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April 1, 2004
Michael L. Shuler
Samuel B. Eckert Professor Cornell University School of Chemical and Biomolecular Engineering Ithaca, NY
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"Integrating
Microfabrication and Cell Culture:
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Abstract
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Our ultimate goal is construction and validation of an in vitro device (cell culture analog or CCA) that realistically and inexpensively mimics uptake, distribution, metabolism, and biological response of humans to exposure to various chemicals and drugs. A cell culture analog (CCA) is a device that is a direct physical replica of a physiologically based pharmacokinetic (PBPK) model. A PBPK model is a mathematical model that represents the body as interconnected compartments representing the functions of selected organs or tissues. The CCA uses living cells in "organ/tissue" compartments to represent some aspects of metabolism in that organ. Coupling of a CCA and corresponding PBPK can provide insight into molecular mechanisms of toxicity. This device will impact biomedical research by providing a cost-effective, pre-clinical system to estimate human response to a wide range of drug leads and assist in risk assessment for environmental exposure to chemicals while reducing dependence on animal studies.
There are a number of advantages to greatly reducing the size of the CCA device to the microscale. Our design calculations for a prototype chip system have shown that we can achieve physiologically realistic organ residence times and ratio of fluid to tissue in an "organ" compartment and maintain fluid flow rates at values that create only physiologic values of shear stress on cells. Only by going to the dimensions of the microsystem can we attain a physiologic design. Further, the microscale reduces the cost of the device and makes effective uses of expensive reagents or difficult to obtain cell cultures.
This talk will describe the motivation for CCA development and discuss proof-of-concept experiments using naphthalene as a model toxicant. Further, we will describe possible extensions to testing for drugs to suppress multi-drug resistance in cancer.
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Room: 1064 Duncan Hall . Time: 2:30 PM For more information contact: |
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