Flexure-FET biosensor to break the fundamental sensitivity limits of nanobiosensors using nonlinear electromechanical coupling

Abstract

In this article, we propose a Flexure-FET (flexure sensitive field effect transistor) ultrasensitive biosensor that utilizes the nonlinear electromechanical coupling to overcome the fundamental sensitivity limits of classical electrical or mechanical nanoscale biosensors. The stiffness of the suspended gate of Flexure-FET changes with the capture of the target biomolecules, and the corresponding change in the gate shape or deflection is reflected in the drain current of FET. The Flexure-FET is configured to operate such that the gate is biased near pull-in instability, and the FET-channel is biased in the subthreshold regime. In this coupled nonlinear operating mode, the sensitivity (S) of Flexure-FET with respect to the captured molecule density (N s ) is shown to be exponentially higher than that of any other electrical or mechanical biosensor.In other words, while S Flexure ∼ e ðγ 1 ffiffiffiffi N s p −γ 2 N s Þ , classical electrical or mechanical biosensors are limited to S classical ∼ γ 3 N S or γ 4 lnðN S Þ, where γ i are sensor-specific constants. In addition, the proposed sensor can detect both charged and charge-neutral biomolecules, without requiring a reference electrode or any sophisticated instrumentation, making it a potential candidate for various low-cost, point-of-care applications.label-free detection | genome sequencing | cantilever | spring-softening | critical-point sensors N anoscale biosensors are widely regarded as a potential candidate for ultrasensitive, label-free detection of biochemical molecules. Among the various technologies, significant research have focused on developing ultrasensitive nanoscale electrical (1) and mechanical (2) biosensors. Despite remarkable progress over the last decade, these technologies have fundamental challenges that limit opportunities for further improvement in their sensitivity ( Fig. 1A) (3-6). For example, the sensitivity of electrical nanobiosensors such as Si-Nanowire (NW) FET (field effect transistor) (Fig. 1B) is severely suppressed by the electrostatic screening due to the presence of other ions/charged biomolecules in the solution (7), which limits its sensitivity to vary linearly (in subthreshold regime) (3, 7) or logarithmically (in accumulation regime) (4,7,8,9) with respect to the captured molecule density N s . Moreover, the miniaturization and stability of the reference electrode have been a persistent problem, especially for lab-onchip applications (1). Finally, it is difficult to detect charge-neutral biological entities such as viruses or proteins using chargebased electrical nanobiosensor schemes.In contrast, nanomechanical biosensors like nanocantilevers (10, 11) (Fig. 1C) do not require biomolecules to be charged for detection. Here, the capture of target molecules on the cantilever surface modulates its mass, stiffness, and/or surface stress (5,11,12). This change in the mechanical properties of the cantilever can then be observed as a change in its resonance frequency (dynamic mode), mechanical deflection, or change in the resist...

Nano-guided cell networks as conveyors of molecular communication

“…By making use of a diversity of biotic and abiotic features, our multidimensional system of ‘responder' populations exemplifies several key metrics that promote executive performance in such environments: active molecule capture, post-capture refining of the detection output and finally the utilization of multiple feedback thresholds 58 59 60 . Here cells facilitate AI-2 recognition autonomously and actively because, as a distributed network they reside planktonically, chemotaxing to and continually processing signals over time.…”

Preparation of Ultrathin Nanowires Using Superfluid Helium Droplets

“…1−5 Ultrathin 1D nanostructures with diameters less than 10 nm possess unusual properties related to quantum confinement and the significantly increased surface-to-volume ratio, such as quantum conductance, 6,7 ballistic conduction, 8,9 ferromagnetism, 10 negative magnetoresistance, 11 and low thermal conductivity. 12 Many exciting applications have already been envisaged from these properties including the development of chemical and biological sensors, 13,14 catalysts, 15 and components for miniature electronic circuits. 16 Synthesis of ultrathin nanowires generally requires some source of anisotropy to bias the growth process in only one direction.…”

SOI-Nanowire Biosensors for High-Sensitivity Protein and Gene Detection

“…A unique growth of sensitivity can be achieved due to combination of a nanowire nano-FET with a nanoelectromechanical structure (NEMS) prepared in the form of a flexible membrane occupying a non-equilibrium position in the vicinity of the field-effect transistor (NEMFET) [52]. Trapping of an analyte molecule at the membrane will cause the shift of the membrane closer to the nanowire and an exponential growth of the analyte-molecule-induced signal.…”