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Fall 2007 Symposium: Toward In Vivo Microsystems

Tuesday, October 2, 2007
University of Maryland Biotechnology Institute Center for Advanced Research in Biotechnology
(UMBI-CARB at Shady Grove)

Speaker Bios

Dr. Ketul Popat, University of California, San Francisco
“Micro and Nanofabricated Interfaces for Therapeutic Delivery”

In vivo cellular and drug delivery strategies are being developed that capitalize on the strengths of micro- and nanofabrication. By taking advantage of our ability to control chemistry and topography at submicron size scales, we can design synthetic devices which modulate cell function. Examples include nanoporous capsules for cellular delivery, microfabricated drug delivery devices to penetrate cellular barriers, and drug-eluting microrods to control tissue regeneration. Such engineered interfaces may be optimized for biomolecular selectivity and surface bioactivity. Micro- and nanotechnology can add flexibility to current delivery practices while becoming an enabling technology leading not only to new laboratory techniques, but also to new platforms for delivering therapy to the patient. Ketul C. Popat received his Ph.D. in Bioengineering from University of Illinois at Chicago in 2003 and M.S. in Chemical Engineering from Illinois Institute of Technology, Chicago in 2000. He will be joining as Assistant Professor in the Department of Mechanical Engineering/School of Biomedical Engineering at Colorado State University from Spring 2008.

Research Interests:
Currently he is working as Associate Specialist in Therapeutic Micro/Nanotechnology Laboratory directed by Dr. Tejal A. Desai at University of California, San Francisco. Prior to that, he was working as a Postdoctoral Research Associate in the Department of Biomedical Engineering at Boston University. He has authored over 20 peer reviewed publications in journals such as Langmuir, Biomaterials, Journal of Orthopedic Research, Journal of Biomedical Materials Research, etc. and has presented his work at numerous national and international level conferences.

Dr. Frances Ligler, Naval Research Laboratory
“The Array Biosensor and Beyond”

Multiplexed detection systems interrogating arrays of immobilized capture molecules make it possible to analyze multiple samples simultaneously for multiple analytes. Three very different types of array biosensors have been explored at NRL. The NRL array biosensor is a fully automated system that captures targets from complex samples onto a glass waveguide. This biosensor takes advantage of a wide variety of biological capture molecules, including antibodies, combinatorial peptides, carbohydrates, and antibiotics, and small optics, including a diode laser and a CCD camera, to measure the detection events. The entire biosensor system integrated into a portable tackle box (< 6 kg). Complex food, environmental or clinical samples can be analyzed with minimal, if any, sample preparation. Data exemplifying applications including food safety, homeland security, disease diagnosis, and human antibody titer measurements will be presented. Much higher density arrays using photolithographically defined DNA probes as capture molecules to resequence genes from a wide variety of pathogens. Investigators at the NRL have combined methods for microbial nucleic acid enrichment, random nucleic acid amplification, gene resequencing, and automated sequence similarity searching of public gene databases for biosurviellance. NRL, in collaboration with the AF, demonstrated the feasibility of this approach by provided medical biosurveillance for the National Capital Area during the months surrounding the Presidential Inauguration in a 24/7 operation. Subsequent development hasrefined the technology to provide better than 95% clinical specificity and sensitivity. While the initial microarray detected any of 25 pathogens and near neighbors, a chip capable of detecting 120 microorganisms has now been fabricated and is under validation. Not all arrays of immobilized capture molecules are immobilized on a planar surface. Other types of arrays are also possible. We have developed a microflow cytometer that can interrogate arrays of coded beads for target binding-one at a time. This device has the potential to be either a continuous monitoring system or a hand-held on site detector for point-of-care and other on-site operations. Frances S. Ligler, D.Phil., D.Sc. (Oxford University), is currently the Navy’s Senior Scientist for Biosensors and Biomaterials and a member of the Bioengineering Section of the National Academy of Engineering. Her ~300 full-length articles in scientific journals and 24 issued patents have been cited over 4000 times. She performs research in biosensors, microfluidics, and nanotechnology. In 2003, she was awarded the Homeland Security Award by the Christopher Columbus Foundation and the Presidential Rank of Distinguished Career Professional by President Bush.

