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Thursday,
June 22, 2000
7:30 Registration, Exhibit/Poster
Set-Up, Coffee and Danish
Manufacturability
Issues: Perspectives from Small and Large Companies
8:30 Conference Chairperson’s
Opening Remarks
Marc Madou, Ph.D., Professor in Chemistry and Materials Science and
Engineering, The Ohio State University
8:40 Practical Aspects
of Micro Total Analysis (µ-TAS) in Pharmaceutical Research
James J. Bao, Ph.D., Senior Scientist, Procter & Gamble Pharmaceuticals,
Inc.
Micro total analysis (µ-TAS) offers many potential applications
in pharmaceutical research. Especially, µ -TAS based screening assays
can offer unprecedented high throughput. However, several key issues,
such as sample preparation and instrument interfacing, have to be resolved
before the potential of µ -TAS can be fully utilized. This talk will
focus on various practical aspects of µ -TAS including how to adapt
to the current industrial standard platform of high throughput screening
assays.
9:10 Design, Material,
and Regulatory Considerations in Developing Microfabricated Products
for Drug Delivery
Don VerLee, Associate Research Fellow, Abbott Hospital Products Division,
Abbott Laboratories
Progress in mapping the human genome has had a dramatic impact in miniaturizing
analytical instrumentation. Successful completion of the genome sequence
will undoubtedly result in new therapies. Some will use current delivery
systems, but a growing need to deliver more potent, shorter half-life,
targeted biochemicals may redirect some miniaturization research to
create new drug delivery devices. The technical and regulatory challenges
to develop and commercialize these new devices will be presented.
9:40 Pre-packaged Genomic
Applications: Miniaturization & Microfluidic Aspects
Michael Albin, Ph.D., Vice President, Science & Technology, Perkin
Elmer Applied Biosystems
As details of the sequence of the human genome become available, the
drive for high-throughput, cost effective discovery and analysis tools
becomes ever more vital. In an effort to meet these challenges, we,
in collaboration with several companies, have focused on providing methods
and formats that address these issues - pre-packaged arrays for real-time
detection of PCR reactions for gene-expression analysis or SNP detection,
separation-based analysis in fabricated structures, and tools for production
of highly variant lot sizes of high-content arrays for expression analyses.
Performance and cost issues will be discussed for the diversity of analytical
approaches.
10:10 Exhibit/Poster Viewing
& Refreshment Break
10:40 Development of Microelectronic
DNA Arrays and Instrument Systems for Pharmacogenetic Research and Drug
Discovery Applications
Michael J. Heller, Ph.D., Chief Technical Officer, Nanogen
Microelectronic chip based systems have been developed for single nucleotide
polymorphism (SNP) analysis, pharmacogenomic research, DNA diagnostics,
and drug screening applications. A 100-test site active microelectronic
chip and fluidic/electronic cartridge device have been fabricated for
numerous DNA hybridization based applications. A programmable chip addressing
system is designed to provide the end-user with “make your own chip”
capabilities. A fluorescent reader and controller system is designed
to carry out rapid and reliable multiplex DNA hybridization for single
nucleotide polymorphism (SNP), point mutation and short tandem repeat
polymorphism (STR) analysis for genetic disease diagnostics and for
forensic applications. For drug discovery applications, a 10,000 test
site CMOS device has been developed as an active array to carry out
a unique process for screening very large combinatorial peptide libraries.
The peptide libraries will be screened on the 10,000 site active CMOS
array for unique three-dimensional ligand-binding complexes and for
ultimate use of the array as a molecular descriptor device for drug
screening applications.
11:10 Plastic Microfluidic
Devices for High-Throughput Screening and Genetic Analysis
Antonio J. Ricco, Ph.D., Director, Microfabrication Technologies,
ACLARA BioSciences, Inc.
Plastic devices employing electrokinetic pumping through interconnected
microcapillaries can revolutionize drug discovery, genetic analysis,
and clinical diagnostics. Applications such as high-throughput screening
of pharmaceutical candidates and clinical diagnostics cannot afford
carryover or contamination. In response, ACLARA has developed low-cost
manufacturing of single-use plastic LabCards(tm). This technology and
its applications in drug screening and genetic analysis will be described.
