Concurrent Tracks

8:00am Coffee Break with Exhibit and Poster Viewing






Symposium Chairperson
Dr. Mak Paranjape, Georgetown University

8:30 Integrated, Plastic Microfluidic Chips for Genetic Sample Preparation
Dr. Piotr Grodzinski, Motorola Inc.
The miniaturization of biological assays to the chip level carries several advantages. They use reduced volumes of reagents and allow for reducing cost per reaction and improving reaction kinetics. On-chip reactions can also be carried in parallel facilitating the development of systems with high throughput. Furthermore, integration of several assay functions on a single chip leads to assay automation and elimination of operator involvement as a variable. Such devices will find use in rapid diagnostic applications in hospitals, doctor’s offices, and field testing.

The use of plastics and plastic fabrication methods is becoming increasingly important in the development of these microfluidic devices. Plastics offer an abundance of material choices with varying physical and chemical material properties. They are optically transparent and biocompatible with most assays. Plastic surfaces can be modified for needed molecule attachment. Finally plastics offer low cost and ease of batch fabrication through molding, embossing, and casting processes.

In this presentation, we will discuss a development of plastic, disposable chip sets for genetic analysis. We will discuss fabrication techniques for stamper development used in embossing and compression molding. We will also show that direct laser writing techniques permit for rapid prototyping and eliminate need for the use of lithography. The structure bonding is handled using lamination or thermal methods.

We will describe the development of components and integration schemes of a complete sample-to-answer genetic analytical system. The back-end detection is handled using channel networks containing in-channel hybridization sites. This approach facilitates a platform for integration of hybridization devices with front-end microfluidic sample preparation structures. It also permits for improved kinetics of hybridization. Front-end cell separation to isolate targets of interest is performed using immunomagnetic techniques within microfluidic channels. Captured targets are subsequently concentrated into smaller volume of 10 – 50 l for amplification of released DNA in plastic micro-PCR reactors.

The details of device fabrication methodologies using high resolution compression molding and embossing, plastic bonding, and approaches to integration will be also described.

8:50 Biophotonic NEMS
Dr. Luke P. Lee, University of California, Berkeley
Biophotonic NEMS is being developed for single molecule detection and manipulation by optical trapping array through integrated nanofluidic devices and microscale Confocal Imagining Arrays (CIAs). Compact, multi-functional, self-aligned nanoscopic CIAs have several advantages in comparison to macroscopic systems: size, cost, and sensitivity. The nanoscopic CIAs are realized using silicon micromachining and optical MEMS technology. The CIAs utilize the precise control of the micro-optical motion and multiple optical trapping capabilities for various biomedical applications. The nanoscopic CIAs have application in non-invasive real-time single molecule detection in living cells that allows dynamic monitoring of individual fluorophores in-vivo in the highly complex cellular environment. With multiple optical trapping setups, the nanoscopic CIAs can be used to study structural and biophysical properties in near future. Hybrid integration of nanofluidics, nanopillars, biophotonic MEMS technology will be useful for ultrasensitive analysis of single molecules detections, functional genomics, proteomics, and very large scale integration of molecular microprocessors in advanced bioinformatics.

9:10 Microfluidic and Implantable Biomedical Microsystems Fabricated in PDMS
Dr. Peter Krulevitch, Lawrence Livermore National Laboratory
Polymer-based microfabrication processes have been applied to a number of biomedical microsystems under development at Lawrence Livermore National Laboratory. PDMS technology developed by the Whitesides group and others has been extended to enable the fabrication of thin, compliant devices with conducting lines for medical implants, and hybrid microfluidic systems. Applications include biological sample preparation modules, microsyringes, electrode arrays for retinal implants, and microfluidic systems with integrated electronics. Applications, fabrication approaches, and materials testing results will be presented.

