Aerolysin Nanopore Electrochemistry

Accounts of Chemical Research, Год журнала: 2025, Номер unknown

Опубликована: Янв. 28, 2025

ConspectusIons are the crucial signaling components for living organisms. In cells, their transportation across pore-forming membrane proteins is vital regulating physiological functions, such as generating ionic current signals in response to target molecule recognition. This ion transport affected by confined interactions and local environments within protein pore. Therefore, can efficiently transduce characteristics of each into ion-transport-mediated with high sensitivity. Inspired nature, various pores have been developed high-throughput label-free nanopore sensors single-molecule detection, enabling rapid accurate readouts. particular, aerolysin, a key virulence factor Aeromonas hydrophila, exhibits sensitivity fingerprints detecting subtle differences sequence, conformation, structure DNA, proteins, polypeptides, oligosaccharides, other molecules. Aerolysin features cap that approximately 14 nm wide on cis side central pore about 10 long minimum diameter around 1 nm. Its lumen, 11 charged rings at two entrances neutral amino acids between, facilitates dwelling single analyte characteristic enables rich between well-defined residues analyte. As result, signal offers unique molecular fingerprint, extending beyond traditional volume exclusion model sensing. 2006, aerolysin was first reported discriminate conformational peptides, opening door rapidly growing field electrochemistry. Over years, mutant nanopores emerged, associated advanced instrumentation data analysis algorithms, simultaneous identification over 30 targets number still increasing. electrochemistry particular allows time-resolved qualitative quantitative ranging from DNA sequencing, proteomics, enzyme kinetics, reactions potential clinical diagnostics. Especially, feasibility dynamic would revolutionize omics studies level, paving way promising temporal omics. Despite success this approach so far, it remains challenging understand how correlate distinguishable signatures. Recent attempts added correction terms account variations mobility caused Account, we revisit origin blockade induced molecules inside nanopore. We highlight contributions noncovalent sensing ability through corrected conductance model. Account then describes design interaction networks nanopore, including electrostatic, hydrophobic, hydrogen-bonding, cation−π, ion–charged acid interactions, ultrasensitive biomolecular quantification. Finally, provide an outlook further understanding network improving manipulating fine-tuning toward broad range practical applications.

Язык: Английский

Nanopore toward Genuine Single-Molecule Sensing: Molecular Ping-Pong Technology

Nano Letters, Год журнала: 2025, Номер unknown

Опубликована: Фев. 26, 2025

Nanopore sensing is a so-called label-free, single-molecule technology; however, multiple events of different molecules are recorded to obtain statistically robust data, which can limit both efficiency and sample use. To overcome these challenges, nanopore molecular ping-pong technology enables precise manipulation, reducing systematic stochastic errors by repeatedly measuring the same molecule. This review introduces fundamentals advancements technology, highlighting recent breakthrough achieving over 10,000 recaptures single dsDNA molecule within minutes. innovation not only minimizes requirements, critical for nonamplifiable samples, but also significantly enhances experimental precision. While current applications focus on dsDNA, extending this protein glycan analysis could transform research. Just as revolutionized DNA sequencing, it holds potential drive development nanopore-based sequencers, paving way groundbreaking in biology biomedicine.

Язык: Английский