Microchip high density hanging drop three-dimension culture platform

A method for preparing a cell and tissue culture, the method comprising the steps of:

• providing an array of surface-oxidized, hydrophilic microwells, wherein each microwell has:
• a depth of between 50 μm to 1000 μm;
• a longest dimension of between 50 μm to 3000 μm;
• a separation distance from an adjacent microwell that prevents unwanted liquid leaking between adjacent microwells;
• forming a removable reservoir over at least a portion of a top surface of the microwells;
• loading a mixture comprising cells in the removable reservoir and forcing the mixture comprising cells in the removable reservoir into the microwells;
• removing the removable reservoir from the microwells;
• covering the microwells with the cells with an immiscible layer;
• partitioning the cells into the individual microwells;
• inverting the array of microwells with the cells and the immiscible layer so that the immiscible layer confines the cells to the individual microwells;
• and
• culturing the cells in the inverted array of microwells, thereby preparing the cell and tissue culture;
• controlling a shape parameter in at least one cell and tissue culture by providing a microwell geometric shape, wherein the shape parameter is one or more of:
• cell and tissue culture size, volume, curvature, cross-sectional shape, a thickness, and/or a linear distance,
• wherein the controlling the shape parameter generates a cell and tissue culture shape, thereby generating a mechanical stress distribution on the cell and tissue culture to generate different cell phenotypes within the cell and tissue culture.