As part of its program to miniaturize and automate biological sample preparation procedures, LLNL devel-oped a polymer-based packaging platform for creating hybrid microfluidic systems. The approach enables the integration of flow channels, reservoirs, glass and silicon microfluidic chips, PC boards and electronics, and commercially available micropumps and valves into microfluidic systems. In the packaging scheme presented here, the PDMS serves two functions: it is the platform that allows hybrid integration of various microfluidic com-ponents, and it provides an interface between meso-scale and micro-scale fluidic devices. The PDMS has complex, three-dimensional fluidic structures molded into it, including reservoirs to deliver and receive fluid samples to/from pipettes or other instruments, flow channels, and mem-branes.

LLNL is developing instrumentation for collecting, processing, and identifying fluid-based biological pathogens in the forms of proteins, viruses, and bacteria. To support this effort, we are developing a flexible fluidic sample preparation unit, using the PDMS packaging platform. The overall goal of this Microfluidic Module is to input a fluid sample containing background particulates and potentially target compounds, and deliver a processed sample for detection. We are developing techniques for sample purification, mixing, and filtration that would be useful to many applications including immunologic and nucleic acid assays. We are integrating these technologies into packaged systems with pumps and valves to control fluid flow through the fluidic circuit.

As part of a collaborative project with other national laboratories, industry, and Universities, we are developing an implantable, stretchable micro-electrode array using PDMS microfabrication techniques. The device will serve as the interface between an electronic imaging system and the human eye, directly stimulating retinal neurons via thin film conducting traces and electroplated electrodes. The metal features are embedded within a thin (~50 micron) PDMS substrate. Advantages of PDMS include biocompatibility, stretchability, oxygen permeability, and low water absorption. The conformable nature of PDMS is critical for ensuring uniform contact with the curved surface of the retina. To fabricate the device, we developed unique processes for metalizing PDMS to produce robust traces capable of maintaining conductivity when stretched (strain = 0.07, SD = 0.01), and for selectively passivating the conductive elements. An in situ substrate curvature measurement taken while curing the PDMS revealed a tensile residual strain of 10%, explaining the stretchable nature of the thin metalized devices.

This work was performed under the auspices of the U.S. Department of Energy by University of California Lawrence Livermore National Laboratory under contract No. W-7405-Eng-48.

9:30 Water-Powered MicroDrug Delivery System
Dr. Liwei Lin, University of California, Berkeley
In recent years, MEMS (Microelectromechanical Systems) techniques have been applied to a variety of medical research to both improve the performance of existing devices and to explore new territories that were not possible without the advanced micromachining technologies. Drug delivery, which covers a broad range of techniques for transporting therapeutic agents into the human body, remains an important challenge in medicine and the applications of MEMS techniques may open up new research opportunities. Implantable and controlled-release drug delivery systems offer benefits over repetitive administration of conventional drug therapy by providing unattended continuous delivery within the therapeutic window. Avoiding highly variable peak concentrations often seen after immediate-release of dosing, a constant drug concentration delivery system as the one presented in this talk can result in enhanced drug efficacy and minimized side effects. Furthermore, these systems have the potential to provide alternative paths to deliver special drugs components such as proteins, which are often difficult to administrate due to rapid degradation and poor absorption in the gastrointestinal tract. Another example is macromolecule, which is difficult to deliver by other techniques.

This talk presents a plastic micro drug delivery system that draws power directly from water without using any electrical power and delivers liquid drugs with pressure up to 25 MPa to overcome possible blockages from microorganisms. The material, design issues and and manufacturing processes will be discussed in details. The system consists of an osmotic micro-actuator, a drug reservoir, a microfluidic channel to control the drug diffusion process and a drug delivery port. The actuating membrane has an initial diameter of 800 ìm and the length of the microfluidic channel is 1 cm with a cross section of 30 x 100 ìm2. Using oxygen plasma to activate polymer surfaces, simultaneous sealing and encapsulation of liquid are accomplished. Employing the net water flow induced by osmosis, this prototype drug delivery system has a measured, constant delivery rate at 0.2 ìl/hr for an operation period of 10 hours with a drug delivery volume of 2ìl. The delivery rate and volume can be designed to target specific disease for the treatment period of hours up to years. As such, this micro drug delivery system has strong potential in bio-medical applications.

