A review of microfabricated devices for gene-based diagnostics

The next technologic revolution may well be the miniaturization of solution phase experimentation through the marriage of microelectronics and molecular biology. Already researchers leading this rapidly emerging technology are developing prototype biochemical "microlaboratories" that offer a millionfold reduction of scale; that is, biochemical analyses are being conducted with picoliter sample volumes rather than conventional microliter formats. Such miniaturization is achieved by exploiting the well-honed tools of microelectronics that accommodate highly parallel automated assays, ultrasensitive detection, high throughput, integrated data acquisition, computation, and distributed data storage/retrieval. The subject of this paper is to survey this evolving bioelectronic miniaturization technology with applications to gene-based diagnostics. Several pioneering microchips are described and compared to traditional biochemical methods. Specifically, miniaturized examples of various diagnostic processes such as sample preparation (PCR), assays (electrophoresis and probe arrays), and detection (integrated CCDs) are presented. Although these microdevices are rather embryonic they represent the first steps toward fabricating a fully integrated diagnostic system on a microchip.