Improved Conductance Blockage Modeling of Cylindrical Nanopores, from 2D to Thick Membranes.

The ionic current blockage from a nanopore sensor is a fundamental metric for characterizing its dimensions and identifying molecules translocating through it. Yet, most analytical models predicting the conductance of a nanopore in both open and obstructed states remain inaccurate. Here, using an oblate spheroidal coordinate framework to study the electrical response of nanopore access regions, we reveal that the widely used model from Kowalczyk et al.

Synthesis of length-tunable DNA carriers for nanopore sensing.

Molecular carriers represent an increasingly common strategy in the field of nanopore sensing to use secondary molecules to selectively report on the presence of target analytes in solution, allowing for sensitive assays of otherwise hard-to-detect molecules such as small, weakly-charged proteins. However, existing carrier designs can often introduce drawbacks to nanopore experiments including higher levels of cost/complexity and carrier-pore interactions that lead to ambiguous signals and elevated clogging rates. In this work, we present a simple method of carrier production based on sticky-ended DNA molecules that emphasizes ease-of-synthesis and compatibility with nanopore sensing and analysis.

Analysis of Nanopore Data: Classification Strategies for an Unbiased Curation of Single-Molecule Events from DNA Nanostructures.

Nanopores are versatile single-molecule sensors that are being used to sense increasingly complex mixtures of structured molecules with applications in molecular data storage and disease biomarker detection. However, increased molecular complexity presents additional challenges to the analysis of nanopore data, including more translocation events being rejected for not matching an expected signal structure and a greater risk of selection bias entering this event curation process. To highlight these challenges, here, we present the analysis of a model molecular system consisting of a nanostructured DNA molecule attached to a linear DNA carrier.

Instrumentation for low noise nanopore-based ionic current recording under laser illumination.

We describe a nanopore-based optofluidic instrument capable of performing low-noise ionic current recordings of individual biomolecules under laser illumination. In such systems, simultaneous optical measurements generally introduce significant parasitic noise in the electrical signal, which can severely reduce the instrument sensitivity, critically hindering the monitoring of single-molecule events in the ionic current traces. Here, we present design rules and describe simple adjustments to the experimental setup to mitigate the different noise sources encountered when integrating optical components to an electrical nanopore system.