The present invention provides methods and devices for the knowledge-based discovery and optimization of differences between cell types. In particular, the present invention provides visual servoing optical microscopy, as well as analysis methods. The present invention provides means for the close monitoring of hundreds of individual, living cells over time: quantification of dynamic physiological responses in multiple channels; real-time digital image segmentation and analysis; intelligent, repetitive computer-applied cell stress and cell stimulation; and the ability to return to the same field of cells for long-term studies and observation. The present invention further provides means to optimize culture conditions for specific subpopulations of cells. This research was supported in part by (i) the U.S. Department of Defense, Breast Cancer Research Program, under the U.S. Army Medical Research and Materiel Command, contract number DAMD17-98-1-8177, (ii) the U.S. Department of Energy, Office of Biological and Energy Research, under contract DE-AC03-76SF00098, and (iii) the University of California Industry-University Cooperative Research Program (IUCRP) UC Discovery Grant (proposal Biostar01-10217) with industry sponsor VSOM, Inc. (www.vsominc.com, St. Louis, MO) under Lawrence Berkeley National Laboratory Cooperative Research and Development Agreement number BG02-363(00).