Bioengineering Department, Box 352255, University of Washington, Seattle, WA 98195, USA
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Bioengineering Department, Box 352255, University of Washington, Seattle, WA 98195, USA |
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Delivery of therapeutic agents to the intended site of action at a controlled rate is often difficult. We have been exploring the potential of lipid complex high axial ratio microstructures (CHARMs) as components of continuous delivery systems for such agents. CHARMs include lipid tubules, helices (like those shown in a darkfield optical micrograph at left), and cochleate cylinders. In collaboration with Michael Gelb of Chemistry, we synthesized dozens of lipopeptides and other surfactants that self-assembled into CHARMs and could associate with therapeutics. We found that covalent attachment of therapeutic molecules to the headgroups of lipopeptides that formed CHARMs could greatly change the bioavailability of that therapeutic. We engaged in 3 in vivo testing collaborations: 1) with Mary L. (Nora) Disis in Oncology to explore the potential for these microstructures as vaccines against cancer and infectious disease, 2) with John Amory of the VA Hospital to explore CHARM-based delivery of testosterone, and 3) with Peter Tarcha of Abbott Research Laboratories. Project completed. |
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Since 1994 we have been designing microfluidic devices and systems for use in monitoring the physical and chemical nature of complex fluids such as blood. The work was initially supported by the Washington Technology Center, DARPA DSO and Senmed Medical Ventures, Micronics, Inc., of Redmond, WA, a company founded on the basis of intellectual property developed in this project. We are currently engaged in expanding the our understanding of the capabilities of the T-sensor, a version of which is shown at left. We are also making a transition from Si microfabrication to materials amenable to use in inexpensive disposable devices. While this project is officially completed, similar work is ongoing in the laboratory (see Current Work). |
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A central problem in the development of Microfluidic Molecular Systems is that while many excellent methods exist for detecting and quantifying chemical and biological warfare (CBW) agents (some of which have already been miniaturized to the MEMS size range), the macroscopic sample preparation methods required to continuously extract the analytes from the extraneous matter in "real world" samples prior to chemical measurements have not been miniaturized.
As shown in the (highly schematic) working drawing above, we worked to design a system that could plug directly into an air sampler, incorporating pumps (thin devices) and flow control modules interconnecting three sequential microfluidic components: a sedimentation device at left (connected to the red sump), an isoelectric focusing element (gold electrodes showing at the center), and an electrophoretic concentrator (at right, also with gold electrodes). Our project was to develop a microfluidic system that would allow sorting of analytes prior to chemical identification.
The multidisciplinary project was funded by the DARPA MTO MicroFlumes program from May 1997 to July 2000. It had the following aims:
1. Development of a chemical separation system that takes advantage of low-Reynolds number conditions present in microfabricated fluid channels. (Yager Group)2. Development of a sample pretreatment system that allows extraction of the relevant analytes from fluids containing interfering non-analyte particles and concentration of analytes initially collected at low concentrations in large volumes of fluid. (Yager Group)
3. Development of on-chip pumping systems that are tolerant of fluids containing particles of widely differing sizes. (Forster Group)
The project was a collaboration between professors Yager, Fred K. Forster (ME), and Martin A. Afromowitz (EE) at UW. Work in the Yager lab focused on the development of sedimentation, electrophoresis and isoelectric focusing as methods for sample fractionation. Several novel microfluidic devices and methods have resulted.
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![[model of silk beta sheet crystallite]](silkcpk.gif) |
Natural silks match many of the properties of high-performance synthetic polymers, yet are processed under significantly milder conditions. High strength, stiffness and impact resistance are achieved in a polymer that is precipitated from aqueous solution at room temperature; also, this material is biodegradable, producing nontoxic breakdown products. A variety of natural silk secretions form liquid crystalline phases en route to solidifying. This project, now complete, was aimed at developing a link between the folding of proteins and liquid crystalline polymer technology through an examination of the molecular and microstructural changes that accompany the spinning of silk fiber. Microstructural and molecular changes were observed in both natural and artificial silk spun through orifices. Key personnel included Kimberly Carlson (nee Trabbic). |
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This project was supported as a subcontract to UW from MesoSystems Technologies. It was ultimately supported by the U.S. Army. It was the most recent in a series of projects we have had supported by DARPA and MesoSystems aimed at improving detection of chemical and biological warfare agents through application of microfluidics. There were two overall tasks to be performed in this project. The first was to determine whether a new design for application of high voltage to microfluidic channels could be used effectively for zone electrophoresis and isoelectric focusing. The second was to apply the best possible method to developing an electrokinetic method for isolation of DNA from bacterial cells. That aspect of the work was to be developed in two stages. In the first phase, the input sample was to consist only of dilute DNA, including DNA from a BW simulant such as Bg. The aim as to be to demonstrate and quantify concentration of this material using either zone electrophoresis or isoelectric focusing. The goal was to be concentration of DNA by a factor of 10. In the second effort, the initial sample was to be vegetative bacteria. Upstream of the isoelectric focusing step, bacteria were to be lysed using detergents. |
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This project was supported the Hewlett Packard Corporation through their thermal inkjet printer group in Corvallis, OR. Proposed was a preliminary collaborative project to determine if HP’s thermal inkjet (TIJ) printer technology could be adapted to the printing of protein arrays useful to the Yager laboratory, and, by extension, useful to the research and medical diagnostic communities. We evaluated the ability of said TIJ printers 1) to eject a small set of representative proteins in functional form, 2) to eject protein solutions without excessive loss of protein to the walls of the ink jet cartridges, and 3) to form small functionalized regions on representative surfaces using thiols and proteins. At left is a false-colored image of the result of a first attempt at a surface plasmon resonance imaging immunoassay using a TIJ-printed surface. The technology was used in a preliminary demonstration of a novel immunoassay using the imaging technique. |
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![[image of lipid tubules and helix]](helixdarkfieldom.GIF)
