MAINSTREAMING MICROFLUIDICS immediately follows the Fourth Annual MACRORESULTS FOR MICROARRAYS conference and runs concurrently with the Third Annual GENOMIC AND PROTEOMIC SAMPLE PREPARATION conference.

Advisors and Chairs
Dr. Thomas Laurell, University of Lund
Dr. Albert van den Berg, University of Twente and MESA+ Research Institute
Dr. Bernhard H. Weigl, Micronics, Inc.
Dr. Achim Wixforth, University of Augsburg
Dr. Paul Yager, University of Washington
Preconference Short Course Tutorial: Microfluidics for Lab-on-a-Chip
Dr. Helene Andersson, Life Science Manager, Microfluidics and Biotechnology, Silex Microsystems, AB
Dr. Albert van den Berg, University of Twente and MESA+ Research Institute

All those who register for the Microfluidics for Lab-on-a-Chip tutorial are cordially invited to attend the Closing Plenary Session of Macroresults for Microarrays on Wednesday, May 14, at 1:30.

Microfluidics Chip Technology
Dr. Achim Wixforth, University of Augsburg
Dr. Andrew Gooley,Proteome Systems Ltd.
Dr. Tanya Kanigan, BioTrove, Inc.
Mr. Raymond Pierce, Epocal, Inc.
Dr. Nicolo Manaresi, Silicon Biosystems srl.
Mr. Mike Lucero, Fluidigm Corporation

Analysis at Microscale
Dr. Gerrit J. van den Engh, Institute for Systems Biology
Dr. Per Andersson, Gyros AB
Dr. Albert van den Berg, University of Twente; and MESA+ Research Institute
Dr. Carl Meinhart, University of California, Santa Barbara
Dr. Andreas Gerlach, Greiner Bio-One GmbH
Dr. Hugh McManus, Nanostream, Inc.
Dr. Paul Sweetnam, Surface Logix

Detection and Diagnostics
Dr. Paul Yager, University of Washington
Dr. Victoria VanderNoot, Sandia National Laboratories
Dr. Jeff T. Ives, Xtrana, Inc.
Dr. Helene Andersson, Royal Institute of Technology
Dr. Dieter Braun, Rockefeller University
Dr. Gary Schultz, Advion Biosciences, Inc.

Joint Session: Microfluidics Sample Preparation
Dr. Thomas Laurell, Professor, Department of Electrical Measurements, University of Lund
Dr. Mike McNeely, President and Chief Executive Officer, BioMicro Systems, Inc.
Dr. Dave Rakestraw, Co-Founder, Eksigent Technologies LLC
Dr. Bernhard H. Weigl, Micronics, Inc.

Wednesday, May 14

Preconference Short Course Tutorial 3:00-4:00pm Tutorial Registration 4:00-8:00pm Microfluidics for Lab-on-a-Chip Dr. Helene Andersson, Life Science Manager, Microfluidics and Biotechnology, Silex Microsystems, ABDr. Albert van den Berg, University of Twente and MESA+ Research Institute The use of microdevices made by advanced micromachining technologies makes it possible to handle very small quantities or very low flow rates of liquids and gases. This provides new opportunities in the medical instrumentation area, in the pharmaceutical industry, and in many other fields. By the end of the course, the attendees will know the present state of the art in Micro Fluidic Systems (MFS) and have an overview of the application areas. The course will also point out future developments of devices and applications. Special attention will be paid to the most important area of application, that of bioanalytics or "Lab-on-a-Chip." Different approaches and examples of solutions for real-life problems will be discussed. All those who register for Microfluidics for Lab-on-a-Chip tutorial are cordially invited to attend the Closing Plenary Session of Macroresults for Microarrays on Wednesday, May 14, at 1:30. Please visit: http://www.healthtech.com/2003/mar/index.asp for details about the plenary session.