11:40 Lab on a Chip Technology
- The Innovator’s Dilemma
Kevin Meldrum, Marketing Manager, Lab on a Chip Systems, Agilent
Technologies
There has been a tremendous amount of interest generated around microfluidics
and the so-called “Lab on a Chip”. In fact, it has been labeled as a
disruptive technology that will supplant traditional approaches to sample
handling and analysis. But successful commercialization of new technologies
is no easy task. The risk is very high that any particular idea or application
will not prove viable. This talk provides a practical process for the
assessment of new product opportunities based on microfluidics technology.
12:10 Panel Discussion:
Brainstorming Targets of Opportunity in the BioMEMS Market
Panel Moderator, Michael J. Heller
Leading industry experts will discuss current and future trends, assess
fundamental obstacles and challenges and evaluate solutions to achieve
commercial success in the BioMEMS market.
12:40 Speaker Roundtable
Luncheon
Do not miss this opportunity to meet one-on-one with our conference
faculty. Delegates are invited to join speakers over lunch to discuss
today’s ‘hot topic’ BioMEMS issues.
New Microfabrication
Techniques in the Pipeline
2:10 Session Chairperson’s
Remarks
Antonio J. Ricco
Keynote Address
2:15 Merging of Top-down
and Bottom-up Manufacturing Methods
Marc Madou, Ph.D., Professor in Chemistry and Materials Science and
Engineering, The Ohio State University
Today we have a choice of top-down machining methods (e.g. microfabrication
and nanofabrication) and bottom-up fabrication methods (e.g. nanochemistry)
to fabricate novel miniaturized systems. In top-down machining, one
builds from the large to the small whereas in nanochemistry, as in nature,
one builds from the small to the large. In this talk the two methods
are compared. Over the next twenty years, and for most applications,
micro- and nanofabrication will remain the most expedient path for progress.
However, I will show, using several examples, how one can already use
concepts (I call them ‘hints’) from nanochemistry and apply them to
more traditional machining methods. These hints include: modularity,
flexible materials, C instead of Si, and beyond batch manufacturing
methods. The examples I will present are: C-MEMS for electrochemical
detectors, soft machines for drug delivery, modular and beyond batch
biosensor fabrication, and a CD fluidic platform.
2:45 Micromanufacturing
of Cellular Systems
Mehmet Toner, Ph.D, Associate Professor, Center for Engineering in
Medicine, Massachusetts General Hospital / Harvard Medical School
I will discuss various microfabrication approaches to create cell-based
devices using biocompatible materials. I will emphasize the importance
of the design of the microenvironment for cell differentiation and function.
I will also discuss the issues concerning the long-term storage of cell-based
devices as these devices enter the marketplace.
3:15 Microtweezers for
BioMEMS
Chris Keller, Ph.D., Engineer, MEMS Precision Instruments MEMS Precision
Instruments develops microtweezers with application to BioMEMS in three
categories: (1) therapeutic microsurgery, (2) manipulation of biological
structures for research, and (3) micro robotic assembly of other BioMEMS
devices. Designs presented here were fabricated by the following methods:
(1) 4-level polysilicon SUMMIT process (Sandia National Labs), (2) molded
polysilicon high aspect ratio Hexsil process, and (3) deep RIE Bosch
process. Three types of actuators used are: thermal expansion, electromagnetic,
and electrostatic. Polysilicon piezoresistive strain gauges are used
for force measurement.
3:45 Exhibit/Poster Viewing
& Refreshment Break
4:15 Extreme Low Liquid
Volume Handling
Nico F. de Rooij, Ph.D., Head of the Sensors, Actuators and Microsystems
Laboratory (SAMLab), University of Neuchatel, Switzerland
Advanced Deep Reactive Ion Etching has allowed micromachining of front-end
injection devices composed of a flow-through reservoir for liquids,
a fully three-dimensional ring-shaped nozzle and a deflectable back-plate
with a piezo actuator. Various applications of these devices will be
discussed, including inhalers as well as micromachined injectors for
introducing liquid DNA samples into the vacuum compartment of a mass
spectrometer with single molecule counting cryodetectors. The size distribution
of the generated droplets is in the femtoliter range. It will be demonstrated
that the injectors can be used for controlled static liquid handling
at the (sub) femtoliter level. In collaboration with Bas de Heij, Philippe
Luginbuhl, Bart van der Schoot, Damian Twerenbold
4:45 New Fluidic Technologies
and Integrated Detectors for (Bio)Chemical Analysis
Albert van den Berg, Ph.D., Professor, MESA Research Institute, University
of Twente, The Netherlands
New techniques for fluid-flow control based upon the electrical field
effect will be presented. The flowFET device, capable of switching liquids
in microfabricated channels is described and its performance characterized.
