Selective deposition of proteins and cells in arrays of microwells

This paper describes a method for depositing proteins and cells selectively into microwells fabricated in poly(dimethylsiloxane)-an elastomeric organic polymer. The arrays of microwells were generated using soft lithography. The surface between the wells was coated with bovine serum albumin, and the surface within the wells was coated with fibronectin (FN)-an adhesive extracellular matrix protein. Fluorescence staining of FN using antibodies indicated that the protein had adsorbed to the wells selectively. Exposure of the FN-coated wells to a suspension of bovine capillary endothelial cells resulted in attachment and spreading of the cells only in the wells. This method for patterning cells was demonstrated with wells of several diameters (less than or equal to 100 mum) and depths (less than or equal to 50 mum). It should be useful for (i) the development of sensors based on arrays of cells, (ii) screening combinatorial libraries of ligands on cells, and (iii) testing the effect on cells of compounds and samples relevant to problems in environmental chemistry, pharmacology, medicinal chemistry, research biology, and biodefense.