Research Interests:
Dr. Culver’s research interests are multidisciplinary with efforts directed at understanding virus biology and its role in disease as well as studies aimed at engineering viruses and other biological components for application in nano-based systems and devices. Dr. Culver received B.S. and M.S. degrees in Microbiology and Plant Pathology from Oklahoma State University and in 1991 a Ph.D. in Plant Pathology from the University of California, Riverside. In 1992, Dr. Culver joined the faculty in the Center for Biosystems Research at the University of Maryland Biotechnology Institute (UMBI).

Dr. James Weiland, Doheny Retina Institute, USC
“Intraocular Retinal Prosthesis”

Retinitis pigmentosa (RP) and age-related macula degeneration (AMD) lead to the degeneration of the light sensitive cells of the eye (photoreceptors), resulting in a significant visual deficit for the afflicted individual. In a normal eye, retinal photoreceptors initiate a neural signal in response to light. In a retina affected by RP or AMD, the photoreceptors are absent, but other cells of the retina remain present in large numbers. Current clinical trials are investigating the feasibility of replacing the function of the photoreceptors with an electronic device that will electrically stimulate the remaining cells of the retina to generate visual perceptions. In tests with human volunteers with little or no light perception, we have used a prototype retinal prosthesis with a limited number of stimulating electrodes to create the perception of discrete spots of light. Subjects were able to distinguish basic shapes and to detect motion. Based on these encouraging results, the current focus is being shifted from feasibility studies to the development of a highresolution retinal prosthesis which will be capable of stimulating the retina at thousands of individual points. Simulations of prosthetic vision predict that 1000 electrodes will be needed to restore visual function such as face recognition, reading, and mobility. The proposed retinal prosthesis system would include an external video camera to capture an image and electronics to code the image and transmit the coded data to an implanted system. The implanted electronics will receive the data, decode the signal and generate the desired current pulse pattern for the stimulating array. James Weiland received his B.S. from the University of Michigan in 1988. After 4 years in industry with Pratt & Whitney Aircraft Engines, he returned to Michigan for graduate school, earning degrees in Biomedical Engineering (M.S. 1993, Ph.D. 1997) and Electrical Engineering (M.S. 1995). He joined the Wilmer Ophthalmological Institute at Johns Hopkins University in 1997 as a postdoctoral fellow and, in 1999, was appointed an assistant professor of ophthalmology at Johns Hopkins. Dr. Weiland was appointed assistant professor at the Doheny Eye Institute-University of Southern California in 2001. Currently, Dr. Weiland is an Associate Professor of Ophthalmology and Biomedical Engineering, University of Southern California.

Research Interests:
Dr. Weiland’s research interests include retinal prostheses, neural prostheses, electrode technology, visual evoked responses, and implantable electrical systems. He is a member of the IEEE EMBS, the Biomedical Engineering Society, Sigma Xi, and the Association for Research in Vision and Ophthalmology.

Dr. William Reichert, Duke University
“Experimental Scenarios for Wound Healing around Biomaterials”

Currently we are studying implant-centered wound healing in two systems — the brain and subcutaneous tissue. In particular, we have been studying the effect of wound healing on implanted sensor performance for a number of years and have learned that the implant bed is best if it is mechanically stable, well-perfused and non-fibrous. The problem is how one achieves this condition in the long term. An important tool that we have in addressing this question is cytokine profiling of cultured monocytes exposed biomaterials samples in vitro (and are attempting the analogous experiments in vivo using the caged implant system). Results show that cytokine expression from monocytes that interrogate common biomaterials that are smooth and nontoxic is relatively mild and indistinct. However, monocytes that are committed to a macrophage phenotype show substantially more pronounced cytokine expression profiles. Similarly, monocytes exposed to phagocytoseable particles have expression profiles similar to monocytes exposed to discs of the same materials with roughnesses on the order of the particle size. The results support two currently prevailing hypotheses. First, any smooth, nontoxic , nondegradable biomaterial is “viewed” essentially the same by monocytes regardless of surface chemistry. Second, surface texturing induces what has been called frustrated phagocytosis, which in turn affects the wound healing response through a change in expression profile. William M. Reichert was born in San Francisco, CA, grew up in Ann Arbor, MI, and lives in Hillsborough, NC with his wife Kate, his son Stephen, and three dogs and a cat. He also has a daughter Elizabeth and a stepdaughter Miranda. He graduated with a B.A. in Biology and Chemistry from Gustavus Adolphus College in 1975, was a part time student, a hospital tech and bartender for a couple of years, and received a doctorate in Macromolecular Science and Engineering from the University of Michigan in 1982. He was a NIH National Research Service Award postdoctoral fellow, a Whitaker Fellow, and a NIH New Investigator Fellow at the University of Utah in the Department of Bioengineering where he ?learned the ropes? from Professors Joe Andrade and Art Janata. He joined the Department of Biomedical Engineering at Duke University in 1989 and is currently Professor of Biomedical Engineering and Chemistry, and Director of the Center for Biomolecular and Tissue Engineering. He is a fellow of the American Institute of Medical and Biological Engineering, and on editorial boards for the Journal of Biomedical Materials Research and Langmuir. He is Program Director of an NIH predoctoral training grant that supports graduate fellowships in biotechnology.

