Especially, for trace-level amount detection, the critical dimensions of the sensing channels need to be comparable to the impact dimensions of charged molecules to maximize the gating effect due to the charged molecules and achieve very low LOD 4, 12, 13. In particular, high-quality, small-size NWs and CNTs are needed to make biosensors with fM-level LOD for concentration monitoring (or single-molecule-level LOD for trace-level amount detection) 11. However, serious constraints imposed on nanofabrication severely prohibit the reliable manufacturing of the affordable biosensor chips utilizing such one dimensional (1D) nanostructures 1, 5, 6. The arrays of such biosensors with consistent transistor responses would serve as reliable lab-on-a-chip platforms for precisely determining the kinetics of various biomolecule interactions. The fM-level limit-of-detection (LOD) achieved by such nanoscale FET biosensors for monitoring biomarker concentrations would enable label-free, single-molecule-level detection of trace-level amount biomarkers. Using field-effect transistor (FET)-based biosensors created from nanowires (NWs) and carbon nanotubes (CNTs), researchers have demonstrated detection of cancer biomarkers from nM to fM range in serum 1, 2, 3, 4, 5, 6, 7, in vitro detection of nM proteins in cell growth systems 8, 9 and quantification of the affinities/kinetics of the protein interactions with fM-level sensitivities 10. This work advanced the critical device physics for leveraging the excellent electronic/structural properties of TMDCs in biosensing applications as well as the research capability in analyzing the biomolecule interactions with fM-level sensitivities. Based on this calibrated sensor model, the time-dependent binding kinetics was also measured and the association/dissociation rates of the antibody-(TNF-α) pair were extracted to be (5.03 ± 0.16) × 10 8 M −1s −1 and (1.97 ± 0.08) × 10 −4 s −1, respectively. In both regimes, all sets of transistors exhibited consistent calibrated responses with respect to TNF-α concentration and they resulted in a standard curve, from which the equilibrium constant of the antibody-(TNF-α) pair was extracted to be K D = 369 ± 48 fM. Such a detection limit was achieved in both linear and subthreshold regimes of MoS 2 transistors. In this work, we demonstrated MoS 2-based transistor biosensors capable of detecting tumor necrosis factor – alpha (TNF-α) with a detection limit as low as 60 fM. To realize such potential biosensing capability, device-oriented research is needed for calibrating the sensor responses to enable the quantification of the affinities/kinetics of biomolecule interactions. Atomically layered transition metal dichalcogenides (TMDCs) exhibit a significant potential to enable next-generation low-cost transistor biosensors that permit single-molecule-level quantification of biomolecules.
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