Click here to download the 2003 Attendee List

Scheduled Immediately Prior to the 2nd Annual Biodefense Conference, August 27-28, 2003

One-year membership in

View Sponsoring Publications

Monday, August 25, 2003

TRACK 1 NANOTECHNOLOGY

Nanotechnology in Drug Delivery and Therapy
Chairperson: Dr. Tejal Desai, Associate Professor, Department of Biomedical Engineering, Boston University

2:00 Intelligent Mucoadhesive Nanospheres for Transmucosal Protein Delivery and Other Pharmaceutical Applications
Dr. Nicholas A. Peppas, Robertson Meek Professor and Cockrell Regents Chair of Chemical, Biomedical Engineering and Pharmaceutics, Department of Chemical Engineering, University of Texas, Austin
Engineering intelligent biomaterials by controlling recognition and specificity is the first step in coordinating and duplicating complex biological and physiological processes. We address design and synthesis characteristics of artificial molecular structures capable of specific molecular recognition of biological molecules. Recent developments of our laboratory in protein delivery have been directed towards the preparation of targeted formulations for protein delivery to specific sites, use of environmentally responsive polymers to achieve pH- or temperature-triggered delivery, usually in modulated mode, and improvement of the behavior of their mucoadhesive behavior and cell recognition. Finally, configurational biomimetic microimprinting techniques that create stereo-specific three-dimensional binding cavities based on a biological compound of interest can lead to preparation of biomimetic materials for intelligent drug delivery, drug targeting, and tissue engineering.

2:30 Optically Controlled Nanocomposites for Modulated Drug Delivery
Dr. Jennifer L. West, Associate Professor, Bioengineering, Rice University
Near infrared light is being investigated as a means to modulate drug delivery rates from implants since these wavelengths of light can penetrate deeply into tissue. To generate materials that are near infrared-responsive, we have fabricated composites of thermally responsive polymers such as poly(N-isopropylacrylamide-co-acrylamide) with strongly absorbing nanoparticles such as gold nanoshells. These composites undergo dramatic phase changes in response to near infrared light and can be used for modulated insulin delivery. Additionally, by forming composites with particles that absorb in different regions of the electromagnetic spectrum, we have formed several composites that can be independently controlled with light. These show promise for use as optically controlled valves or actuators in microfluidics and MEMS.

3:00 Complex Nanostructured Materials Designed as Sophisticated, Yet Simple, Vessels for Drug Delivery
Dr. Karen L. Wooley, Professor, Department of Chemistry, Washington University
Regioselective reactivity of macromolecules, controlled over nanoscale dimensions, is providing the means to prepare unique nanostructures to advance the availability of materials for fundamental and applied studies in nanoscience and nanotechnology. This presentation will highlight the preparation and study of core-shell nanoparticles that result from segregation of the chain segments of amphiphilic block copolymers, carried out in solution, followed by intramicellar crosslinking, selectively throughout the shell layer. The crosslinking chemistry transforms the supramolecular assemblies into robust nanomaterials, and allows for them to serve as nanoscale constructs for further manipulation of the composition, structure, properties and functions. The block copolymer composition and the crosslinking agents determine independently the dimensions, compositions, and thus the properties, of the nanoparticle core and shell.

TRACK 2 BIOMEMS 

Biochip Design
Chairperson: Dr. Michael R. McNeely, President and Chief Technology Officer, BioMicro Systems Inc.

2:00 DNA Chip Flow Cell Design Issues and Concepts for Integrated Sample Amplification and Labeling
Dr. Michael R. McNeely
A disposable 25um high microfluidic flow cell has been developed that integrates sample delivery and mixing over a glass slide microarray. The product's bubble free filling and mixing designs will be discussed as well as alternative technologies that were attempted and abandoned. Future plans for the system will be described, including the integration of sample amplification and labeling into the disposable chamber, as well as the ability to process multiple samples simultaneously on the same glass microscope slide array.

