Site-Directed Bioreagent Immobilization for Development of Microbiosensor Arrays

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This project will attempt to merge microelectronics, chemical- selective membranes, and bioreagents (enzymes and antibodies) to produce integrated biosensor arrays. It will capitalize on recent advances in all three of these areas. The enabling technology to be developed under this proposal is the ability to selectively bind bioactive species to specific sites on the underlying chemical sensor chip, in a methodology which allows processing of full wafers (thousands of sensors) at once. This will be done using photoreactive heterobifunctional cross-linking reagents in process steps which are similar to conventional integrated circuit photolithography, and require only slight modifications to standard integrated-circuit processing equipment. Microbiosensor arrays for multianalyte analysis will be formed by repeating the immobilization procedure on a wafer, using different bioreagents, and a photomask aligned to select different immobilization sites. The well-controlled linking process should yield biomolecule layers which have a high and predictable activity. This general approach is directly adaptable to detecting a very wide range of compounds by varying the immobilized biological components. The resulting biosensors will utilize the natural recognition, affinity and catalysis of bioreagent species in conjunction with selective chemical transducers and integrated electronics. These sensors will significantly advance capabilities for low-cost direct measurement of pollutants, drugs, hormones and metabolic compounds.