A fully multiplexed CMOS biochip for DNA analysis

We have developed a technology that brings together electronically active semiconductor chips with biomedical assays or tests. By creating an array of electrodes that can be individually addressed, it is possible to manipulate DNA and other biological molecules to perform bioassays in a number of different formats. Recently, we have fabricated and tested chips that support independent, electronically driven reactions at 400 or more sites. To control these sites, we have utilized a CMOS architecture which incorporates row and column addressing, and active current control and self-test at each site. We have developed an electronically driven hybridization assay for an application in genetic identification that takes advantage of the large number of available assay locations. To perform the assay, sample DNA is electrophoretically propelled and hybridized to an immobilized DNA probe on the chip and to a fluorophore-labeled DNA probe in solution. Detection of a positive assay result depends on light emitted by the fluorophore-labeled probe in a hybridization complex that also contains the immobilized capture probe and the sample DNA. The fluorophore is excited by light from a diode laser, which is coupled into the chip by a unique cartridge design that incorporates a polymer waveguide for dark field illumination. The light emitted by fluorophores is detected by a CCD camera. The present generation of chips will potentially enable a wide range of applications including genetic identification tests, detection of bacteria and other infectious agents, assays for genetic diseases, examination of the products of many genes and screening for potential drugs. (C) 2000 Elsevier Science S.A. All rights reserved.