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Field-effect transistor (FET)-based biosensors have demonstrated highly sensitive label-free detection of a plethora of biomolecules as next-generation binding assays. While the dose–response curve of affinity-based binding assays generally has a nonlinear shape, any distortion contributed by the FET transducers has not been well understood. In this paper, we show that the signal transduction of FET sensors plays an important role in shaping their dose–response curves when operating in the nonlinear screening regime. We have found that the nonlinearity arising from the counterion screening in the electrical double layer could distort the relationship between the device flatband voltage shift and the analyte concentrations in (1) lowering its half-maximal response concentration as well as the sensitive detection range and (2) expanding its dynamic range. Negligence of such nonlinearity would introduce errors in the extracted affinity properties of the analyte–receptor pair. This work provides useful guidelines for designing FET-based binding assays and interpreting their measurement data.

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