Research Interests:
His current research interests are wound healing related implant failure, biosensors, vascular graft endothelialization, and cytokine profiling. He has trained a number of doctoral and postdoctoral students now working in academics and industry, published nearly 100 scientific papers, and holds patents in multianalyte waveguide sensors and protein detection arrays.

Dr. James Culver, University of Maryland Biotechnology Institute
“An Infectious Approach to BioFabrication”

Advances in nanotechnology offer significant improvements in a range of applications including, light weight materials with greater strength, increased energy efficiency from electronic devices, and better sensors for a range of medical and environmental uses. Furthermore, since size constraints often produce qualitative changes in the characteristics of matter, it is anticipated that the exploitation of nanotechnology will result in the identification of new phenomena and functionalities derived from the physics, chemistry, and biology of matter at the nanoscale level. However, these advances require the development of systems for the design, modeling, and synthesis of nanoscale materials. Interestingly, many biological molecules function on this scale and possess unique properties that impart the ability to assume defined conformations and assemblies, as well as interact with specific chemical or biological substrates. Studies in our laboratory utilize RNA plant viruses as templates for the self-assembly and patterning of novel nanomaterials. Such viruses represent very simple macromolecular assemblies, consisting of a single molecule of nucleic acid packaged by many copies of an identical coat protein. These properties make them ideal models for understanding fundamental mechanisms that underlie the abilities of molecules to self-associate and assemble into ordered structures. Utilizing molecular genetic and chemical methods we have investigated strategies to functionalize and pattern these viruses with dyes, peptides and metals to produce assembled virus arrays with applications in energy production, sensor development and drug delivery.

Research Interests:
Dr. Culver’s research interests are multidisciplinary with efforts directed at understanding virus biology and its role in disease as well as studies aimed at engineering viruses and other biological components for application in nano-based systems and devices. Dr. Culver received B.S. and M.S. degrees in Microbiology and Plant Pathology from Oklahoma State University and in 1991 a Ph.D. in Plant Pathology from the University of California, Riverside. In 1992, Dr. Culver joined the faculty in the Center for Biosystems Research at the University of Maryland Biotechnology Institute (UMBI).

Dr. Kimberly Turner, University of California Santa Barbara
“Challenges in Microscale sensors: Is Nonlinearity the Answer?”

Many nonlinear phenomena occur in micro and nanoscale sensors. For in-vivo microsystems, as well as in-air microsensors, it is important to understand these phenomena. This talk will highlight utilizing nonlinearities to enhance sensitivity in a variety of MEMS sensors. Kimberly L. Turner is an Associate Professor in Mechanical Engineering at UCSB, where she is also co-vice-chair of the department. She has been at UCSB since 1999. She received her B.S. from Michigan Technological University in 1994, and her Ph.D. from Cornell University in 1999.

Research Interests:
Her interests lie in the mechanics of micro and nanoscale systems, namely nonlinear dynamics, tribiology, and micro/nanofabrication. She currently supports a laboratory of 8 graduate student researchers, and 2 undergraduate researchers. She is heavily involved in teaching and mentoring, currently serving as faculty advisor to the UCSB Society of Women engineers chapter, as well as receiving the UCSB Academic Senate Distinguished Teaching Award in 2005. Prof. Turner is also the recipient of the 2007 Michigan Tech University Outstanding Young Alumni Award, given to an alumni under age 35. She is on the executive committee for the UCSB/MIT/CalTEch ARMY Institute for Collaborative Biotechnology, and has published over 50 refereed publications. Her work is currently funded by ARMY, AFOSR, NSF, and industry.

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