Solid‐State Quad‐Nanopore Array for High‐Resolution Single‐Molecule Analysis and Discrimination

Abstract

The ability to detect and distinguish biomolecules at the single‐molecule level is at the forefront of today's biomedicine and analytical chemistry research. Increasing the dwell time of individual biomolecules in the sensing spot can greatly enhance the sensitivity of single‐molecule methods. This is particularly important in solid‐state nanopore sensing, where the detection of small molecules is often limited by the transit dwell time and insufficient temporal resolution. Here, a quad‐nanopore is introduced, a square array of four nanopores (with a space interval of 30–50 nm) to improve the detection sensitivity through electric field manipulation in the access region. It is shown that dwell times of short DNA strands (200 bp) are prolonged in quad‐nanopores as compared to single nanopores of the same diameter. The dependence of dwell times on the quad‐pore spacing is investigated and it is found that the “retarding effect” increases with decreasing space intervals. Furthermore, ultra‐short DNA (50 bp) detection is demonstrated using a 10 nm diameter quad‐nanopore array, which is hardly detected by a single nanopore. Finally, the general utility of quad‐nanopores has been verified by successful discrimination of two kinds of small molecules, metal‐organic cage and bovine serum albumin (BSA).

Direct and Continuous Monitoring of Multicomponent Antibiotic Gentamicin in Blood at Single-Molecule Resolution

“…20 However, it is obvious that the majority of small molecule sensing strategies rely on nanopores with channel constriction diameters of 1 nm and above, including biological nanopores (α-HL, 21,22 MspA, 23,24 FraC, 25 et al), as well as certain types of solid-state nanopores. 26,27 These nanopores often require additional modification or molecule labeling due to their large channel diameter when detecting small molecules, which necessitates advanced engineering skills and may potentially limit their capability for continuous monitoring. More notably, the vestibule of the aforementioned biological nanopores is connected with a single large opening, a channel structure that is easily blocked by nontarget macromolecules when directly detecting small molecules in biofluids.…”

“…Renowned for its breakthroughs in DNA sequencing and protein analysis, − nanopore technology possesses advantages such as real-time and single-molecule detection, miniaturization, low-cost, and high throughput. − These advantages indicate its potential for point-of-care monitoring of small molecules. , Up to now, nanopore-based methods for small-molecule analysis have exhibited exceptional molecular resolution and sensitivity. , Besides, they markedly enhance the convenience of detecting biofluids, − diminishing the reliance on specialized laboratory environments . However, it is obvious that the majority of small molecule sensing strategies rely on nanopores with channel constriction diameters of 1 nm and above, including biological nanopores (α-HL, , MspA, , FraC, et al), as well as certain types of solid-state nanopores. , These nanopores often require additional modification or molecule labeling due to their large channel diameter when detecting small molecules, which necessitates advanced engineering skills and may potentially limit their capability for continuous monitoring. More notably, the vestibule of the aforementioned biological nanopores is connected with a single large opening, a channel structure that is easily blocked by nontarget macromolecules when directly detecting small molecules in biofluids.…”

Ion Transport in Multi-Nanochannels Regulated by pH and Ion Concentration

“…Consequently, nanochannel arrays can detect ultrashort DNA strands that are hardly detectable using individual nanochannels of similar size. 18 Multinanochannel systems with different or identical properties in parallel or series can be used to build ionic circuits. 19 Nanochannel arrays also promise to improve process efficiency for applications such as power generation, 20 desalination, 21−24 virus filtration, 25 biomolecule separation, 26 gas storage, 27−30 catalysis, 31 and drug delivery.…”

“…Nanochannel arrays can be used to slow the transportation of tiny molecules through nanochannels, including proteins, metal–organic cages, and short DNA strands. Consequently, nanochannel arrays can detect ultrashort DNA strands that are hardly detectable using individual nanochannels of similar size . Multinanochannel systems with different or identical properties in parallel or series can be used to build ionic circuits .…”

Nanopore sensitization based on a double loop hybridization chain reaction and G-quadruplex

“…Owing to its distinctive advantages, such as high throughput, label-free capability, and ultra-sensitivity, as well as its potential applications in other industries such as biosensing and genomics, nanopore analysis has garnered significant interest in recent years. 1–6 The principle of nanopore detection is straightforward: when particles are driven through a voltage-oriented nanopore, the volume exclusion effect causes them to instantaneously occupy a portion of the conductive particle volume within the pore, thereby inducing a change in ion current. 7,8 Each current blockade represents a single-molecule event, given that the micron-sized pores only permit the passage of one particle of the appropriate size at a time.…”