Combining iontronic, chromatography and nanopipette for Aβ42 aggregates detection and separation

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. [Display omitted] •Multipore and single pore track-etched membrane was designed to detect and trap Aβ42 aggregates.•The membranes are functionalized with Lecanemab to ensure the selectivity to Aβ42 aggregates.•Nanopipette was used to confirm of affinity of Aβ42 aggregates with the multipore membrane.