A microfabricated device and method having a substrate with an array of curvilinear cavities that is used for high throughput single cell screening. The substrate of the device is preferably fabricated in a low elastic modulus polymer such as polydimethylsiloxane. The architecture of the cavity forms a small volume micro-niche that seeded cells can rapidly condition to promote survival and proliferation which can be monitored for hours to days to weeks. The cavity architecture allows independent assays to be conducted with minimal influence from nearest neighbor cavities. Methods are disclosed to use the device to, for example, screen single cells by clonal proliferation, clonal morphology, secreted factors, secretion rate, surface markers, and cell functional characteristics including but not limited to migration, drug resistance, the ability to block or promote signaling pathways, or to enhance opsonization.