Gregory L. Kirk

Soft lithography and surface chemistry: enabling tools for new bioassays

The process of drug discovery can be accelerated by increasing the information content of bioassays and by employing assay platforms that are amenable to high throughput screening techniques. In this paper, we demonstrate how the combination of soft lithography with controlled surface chemistry achieves these goals in a wide spectrum of bioassays. A number of soft lithographic methods can be used to generate micro-structures for the purposes of increasing assay density, diversity of test conditions and improving assay detection qualities. In addition, soft lithography, combined with specific surface chemistry modification procedures and protein engineering, may be used to control the localized molecular and biological properties of substrates, thereby enabling the development of new types of bioassays. The developed methodologies are simple, easily implemented, and lend themselves well to automation. Experimental results and prototypes are presented to illustrate the capabilities of these new techniques. For example, soft lithography and surface chemistry are employed for chemically patterning substrates, stenciling biological entities onto substrates and confining solutions. As a result, information-rich, highdensity bioassays can be obtained where biological targets, surface properties and medium solutions are carefully determined and controlled.