in the silicon part, whereas less critical structures will be situated in the polymer shell. Microstructured coatings with feature sizes down to approximately 2 micrometer allow for control of cell adhesion and repulsion, i.e., the controlled positioning of living cells.

9.05 GlycoChip™ Technology: Enabling Novel Approaches for Post-genomic Analysis and Discovery
Dr. Nir Dotan, President and CTO, Glycominds Ltd.
Despite their tremendous functional significance in a wide range of physiological processes, ranging from cell development to immunity, glycans' importance as biological information molecules has been largely overlooked. Glycominds has developed the powerful GlycoChip technology to capitalize on the unmistakable potential of "glyco-knowledge" in the discovery, prioritization, and development of targets and drugs. This unique array enables unprecedented throughput for analysis of glycan-protein (including antibodies, enzymes, and lectins) interactions, opening the door for novel post-genomic approaches in biomarker identification, pharmacoglycomics, and drug development.

9.35 New Microfluidic Cards based on Assay-on-Demand™ Products for Quantitative Gene Expression Analysis
Dr. Roland Wicki, Business Development Specialist, Applied Biosystems
The Assays-on-Demand products translate the human genome sequence data from both public and private sources into an immense catalog of validated, ready-to-use assays for gene expression and SNP genotyping, covering the whole human genome. Those products are based on the familiar 5' nuclease chemistry with TaqMan® MGB probes. We would like to present novel microfluidic cards as an addition to these single-tube assay products. The cards perform 384 quantitative gene expression analyses simultaneously and are fully customizable. Each microfluidic card can be preloaded with the whole range of assay products, allowing accurate quantitation of gene expression in a fraction of the time of custom microarrays or do-it-yourself methods. First data and results will be presented.

10.45 PamChip®: Second Generation Microarray Technology for Genomics and Proteomics
Dr. Riet Hilhorst, Senior Scientist, PamGene BV
The microarray concept has been shown to be a versatile hybridization tool for e.g. gene expression. We describe the use of a porous inorganic substrate, with covalently coupled oligonucleotides or proteins, for temperature controlled, online monitoring of the hybridization process. Oligonucleotide or protein spots of 325 pL are deposited at 200 mm pitch on this material with piezo inkjet spotter technology and coupled covalently. The hybridization process of labeled target molecules can be visualized real time in concentrations as low as 5 pM, using a microscope and CCD camera. The temperature can be varied during hybridization to adjust for stringency and thus maximal sensitivity (as desired in gene expression studies) or maximal specificity (as desired in mutation detection) can be obtained. The properties of the PamChip® will be explained. The potential of this new platform technology for genotyping, expression profiling and proteomics will be illustrated with examples.

11.15 CodeLink™ Expression Bioarrays: An Accurate and Precise Microarray Platform with Solution-Phase Hybridization Behavior
Dr. Theresa L. Giesler, Scientist, Development-Gene Expression, Amersham Biosciences
The usefulness of DNA microarrays for gene expression profiling depends on the quality of the microarray results. Sensitivity, specificity, precision, and accuracy are all important for analysis of complex expression profiles using microarray t echnology. We demonstrate solution-phase hybridization performance with CodeLink™ Bioarrays by showing a strong correlation between the effect of mismatches of probes attached to the three dimensional matrix of the microarray and solution-based, thermodynamic duplex melting studies. Such solution-phase behavior results in accurate differential expression ratios similar to ones obtain with real-time RT-PCR. These features of the CodeLink™ platform, combined with its high reproducibility, allow accurate ratio determination with a single probe per transcript. Accurate differential expression ratios, coupled with sensitivity of less than 0.3 transcripts per cell, suggest that the CodeLink™ Bioarray system has intrinsic advantages for identification of differentially expressed genes.

