Abstract: Microfluidic devices and methods are provided for high-throughput generation, culturing, and analysis of cell spheroids, with subsequent isolation of selected cell spheroids for further analysis or isolation and expansion of cells from the spheroids. Any desired types of cells and matrices can be combined to form the cell spheroids and used to screen drugs and immunotherapy agents or methods, including in a personalized medicine format. Cell spheroids also can be cultivated and analyzed under hypoxic conditions. A particular advantage of the technology is the ability to isolate, enrich, and/or expand cells identified as having, or induced to have, desirable properties, such as immune cells that can be produced ex vivo and returned to the patient to combat a tumor or pathogen in vivo.

Abstract: The technology provides arrays of microwells with reversible shape for culture, analysis, and recovery of individual cells or groups of cells. The microwells are reversibly formed by vacuum-induced deflection of an elastomeric membrane into an array of microwell molds formed in a microwell substrate. The shape of each microwell or groups of microwells can be selectively altered by applying or releasing vacuum to individual microwells. The devices, systems, and methods utilizing the technology enable collection of individual cells for further study or therapeutic use without the need for micromanipulation.