Abstract

Biology is evolving from a descriptive, qualitative science to a quantitative discipline.  Methods from engineering and the physical sciences are now being used to create novel tools to study basic biological phenomena in order to elucidate the complex relationships that underlie the behaviors of living cells with a focus on individual cells and cellular microenvironments.  Much of my research is focused on the development and testing of bioanalytical platforms to enable the study of how single cells receive and process information.  To formulate a response, each cell possesses complex signaling circuitry that integrates all of the incoming information and produces a biochemical response; however, much remains unknown about these signal processing pathways mainly due to the lack of high-throughput technologies to assess the state of these pathways at the level of a single cell.  We are currently developing integrated microanalytical platforms in both array and microfluidic formats to address critical preclinical and clinical needs in accurately monitoring drug action and identifying the patient who will respond to new therapies aimed at modulating signal transduction pathways.  In order to manipulate individual cells, the lab has also pioneered the development of novel microfabricated devices to enable the analysis and isolation of cells while they remain in culture.  These technologies possess a number of advantages over current cell separation methods as cells can be monitored over time and selected based on a wide range of characteristics.  The devices are made in almost any size for use with small samples obtained from needle biopsies to large-scale arrays with millions of sites for high-throughput screens and rare cell isolation.  Numerous applications of these microfabricated devices are being pursued, including efficient cloning of mouse stem cells, purification of cancer stem cells from patient samples and isolation of tumor-targeted lymphocytes for cancer immunotherapy.