CMOS Spectrally-Multiplexed FRET-on-a-Chip for DNA Analysis

Abstract—A spectral-multiplexed fluorescence contact imaging microsystem for DNA analysis is presented. The microsystem in-tegrates a filterless CMOS Color PhotoGate (CPG) sensor that ex-ploits the polysilicon gate as an optical filter, and therefore does not require an external color filter. The CPG is applied to fluo-rescence-based transduction in a spectrally multiplexed format by differentiating amongmultiple emission bands, hence replacing the functionality of a bank of emission filters. A microsystem has been quantitatively modeled and prototyped based on the CPG fabri-cated in a standard CMOS technology. The multi-color imaging capability of the microsystem in analyzing DNA targets has been validated in the detection of marker gene sequences for spinal muscular atropy disease and Escherichia coli (E. coli). Spec-tral-multiplexing enables the twoDNA targets to be simultaneously detected with a measured detection limits of 240 nM and 210 nM for the two target concentrations at a sample volume of for the green and red transduction channels, respectively. Index Terms—Black hole quencher, CMOS image sensor, con-tact imaging, DNA detection, fluorescence, point-of-care diagnos-tics, quantum dot, spectral-multiplexing. I