A fully multiplexed CMOS biochip for DNA analysis

We have developed a technology that brings together electronically active s emiconductor chips with biomedical assays or tests. By creating an array of electrodes that can be individually addressed, it is possible to manipulat e DNA and other biological molecules to perform bioassays in a number of di fferent formats. Recently, we have fabricated and tested chips that support independent, electronically driven reactions at 400 or more sites. To cont rol these sites, we have utilized a CMOS architecture which incorporates ro w and column addressing, and active current control and self-test at each s ite. We have developed an electronically driven hybridization assay for an application in genetic identification that takes advantage of the large num ber of available assay locations. To perform the assay, sample DNA is elect rophoretically propelled and hybridized to an immobilized DNA probe on the chip and to a fluorophore-labeled DNA probe in solution. Detection of a pos itive assay result depends on light emitted by the fluorophore-labeled prob e in a hybridization complex that also contains the immobilized capture pro be and the sample DNA. The fluorophore is excited by light from a diode las er, which is coupled into the chip by a unique cartridge design that incorp orates a polymer waveguide for dark field illumination. The light emitted b y fluorophores is detected by a CCD camera. The present generation of chips will potentially enable a wide range of applications including genetic ide ntification tests, detection of bacteria and other infectious agents, assay s for genetic diseases, examination of the products of many genes and scree ning for potential drugs. (C) 2000 Elsevier Science S.A. All rights reserve d.