6:00-7:00 Early Conference Registration and Exhibit and Poster Setup

 

Thursday, May 15

7:30am Registration and Light Continental Breakfast

 

Microfluidics Chip Technology

8:30 Chairperson’s Opening Remarks
Dr. Achim Wixforth, Chair for Experimental Physics I, Institute of Physics, University of Augsburg

8:40 Flat Fluidics: Acoustically Driven Microfluidic Devices for Biological Applications
Dr. Achim Wixforth
For small sample volumes, surface effects represent the dominant forces in fluidic applications. We present a novel approach for liquid handling in the nanoliter regime, where the fluid is confined to virtual beakers and fluidic tracks being prepared directly on the flat surface of a chip. Actuation, mixing, and stirring of such small fluid volumes are achieved by surface acoustic waves propagating on the same substrate. We demonstrate applicability of our technology for biological assays ranging from FISH on a chip to microarray hybridization and SNP analyses.

9:10 CHIP (CHemical Inkjet Printing), an Automated Microfluidics System Bringing the Chemistry to the Protein
Dr. Andrew Gooley, Chief Scientific Officer, Proteome Systems Ltd.
CHIP (CHemical Inkjet Printing) technology is an automated microfluidics system that brings the chemistry to the protein. The fidelity of inkjet technology allows the biochemist to use noncontact microarray dispensing of most, if not all, biochemicals typically used in protein biochemistry. The advantages of the CHIP approach are that authentic proteins are arrayed onto membranes, essentially creating an archive of valuable samples. This enables multiple biochemical reactions to be dispensed over an extended time period.

9:40 Living Chip Technology
Dr. Tanya Kanigan, Director, Chip Technology, BioTrove, Inc.
The Living Chip is a novel nanotiter plate technology consisting of a precisely constructed, high-density array of through-holes in a plate. A combination of manual and robotic sample handling schemes is used to rapidly introduce and retrieve samples into and out of the chips. By aligning and stacking a second chip on top of the first one, mixing of reagents occurs between reagents in coaligned through-holes, thus simultaneously initiating tens of thousands of assays. Reactions are monitored in parallel by a variety of means including colorometric, fluorometric, or luminescent readout. We will present an overview of the technology and recent results from projects related to ultrahigh-throughput screening, storage of chemical drug libraries, genomics, and other applications.

10:10 Refreshment Break, Poster and Exhibit Viewing (Exhibit Hall will close from 11:00am-3:00pm)

10:45 Integrated Electrokinetic Circuit Arrays: Pushing the Envelope of On-Chip Reagent Integration
Mr. Raymond Pierce, Vice President, Biochip Development, Epocal, Inc.
Epocal’s solid-state electrokinetic devices are dry hydrophilic matrices and reagents microfabricated as fluidic circuits enclosed within a water-vapor permeable membrane. The company is focused on integrating this enabling fluidic technology into various biochip assay formats. For example, the integration of on-chip, real-time pico-scale reagent injection will enable highly sensitive, quantitative, high-content assays for application in genomics, proteomics, drug development, and clinical diagnostics.

11:15 A Programmable Lab-on-a-Chip for Individual Cell-Biology
Dr. Nicolo Manaresi, Chief Executive Officer, Silicon Biosystems srl.
This presentation will introduce a programmable lab-on-a-chip for cell-biology applications. The sample microchamber (4µl) is delimited by a microelectronic chip and a conductive-glass lid spaced a few tens of microns apart. The chip surface encompasses a two-dimensional array of more than 100,000 20-x-20-µm-wide microsites, each consisting of a superficial electrode, an embedded impedance or optical sensor, and logic. Control of cells’ position is based on dielectrophoresis (DEP), the motion of neutral particles in response to nonuniform electric fields. The electrodes induce closed DEP cages in the regions above selected microsites, where single cells or microbeads in liquid suspension may be individually trapped and levitated.

