The specific aims are to develop novel techniques and devices for experimentation on cells as performed in flow cytometry and microscopy. This project will be based on flow injection analysis, which is a well established technique for the automated, fluidic handling of samples and reagents in analytical chemistry. Central to this endeavor is that greater sophistication in fluid handling will enhance current research in cell biology and drug discovery by providing reliable and reproducible measurements. Moreover, unique information on the kinetics of biologcial processes in time frames and experimental designs inaccessible by any other means can be obtained. The long term objectives are the development of: (1) rapid mixing devices/protocols for kinetic analyses in flow cytometry, (2) fluidic based cell manipulation and sorting for imaging cytometry using microfabricated flow chambers, (3) cell stimulation methods for work in drug discovery and fundamental stimulus/receptor interactions and (4) novel perifusion devices for the measurements of cellular secretion products with respect to intracellular signals. The results of the proposed work will provide researchers with new methods for experimentation and cell handling in fields such as pharmacology, pathology, immunology, hematology and the biotechnological industry. Benefits will impact basic resaerch involved in elucidating dynamic or kinetic cellular interactions. Moreover, practical research that requires automated methods for testing/evaluating cells with respect to drug/agonist, antibody and protein synthesis will also benefit.
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