9:50-10:30 Refreshment Break with Exhibit and Poster Viewing



8:00am Coffee Break with Exhibit and Poster Viewing

Symposium Chairperson
Dr. Rashid Bashir, Purdue University






8:30 Using ink-jet micro-dispensing technology to generate nerve guidance conduits.
David S. Silva, Donald J. Hayes, Michael Grove
In this paper, we will discuss the use of a micro-dispensing system as a means of creating scaffolds for various tissue-engineering applications, as well as discuss one specific application, nerve guidance conduits, in detail. MicroFab’s ink-jet printing technology can reproducibly dispense precision spheres of fluid with diameters of 20-200: m (5pL to 5nL) at rates of up to 4,000 per second for droplets on-demand, and rates up to 1MHz for continuous droplets. The drops can be printed in such close proximity as to create columns, lines, and other continuous structures depending upon the application. Due to the digital basis of ink-jet technology based microdispensing, a high degree of control is available for droplet placement allowing printing of specific, complex, uniform patterns readily available to many applications. Current applications include loading bioabsorbable microspheres with medicaments for controlled drug delivery and tissue engineering.

With regard to tissue engineering, MicroFab’s dispensing technology has shown incredible potential for success. As many applications within tissue engineering rely on the precise dimensions of polymer scaffolds, placement of biomolecules and surface texture, our involvement with tissue engineering was a natural step with regard to our printing platforms. Incorporating our printing technology, we have created a Tissue Engineering platform capable of precise printing of bioabsorbable polymers, growth factors and other biological proteins and growth promoting agents. This platform relies upon proprietary technology that allows precision dispensing onto a movable stage in three dimensions. Using this technology, we are fabricating nerve guidance conduits by dispensing bioabsorbable polymer onto glass and rolling the materials into conduits. On the other hand, our dispensing technology allows for solvent based and hot-melt polymers to be used availing us to other methods of conduit manufacture.

Factors such as conduit micro-texture, permeability, biomolecule location and dimensions have all remained traits which researchers attempting to repair peripheral nerve deficits must control to be successful. The relative difficulty in successfully manipulating these factors to a favorable outcome has long been a matter related to the level of control and alteration available within a specific fabrication method. Although certain technologies (i.e., mold-casting, polymer foaming) have allowed production of porous conduits of bioabsorbable material and conduits containing regeneration promoting biomolecules, these procedures still rely on crude manufacturing technology. The availability of Ink-Jet microdispensing technology applied to generating nerve guidance conduits will allow researchers to manipulate variables currently disallowed by present manufacturing techniques. The system presented in this paper is being used for several MEMS and BioMEMS applications.

In our current study, we are printing bioabsorbable polymer, and altering that polymer to accept biomolecules, which are also printed onto the substrate in a specific pattern to elicit neurite extension. We are researching the effect of ligated NGF printed onto the modified surface. These patterns are designed to control neurite extension from a differentiated PC-12 cell. Successful results will show this method of printing is useful for tissue engineering applications, as it offers a level of control otherwise unavailable with current techniques for nerve conduit generation.

