Patterning amyloid-β aggregation under the effect of acetylcholinesterase using a biological nanopore - an in vitro study

Subramanian, Nandhini; Watson, Brittany E.; Li, Chen-Zhong; Moss, Melissa A.; Liu, Chang

doi:10.1016/j.snr.2023.100170

Cited by 4 publications

(2 citation statements)

References 50 publications

(39 reference statements)

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“…The task of developing a uniform modification method for different AAs is further complicated by the need to incorporate target AAs into predesigned, charged peptide chains while preserving the self-identity of the AAs. Furthermore, due to the diversity of AAs, current blockage measurements commonly used for analyte identification are insufficient for protein sequencing; more parameters from current traces, such as standard variation of the current, , peak shape, and the frequency in the current recording need to be considered. ,, Evidently, achieving nanopore protein sequencing through AA discrimination remains an ongoing endeavor that requires a multidisciplinary approach and a systematic engineering solutions.…”

Section: Challenges and Opportunitiesmentioning

confidence: 99%

Engineering Biological Nanopore Approaches toward Protein Sequencing

Wei,

Penkauskas,

Reiner

et al. 2023

ACS Nano

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Biotechnological innovations have vastly improved the capacity to perform large-scale protein studies, while the methods we have for identifying and quantifying individual proteins are still inadequate to perform protein sequencing at the single-molecule level. Nanopore-inspired systems devoted to understanding how single molecules behave have been extensively developed for applications in genome sequencing. These nanopore systems are emerging as prominent tools for protein identification, detection, and analysis, suggesting realistic prospects for novel protein sequencing. This review summarizes recent advances in biological nanopore sensors toward protein sequencing, from the identification of individual amino acids to the controlled translocation of peptides and proteins, with attention focused on device and algorithm development and the delineation of molecular mechanisms with the aid of simulations. Specifically, the review aims to offer recommendations for the advancement of nanopore-based protein sequencing from an engineering perspective, highlighting the need for collaborative efforts across multiple disciplines. These efforts should include chemical conjugation, protein engineering, molecular simulation, machine-learning-assisted identification, and electronic device fabrication to enable practical implementation in real-world scenarios.

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Section: Challenges and Opportunitiesmentioning

confidence: 99%

Engineering Biological Nanopore Approaches toward Protein Sequencing

Wei,

Penkauskas,

Reiner

et al. 2023

ACS Nano

Self Cite

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“…Utilizing nanometer-scale pores in biological proteins or fabricated from artificial, solid-state membranes, nanopore sensing has shown single-molecule sensitivity and demonstrated excellent accuracy for amino acid identification and nucleic acid sequencing. − Nanopore sensing has also displayed great potential for protein analysis, and has begun to emerge as a biomarker detection tool for clinical use. − Theoretically, the concentration of an analyte can be determined by recording and statistically analyzing the frequency of ionic current blockade events induced by translocation of single analyte molecules through the nanopore under an applied electrical potential. − In practice, to obtain statistically significant numbers of translocation events within a reasonable measurement time, the concentrations of the analyte must be higher than the nanomolar level . Additionally, due to the nonselective translocation of analytes in nanopores and the stochastic nature of the electrical current blockade signals, different analytes often generate similar signals.…”

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confidence: 99%

Quantitation of Circulating Mycobacterium tuberculosis Antigens by Nanopore Biosensing in Children Evaluated for Pulmonary Tuberculosis in South Africa

Wang,

Wei,

van der Zalm

et al. 2023

ACS Nano

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Nanopore sensing of proteomic biomarkers lacks accuracy due to the ultralow abundance of targets, a wide variety of interferents in clinical samples, and the mismatch between pore and analyte sizes. By converting antigens to DNA probes via click chemistry and quantifying their characteristic signals, we show a nanopore assay with several amplification mechanisms to achieve an attomolar level limit of detection that enables quantitation of the circulating Mycobacterium tuberculosis (Mtb) antigen ESAT-6/CFP-10 complex in human serum. The assay's nonsputum-based feature and low-volume sample requirements make it particularly well-suited for detecting pediatric tuberculosis (TB) disease, where establishing an accurate diagnosis is greatly complicated by the paucibacillary nature of respiratory secretions, nonspecific symptoms, and challenges with sample collection. In the clinical assessment, the assay was applied to analyze ESAT-6/CFP-10 levels in serum samples collected during baseline investigation for TB in 75 children, aged 0−12 years, enrolled in a diagnostic study conducted in Cape Town, South Africa. This nanopore assay showed superior sensitivity in children with confirmed TB (94.4%) compared to clinical "gold standard" diagnostic technologies (Xpert MTB/RIF 44.4% and Mtb culture 72.2%) and filled the diagnostic gap for children with unconfirmed TB, where these traditional technologies fell short. We envision that, in combination with automated sample processing and portable nanopore devices, this methodology will offer a powerful tool to support the diagnosis of pulmonary TB in children.

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Biosensing strategies for amyloid‐like protein aggregates

Zhou,

Yan,

Dong

et al. 2023

BMEMat

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Protein aggregate species play a pivotal role in the pathology of various degenerative diseases. Their dynamic changes are closely correlated with disease progression, making them promising candidates as diagnostic biomarkers. Given the prevalence of degenerative diseases, growing attention is drawn to develop pragmatic and accessible protein aggregate species detection technology. However, the performance of current detection methods is far from satisfying the requirements of extensive clinical use. In this review, we focus on the design strategies, merits, and potential shortcomings of each class of detection methods. The review is organized into three major parts: native protein sensing, seed amplification, and intricate program, which embody three different but interconnected methodologies. To the best of our knowledge, no systematic review has encompassed the entire workflow, from the molecular level to the apparatus organization. This review emphasizes the feasibility of the methods instead of theoretical detection limitations. We conclude that high selectivity does play a pivotal role, while signal compilation, multilateral profiling, and other patient‐oriented strategies (i.e. less invasiveness and assay speed) are also important.

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Patterning amyloid-β aggregation under the effect of acetylcholinesterase using a biological nanopore - an in vitro study

Cited by 4 publications

References 50 publications

Engineering Biological Nanopore Approaches toward Protein Sequencing

Engineering Biological Nanopore Approaches toward Protein Sequencing

Quantitation of Circulating Mycobacterium tuberculosis Antigens by Nanopore Biosensing in Children Evaluated for Pulmonary Tuberculosis in South Africa

Biosensing strategies for amyloid‐like protein aggregates

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