2:30 Single Molecule Manipulation and Measurement; SM3
Dr. Angela R. Hight Walker, Optical Technology Division, National Institute of Standards and Technology
NIST has launched a multidisciplinary team project to develop new ways to measure the structure, function, and behavior of single biomolecules. A nanobiotechnology platform is under design to integrate nanopores, nanofluidic pathways, nanoparticles, and other devices for isolating, manipulating, and characterizing single biomolecules. The development of this platform provides experimental staging areas where single molecules can be observed and analyzed with a wide variety of tools, which are also under development, including fluorescence energy transfer (FRET), surface enhanced Raman spectroscopy (SERS), and ion transport.

3:00 The Fundamental Trade-off between Size and Sensitivity in Nanosensors
Dr. Paul E. Sheehan, Research Chemist, Naval Research Laboratory
A significant design consideration has often been overlooked in miniaturization, that analyte flux to a sensor decreases with the sensor's size. Indeed, there is a fundamental trade-off between the size of the sensor, that sensor's sensitivity, and the detection time. We examine the common situation where the diffusive properties and the concentration of an analyte are low (e.g., unamplified DNA in buffer) and show that, for a single nanosensor, diffusive flux alone will be insufficient to make it useful on a reasonable time scale. Analytic solutions for several sensor configurations will be presented as well as simulations for more complex situations such as laminar flow. Interestingly, laminar flow is not very effective at increasing flux to nanoscale sensors. Different design strategies for increasing the flux will be presented along with their relative advantages and disadvantages. Finally, strategies developed at the Naval Research Laboratory for overcoming these limitations will be presented.

MOLECULAR SURFACE ENGINEERING FOR THE BIOLOGICAL INTERFACE:
Cell Paterning 
Chairperson: Tejal Desai

4:00 Chip-Based Approaches to Screening BioMolecular Interactions
Dr. Milan Mrksich, Associate Professor, Department of Chemistry, Institute for Biophysical Dynamics, The University of Chicago
This presentation will describe a surface engineering approach to preparing biochip arrays for assays in drug discovery, diagnostics and biowarfare defense. The strategy combines self-assembled monolayers that are inert to biological interactions with immobilization reactions that control the activities and densities of proteins, peptides and carbohydrates on the chip. Further, the surfaces are engineered for detection by MALDI-TOF mass spectrometry. Applications of the SAMDI technique to drug discovery will be described.

4:30 Dielectrophoresis for Cell Biology
Dr. Joel Voldman, Electrical Engineering, MIT
As bioscience drives toward the study of whole cellular subsystems, there has been an increasing need for new methods to study and manipulate many individual cells. These methods allow the acquisition of new kinds of biological information, leading to new insights into how cells work. This talk will describe the use of non-uniform electric fields for manipulating cells at the microscale. This technique, known as dielectrophoresis, can be used to develop new methods to physically manipulate--capture, hold, and release--multiple individual cells. I will present several examples of current research exploiting this phenomenon for cell biology.

5:00 Controlling Cellular Activity for Drug Discovery Using Soft Lithography and Surface Engineering
Dr. Emanuele Ostuni, Surface Logix, Inc.
Patterns of cells and proteins that echo physiological states and arrangements can only be created using microscopic structures that are biocompatible and surfaces that are biospecific. Our disease-specific biosystems address bottlenecks in areas of drug discovery that include: the cell biology of white cells; the differentiation of endothelial cells in tumor environments; and the discovery of kinase and carbohydrate modifying enzymes. Accurate molecular-level control allows us to dissect disease pathways in assays with high information density. Key to this success are our abilities to control cellular interfaces with: (i) matrices, (ii) other cells, and (iii) the fluidic microenvironment. Soft lithography makes it possible to fabricate biocompatible microstructures rapidly and inexpensively while surface engineering makes it possible to fine-tune the specific interaction of these microstructures with complex biological systems.