8:50 Microfluidic Manipulation of Particles, Cells, Viruses, and Molecules
Dr. Steve Wereley, Purdue University
A wide variety of biomedical microdevices have been developed recently which transport samples to be tested from an inlet area to a sensing area and then on to a waste collection area. Often the sample is a distributed phase such as particles, cells, viruses, or molecules being carried by a micro-scaled flow. The dynamics by which these small distributed constituents are transported from one place to another in a biomedical microdevice can be quite complicated, despite the low Reynolds number behavior of the transporting flow. In a system of small ‘particles’ suspended in a fluid, the particles are subject to thermal noise, typically called Brownian motion. Particles suspended in a fluid will also experience deterministic forces, particularly when they are being carried through the long, narrow channels often found in biomedical microdevices. In addition to being simply convected along with the suspending fluid, the particles experience a lateral migration force generally away from the boundaries of the flow where the fluid shear is at its highest. Poiseuille (1836), providing the earliest report of this migration, observed that blood flowing through capillaries contained a cell-free region near the walls of the capillaries. This same behavior occurs, for better or worse, in biomedical microdevices transporting cells suspended in fluid and, despite over 170 years of considering this phenomenon, little attention has been paid to the migratory behavior of Brownian particles. The interplay of these and other forces found in biomedical microdevices will be discussed. Experimental evidence of their presence will be presented and methods for either eliminating deleterious effects or harnessing useful ones will be presented.

9:10 Analysis of Microscale Transport of Biomems
Dr. Carl D. Meinhart, 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.

9:30 Microintegrated Technology Platform for the Detection of Cells and Microorganisms
Prof. Rashid Bashir
The merger of life-science and engineering, specially at the micro and nanoscale, can bring about some very exciting and practical possibilities
for the development of integrated systems. Micro and nanoscale engineering can be used to solve important problems in life-sciences such as detection
of biological organisms, while concepts from life sciences such as bio-inspired assembly can be used to meet significant engineering challenges such as novel techniques for material synthesis and manufacturing. This talk will present the interdisciplinary work in progress in our group in these exciting research areas specifically focusing on micro-integrated technology platforms for the detection of microorganism within micro-fluidic bio-chips. These devices (micro-fermentators and bioreactors-on-a-chip) are being used to concentrate, capture, and detect the viability of with an emphasis on rapid
time to result.

9:50-10:30 Refreshment Break with Exhibit and Poster Viewing



8:00am Coffee Break with Exhibit and Poster Viewing







Symposium Chairperson
Dr. Meyya Meyyappan, NASA Ames Research Center

8:30 Application of Carbon Nanotube Electrodes in Chemical and BioSensors
Dr. Jun Li, NASA Ames Research Center
The merger of life-science and engineering, specially at the micro and nanoscale, can bring about some very exciting and practical possibilities  for the development of integrated systems. Micro and nanoscale engineering can be used to solve important problems in life-sciences such as detection of biological organisms, while concepts from life sciences such as bio-inspired assembly can be used to meet significant engineering  challenges such as novel techniques for material synthesis and manufacturing. This talk will present the interdisciplinary work in progress in our group in these exciting research areas specifically focusing on micro-integrated technology platforms for the detection of microorganism within micro-fluidic bio-chips. These devices (micro-fermentators and bioreactors-on-a-chip) are being used to concentrate, capture, and detect the viability of with an emphasis on rapid time to result.

8:50 Highly Organized Carbon Nanotube Structures
Dr. Pulickel Ajayan, Rensselaer Polytechnic Institute
This talk will focus on the directed assembly of multiwalled carbon nanotubes on planar substrates into highly organized structures that include vertically and horizontally oriented arrays, ordered fibers and porous membranes, and singlewalled nanotubes that include macroscopic strands. The concept of growing multiwalled nanotube architectures on planar substrates is based on growth selectivity on certain surfaces compared to others. Selective placement of ordered nanotube arrays is achieved on patterned templates (Si/SiO2) prepared by lithography or oxide templates with well-defined pores. Growth of nanotubes is achieved by chemical vapor deposition (CVD) using hydrocarbon precursors and vapor phase catalyst delivery. The new technique developed in our laboratory allows enormous flexibility in building a large number of complex structures based on nanotube building units. We will present our understanding of the early stages of nanotube film growth during this CVD process. It is observed that there are select pathways during the growth process of nanotube films on substrates, influencing the final morphology of the films developed, and these pathways can be tailored by tuning the catalyst concentration in the vapor phase. For the case of singlewalled nanotubes, the CVD process is modified by introducing, thiophene and hydrogen to obtain high yields of macroscopic strands (several centimeters long), which can be manipulated quite easily. The importance of such macroscopic structures based on nanotube will be discussed. We will also discuss some of our recent efforts in creating nanotube junctions and networks of related nanostructured materials by post-processing techniques and local probe techniques such as electron beam welding.

