A proximal CCD imaging system for high-throughput detection of microarray-based assays.

Abstract

The DNA microarray (chip) has stimulated the development of scanning-proximal CCD detection system that offers 10-fold enhancement of sensitivity over conventional CCD lens-based scientific imaging systems with the added benefit of quickly scanning multiple microarrays of DNA probe/target complexes. DNA microarrays have emerged as powerful tools applicable to numerous high-throughput screening assays such as genotyping, gene expression analysis, gene mutation detection, DNA sequencing, and ELISA immunoassays. DNA microarray-based assays offer tremendous potential in both diagnostic and pharmaceutical applications due to their extreme versatility and miniaturized formats. Specifically, functional applications such as population-wide genetic screening, clinical diagnostics, and determining disease risk and drug toxicity are perfectly suited for microarray formats due to the small sample volume requirements, multiplexed parallel configurations, and susceptibility to customization. Novel supporting technologies such as the Proximal CCD Imager will be essential for detection and quantification of these highly miniaturized and multiplexed microarray assays to achieve both the throughput and cost reduction goals of these demanding medical applications. For example, typical high-throughput drug discovery screening assays often require 100,000 experiments to be conducted in a year. Employing microarrays for conducting these experiments, high-throughput instruments such as the Proximal CCD Imager are necessary to alleviate the bottlenecks associated with imaging and detection. Conventional imaging systems such as a confocal laser scanner or CCD lens-based imager currently take 1-10 minutes per microarray, thereby being impractical for such demanding applications.