The use of powder blasting technique for rapid prototyping of fluid
manifolds is discussed and various examples will be shown. The potential
of integrating planar waveguides for optical absorption measurements
and an integrated conductivity detector in combination with a planar
CE device will be shown.
5:15 Close of Day One
5:30 Cocktail Reception
& Cash Bar
Friday, June
23, 2000
8:30 Exhibit/Poster Viewing,
Coffee and Danish
9:00 Conference Chairperson’s
Opening Remarks
Marc Madou
New Microfabrication Techniques in the Pipeline- Continued
9:10 Session Chairperson’s
Remarks
Antonio J. Ricco
9:15 Soft Lithography
and its Application in Miniaturized Bioanalytical Systems
David C. Duffy, Ph.D., Senior Scientist, Gamera Bioscience Corporation
Soft lithography is a set of non-photolithographic microfabrication
techniques (including microcontact printing (mCP), replica molding,
and patterning using elastomeric membranes) that makes it possible to
create complex microstructures in biocompatible materials simply and
at low cost. The central component of soft lithography is an element
made from poly(dimethylsiloxane) (PDMS) that has been textured on the
micron-scale. This element can serve as the functional microstruture
itself (e.g., as a microfluidic network or a diffraction grating) or
as a pattern transfer element to create microstructures in other materials
(e.g., arrays of proteins or cells). The main advantages of these techniques
over conventional microfabrication methods are: the diversity of materials
that can be patterned; compatibility with biological systems; low cost;
ability to create 3D structures; and patterning of non-planar surfaces.
This talk will describe many of the soft lithographic techniques and
their application, particularly in microfluidics and array-based technology.
9:45 Polymer Replication
of Microfluidic CD Devices
Ove Öhman, Vice President of Research and Development, Ĺmic AB, Sweden
Microfluidics demand low unspecific adsorption to the chip. One way
to avoid cross-contamination and other unwanted effects of adsorption
is to use disposable chips. Here, we present a manufacturing scheme
for polymer based microfluidic devices in conventional CD size. The
manufacturing costs match the criteria for a disposable chip. The effects
of replication fidelity are shown by structural measurements and in
addition by microfluidic functions used in a re-sequencing application.
In collaboration with Per Andersson, Research Scientist, Amersham Pharmacia
Biotech AB, Sweden
10:15 Exhibit/Poster Viewing
& Refreshment Break
10:45 Liver Chips for
the Detection of Pathogens and Toxins
Karel Domansky, Ph.D., Research Scientist, Department of Bioengineering
and Environmental Health, Massachusetts Institute of Technology
Harnessing living cells organized into perfused tissue microstructures
is one of the most promising technologies for the fieldable detection
of pathogens and toxins. We used a suite of microfabrication techniques
including deep reactive ion etching (DRIE), wire and die-sinking electro-discharge
machining (EDM), UV laser micromachining, micromechanical milling, and
thermal diffusion bonding to generate flow-through bioreactor chips.
The issues related to seeding and culturing liver cells in the chips
will be summarized. Means for providing control of environmental conditions
for long-term operation of liver chips will be described. Results documenting
extended functional maintenance of cells in the liver chips will be
presented and data from live/dead assays upon an agent exposure will
be discussed. Progress made towards system miniaturization, integration,
and portability will be explained and a path for low cost large-scale
production of the liver chips will be suggested. In collaboration with
Colin Brenan, Petra Kurzawski, Mark J. Powers, and Linda G. Griffith.
11:15 DARPA and BioMEMS
Abe Lee, Ph.D., Program Manager, Defense Advanced Research Agency
(DARPA), Microsystems Technology Office (MTO)
The Defense Advanced Research Agency (DARPA) is investing heavily in
BioMEMS to achieve goals different from the biotech and healthcare industries.
However, these investments will lead to new applications for BioMEMS
that will, in time, create new industries and new commercialization
opportunities. Several DARPA programs will be described to illustrate
the motivation behind these investments.
