Application of Solid-State Nanopore in Protein Detection

Luo, Yuhan; Wu, Linlin; Tu, Jing; Zhang, Lu

doi:10.3390/ijms21082808

Cited by 33 publications

(19 citation statements)

References 130 publications

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“…Nanopore sensors have been developed for decades to target multiple applications, including DNA sequencing, protein profiling, small chemical molecule detection, , and nanoparticle characterization. , Nanopore sensor is inspired by the Coulter cell counter and realizes a task by matching its dimension to that of analytes, molecules or nanoparticles. Thus, it possesses an extremely succinct structure, a nanoscale pore in an ultrathin membrane.…”

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confidence: 99%

A Guide to Signal Processing Algorithms for Nanopore Sensors

2021

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Nanopore technology holds great promise for a wide range of applications such as biomedical sensing, chemical detection, desalination, and energy conversion. For sensing performed in electrolytes in particular, abundant information about the translocating analytes is hidden in the fluctuating monitoring ionic current contributed from interactions between the analytes and the nanopore. Such ionic currents are inevitably affected by noise; hence, signal processing is an inseparable component of sensing in order to identify the hidden features in the signals and to analyze them. This Guide starts from untangling the signal processing flow and categorizing the various algorithms developed to extracting the useful information. By sorting the algorithms under Machine Learning (ML)-based versus non-ML-based, their underlying architectures and properties are systematically evaluated. For each category, the development tactics and features of the algorithms with implementation examples are discussed by referring to their common signal processing flow graphically summarized in a chart and by highlighting their key issues tabulated for clear comparison. How to get started with building up an ML-based algorithm is subsequently presented. The specific properties of the ML-based algorithms are then discussed in terms of learning strategy, performance evaluation, experimental repeatability and reliability, data preparation, and data utilization strategy. This Guide is concluded by outlining strategies and considerations for prospect algorithms.

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confidence: 99%

A Guide to Signal Processing Algorithms for Nanopore Sensors

2021

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“…[12] In recent years, solid-state nanopore sensing has attracted increasing attention in detecting single molecules with many advantages, including controllable feature size, high sensitivity, simple readout, and label-free electronic sensing. [13,14] The technology has been applied to many areas such as DNA sequencing, [15,16] protein detection, [17] nanoparticle separation, [18] and energy conversion. [19] The principle behind nanopore detection is resistive pulse sensing.…”

Section: Introductionmentioning

confidence: 99%

Gold Nanoparticle‐Labeled CRISPR‐Cas13a Assay for the Sensitive Solid‐State Nanopore Molecular Counting

Liu

Awayda

et al. 2022

Adv Materials Technologies

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the critical need for rapid and sensitive molecular diagnostics to combat current and future pandemics. Sensitive polymerase chain reaction (PCR) based tests are the gold standard for molecular diagnostics but rely on bulky and expensive instruments. Thus, they are not suitable for self-diagnosis or point-of-care (POC) settings. [2] High-throughput sequencing can decipher the entire genomic landscape of the pathogens but is time consuming and requires bioinformatics for data interpretation. [3] Immunoassays, such as rapid antigen tests, are simple and rapid diagnostic methods but normally lack the sensitivity to reporting the low concentration biomarkers. [4] Assays with high limits of detection and low accuracy have been acceptable out of necessity, but there are many scenarios where a rapid, sensitive, POC device would be beneficial. Therefore, developing a simple to use, portable, and sensitive diagnostic platform is one important key to addressing the current challenges for molecular diagnostics.Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) are bacterial systems evolved to combat bacteriophage infections by recognizing specific nucleic acid sequences to activate nucleolytic cleavage activities. The trans-cleavage of A gold nanoparticle (AuNP)-labeled CRISPR-Cas13a nucleic acid assay is developed for sensitive solid-state nanopore sensing. Instead of directly detecting the translocation of RNA through a nanopore, the system utilizes non-covalent conjugates of AuNPs and RNA targets. Upon CRISPR activation, the AuNPs are liberated from the RNA, isolated, and passed through a nanopore sensor. Detection of the AuNPs can be observed as increasing ionic current in the chip. Each AuNP that is detected is enumerated as an event, leading to quantitative of molecular targets. Leveraging the high signal-to-noise ratio enabled by the AuNPs, a detection limit of 50 fM before front-end target amplification is achieved using SARS-CoV-2 RNA segments as a Cas13 target. Furthermore, a dynamic range of six orders of magnitude is demonstrated for quantitative RNA sensing. This simplified AuNP-based CRISPR assay is performed at the physiological temperature without relying on thermal cyclers. In addition, the nanopore reader is similar in size to a smartphone, making the assay system suitable for rapid and portable nucleic acid biomarker detection in either low-resource settings or hospitals.

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“…Nanopores, as one kind of sensor platform, have attracted extensive attention of researchers [1][2][3] and have been widely applied in many fields such as metal ion detection [4], protein molecule detection [5,6] and DNA sequencing [7]. On account of their stability and adjustable pore diameter, the glass capillary-based nanopores are especially interesting [8,9].…”

Section: Introductionmentioning

confidence: 99%

Boronic Acid‐containing Stimuli‐responsive Polymers Modified Nanopores for Label‐free Dual‐signal‐output Detection of Glucose

Zheng

Zhu

2021

Electroanalysis

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Herein, a dual-signal-output glass nanopore system was developed for sensing glucose. Upon binding glucose, the boronic acid-containing stimuli-responsive polymer underwent a wettability switch and pKa shift. When the polymer was immobilized on the inner wall of nanopore, the nanopore offered a sensitive method for evaluating glucose by ion rectification. Besides, due to the electrostatic assembly of cationic pyrene onto the glucosebound anionic polymer, the pyrene excimer emission was observed. By separating the substrate binding and fluorescence reporting process, this work avoided the fluorescence labeling of the target and nanopore, thus simplifying the design of dual-signal-output nanopore for potential point-of-care test.

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Application of Solid-State Nanopore in Protein Detection

Cited by 33 publications

References 130 publications

A Guide to Signal Processing Algorithms for Nanopore Sensors

A Guide to Signal Processing Algorithms for Nanopore Sensors

Gold Nanoparticle‐Labeled CRISPR‐Cas13a Assay for the Sensitive Solid‐State Nanopore Molecular Counting

Boronic Acid‐containing Stimuli‐responsive Polymers Modified Nanopores for Label‐free Dual‐signal‐output Detection of Glucose

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