11:45 Enabling a Single Chip to Serve Many Functions through Multilayer Soft Lithography
Mr. Mike Lucero, Senior Vice President of Marketing, Fluidigm Corporation
Fluidigm Corporation has mastered fluidics at the microscale through miniature valves, pumps, and channels that act within a chip as fluidic circuitry. This microcircuitry is fabricated using a proprietary process called Multilayer Soft Lithography, MSL™, which enables a single chip to serve many functions. This versatility gives an unparalleled advantage in transforming microfluidics into integrated systems for protein crystallization. Protein structure studies, the province of the expert crystallographer, has up until now been too esoteric and expensive for routine use in drug discovery and development. MSL™ microfluidics overcomes these obstacles by automating mixing, pumping, and isolation of proteins and precipitating reagents. Protein sample requirements can be reduced to a few nanograms and mixed with 96 screening conditions, at three different concentrations simultaneously. We will discuss how to use MSL™ microfluidics to scale protein structure studies and to generate crystals with miniscule amounts of purified protein.

12:15 Lunch (on your own)

 

Analysis at Microscale

1:45 Chairperson’s Remarks
Dr. Gerrit J. van den Engh, Professor, Institute for Systems Biology

1:50 Developing nL Scale Centrifugal Analyzer
Dr. Gunnar Thorsén, Scientist, Gyros AB
We have developed a nanoliter-scale, microfluidic technology based on the long-established, but little developed, centrifugal analyzer concept. Using a CD format we are able to benefit from working at microscale (saving sample, reagents, and time). Most importantly, we can incorporate new functionalities into the CD format, greatly increasing versatility. We will present results from immunoassays performed in parallel on 100 x 100 nL samples and an example of sample preparation prior to mass spectrometry analysis where 96 samples are concentrated, desalted, and crystallized in parallel.

2:20 Micro- and Nanofluidics for Labs-on-a-Chip
Dr. Albert van den Berg, Professor, Miniaturized Chemical Analysis Systems, University of Twente; and MESA+ Research Institute
Silicon and glass still offer certain advantages for realization of Lab-on-a-Chip devices and systems. An integrated microsystem for ammonia analysis integrated in silicon will be presented, as well as a hydrodynamic chromatography chip for polymer separation. In the area of medical diagm\nostics a capillary electrophoresis chip for measurement of lithium in whole blood is shown, and some new technologies for picoliter dispensing and fabrication of nanometer channels will be discussed. An outlook for future focus on cell analysis using silicon nanoneedles is shown.

2:50 Cell-Sorting Technology for High-Throughput Sample Analysis in Combination with Single Cell Selection Techniques with Carrier Tapes for High-Throughput Process and Evaluation
Dr. Gerrit J. van den Engh
Biological discovery experiments often require that investigators wade through very large numbers of mutants to find a few desirable clones. To speed up this process we are exploring the use of cell sorting onto conveyer tapes that contain a large number of sample wells. Tapes filled with single cells are easily processed in automated machines. We have built a clone selection/PCR amplification process capable of generating 25,000 clones per day. This technology is used in a range of applications varying from genome sequencing and the discovery of regulatory sequences to the analysis of marine microorganisms.

3:20 Refreshment Break, Poster and Exhibit Viewing

4:00 Analysis of Microscale Transport for BioMEMS
Dr. Carl Meinhart, Associate Professor, Department of Mechanical & Environmental Engineering, University of California, Santa Barbara
A fully integrated tunable laser cavity sensor for optical immunoassays is presented. This device incorporates a pair of Distributed Bragg Reflector (DBR) lasers to sense- specific antigen/antibody binding events that occur in the evanescent field of the laser cavity. The binding event modifies the modal index of the laser through coupling of the evanescent field. The modal index can be detected theoretically to within a resolution of n ~ 10-7. Dielectrophoresis (DEP) and the electrothermal effect are proposed as methods for manipulating the antigen concentration fields, thereby enhancing the sensitivity of the device. Micron-resolution Particle Image Velocimetry (micro-PIV) is demonstrated by measuring the flow field in a 30-x-300-micron channel.

By overlapping the interrogation spots by 50%, a velocity-vector spacing of 450 nm is achieved. Surprisingly, the velocity measurements indicate that the well-accepted no-slip boundary condition may not be valid for hydrophobic/hydrophilic boundaries at the microscale. These results represent the first direct experimental measurement of this phenomenon. In addition, flow fields resulting from electrothermally induced motion in microfluidic devices are measured using micro-PIV.

