Multiple MoS2 Transistors for Sensing Molecule Interaction Kinetics (original) (raw)

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. 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. 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. Such a detection limit was achieved in both linear and subthreshold regimes of MoS 2 transistors. 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. 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 −1 s −1 and (1.97 ± 0.08) × 10 −4 s −1 , respectively. 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. 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 1-7 , 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. 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. 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. 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. 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. 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. CNTs and many NWs are usually produced by using bottom-up synthesis methods (e.g., chemical vapor deposition (CVD)). The community currently lacks proper top-down planar nanofabrication processes to produce ordered arrays of such nanostructures, which makes it very challenging to realize parallel high-throughput assay using biosensors made from these nanostructures. High-quality Si NW biosensor arrays can be made