11:45 Lunch on Your Own
Emerging
Applications
1:10 Session Chairperson’s
Remarks
Michael J. Heller
1:15 Microfluidics Technology
for Complex Measurement and Diagnostics
Barbara K. McQuiston, Vice President, Product Technology, YSI Inc.
YSI has developed an integrated measurement system for long-term monitoring.
The chip-based system utilizes amperometric biosensors with a microfluidic
monolithic device to create a miniature Flow Injection Analysis analytical
system. The disposable fluidic was developed using a bondable polymeric
film built with features and layered into a monolithic structure. This
presentation will discuss design considerations, system performance
characteristics and applications.
1:45 Microfluidic Devices
for Biomedical Applications
Gert Blankenstein, Ph.D., R&D Manager, microParts GmbH, Germany
microParts has built up the capacity for the development and production
of microstructured plastic devices. These microfluidic disposables,
e.g. for PCR, genomics/proteomics, immunoassays, hematology or high
throughput screening, integrate multiple functions. They may contain
microstructures for sample preparation and collection, for mixing and
dosing, deposition of chemicals or include sensors in detection zones.
microParts technological portfolio is allowing rapid prototyping as
well as mass fabrication of plastic disposables by micro injection molding
under GMP and ISO9001. microParts competence in surface treatment is
giving the opportunity to modify a surface for a desired application
to increase e.g. the wettability or to create a bioactive surface. A
microfabricated fluidic nanotiterplate LILPUTTM is presented as an example
of microParts capability to develop a Lab-on-a-chip system from stretch
to mass production by micro injection molding. The 96-well-plate with
a size of a stamp was developed for Merlin Diagnostika GmbH and is demonstrating
microParts know-how in Polymer microfabrication, in surface modification
and assembling technology. LILPUTTM is compatible to microParts microspectrophotometer
which can be used as an optical plate reader. Experimental data will
be presented showing the capability of the system for diagnostic screening.
2:15 Fully Integrated
Generic Microfluidic Systems for Portable Biochemical Detection or Clinical
Diagnostic Systems
Chong H. Ahn, Ph.D., Associate Professor, Center for Microelectronic
Sensors and MEMS, University of Cincinnati
Development of a fully integrated generic microfluidic system is essential
for portable bio/chemical detection or clinical diagnostic systems.
This presentation will discuss the relevant issues to the implementation
and characterization of: (a) an integrated microfluidic motherboard
which includes microvalves, micropumps, flow sensors, biosensors and
reservoirs; (b) an electrochemical immunoassay which works through bio-samplers
and immunosensors using magnetic beads as a carrier; and (c) a fully
integrated portable bio/chemical detection or clinical diagnostic system
which has sampling, sensing and diagnostic capabilities of living cells
or clinical parameters from liquid samples.
2:45 Exhibit/Poster Viewing
& Refreshment Break
3:15 Microfluidic Systems
for Animal Reproduction
David J. Beebe, Ph.D., Co-founder, Micro Agri Systems
Assisted animal reproduction technology has changed little over the
past several decades. Manually performed labor-intensive procedures
are still the norm. Micro Agri Systems is pioneering the use of micro
fluidic systems in animal reproduction. Networks of microfluidic channels
are used for transport, manipulation and culture of mammalian embryos.
The costs associated with many assisted reproduction technologies can
potentially be significantly lowered via microfluidic systems.
3:45 Silicon-Based Ultrasonics
for Mircosurgery and Microfluidics
Amit Lal, Ph.D., Assistant Professor, University of Wisconsin
Silicon-based ultrasonic tools that have been used for ophthalmic and
skin surgery with and without ultrasonic drive will be described. Measurement
of cutting forces using integrated sensors and the implications to surgery
will be discussed. The past and future of micro-scale surgery in the
context of previous work on micro-needles and micro-probes will be described.
Ultrasonic microfluidic systems integerated on silicon surgical platforms
will also be presented.
4:15 Panel Discussion:
Summation of the Conference
Panel Moderator, Marc Madou
Based on the success of last year’s conference wrap-up panel discussion,
we’re pleased to once again offer this exciting interactive strategy
session. Conference participants are encouraged to submit their questions
in advance as we would like to make sure that this conference addresses
the issues that are of most interest to you.
4:45 End of Conference
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