Non-Faradaic electrochemical detection of protein interactions by integrated neuromorphic CMOS sensors

Electronic detection of the binding event between biotinylated bovine serum albumen (BSA) and streptavidin is demonstrated with the chemoreceptive neuron MOS (CνMOS) device. Differing from the ion-sensitive field-effect transistors (ISFET), CνMOS, with the potential of the extended floating gate determined by both the sensing and control gates in a neuromorphic style, can provide protein detection without requiring analyte reference electrodes. In comparison with the microelectrode arrays, measurements are gathered through purely capacitive, non-Faradaic interactions across insulating interfaces. By using a (3-glycidoxypropyl)trimethoxysilane (3-GPS) self-assembled monolayer (SAM) as a simple covalent link for attaching proteins to a silicon dioxide sensing surface, a fully integrated, electrochemical detection platform is realized for protein interactions through monotone large-signal measurements or small-signal impedance spectroscopy. Calibration curves were created to coordinate the sensor response with ellipsometric measurements taken on witness samples. By monitoring the film thickness of streptavidin capture, a sensitivity of 25 ng/cm2 or 2 Å of film thickness was demonstrated. With an improved noise floor the sensor can detect down to 2 ng/(cm2 mV) based on the calibration curve. AC measurements are shown to significantly reduce long-term sensor drift. Finally, a noise analysis of electrochemical data indicates 1/fα behavior with a noise floor beginning at approximately 1 Hz.