Micropatterning proteins and synthetic peptides on solid supports: a novel application for microelectronics fabrication technology.

In this paper, we describe a method for immobilizing proteins and synthesizing peptides in micrometer-dimension patterns on solid supports. Microelectronics fabrication technology was adapted and used to lithographically direct the location of immobilization of proteins on appropriately derivatized surfaces. As examples, we micropatterned the protein bovine serum albumin (BSA) and the enzyme horseradish peroxidase (HRP). The catalytic activity of HRP was shown to be retained after being cross-linked to the support. When coupled with solid-phase peptide synthesis, the technique allowed synthetic peptides to be constructed in patterns again having micrometer dimensions. Synthetic polypeptides, polylysine, were constructed in patterns with dimensions that approached the practical limit of resolution for optical lithography at 1-2 microns. The patterns of immobilized molecules and synthetic peptides were visualized using histochemical methods together with light and fluorescence microscopy. The protein and peptide patterning technique described here is an advance in the field of bioelectronics. In particular, it should now be possible to devise novel methods for interfacing with biological systems and constructing new devices for incorporation into miniaturized biosensors.