13.30 Chair's Remarks
Dr. Elaine Broomfield, European Sales Development Manager, Lab-on-a-Chip, Microarray Products, Life Science and Chemical Analysis Group, Agilent Technologies

13.35 Multiplex Detection of Plant (Quarantine) Pathogens by Microarrays: An Innovative Tool for Plant Health Management
Dr. Cor D. Schoen, Senior Scientist, Business Unit Bio-Interactions and Plant Health, Plant Research International B.V.
Detecting harmful quarantine (Q) organisms in plant propagation material is necessary in order to ensure safe and sustainable agriculture. The multiplicity of assays available for a specific pathogen leads to a lack of consistency among the various testing agencies in Europe and hampers standardization. The newest development in the analysis of nucleic acids is microarray technology in which different oligos can be spotted on little more than one square mm. The use of these microfabricated DNA analysis tools will provide the next generation of inexpensive DNA diagnostics to measure different pathogens in a massively parallel manner on a single chip. To develop the microarray technology for diagnostic purposes, generic DNA/RNA extraction and generic pre-amplification methods to increase sensitivity have to be developed. Recent data to detect plant-pathogens in this multiplex setting will be discussed.

14.05 Protein Microarrays: Overcoming the Difficulties for Use in the Study of Breast Cancer
Dr. Linda E. Cammish, Director of Business Development, NextGen Sciences Ltd.
NextGen Sciences is developing a series of protein microarrays to investigate their use as a prognostic indicator in breast cancer studies. As part of this development process we have worked at providing solutions to a number of the major problems associated with use of protein microarrays including (1) attachment of functional protein to a biochip substrate, (2) achieving high levels of assay sensitivity, (3) developing a universal mechanism for attaching Protein Recognition Molecules (typically, but not limited to, antibodies, antibody fragments, or phage) to a biochip substrate, (4) achieving reproducible assay results, and (5) performing protein biochip processing in a high-throughput manner. During this presentation, NextGen Sciences' solutions to these issues will be presented and illustrated with experimental data from studies that include protein expression analysis of complex breast cancer samples, recombinant protein expression monitoring in cell culture, and antibody screening. Details of a new microfluidics system to automate protein biochip processing will also be described.

14.35 Application of the GeneStick Microarray Platform for Cancer Diagnostics
Dr. Andreas Schütz, Director, Institute for Molecular NanoTechnology
The GeneStick comprises a stick-shaped biochip made of an optical-grade plastic material. Hybridization is performed in a closed tube with a heated standard laboratory shaker, ensuring temperature-controlled hybridization under constant mixing. The readout of the GeneStick is performed with a newly developed, chemiluminescence detector. Several applications have been successfully used with this new diagnostic platform, covering most aspects of cancer diagnosis like (early) detection of tumors, characterization of tumors, and optimum therapy selection and control. For the detection of lung cancer a microarray has been developed that allows the determination of the promoter methylation status of the five most frequently methylated promoters in lung tumors. Further examples will be given for the detection of k-ras mutations from stool samples for the early detection of colon or pancreas cancer and for phenotyping of disseminated cancer cells by measuring the expression level of tumor-related genes.

15.30 Tissue Microarrays for Miniaturized High-Throughput Molecular Pathology
Dr. Guido Sauter, Division of Molecular Pathology, Institute of Pathology, University of Basel
A rapidly increasing number of genes are being suspected of playing a role in cancer biology. To evaluate their clinical significance, it is usually required to examine a high number of well-characterized primary tumors with clinical information. To allow for a high-throughput tissue analysis we have developed a "tissue microarray." Using this technology, samples from up to 1,000 different tumors can be arrayed in one recipient paraffin block, sections of which can be used for all kinds of in situ analyses. In our laboratory, studies aiming at a comprehensive evaluation of new potential biomarkers use a two-step approach. First, genes of interest are analyzed on a normal-tissue TMA containing samples from 76 different normal tissue types and on a multitumor TMA containing more than 3,000 samples from 130 different tumor types. In a second step, organ-specific TMAs containing tissues with clinical endpoint information are used to test the clinical significance of the biomarker in these tumor entities where alterations were detected on the multitumor TMA. Another strongpoint of the TMA method is the applicability of automated analysis for RNA-ISH, immunohistochemistry, and FISH. We anticipate that "tissue chips" will greatly accelerate the transition of basic research findings to clinical applications.

