Designing nanotheranostics with machine learning

Nature Nanotechnology, Год журнала: 2024, Номер unknown

Опубликована: Окт. 3, 2024

Язык: Английский

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Identification and Detection of a Peptide Biomarker and Its Enantiomer by Nanopore

ACS Central Science, Год журнала: 2024, Номер 10(6), С. 1167 - 1178

Опубликована: Май 3, 2024

Until now, no fast, low-cost, and direct technique exists to identify detect protein/peptide enantiomers, because their mass charge are identical. They essential since l- d-protein enantiomers have different biological activities due unique conformations. Enantiomers potential for diagnostic purposes several diseases or normal bodily functions but yet be utilized. This work uses an aerolysin nanopore electrical detection vasopressin l-AVP d-AVP, associated with processes pathologies. We show identification according conformations, in either native reducing conditions, using specific signature. To improve identification, we used a principal component analysis approach define the most relevant parameters identification. Finally, Monte Carlo prediction assign each event type d-AVP enantiomer.

Язык: Английский

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Nanopore‐Functionalized Hybrid Lipid‐Block Copolymer Membranes Allow Efficient Single‐Molecule Sampling and Stable Sensing of Human Serum

Advanced Materials, Год журнала: 2025, Номер unknown

Опубликована: Март 4, 2025

Abstract Biological nanopores are powerful tools for single‐molecule detection, with promising potential as next‐generation biosensors. A major bottleneck in nanopore analysis is the fragility of supporting lipid membranes, that easily rupture after exposure to biological samples. Membranes comprising PMOXA‐PDMS‐PMOXA (poly(2‐methyloxazoline‐b‐dimethylsiloxane‐b‐2‐methyloxazoline)) or PBD‐PEO (poly(1,2‐butadiene)‐b‐poly(ethylene oxide)) polymers may form robust alternatives, but their suitability reconstitution a broad range has not yet been investigated. Here, membranes found be highly toward applied voltages and human serum, while providing poor environment reconstitution. However, hybrid containing similar molar ratio PBD 11 PEO 8 diphytanoyl phosphatidylcholine (DPhPC) lipids show best both worlds: suitable wide variety nanopores. Molecular dynamics simulations reveal ≈12 nm domains interspersed by polymer matrix. Nanopores partition into these nanodomains sequester lipids, possibly offering same binding strength native bilayer. reconstituted yield efficient sampling biomolecules enable sensing high concentrations serum. This work thus shows functionalized allow sensing, forming interfaces, resolving an important novel nanopore‐based

Язык: Английский

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

ACS Nano, Год журнала: 2024, Номер 18(12), С. 9137 - 9149

Опубликована: Март 12, 2024

Point-of-care monitoring of small molecules in biofluids is crucial for clinical diagnosis and treatment. However, the inherent low degree recognition complex composition present significant obstacles current detection technologies. Although nanopore sensing excels analysis molecules, direct remains a challenge. In this study, we method molecule drug gentamicin whole blood based on mechanosensitive channel conductance Pseudomonas aeruginosa (PaMscS) nanopore. PaMscS can directly detect distinguish its main components with only monomethyl difference. The 'molecular sieve' structure enables measurement human within 10 min. Furthermore, continuous device constructed achieved live rats approximately 2.5 h without consumption, while be analyzed situ. This approach rapid convenient single-molecule level resolution, which significantly lower threshold concentration promote more efficient use. Moreover, work also lays foundation future development technology resolution living body.

Язык: Английский

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Nanopore approaches for single-molecule temporal omics: promises and challenges

Nature Methods, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 18, 2024

Язык: Английский

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Complex and Non-sequential Current Signatures of a β-Hairpin Peptide Confined in a Nanopore

Analytical Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Янв. 22, 2025

Nanopore sensing is widely used for single-molecule detection, originally applied to nucleic acids and now extended protein sensing. Our study focuses on the complex conformational changes of peptides in nanopores, which may have implications peptide fingerprinting identification. Specifically, we investigated interaction a β-hairpin (SV28) within an α-hemolysin (αHL) nanopore. experiments revealed that SV28 captured via dielectrophoresis exhibits long dwell times nanopore, leading multiple current blockade levels. Unlike DNA hairpins, showed non-sequential transitions among four distinct This behavior indicates dynamics nanopores cannot be simply modeled along single reaction coordinate. findings provide insights into peptide-nanopore interactions, are potentially useful developing nanopore-based identification technologies.

Язык: Английский

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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

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Obtaining Narrow Distributions of Single-Molecule Peptide Signals Enables Sensitive Peptide Discrimination with α-Hemolysin Nanopores

Journal of the American Chemical Society, Год журнала: 2025, Номер unknown

Опубликована: Март 10, 2025

Biological nanopore technology has emerged as a promising tool for analyzing peptides and post-translational modifications at the single-molecule level. However, broader application is currently limited by partial separation of low-throughput, mainly due to nonuniform peptide signals detected nanopores. Narrowing signal distribution crucial improving nanopore's sensing ability but remains bottleneck. Here, we demonstrate that capturing with electrophoretic force against electroosmotic flow can provoke more uniform blockades in α-hemolysin By using buffers 2 M KCl pH 3.8, obtain most signals, which may be correlated shape, linearization, actual dwelling position peptides. Five acetylation phosphorylation, including isomeric peptides, readily separated from each other. The citrullination replacement arginine β-hydroxybutyrylation modification another sequence are also discriminated mixture. A series different compositions induced when they were analyzed our method. Our work presents an efficient approach optimize analysis

Язык: Английский

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An aptazyme-based logic gate biosensor for tumor detection in postoperative analysis

Sensors and Actuators B Chemical, Год журнала: 2025, Номер unknown, С. 137594 - 137594

Опубликована: Март 1, 2025

Язык: Английский

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Emerging protein sequencing technologies: proteomics without Mass spectrometry?

Expert Review of Proteomics, Год журнала: 2025, Номер unknown

Опубликована: Март 19, 2025

Liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been a leading method for proteomics thirty years. Advantages provided by LC-MS/MS are offset significant disadvantages, including cost. Recently, several non-mass spectrometric methods have emerged, but little information is available about their capacity to analyze the complex mixtures routine spectrometry. We review recent non-mass-spectrometric sequencing proteins and peptides, using nanopores, degradation, reverse translation, short-epitope mapping, with comments on bioinformatics challenges, fundamental limitations, areas where new technologies will be more or less competitive LC-MS/MS. In addition conventional literature searches, instrument vendor websites, patents, webinars, preprints were also consulted give up-to-date picture. Many promising. However, demonstrations that they outperform in terms of peptides identified not yet published, astute observers note important especially relating dynamic range single-molecule measurements mixtures. Still, even if performance emerging proves inferior LC-MS/MS, low cost could create different kind revolution: dramatic increase number biology laboratories engaging forms research.

Язык: Английский

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