MASS SPEC INTERFACE
Chairperson: Dr. Carol A. Dahl, Vice President,
Strategic Partnerships, Biospect

4:00 Automated Nanoelectrospray Mass Spectrometry: A Chip-Based Strategy for High-Throughput Bioanalysis
Dr. Thomas Corso, Director of Microtechnology, Advion BioSciences, Inc.
We are interested in developing improved methods and devices which can provide high-throughput bioanalysis capabilities. This lecture will show examples which represent significant advancements in sample throughput. These applications are based on chip-based nanoelectrospray mass spectrometry. The ESI Chip is an array of 100 microfabricated nanoelectrospray nozzles which can be sequentially used to rapidly spray individual samples collected from a 96-well microtiter plate. Presently the sample extracts are delivered directly to the chip without any prior chromatographic or electrophoretic separation.

4:30 Microfluidics for Mass Spec
Dr. Aaron Timperman, Assistant Professor, Chemistry, West Virginia University and Scientific Advisor, Protea Biosciences
Current methods for comprehensive proteome analysis suffer from an inability to identify low abundance proteins that play crucial roles in cell signaling and regulation. To overcome many of the current limitations, we are developing microfluidic devices which integrate solution phase separations and enzymatic digestion of the separated proteins prior to direct analysis using mass spectrometry. Nanocapillary arrays have been integrated into the microfluidic channels, and are used to concentrate the separated proteins. It is anticipated that the fully developed devices will provide significant gains in sample throughput and identification of low abundance proteins.

5:00 Biotic/Abiotic Hybrid Electronics
Dr. Brian Pierce, Executive Director, Electronics Division, Rockwell Scientific Co.
Biotic/abiotic hybrid electronics concerns the interface between biology and semiconductor electronics. This technology has applications ranging from biosensors to prosthetics for specific physiological functions. The talk will focus on issues from the abiotic (semiconductor) electronics perspective, which include the coupling between the cells/tissue and the electronics, biocompatibility, as well as the thermal management, power source and reliability of the semiconductor electronics.

8:00 Close of Day One

TUESDAY, AUGUST 26, 2003

8:00 Poster and Exhibit Viewing, Coffee

INTERFACING CELLS WITH MICRO AND NANO TECHNOLOGIES
Co-Chaired by: Dr. Nitish V. Thakor, Professor, Biomedical Engineering, Johns Hopkins University School of Medicine, and Dr. Michael F. Huerta, Director, Office of Translational Research and Scientific Technology, Associate Director, Division of Neuroscience and Basic Behavioral Science, National Institute of Mental Health, National Institutes of Health

8:30 Brain-Machine Interaction
Dr. Paul Bach-y-Rita, Professor, Department of Biomedical Engineering, University of Wisconsin, Madison
The tactile system offers a number of opportunities for brain-machine interfaces (BMI), and recently the technology to do so has become available. Although interfaces can be developed through virtually any tactile surface, the tongue offers unique advantages: the presence of an electrolytic solution, (saliva), assures good electrical contact. Perception with electrical stimulation of the tongue appears to be better than with finger-tip electrotactile stimulation, and the tongue requires only about 3% (5-15 V) of the voltage, and much less current (0.4-2.0 mA), than the finger-tip. The potential exists for a simple, practical, and cosmetically acceptable (built into an orthodontic retainer) interface, with FM signals from the artificial sensor carrying the information wirelessly to the tongue display, for relay to the brain. The display has potential applications for persons with sensory loss, (e.g., blindness, deafness); for communications, (e.g., sensate Internet); for transportation, (e.g., night vision); for surgery (e.g., sensate probes); and many others.

9:00 Brain-machine Interface Systems Using Implantable MEMS-based Microelectrode Arrays
Prof. Daryl R. Kipke, Associate Professor, Department of Biomedical Engineering, University of Michigan
The outlook for direct brain neuroprosthetic systems is closely related to the continued development of technologies to interface with specific areas of the central nervous system. Thin-film silicon microelectrodes have been developed as front-end sensors in MEMS-based integrated microsystems for long-term neural recording. Adaptive, real-time signal processing algorithms are being developed to decode neuronal signals into command streams for controlling machines and computer interfaces. Ongoing advances at the nano-, micro-, and systems-levels are bringing these brain-machine interface technologies closer to becoming next-generation therapeutic neurological devices.

