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.
[1]
R. Houghten.
General method for the rapid solid-phase synthesis of large numbers of peptides: specificity of antigen-antibody interaction at the level of individual amino acids.
,
1985,
Proceedings of the National Academy of Sciences of the United States of America.
[2]
C. Gonzalez,et al.
MicroJoinery: concept, definition, and application to microsystem development
,
1998
.
[3]
M. Lerner,et al.
Combinatorial diffusion assay used to identify topically active melanocyte-stimulating hormone receptor antagonists.
,
1995,
Proceedings of the National Academy of Sciences of the United States of America.
[4]
J. Neilly,et al.
Elemental Analysis of Individual Combinatorial Chemistry Library Members by Energy-Dispersive X-Ray Spectroscopy
,
1999
.