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Abstract
Biochip arrays have enabled the massively parallel analysis of genomic DNA and hold great promise for application to the analysis of proteins, carbohydrates, and small molecules. Surface chemistry plays an intrinsic role in the preparation and analysis of biochips by providing functional groups for immobilization of ligands, providing an environment that maintains activity of the immobilized molecules, controlling nonspecific interactions of analytes with the surface, and enabling detection methods. This review describes recent advances in surface chemistry that enable quantitative assays of a broad range of biochemical activities. The discussion emphasizes the use of self-assembled monolayers of alkanethiolates on gold as a structurally well-defined and synthetically flexible platform for controlling the immobilization and activity of molecules in an array. The review also surveys recent methods of performing label-free assays, and emphasizes the use of matrix-assisted laser desorption/ionization mass spectrometry to directly observe molecules attached to the self-assembled monolayers.