Harsh Bais, PhD

RESEARCH


 

CMOS electrochemical-based active microarrays

This project is a multidisciplinary effort to exploit CMOS microelectronics in the design of low-cost, portable, self-contained "gene chip" technology for nucleic acid measurement and detection. In addition to our effort in fluorescent-based arrays, we are also exploring electrochemical-based detection approaches, both label-based and label-free.

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figure 2The die photo shows one of our detection chips, implemented in a standard 2.5-V, 0.25-um CMOS technology. The 5-mm-by-3-mm chip contains a 4-by-4 array of square Au working electrodes (fabricated through a novel post-processing method) on which single-stranded DNA probe molecules are attached via incubation or non-contact inkjet spotting. An integrated dual-slope ADC at each array site measures the current flowing through the working electrode that results from the oxidation or reduction of redox-active labels that have been covalently attached to single-stranded DNA target molecules. The chip also contains integrated control-loop amplifiers which drive on-chip counter electrodes and an off-chip reference electrode and that, along with the working electrodes, form a standard potentiostat that can be used to perform classical electrochemical measurements such as cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). Global and local control circuitry perform such tasks as transmitting digital data from sensing experiments off chip for analysis and setting the chip mode of operation while integrated diagnostic circuitry is used to electronically characterize the ADCs.

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We have validated our platform using ferrocene-conjugated DNA target molecules in which the measured CV curves indicate the amount of DNA target molecules hybridized to complementary probes on the working electrode surface. In addition, we have measured target concentrations down to approximately 4 nM, which is lower than previously-reported CMOS electrochemical DNA detection systems. Furthermore, the generalized potentiostatic functionality offered by our platform, coupled with direct covalent labeling of DNA targets, allows us to monitor the extent of DNA hybridization in real time, a task that is difficult, if not impossible, using traditional fluorescence-based microarrays. The ability to perform real-time DNA sensing could increase assay throughput and improve detection limits through the use of temporal averaging. Also, we have demonstrated multiplexed, real-time DNA detection in the presence of both complementary and non-complementary targets in a multi-probe environment.

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We believe that our approach to electrochemical biosensor implementation will provide a basis for future technological developments in high-throughput, portable DNA diagnostic platforms. It is expected that fully-integrated CMOS electrochemical biosensors will reduce the cost of nucleic-acid diagnostic platforms in the future, leveraging the tremendous economies of scale associated with the semiconductor industry.

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