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Integration of Cell Culture and Microfabrication Technology

Authors

  • Tai Hyun Park,

    1. School of Chemical Engineering and Institute of Chemical Processes, Seoul National University, Seoul 151–744, Korea
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      Tai Hyun Park is an Associate Professor in the School of Chemical Engineering at Seoul National University in Korea. He received his B.S. degree (Seoul National University, Korea, 1981), M.S. degree (KAIST, Korea, 1983), and Ph.D. degree (Purdue University, 1990) all in Chemical Engineering and was a postdoctoral fellow at the University of California at Irvine. He worked for several years at the LG Biotech Research Institute and taught at Sung Kyun Kwan University before joining Seoul National University in 1997. He was a visiting professor at the University of California at Irvine and Cornell University in 1996 and 2001, respectively. His research interests include recombinant cell engineering, anti-apoptosis engineering, and biosensors.

  • Michael L. Shuler

    Corresponding author
    1. School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, New York 14850
    • School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, New York 14850. Tel: (607) 255–7577. Fax: (607) 255–9166
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      Michael L. Shuler is the Samuel B. Eckert Professor of Chemical Engineering and Current Director of both the School of Chemical and Biomolecular Engineering and the Biomedical Engineering Program at Cornell University. He received both his B.S. degree (University of Notre Dame) and Ph.D. degree (University of Minnesota) in Chemical Engineering. He joined Cornell University in 1974. His research interests are in mathematical models of bacteria, heterologous protein expression in a variety of host systems, production of secondary metabolites from plant cell cultures, and predictive pharmacology and toxicology using in vitro cell culture systems.


Abstract

Recent progress in cell culture and microfabrication technologies has contributed to the development of cell-based biosensors for the functional characterization and detection of drugs, pathogens, toxicants, and odorants. The cell-based biosensors are composed of two transducers, where the primary transducer is cellular and the secondary transducer is typically electrical. Advances in gene manipulation and cell culture techniques have contributed to the development of the cell as a transducer, while microfabrication techniques have been applied to the development of integrating the cell with the second transducer. Cellular patterning using microfabrication techniques is essential for cell-based biosensors, cell culture analogues, tissue engineering, and fundamental studies of cell biology. The photolithographic technique is highly developed and has been widely used for patterning cells. Recently, a set of alternative techniques, largely based on soft lithoghraphy, has been developed for biological applications. Those techniques include microcontact printing, microfluidic patterning using microchannels, and laminar flow patterning. A classical metallic stencil patterning method has been improved by employing a rubber-like stencil. These cellular micropatterning techniques have been usefully employed to understand questions in fundamental cell biology, especially cellular interactions with various materials and other cells. Using these micropatterning tecchniques and insights into the interaction of cellular biology with surfaces, a wide array of biosensors have been developed. In this manuscript examples of cell-based biosensors are described. Neurons have a great potential for use in a cell-based biosensor because they are electrically excitable cells, from which electrical signals are generated with the binding of detecting molecules. Consequently, the electrical signals generated in the cell can be determined in a noninvasive manner. A microphysiometer is a device to detect functional responses from cells by measuring the change of extracellular pH. The main application of the microphysiometer is the analysis of functional responses of cells upon receptor stimulation. Development of a microscale cell culture analogue system, an in vitro animal or human surrogate, is another promising area using cell culture and microfabrication technologies. Such devices are potentially very useful in the fields of toxicology and drug testing because they may increase the accuracy of in vitro predictions, simplify testing procedures, and reduce the cost of such tests, allowing many more tests to be done with a limited set of resources.

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