4:30 Plastic Microfluidic Platforms for High-Throughput Applications
Dr. Andreas Gerlach, Project Leader, Microsystem Technology Group, Microfluidic Devices, Greiner Bio-One GmbH
For high-throughput applications, i.e., in drug discovery, plastic microfluidic platforms in the standardized microplate footprint have been developed. Experiments in microfluidic structures were performed with different modified plastic materials to validate the suitability for capillary electrophoresis and enzymatic assays. Experimental results with microplates containing 96 and 384 identically microfluidic structures will be presented. In addition, we will demonstrate nanoliter liquid handling with a new developed plastic 384-fold microfluidic dispensing well plate.

5:00 A Microfluidics Approach to High-Throughput Liquid Chromatography
Dr. Hugh McManus, Vice President, Nanostream, Inc.
This talk will focus on some novel microfluidic technologies aimed at increasing R&D productivity during lead optimization. It will also address the development of two devices of critical importance in drug discovery. The first is a serial dilution chip, which has streamlined routine activities such as the development of IC-50 curves, and results of enzyme and cell-based assays will be presented. The second device is a separations chip, which has 24 chromatographic columns (C-18) coupled to UV/mass spectrometric detection. An application in compound library screening will also be presented.

5:30 Bridging the Widening Gap between Early Drug Discovery and Classical in vivo Pharmacology
Dr. Paul Sweetnam, Chief Scientific Officer, Surface Logix
Today micro- and nanotechnologies target bottlenecks associated with the early stages of drug discovery process, i.e., genomics, proteomics, and chemogenomics. In contrast, Surface Logix is applying soft lithographic microfabrication, surface chemistry, and human cell biology to create high-content in vitro models for drug discovery and development. Using inflammation as an example, we will illustrate our rapid and reliable approach to obtaining a wide range of disease related data, data that are often difficult or impossible to obtain using traditional drug discovery tools. Surface Logix is focused on bridging the widening gap between early drug discovery and classical in vivo pharmacology, resulting in more successful prosecution of preclinical and clinical candidates.

6:00 Joint Networking Reception in Exhibit Hall

7:00 Close of Day One

 

Friday, May 16

8:00am Poster and Exhibit Viewing and Light Continental Breakfast

 

Detection and Diagnostics

8:30 Chairperson’s Remarks
Dr. Paul Yager, Professor and Vice Chair, Adjunct with Chemical Engineering and Chemistry, University of Washington

8:35 Bringing Microfluidics to Point-of-Care Diagnostics: Creating a Point-of-Care Diagnostic
Dr. Paul Yager
A major project in our laboratory involves creating a point-of-care diagnostic assay system that incorporates polymeric laminate cartridges as an inexpensive disposable element. A key feature is the incorporation in those laminate cartridges of all reagents needed for a set of ~20 immunoassays in dry form for storage. The dry reagents are then hydrated to form controlled "plumes" of molecules in laminar flow that, in turn, modify surfaces of act as reaction zones. Progress on creation of this technology will be presented.

9:05 Phosphoprotein Signatures for Early Pathogen Detection Using µChemLab
Dr. Victoria VanderNoot, Senior Member, Technical Staff, Biosystems Research Department, Sandia National Laboratories
µChemLab/CB is a portable micro total analysis platform that can be used to detect a broad range of chemical and protein analytes in the liquid phase. The technical approach combines parallel electrophoretic analyses carried out in the microchip scale and sensitive laser-induced fluorescence detection that are fully integrated in a stand-alone device. To develop a more rapid and potentially portable technology for determining pathogen exposure, we have focused on the cellular signaling events associated with the ramping up of an immune response. Some of the earliest signaling events involve the phosphorylation of key proteins, and we have selectively collected phosphorylated proteins from immune cells using affinity chromatography and subjected them to a number of microscale electrophoretic separations, amenable to the µChemLab/CB platform. To date, we have been able to distinguish differential phosphoprotein signatures from resting and stimulated cells and are currently extending this work to more complicated systems involving samples from whole-animal studies.

