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Solid-state nanopore has the ability to detect proteins at a single-molecule level with its high sensitivity, high-throughput, and low cost. Improvements in fabrication, functionalization, and characterization of solid-state nanopores keep evolving. Various analytical methods targeted towards diagnostic applications using nanopore-based devices are appearing. This review article provides an overview of recent progress in the field of solid-state and biological nanopores for protein detection in a complex analyte. The advantages and challenges involved in nanopore sensing have been discussed. Further, the review surpasses the steady-state resistive pulse techniques of sensing and incorporate transient variations in the nanopore conductance. Application of the power spectral density of these fluctuations toward sensing has been highlighted with importance on reducing the detection limit in a complex environment. Lastly, the current problems and future perspectives have been discussed with a perspective to increase nanopores performance towards diagnostic applications in complex medium., (Copyright © 2022 Elsevier B.V. All rights reserved.)

An understanding of the current change in a solid state nanopore due to particle movement or capture is crucial for improvement of nanopore based sensing technologies. For lower aspect ratio pores, which are gaining importance due to their high sensitivity, there is interplay between access and pore resistance and the existing theories for computation of access resistance cannot explain most of the experimental observations. Hence, there is a need to develop a comprehensive model for calculating the effective conductance drop in presence of particles in a solid state nanopore. In this paper, we develop analytical models to calculate both the access and pore resistance in presence of particle at different positions during translocation and also when captured by receptors in functionalized nanopores. A wide range of pore geometry and molar strength has been investigated. Taking into consideration the positional uncertainty during particle translocation, the effective resistance sensitivity has been found to agree very well with the experimental observations in low aspect ratio pore. Additionally, we observe that in functionalized nanopores, a pore of higher diameter results in around 50% increase in sensitivity compared to a pore with half its diameter, which indicates the scope of design optimization in such systems.

This article investigates the impact of incorporating silica nanoparticles of varying diameters in label free impedance immunosensor. It has been observed that even if the surface area improvement has been adjusted to be similar for all the diameters, the sensitivity is enhanced by five times at a particular diameter of 100 nm due to the optimum combination of intersection with electric field lines and surface convexity. This study has enabled the detection of 0.1 fM Hep-B surface antigen with a reliable sensitivity of around 75%. Further, it has been observed that the SNR corresponding to 0.1 fM is 20 dB only for 100 nm particle. This SNR is comparable to a recent report on Hep-B virus detection but the limit of detection in the proposed sensor is lowered by more than three orders of magnitude. [ABSTRACT FROM AUTHOR]

We report an electrochemically fabricated silicon oxide nanoporous structure for ultrasensitive detection of AfB1 in food by shift in peak frequency corresponding to maximum sensitivity. It has been observed that the impedance sensitivity changes from 19% to 40% (which is only twice) where as the peak frequency shifts from 500 Hz to 50 kHz, for a change in concentration from 1 fg/ml to 1 pg/ml. This has been attributed to the combined effect of the significant pore narrowing with increasing AfB1 concentration and the opposing nature of impedance change within the nanopores and the conducting substrate immediately below the nanoporous layer. [ABSTRACT FROM AUTHOR]