16.00 Pharmacogenetic Profiling with Biochips: An Innovative Concept to Improve the Efficiency of Clinical Trials
Dr. Daniela Massa,, Genescan Europe AG
Due to their highly parallel nature, DNA chips are valuable tools for the simultaneous detection of known SNPs in numerous genes. In the field of pharmacogenetics SNPs, with a well-described genotype-phenotype correlation in several drug-metabolizing enzymes, have been known for quite a while, but their parallel detection was laborious in the past. GeneScan's Pharm-O-Kin Chip® was designed to meet the needs of clinical research and pharma customers as it presents a fast and reliable method of detecting SNPs in several genes of pharmacogenetic relevance. In total, 39 polymorphisms from CYP2D6, CYP2C9, and CYP2C19, as well as NAT2 and MDR1, are represented on the chip, thus covering important enzymes from drug metabolism as well as a transporter protein known to play a role in the bioavailability of administered drugs. This allows a better design of clinical trials in terms of minimizing the risks for probands and, in addition, will help to save costs in the drug development process.

Corporate Sponsor Biographies

Gene Logic Inc. is a leading genomics-based biocontent and bioinformatics company focused on developing information products related to gene activity in human disease and toxicity to optimize rapid, reliable and cost-effective pharmaceutical and biotechnology research and development. Through its expertise in biosamples, high-throughput genomics technologies and software development, the Company has developed a series of gene expression information solutions based on its core product, the GeneExpress® Suite.

Iobion Informatics presents GeneTraffic software for two-color microarray data management and analysis. GeneTraffic software allows you to access data and projects on a desktop PC, from any location within your Network, manage data, perform computational analyses and query your data. With GeneTraffic software you can qualify and validate your microarray data prior to biological analysis.

Iobion Informatics is a Delaware LLC, headquartered in La Jolla, CA with offices in Toronto, Canada, and Austin, Texas.

Hotel Information

Swissôtel Zurich
Am Marktplatz Oerlikon
CH-8050 Zurich, Switzerland
T: 41-1-317-3111
F: 41-1-312-3425
Room Rate: 270 CHF S/D
Cut-off Date: December 20, 2002

Please call the hotel directly to make your room reservation. Identify yourself as a Cambridge Healthtech Institute conference attendee to receive the reduced room rate. Reservations made after the cut-off date or after the group room block has been filled (whichever comes first) will be accepted on a space-and-rate-availability basis. Rooms are limited, so please book early.

Call for Sponsors and Exhibitors

This exciting event will cover many aspects of microarray data analysis as well as latest advances and innovation in miniaturized platform technologies. Many sponsorship opportunities are available for your company to maximize its exposure and influence—including overall event and conference specific sponsorships as well as technology workshops, networking receptions, delegate bags, and badge lanyards. Over the course of the week, over 400 delegates will have access to the exhibit hall. The early rate for exhibit spaces is October 25, 2002; exhibit registrations received by that date will save your company up to $675!

For more information on available sponsorship packages and exhibit space, please contact Angela Parsons at 781-972-5467 aparsons@healthtech.com or Deborah Brooks at 781-972-5412 dbrooks@healthtech.com.

Call for Posters

Cambridge Healthtech Institute encourages attendees to gain further exposure by presenting their work in the poster sessions. Please fill out the registration form, with the poster title and primary author. To ensure inclusion in the conference CD, a one-page summary must be submitted and registration must be paid in full by January 3, 2003. Click here for poster instructions

Executive Sponsor:

Corporate Sponsors:

Sponsoring Publications:
Arnold Genome Research IOS Press Taylor and Francis Scientific Computing World CHI's Outlook for DNA Microarrays CHI's Life Sciences Informatics: From Data to Drugs

Sponsoring Society: International Informatics Society

Web Partners: Lab-on-a-Chip.com Biochipnet

12.30-1.30pm Technology Luncheon Product Launch Workshop
Codelink Roadshow presentation Presented by Jim George	Sponsored by