9:10 DNA Alignment, Characterization, and Nanofabrication on Surfaces
Dr. Adam T. Woolley, Brigham Young University
We are developing tools for surface manipulation and analysis of nucleic acid molecules for use in nanofabrication and DNA sequencing. We are working to characterize, understand and optimize conditions for controlled alignment of DNA fragments on Si, mica and other substrates, and these surface bound nucleic acid molecules are being used as templates for construction of nanowires. This work builds upon our earlier results in devising methods for reproducible alignment of well-extended single-stranded and double-stranded DNA fragments on surfaces.1 We have now carried out a thorough study of the deposition and alignment of both single-stranded and double-stranded nucleic acids on surfaces to optimize our techniques. We have also performed single-molecule experiments to understand the underlying biophysical mechanisms that lead to directional alignment of DNA on surfaces under different conditions. These aligned, surface deposited nucleic acid molecules are being utilized as templates for construction of nanowires. One approach involves photochemical and electrochemical reduction of ions associated with surface bound DNA to build up conductive nanostructures. Techniques for DNA-templated construction of carbon nanotube nanowires on surfaces are also being pursued. These results show great promise for DNA-based fabrication of materials with nanometer dimensions, and that biotemplated nanolithography should become an important component of the nanotechnology toolbox.

9:30 The BioNano Interface: Template - Synthesized Nanotubes in Bioseparations and Biosensors
Dr. Charles Martin, University of Florida
Beginning in the 1980's our research group has pioneered a versatile approach for preparing nanomaterials called template synthesis. This method entails synthesizing nanoscopic particles of the desired materials within the pores of a nanopore membrane or other solid. Because the membranes used contain cylindrical pores with monodisperse diameters, corresponding cylindrical nanoparticles are obtained. Depending on the material and the chemistry of the membrane, these cylindrical nanostructures may be either solid (nanowires) or hollow (nanotubes).

We have been especially interested in biomedical applications of template-prepared nanotubes. We have shown that the template method can be used to make synthetic polymer membranes that contain monodisperse, cylindrical nanotubes that span the complete thickness (~10 m) of the membrane. The inside diameter of the nanotubes can be controlled at will, down to molecular dimensions (<1 nm). Furthermore these nanotubes can be composed of nearly any material – e.g., carbons, metals, polymers, semiconductors.

One area of interest concerns using these nanotube-containing membranes as highly selective molecular filters for bioseparations. We are especially interested in membranes for enantioseparations - one of the most challenging and important problem in modern biomedical science. In addition, we have recently shown that these nanotube-containing membranes can be used for protein separations. We have also shown that these tube-containing membranes can be used in a new approach to biosensing. We have achieved detection limits with these nanotube sensors as low as 10-11 M. Both the bioseparations and biosensors applications entail immobilization of biochemical molecular-reagents - antibodies, enzymes, DNA, etc. - to the inside nanotube walls. Various aspects of this bio nanotube research effort will be discussed in this presentation.

9:50-10:30 Refreshment Break with Exhibit and Poster Viewing




Gain visibility for your research by participating in the poster session.
Posters will be judged by a Scientific Advisory Board; over 60 posters are expected to be submitted. Cash prizes will be awarded.
Please fill out the registration form, giving the poster title and the poster's primary author. All submissions will be reviewed for possible inclusion for poster presentation.
Click here for poster instructions
Full-length papers based on podium or poster presentation at the conference will be reviewed for fast-track publication in Biomedical Microdevices. Submitted typed manuscripts are due at the conference.
DNA Microarray Informatics: Key Technological Trends and Commercial Opportunities
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For more information about this and other CHI Life Science Reports, please visit www.chireports.com or contact Cindy Ohlman at 781-972-5434.

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