9:30 The Brain Challenge
Dr. Dennis Glanzman, Chief, Theoretical and Computational Neuroscience
In order to understand the brain, and the manner in which disease and trauma affect the mind, technologies are needed to probe the brain at a wide range of spatial and temporal scales-from nanometers to meters, and from microseconds to years. This presentation will describe the large number of challenges this organ presents to those interested in developing new technologies to study it, and will describe some capa-bilities

INNOVATIONS IN MICROFLUIDIC DESIGN
Chairperson: Dr. Aran Paulus, Program Manager, Research, Amersham Biosciences

8:30 Automated Sample Preparation for DNA Sequencing Using Microfabricated Devices
Dr. Aran Paulus
Microfabricated devices are being developed as an alternative platform for capillary electrophoretic applications. The advantages of channel structures in planar devices instead of capillaries are in three areas: separation speed, multiplexing and integration. The evolving platform suitable for working with nano-to-picoliter volumes allows high speed separations due to short, effective separation lengths, simplifies multiplexing for highly parallel operation, and enables integration of sample preparation with low dead-volume interconnections. This is most evident for nucleic acid applications in general, and DNA sequencing in particular. An example of an integrated amplification reaction, clean up to remove sample, UN-incorporated nucleotides and the template and subsequent injection into a microfabricated channel for high speed DNA sequence analysis will be presented. Especially the integration issues to couple three independent steps on a glass microfabricated device will be discussed.

9:00 Micro-Physiometry Systems based on Dielectrophoresis
Dr. Ronald Pethig, President, AURA BioSystems, Inc.
Dielectrophoresis (DEP) refers to the motion of a particle induced by a non-uniform D.C. or A.C. electric field. The motion is related to the particle's dielectric properties. The dielectric properties of a cell (e.g., membrane capacitance, membrane resistance and cytoplasm conductance) reflect the cell's ability to maintain ion balances and are also a measure of metabolic work and biological organization. The development of devices based on DEP provides new research tools for the biomedical sciences, as well as a broad range of applications in drug discovery, diagnostics and cell therapy. This technology lends itself readily to miniaturization, involving the integration of microelectrodes and microfluidics.

9:30 The Biochip Approach to Cell Biology
Dr. Lei Wu, Chief Operating Office, AVIVA Biosciences Corporation
The manipulation of cells and performance of biological assays on the cellular levels are critical for both pharmaceutical research and diagnostics. We have combined microfabrication, microfluidics, and cell biology to develop biochips that isolate, sort, and prepare cells for analysis, high-throughput assays, or diagnostic applications. In this presentation, we will describe two different types of biochips for patch clamp electrophysiology aimed at the discovery of drugs affecting ion channels and rare cell enrichment aimed at the fetal cells in maternal blood, cancer cell detection, and stem cell harvesting.

NANOASSAYS AND PROBES
Chairperson: Dr. Mihail Roco

10:30 Highly Specific and Sensitive Gold Nanoparticle Probe based Biomolecule Detection Systems
Dr. James J. Storhoff, Senior Scientist, Nanosphere Inc.
The push towards point-of-care diagnostics will require fast, robust, inexpensive, and simple, but nevertheless highly sensitive and specific detection systems for protein and nucleic acid targets. Nanosphere, Inc. is currently developing a gold nanoparticle based diagnostic platform that is aimed at achieving these goals. The key to sensitive and specific detection of DNA targets is the coating of gold nanoparticles with appropriately designed oligonucleotides which results in probes with higher melting temperatures and sharper melting transitions than can be achieved by conventional labeling of DNA probes. Using silver based amplification and a simple and inexpensive optical detection device built at Nanosphere that measures Rayleigh scattering, we have successfully developed PCR-less detection assays for infectious disease agents and even SNPs in the human genome.

11:00 Life Sciences Applications of Dip Pen Nanolithography
Dr. Guy della Cioppa, Executive Vice President, Business Development, NanoInk, Inc.
DPN™ technology is a patented process that enables the building of nanoscale structures and patterns by literally drawing molecules onto a substrate. Structures can be assembled onto microelectronic devices with feature sizes in the 10-12nm size range using virtually any material. The ability to routinely build at this resolution combined with almost unlimited material and substrate flexibility allows users of DPN technology to manufacture ultra-high density nanoarray and nanosensor devices.

