Optimizing the Single-Molecule Counting Process of Solid-State Nanopores

Title: Optimizing the Single-Molecule Counting Process of Solid-State Nanopores
Authors: Charron, Martin
Date: 2020-01-28
Abstract: Due to their intrinsic single-molecule resolution and now easy fabrication and microfluidic integration, solid-state nanopores show great potential of becoming flexible low-cost, point-of-need, ultra-sensitive biomarker detection sensors. Since nanopores are still limited by the arrival time of the analyte to the sensor, reaching ultra-low concentration levels (fM) in a reasonable measurement time remains a challenge. Before approaches solving this problem become possible, one subject, not often discussed, needs to be addressed: The reliability and uncertainty of capture-based nanopore measurements. Counting with nanopores is often accomplished through measuring translocation frequencies. However, limitations of nanofabrication techniques tend to produce solid-state nanopores with, at the atomic scale, different geometries or chemical structures. A question then arises: How different will the measured capture rate be for two seemingly identical pores, i.e. pores intended to have same diameter and thickness within the fabrication capabilities? One solution to circumvent this problem is to use calibration curves by measuring the capture frequency of different concentrations, which prompts a follow up question: Does a single nanopore capture frequency change over time during the course of an experiment? This thesis investigates these two questions and experimentally shows that intra-pore and inter-pore capture variations can be significant, thus reducing the precision of simple nanopore counting to determine concentration of an analyte. To address these complications, a solution involving an internal calibrator is presented and is demonstrated to increase the sensitivity of concentration measurements.
URL: http://hdl.handle.net/10393/40123
CollectionThèses, 2011 - // Theses, 2011 -