A versatile biochip for gene-based diagnostics

Towards the pursuit of highly automated, cost-effective gene-based diagnostic testing, microfabricated diagnostic systems are being developed to perform sample preparation, assay, detection and information analysis in a miniaturized format. These microfabricated systems exploit the inherent characteristics of microelectronics that accommodate highly parallel assays, ultrasensitive detection, high throughput, integrated data acquisition and computation. The focus of this paper is a miniaturized molecular detection device that is directly coupled to a DNA probe-based diagnostic assay. High detection sensitivities have been reported previously by the authors utilizing this proximal CCD approach for fluorescent and radioisotope reporter groups. The present work demonstrates quantitative detection and imaging capabilities for both flash (acridinium ester) and glow (dioxetane-based) chemiluminescent reporter groups used in DNA/RNA-based diagnostics. A detection limit of 0.9 fmole was demonstrated with immobilized AE reporter groups within a 0.3 second integration time. Also highly resolved images of labeled DNA hybridized to probe arrays was achieved with dioxitane-based chemiluminescence with high selectivity. These recent chemiluminescent results combined with the previous fluorescent and radioisotope feasibility demonstrate the versatility of proximal CCD detection and imaging for DNA-based diagnostics.