11:30 Nanostructures for Single-molecule Biotechnology
Dr. Stephen Turner, Chief Scientist, Nanofluidics, Inc.
Recent advances in nanostructure fabrication have significantly broadened the scope of biological questions that can be posed at the single-molecule level. Single-molecule approaches have intrinsic advantages over bulk methods for studying biomolecular interactions. In many contexts both the biological samples and the reagents used to study them are precious, often contributing the largest single component of the overall cost of a study. Single-molecule approaches can reach the theoretical limits of frugality. In addition, bulk measurements are often plagued by multiplicative error factors resulting from fluctuations in the various components of a system. Single-molecule detection systems can be designed to have robust immunity against most of these sources of error, and are limited primarily by the uncertanties inherent in counting statistics. Aside from being more cost-effective and improving signal-to- noise, often single-molecule approaches can provide insights unavailable by any other means. A new and promising method for rapid sequencing of single DNA molecules will be used as a case study in how novel nanostructures holds the potential to revolutionize the way information about biological systems is obtained.

MINIMALLY INVASIVE TECHNOLOGIES
Chairperson: Dr. Mak Paranjape, Assistant Professor, Department of Physics and GAEL Health Microsystems , Georgetown University

10:30 Development of An Innovative Hand-Held Point-of-Care Testing (POCT) System with Disposable Smart Plastic Lab-on-a-Chips for Blood Analysis
Prof. Chong H. Ahn, Professor and Director, MicroSystems and BioMEMS Lab Associate Director, Center for Microelectronic Sensors and MEMS, University of Cincinnati
In this presentation, an overview of the recent research achievements for the smart and disposable plastic lab-on-a-chip for blood sampling and analysis will be presented, discussing the relevant microfluidics and BioMEMS issues to the design, fabrication, and characterization of microfluidic devices, biochemical sensors, disposable plastic lab-on-a-chips, and wrist watch type point-of-care testing (POCT) systems.

11:00 Non-intrusive Transdermal Glucose Monitor
Dr. John F. Currie, Director GAEL Health Microsystems (Georgetown Advanced Electronics Laboratory), Departments of Physics & of Pharmacology, Georgetown University
Our research goal is to fabricate a prototype microfluidic system, called BFIT, for the non-intrusive, sequential, real-time trans-dermal sampling & analysis of molecules that ordinarily do not diffuse across the skin, such as polar molecules. Our BFIT system aims to provide an individual, personal baseline while being both disposable and sterile. Our approach employs the non-invasive sampling of living tissue, in a unique and minimally disruptive fashion. It retrieves a tiny mass of analyte without body fluid sampling, that is without removing interstitial fluid, ISF. The monitoring is time controlled and can cover short- or long-term time periods (days-months). It is an absolute measurement with no need for an external or on-board glucose reference. Finally, it is generalizable to the monitoring of almost any moderately hydrophilic/soluble bio-molecule or molecular weight of less than 60k Daltons, as are commonly found in measurable concentrations in the interstitial fluid just under the skin's stratum corneum.

11:30 Creatinine Chip
Dr. G. Bruce Collier, Biochemistry Manager, Technology Group, R&D, i-STAT Canada Ltd.
The i-STAT Creatinine cartridge provides a rapid diagnosis of peripheral blood creatinine concentrations using a single drop of blood in minutes, right at the patient's bedside. This test is an indication of liver function, and has proven particularly useful for oncologists and radiologists to quickly assess the ability of the patient to tolerate doses of chemotherapy and imaging agents before administration. We will discuss the application, function and performance of this biosensor.

