High-throughput (HT) screening of live cells is crucial to accelerate both fundamental biological research and discovery of new drugs. Current methods for HT cell screenings, however, either require a large number of microplates, are prone to cross-contaminations and are limited to adherent cells (cell microarrays), or are not compatible with adherent cells as well as with spatial indexing (droplet microfluidics). We recently demonstrated the use of superhydrophobic-superhydrophilic microarrays to create high-density arrays of microdroplets or hydrogel micropads. We propose here to develop a new platform for HT cell screening experiments using the unique properties of the superhydrophilic microarrays separated by superhydrophobic thin barriers. The new technology will allow us to perform up to 300K cell experiments in parallel using a single chip. Individual cell experiments will be performed in thousands of completely isolated microdroplet at defined locations on the chip. This will enable spatial indexing, time-lapse measurements and screening of either adherent or non-adherent cells. Parallel manipulations within individual microreservoirs, such as washing, addition of chemical libraries, or staining will be developed to open new possibilities in the field of live cell studies. Superhydrophobic barriers will allow complete isolation of the microreservoirs, thus preventing cross-contamination and cell migration. We will also develop a technology for the HT screening of cells in 3D hydrogel micropads. We will use these methods to gain better understanding of how different parameters of the 3D cell microenvironment influence various aspects of cell behavior. The project will require the development of new technological tools which can later be applied to a wide range of cell screening experiments and biological problems. Our long term aim is to replace the outdated microplate technology with a more powerful and convenient method for cell screening experiments.