9:35 Point-of-Care Microfluidic Device for Nucleic Acid Diagnostics
Dr. Jeff T. Ives, Director, Solid Phase Chemistry and Microfluidics, Xtrana, Inc.
A low-cost disposable card and an associated base unit are being developed for point-of-care and field diagnostics of infectious, pathogenic organisms. By fully integrating all the steps of nucleic acid analysis; extraction, amplification, and detection, this device overcomes longstanding obstacles to microanalytical integration, particularly the challenges of nucleic acid sample preparation. This presentation will discuss the design and operation of the device, as well as the identification of infectious targets such as chlamydia and gonorrhea from urine and E. coli in water.

10:05 Refreshment Break, Poster and Exhibit Viewing

10:35 Detection of Single Nucleotide Incorporation Using Pyrosequencing in a Microfluidic Device
Dr. Helene Andersson, Research Associate, Microsystem Technology, Royal Institute of Technology
DNA pyrosequencing in a microfluidic device will be presented. The microfluidic platform allows detection of single-base incorporations enabling base-by-base DNA sequencing. The miniaturization has led to a 1000-fold reduction in reagent consumption compared with present standard volume in pyrosequencing and will hopefully enable reading of longer DNA sequences.

11:05 Thermophoresis of DNA: Trapping and Replicating DNA by Heat
Dr. Dieter Braun, Postdoctoral Fellow, Center for Studies in Physics and Biology, Rockefeller University
We investigated the movement of DNA by temperature gradients. In measuring thermophoresis of DNA for the first time, we found interesting exponential dependencies upon DNA length and temperature gradients. By combining with convection, we could accumulate plasmid-sized (5000pb) DNA more than 1000-fold. Furthermore, the same laminar convection flow was tuned to drive a PCR reaction at high speeds. Besides that, we propose both effects to be relevant for the origin of life near hot volcanic activity in the sea floor. Microfluidic applications of these effects appear promising.

11:35 11:35 Integrated Microfluidics for Universal Molecular Analysis Platform
Dr. Vincent Gau, President, CEO, GeneFluidics, Inc.
GeneFluidics has developed a novel 3-D microfluidic platform with an embedded electrochemical sensor array, which it is applying for the molecular analysis of DNA and proteins in raw samples. The Company's high precision plastic microfluidic cartridges are mass produced with nano-meter features and internal fluidic control mechanisms. These processes allow economies of scale that result in very low-cost, single-use, disposable cartridges. GeneFluidics leverages nanotechnology, biotechnology, MEMS, and microfluidics in its revolutionary molecular analysis system, which has been validated through detection of urinary tract infection, middle ear infection, Factor V Leiden, PSA, and other disease states.

12:05 Detection Strategies: Enabling Automated Chip-Based Nanoelectrospray Mass Spectrometry Using the NanoMate System
Dr. Gary Schultz, Vice President of R&D, Advion Biosciences, Inc.
The NanoMate 100 is a fully automated nanoelectrospray system for routine analysis of samples. The NanoMate samples from a 96-well plate using disposable pipette tips and infuses samples through the ESI Chip, an array of nozzles etched in silicon, at flow rates as low as 100 nL/min. Results will be presented showing the identification of peptides from off-line collected liquid chromatography fractions of crude cell digests, biomarker discovery as well as quantitation of small molecules in plasma after protein precipitation. All will be demonstrated at the low nanogram per ml level using an automated chip-based nanoelectrospray system.

12:30 Luncheon in the Exhibit Hall (Exhibit Hall will close at 1:45pm)