12:00 Lunch (on your own)

Clinical Applications: Applying MEMS to Medicine
Chairperson: Dr. Shuvo Roy, Co-Director, BioMEMS Laboratory,
Department of Biomedical Engineering, The Cleveland Clinic Foundation

1:30 Chronic Deep Brain Microstimulation System for Parkinson's Disease
Dr. Jack W. Judy, Assistant Professor, Department of Electrical Engineering, Co-Director, Neuroengineering Program, University of California, Los Angeles
Parkinson's disease is a severely debilitating and degenerative neurological disease that afflicts more than 500,000 people in the United States. Although drug treatments are available and are initially effective, after prolonged use the drugs become less effective and the side effects (e.g., dyskinesia) become more severe. Deep-brain stimulation (DBS), which is a technique that reversibly lesions regions deep within the brain, was serendipitously discovered in the operating room to be effective at eliminating debilitating tremors and other motor-control deficits caused by neurological disorders (e.g., Essential Tremor). It has long been suspected that DBS will be effective at addressing Parkinson's disease. In order to fully investigate this hypothesis, a comprehensive long-term stimulation study in an animal model is needed. My lab has designed, fabricated, and tested a novel micromachined probe and stimulation system for rat models to further the research on Parkinson's Disease and its hopeful mitigation.

2:00 Nanoporous Hemofiltration Membranes for Bioartificial Kidneys
Dr. William H. Fissell, Lecturer, Division of Nephrology, University of Michigan Hospitals
End-stage renal disease affects 378,000 Americans and is increasing in prevalence at 8%/year. The primary treatment at present is in-center hemodialysis, which is more costly and offers inferior survival when compared with renal transplant. Our group at University at Michigan has completed a Phase I clinical trial of a bioartificial kidney in critically ill patients. Our progress in engineering a miniaturized implantable artificial kidney will be discussed.

2:30 Cell-Based Therapies for Musculoskeletal Repair
Dr. George Muschler, Orthopaedic Surgery and Biomedical Engineering, The Cleveland Clinic Foundation
One of the most fundamental principles in medicine and biology is that cells do all of the work. No growth factor nor bone graft matrix is capable of forming tissue unless it is placed in a site that contains a sufficient number of stem cells or progenitor cells that are both responsive to the stimulus provided and capable of forming bone. Several lines of research have demonstrated that increasing the number of competent cells in a graft site provides improved outcome in bone grafting. These findings imply that many sites in which clinical grafting is performed may be deficient or sub-optimal with respect to the number of stem cells or progenitors. Microfabrication methods allow design of unique microtextured surfaces with defined morphology. These surfaces provide a unique system for assessing the effect of surface texture on the biologic response of stem cells and progenitor. Some of these methods may offer practical tools for fabrication of three dimensional matrices which strategically incorporate selected surface textures to enhance the biological result.

3:00 Refreshment Break, Poster & Exhibit Viewing

3:30 Neural Prosthetic Interface for Retinal Replacement
Dr. Robert Greenberg, President and Chief Executive Officer, Second Sight, LLC
Second Sight, located in Valencia, California, was founded in 1998 to create a retinal prosthesis to provide sight to patients blinded from outer retinal degenerations, such as Retinitis Pigmentosa and Macular Degeneration. Through dedication and innovation, Second Sight's mission is to develop, manufacture and market implantable visual prosthetics to enable blind individuals to achieve greater independence. Currently, Second Sight is developing an implantable device that acquires power and data from external hardware and electrically stimulates the retina through an array of electrodes. Simple arrays, used in short-term experiments, have produced formed vision in patients with Retinitis Pigmentosa. Further, research conducted by Second Sight has shown that more advanced array designs are possible, and that these arrays should significantly improve the quality of the images seen by patients.

4:00 Implantable BioMEMS for Drug Delivery
Dr. John T. Santini, Jr., Founder, President & Chief Scientific Officer, MicroCHIPS, Inc.
Microfabrication technology has enabled the creation of intelligent drug delivery systems. Microchip devices (bio-micro-electro-mechanical systems or BioMEMS) containing an array of sealed, drug-filled reservoirs have been developed and can be implanted in the body. Release of drug from the microchip's reservoirs is controlled by pre-programmed microprocessors, wireless telemetry, or biosensors. Our group was the first to demonstrate both in vitro and in vivo, on-demand release of chemicals stored inside a microchip device. This presentation will review recent progress in the development of these implantable bioMEMS for drug delivery applications.

LIST OF POSTER PRESENTATIONS