However, new electrochemical detection methods are emerging that may make it possible to design portable devices for point-of-care applications without the need for physically bulky optical instrumentation. Multiplexed electrochemical detection, in contrast to fluorescence detection, which can work well with a passive substrate, requires an electronically active substrate to analyze each array site. Multiplexed electrochemical detection makes use of integrated electronic instrumentation to further reduce platform size and get rid of electromagnetic interference that can come from bringing non-amplified signals off the chip. For the purpose of performing quantitative DNA hybridization detection on chip using targets conjugated with redox labels, we present an active electrochemical biosensor array constructed using standard complementary metal-oxide-semiconductor (CMOS) technology. On a custom-designed mm2 CMOS chip, a collection of gold working electrodes and integrated potentiostat electronics, including control amplifiers and current-input analogy-to-digital converters, use cyclic voltammetry to drive redox reactions, detect DNA binding, and transmit digital data off the chip for analysis. We show that conventional fluorescence-based microarrays are difficult, if not impossible, to perform real-time monitoring of hybridization and multiplexed, specific detection of DNA targets.
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