Moderne Mathilde, Abrao-Nemeir Imad, Meyer Nathan, Du Jun, Charles-Achille Saly, Janot Jean-Marc, Torrent Joan, Lepoitevin Mathilde, Balme Sebastien
Institut Européen des Membranes, UMR5635 University of Montpellier ENCSM CNRS, Place Eugène Bataillon, 34095, Montpellier, Cedex 5, France.
Institut Européen des Membranes, UMR5635 University of Montpellier ENCSM CNRS, Place Eugène Bataillon, 34095, Montpellier, Cedex 5, France; INM, University of Montpellier, INSERM, Montpellier, France.
Anal Chim Acta. 2023 Sep 22;1275:341587. doi: 10.1016/j.aca.2023.341587. Epub 2023 Jul 4.
In this work, we aim to capture, detect and analysis at single molecule level Aβ42 aggregates. To this end, two strategies of track-etched nanopore membranes functionalization were investigated. The first one uses an aptamer and requires only three steps, whereas the second strategy uses Lecanemab antibodies and requires six steps. Out of the two presented strategies, the second one was found to be the most suitable to detect Aβ42 aggregates using a quick current-voltage readout. The resulting single nanopore was then upscale to multipore membranes to capture the Aβ42 aggregates before analysis through them through a single-molecule approach. By comparing the species present in the retentate and filtrate, we confirmed the membrane's affinity for the larger Aβ42 aggregates present in the sample. We found that chromatographic membranes combined with an ionic diode for binary on/off readout are powerful tools for detecting rare biomarkers before single molecule analysis.
在这项工作中，我们旨在在单分子水平上捕获、检测和分析Aβ42聚集体。为此，研究了两种径迹蚀刻纳米孔膜功能化策略。第一种使用适配体，仅需三步，而第二种策略使用Lecanemab抗体，需要六步。在提出的两种策略中，发现第二种最适合使用快速电流-电压读数来检测Aβ42聚集体。然后将所得的单个纳米孔放大到多孔膜，以捕获Aβ42聚集体，然后通过单分子方法对其进行分析。通过比较截留物和滤液中存在的物种，我们证实了膜对样品中较大的Aβ42聚集体的亲和力。我们发现，结合离子二极管进行二进制开/关读数的色谱膜是在单分子分析之前检测稀有生物标志物的强大工具。
