We have designed, constructed, and evaluated an automated instrument that has produced high-density arrays with more than 30 000 peptide features within a 1.5 cm2 area of a glass slide surface. These arrays can be used for high throughput library screening for protein binding ligands, for potential drug candidate molecules, or for discovering biomarkers. The device consists of a novel fluidics system, a relay control electrical system, an optics system that implements Texas Instrumentspsila digital micromirror device (DMD), and a microwave source for accelerated synthesis of peptide arrays. The instrument implements two novel solid phase chemical synthesis strategies for producing peptide and peptoid arrays. Biotin-streptavidin and DNP anti-DNP (dinitrophenol) models of antibody small molecule interactions were used to demonstrate and evaluate the instrument's capability to produce high-density protein detecting arrays. Several screening assay and detection schemes were explored with various levels of efficiency and assays with sensitivity of 10 nM were also possible.
Bibliographical noteFunding Information:
Manuscript received March 5, 2007; revised October 15, 2007. This work was supported in part by the Hudson Foundation and P.O’B Montgomery Distinguished Chair and in part by the National Institute of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI) Center for Proteomics Research under Contract NO1-HV-28185. Asterisk indicates corresponding author.
- Combinatorial chemistry
- Digital micromirror device (DMD)
- Fluorophores and dyes
- Screening assay