| Over the past decade, silicon nanowire/nanoribbon field-effect transistors (NWFETs) have demonstrated great sensitivity to the detection of biomolecular species, with limits of detection (LOD) down to femtomolar concentrations. Several well known factors limit the LOD; among them, screening effects, efficiency of the biomolecule-specific surface functionalization, binding kinetics and equilibria, and the delivery of the analyte to the sensor surface. Recently, the noise properties of such biosensors have been receiving more attention, both as a factor that determines the LOD as well as a diagnostic tool to extract information about the electronic properties of the FET sensors. However, the signal-to-noise ratio (SNR) of these bioFET sensors, and the device parameters that determine the LOD, are not well understood.;We discuss our experiments on applying noise spectroscopy to silicon NWFETs with the goal of understanding and improving the detection limit of such devices. Using low frequency noise measurements and modeling, we are able to compare different devices/material systems and quantify the effect on device performance of different process parameters. We also consider the effects of temperature on the noise generating mechanism and investigate the fundamental origin of 1/f noise in these devices.;We then introduce SNR as a universal performance metric, which includes both the effects of noise and signal transduction, and we show that the SNR is maximized at peak transconductance due to the effects of 1/f noise, and not in the subthreshold regime where sensitivity is maximized. We also correlate the LOD predicted by the measurement of the SNR to pH sensing experiments, highlighting the relevance of this metric for the ultra-sensitive detection of biomolecules. The effects on the SNR, of surface functionalization, gating scheme and device scaling are also considered and quantified, yielding interesting results which will have a profound impact on the design of sensors with lower LOD.;The nanowire-based devices have shown a theoretical LOD of 4 electronic charges, ignoring the effects of screening. Using these devices, with very good performance in terms of SNR, we were able to measure and extract the binding kinetics of protein interactions, which have never been done with NWFETs. Binding constant (KD) determination is a critical parameter for biomolecular design and has until now been primarily assessed by surface plasmon resonance (SPR). The KD determines the magnitude of the sensor signal for a particular concentration of analyte and therefore, is an important factor in determining the smallest measurable concentration. Utilizing the low LOD and reproducibility of sensing signals from our bioFETs, we study the reaction kinetics of low and high KD systems and demonstrate the viability of the bioFET platform as a potential replacement for SPR.;Our investigation of different solution gate electrodes and their noise performance show that both the accuracy of biosensing results and the LOD are significantly affected by the choice of the solution gate electrode. A full reference electrode is difficult to integrate into a miniaturized system and pseudo reference electrodes require careful control of the sensing buffer in order to avoid measurement artifacts. We finally propose and demonstrate some initial results on the integration of an on-chip Ag/AgCl pseudo reference electrode for improved noise performance and better LOD, especially under fluid flow conditions. |
