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This work presents miniaturized CMOS (complementary metal oxide semiconductor) impedimetric sensors for detection of avian influenza virus (AIV) in the femtomolar level. The sensing resolution is significantly enhanced owing to monolithic sensor integration to reduce the parasitic effect and the use of sub-μm interdigitated microelectrodes to promote signal coupling efficiency. The 4×4 sensor array contains four electrode designs of different sizes. Capacitance changes associated with surface modification, functionalization, and DNA hybridization were extracted from measured frequency responses based on an equivalent circuit. Hybridization of AIV H5 capture and target DNA produced a percentage capacitance change of -12.8+3% among the four designs for target DNA concentrations from 1 fM to 10 fM, while capacitance increases were observed for non-specific binding of the H5 and H7 DNA probes.