A Calibration Strategy\nfor Silicon Nanowire Field-Effect\nTransistor Biosensors and Its Application in Ultra-Sensitive, Label-Free\nBiosensing

The silicon nanowire field-effect transistor (SiNW FET)\nhas been\ndeveloped for over two decades as an ultrasensitive, label-free biosensor\nfor biodetection. However, inconsistencies in manufacturing and surface\nfunctionalization at the nanoscale have led to poor sensor-to-sensor\nconsistency in performance. Despite extensive efforts to address this\nissue through process improvements and calibration methods, the outcomes\nhave not been satisfactory. Herein, based on the strong correlation\nbetween the saturation response of SiNW FET biosensors and both their\nfeature size and surface functionalization, we propose a calibration\nstrategy that combines the sensing principles of SiNW FET with the\nLangmuir–Freundlich model. By normalizing the response of the\nSiNW FET biosensors (Δ<i>I</i>/<i>I</i><sub>0</sub>) with their saturation response (Δ<i>I</i>/<i>I</i><sub>0</sub>)<sub>max</sub>, this strategy fundamentally\novercomes the issues mentioned above. It has enabled label-free detection\nof nucleic acids, proteins, and exosomes within 5 min, achieving detection\nlimits as low as attomoles and demonstrating a significant reduction\nin the coefficient of variation. Notably, the nucleic acid test results\nexhibit a strong correlation with the ultraviolet–visible (UV–vis)\nspectrophotometer measurements, with a correlation coefficient reaching\n0.933. The proposed saturation response calibration strategy exhibits\ngood universality and practicability in biological detection applications,\nproviding theoretical and experimental support for the transition\nof mass-manufactured nanosensors from theoretical research to practical\napplication.