Microfluidics Sample Preparation (Joint Session) 1:45 Chairperson’s Remarks Dr. Thomas Laurell, Professor, Department of Electrical Measurements, University of Lund 1:50 Microfluidics for Broad Applicability and Broad Acceptance Areas Dr. Mike McNeely, President and Chief Executive Officer, BioMicro Systems, Inc. Of many microfluidic technologies, few have the characteristics necessary for broad applicability and broad acceptance. Some relevant characteristics include simple yet sophisticated processing and easy adoption and implementation, a clear improvement over existing technologies, all at an acceptable price. BioMicro’s PFC™ technology has been shown to address multiple technological needs simply and inexpensively. Examples of its application will be shown in microarray processing, diagnostics, and genomics, demonstrating its present and future value in these areas. 2:20 Chip-Integrated Solid-Phase Sample Preparation and Enrichment Prior to MALDI-TOF MS Dr. Thomas Laurell Solid-phase microextraction is widely used for proteomic sample preparation in standard robotic sample handling equipment. In hand with the development of lab-on-a-chip concepts the need for new miniaturized sample handling protocols becomes evident. Our developments on chip-integrated solid-phase sample preparation and enrichment prior to MALDI-TOF MS readout will be overviewed. In line with the chip development the importance of proper microfluidics in the chip will also be emphasized.2:50  Microfluidic HPLC Systems for Proteomics and High Throughput Small Molecule Analysis Dr. Karen Hahnenberger, Eksigent Technologies LLC Microfluidic systems play an important role in proteomics, where the ability to control the separation of peptides at nanoscale flow rates improves the mass spectrometer's ability to detect low-abundance proteins. Achieving precise flow control at low flow rates has proven difficult and has often required flow splitting techniques. We will describe the development of a microfluidic HPLC system that provides direct, pulseless control at separation column flow rates of 10 to 500 nL/min, without the need for flow splitting. The NanoLC's microfluidic flow control system provides the ability to reduce the separation column flow rate rapidly while maintaining the gradient profile. This capability, known as peak parking, provides additional time to run tandem MS on chosen peptides. System data for peptide separations, sensitivity data and peak parking results will be presented.  We will also describe a microscale HPLC system optimized for 300 mm id columns with flow rates of 0.5 - 10 mL/minute. This system makes use of a microfabricated 45 nL flow cell for UV detection (200-380 nm). Results for system reproducibility, sensitivity and separation efficiency will be presented. 3:20 Refreshment Break 3:45 Microfluidic Platform for Complex Sample Analysis: Integrated On-Chip Sample Preparation, Cellular, and Chemical Analysis Starting from Raw Samples Dr. Bernhard H. Weigl, Micronics, Inc. A microfluidic platform and devices for the analysis of complex samples such as whole blood and biological cell suspensions are presented. These devices use at their core flow structures based on Laminar Fluid Diffusion Interfaces (LFDIs). The method is being applied to, among other examples, the extraction and subsequent detection of drugs and small proteins from whole blood and cell suspension samples, the lysing and detection of blood particles, and the chemical detection of various constituents in whole blood and urine. These devices combine several different individual analysis steps in a single on-chip process that does not require user intervention. The analysis frequently involves sample cleanup, cell lysing, extraction and concentration of analytes, concentration determination, and on-chip waste storage. 4:15 Advanced Technologies for Interfacing Microfluidic Devices to High Throughput Analysis and Screening Instrumentation" Dr. Manish Deshpande, Vice President of Engineering, Teragenics, Inc. One of the major impediments to the use of microfluidic devices in drug screening and other high-throughput analytical applications has been the lack of appropriate interfaces between standard robotic lab automation equipment and microfluidic systems. In this presentation, a novel way of interfacing robotic automation systems with microfluidic chips will be presented. The technology can be applied to applications in capillary electrophoresis, protein separation, on-line gradient spotting, compound dispensing, serial dilution and Mass Spectrometry applications. Experimental results obtained in applications such as drop dispensing, direct injection into a microchannel and formation of a sample plug for CE separation will be provided. 4:45 Close of Conference

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Sponsoring Publications:
American Journal of PharmacoGenomics		BioDrugs		Expert Review of Molecular Diagnostics
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In addition to exhibiting, many sponsorship opportunities are available for your company to maximize its exposure and influence. They include overall event and conference specific sponsorships, technology workshops, networking receptions, delegate bags, and badge lanyards.  For more information on available sponsorship packages and exhibit space, please contact Angela Parsons at 781-972-5467 or aparsons@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 April 4, 2003.  Click here for poster instructions

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Cut-off Date: April 21, 2003

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.

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