Miniature Tools for Combinatorial Chemistry

Abstract

Microfabricated tools have been designed, fabricated, and tested for assisting in the identification of active compounds from large mixtures of combinatorial chemistry library members bound to polystyrene beads. These beads, which are typically 100–200 microns in diameter, are in an ideal size range for manipulation with tools fabricated from silicon, Pyrex and stainless steel using bulk micromachining and MicroJoinery interlocking technologies. Silicon bead spreading plates allow pools of tens of thousands of beads to be easily and quickly separated into single beads and spread to at least a one-millimeter spacing for biological screening. Beads that are associated with active compounds can then be individually picked and placed into silicon trays for automated Raman micro-spectroscopy (RS) and energy-dispersive x-ray spectroscopy (EDS) analysis. Due the MicroJoinery-based drawer design of these plates, they have also proven to be excellent storage trays for future analysis. Silicon ‘tea bags’ allow the rapid resynthesis of small pools of beads for confirmation testing. These miniature interlocking and stackable drawers trap groups of beads within silicon wells while allowing solutions or reagents to simultaneously wash past all beads without inter-group mixing. These tools make the handling and analysis of combinatorial beads faster, easier, and more suitable for automation.