Virtual microwells for three-dimensional cell culture on a digital microfluidic platform

Three-dimensional hydrogel based cell culture has increased in prominence as a function of the in vivo-like phenotypes observed for cells cultured in this way. Unfortunately, cost and challenges in the physical manipulation of delicate hydrogel materials has impeded widespread use of these methods. Here we report the first digital microfluidic platform for the on-demand formation of hydrogel structures in virtual microwells. Moreover, we use the device to automate seeding of cells in hydrogels, exchange media at regular intervals, and perform fixing and staining of cells for on-device light and confocal microscopy. Further we apply this method for the recapitulation of higher-order tissue formation in a model of kidney epithelialization. These findings demonstrate the potential of digital microfluidics as a useful tool for a broad range of hydrogel based technologies.