Nanopores have been explored for various biochemical and nanoparticle analyses, primarily via characterizing the ionic current through the pores. At present, however, size determination for solid-state nanopores is experimentally tedious and theoretically unaccountable. Here, we establish a physical model by introducing an effective transport length, L (eff) that measures, for a symmetric nanopore, twice the distance from the center of the nanopore where the electric field is the highest to the point along the nanopore axis where the electric field falls to e-(1)of this maximum. By G = sigma(s0)/L-eff, a simple expression S-0=/(G, sigma, h, beta) is derived to algebraically correlate minimum nanopore cross-section area S (0)to nanopore conductance G, electrolyte conductivity a, and membrane thickness h with (3 to denote pore shape that is determined by the pore fabrication technique. The model agrees excellently with experimental results for nanopores in graphene, single-layer MoS2, and ultrathin SiNx films. The generality of the model is verified by applying it to micrometer-size pores.

High-fidelity analysis of translocating biomolecules through nanopores demands shortening the nanocapillary length to a minimal value. Existing nanopores and capillaries, however, inherit a finite length from the parent membranes. Here, nanocapillaries of zero depth are formed by dissolving two superimposed and crossing metallic nanorods, molded in polymeric slabs. In an electrolyte, the interface shared by the crossing fluidic channels is mathematically of zero thickness and defines the narrowest constriction in the stream of ions through the nanopore device. This novel architecture provides the possibility to design nanopore fluidic channels, particularly with a robust 3D architecture maintaining the ultimate zero thickness geometry independently of the thickness of the fluidic channels. With orders of magnitude reduced biomolecule translocation speed, and lowered electronic and ionic noise compared to nanopores in 2D materials, the findings establish interfacial nanopores as a scalable platform for realizing nanofluidic systems, capable of single-molecule detection.

Nanopore technology has been extensively investigated for analysis of biomolecules, and a success story in this field concerns DNA sequencing using a nanopore chip featuring an array of hundreds of biological nanopores (BioNs). Solid-state nanopores (SSNs) have been explored to attain longer lifetime and higher integration density than what BioNs can offer, but SSNs are generally considered to generate higher noise whose origin remains to be confirmed. Here, we systematically study lowfrequency (including thermal and flicker) noise characteristics of SSNs measuring 7 to 200 nm in diameter drilled through a 20-nmthick SiNx membrane by focused ion milling. Both bulk and surface ionic currents in the nanopore are found to contribute to the flicker noise, with their respective contributions determined by salt concentration and pH in electrolytes as well as bias conditions. Increasing salt concentration at constant pH and voltage bias leads to increase in the bulk ionic current and noise therefrom. Changing pH at constant salt concentration and current bias results in variation of surface charge density, and hence alteration of surface ionic current and noise. In addition, the noise from Ag/AgCl electrodes can become predominant when the pore size is large and/or the salt concentration is high. Analysis of our comprehensive experimental results leads to the establishment of a generalized nanopore noise model. The model not only gives an excellent account of the experimental observations, but can also be used for evaluation of various noise components in much smaller nanopores currently not experimentally available.

DNA sequencing, i.e., the process of determining the succession of nucleotides on a DNA strand, has become a standard aid in biomedical research and is expected to revolutionize medicine. With the capability of handling single DNA molecules, nanopore technology holds high promises to become speedier in sequencing at lower cost than what are achievable with the commercially available optics-or semiconductor-based massively parallelized technologies. Despite tremendous progress made with biological and solid-state nanopores, high error rates and large uncertainties persist with the sequencing results. Here, we employ a nano-disk model to quantitatively analyze the sequencing process by examining the variations of ionic current when a DNA strand translocates a nanopore. Our focus is placed on signal-boosting and noise-suppressing strategies in order to attain the single-nucleotide resolution. Apart from decreasing pore diameter and thickness, it is crucial to also reduce the translocation speed and facilitate a stepwise translocation. Our best-case scenario analysis points to severe challenges with employing plain nanopore technology, i.e., without recourse to any signal amplification strategy, in achieving sequencing with the desired single-nucleotide resolution. A conceptual approach based on strand synthesis in the nanopore of the translocating DNA from single-stranded to double-stranded is shown to yield a 10-fold signal amplification. Although it involves no advanced physics and is very simple in mathematics, this simple model captures the essence of nanopore sequencing and is useful in guiding the design and operation of nanopore sequencing.

Solid-state nanopore technology presents an emerging single-molecule-based analytical tool for the separation and analysis of nanoparticles. Different approaches have been pursued to attain the anticipated detection performance. Here, we report the rectification behaviour of protein translocation through silicon-based truncated pyramidal nanopores. When the size of translocating proteins is comparable to the smallest physical constriction of the nanopore, the frequency of translocation events observed is lower for proteins that travel from the larger to the small opening of the nanopore than for those that travel in the reverse direction. When the proteins are appreciably smaller than the nanopore, an opposite rectification in the frequency of translocation events is evident. The maximum rectification factor achieved is around ten. Numerical simulations reveal the formation of an electro-osmotic vortex in such asymmetric nanopores. The vortex–protein interaction is found to play a decisive role in rectifying the translocation in terms of polarity and amplitude. The reported phenomenon can be potentially exploitable for the discrimination of various nanoparticles.

Nanopores have been widely studied for power generation and single-molecule detection. Although the power level generated by a single nanopore based on electrolyte concentration gradient is too low to be practically useful, such a power level is found sufficient to drive analyte translocation in nanopores. Here, we explore the simultaneous action of a solid-state nanopore as a nanopower generator and a nanoscale biosensor by exploiting the extremely small power generated to drive the analyte translocation in the same nanopore device. This autogenic analyte translocation is demonstrated using protein and DNA for their distinct shape, size and charge. The simple device structure allows for easy implementation of either electrical or optical readout. The obtained nanopore translocation is characterized by typical behaviors expected for an ordinary nanopore sensor powered by an external source. Extensive numerical simulation confirms the power generation and power level generated. It also reveals the fundamentals of autogenic translocation. As it requires no external power source, the sensing can be conducted with simple readout electronics and may allow for integration of high-density nanopores. Our approach demonstrated in this work may pave the way to practical high-throughput single-molecule nanopore sensing powered by the distributed energy harvested by the nanopores themselves.

Nanopores have been implemented as nanosensors for DNA sequencing, biomolecule inspection, chemical analysis, nanoparticle detection, etc. For high-throughput and parallelized measurement using nanopore arrays, individual addressability has been a crucial technological solution in order to enable scrutiny of signals generated at each and every nanopore. Here, an alternative pathway of employing arrayed nanopores to perform sensor functions is investigated by examining the group behavior of nanoparticles translocating multiple nanopores. As no individual addressability is required, fabrication of nanopore devices along with microfluidic cells and readout circuits can be greatly simplified. Experimentally, arrays of less than 10 pores are shown to be capable of analyzing translocating nanoparticles with a good signal-to-noise margin. According to theoretical predictions, more pores (than 10) per array can perform high-fidelity analysis if the noise level of the measurement system can be better controlled. More pores per array would also allow for faster measurement at lower concentration because of larger capture cross sections for target nanoparticles. By experimentally varying the number of pores, the concentration of nanoparticles, or the applied bias voltage across the nanopores, we have identified the basic characteristics of this multievent process. By characterizing average pore current and associated standard deviation during translocation and by performing physical modeling and extensive numerical simulations, we have shown the possibility of determining the size and concentration of two kinds of translocating nanoparticles over 4 orders of magnitude in concentration. Hence, we have demonstrated the potential and versatility of the multiple-nanopore approach for high-throughput nanoparticle detection.