2D MoS₂ nanopores: ionic current blockade height for clustering DNA events

Abstract

2D nanopores can be used to electrophoretically drive DNA molecules, which can in turn be identified through measurable electronic current blockades. In this work, we use experimental data from molybdenum disulfide nanopores threading DNA nucleotides and propose a methodological approach to interpret DNA events. Specifically, the experimental ionic traces are used to train an unsupervised machine learning model for identifying distinct molecular events through the 2D nanopore. For the first time, we propose a clustering of experimental 2D nanopore data based on the ionic current blockade height and unrelated to the traditional dwell time for each DNA event. Within this approach, the blockade level information is implicitly included in the feature space analysis and does not need to be treated explicitly. We could show the higher efficiency of the blockade height over the traditional dwell time also in coping with sparse nanopore data sets. Our approach allows for a deep insight into characteristic molecular features in 2D nanopores and provides a feedback mechanism to tune these materials and interpret the measured signals. It has, thus, a high impact on the efficiency of 2D nanopore-based DNA sequencers.

Development of an Artificially Intelligent Nanopore for High-Throughput DNA Sequencing with a Machine-Learning-Aided Quantum-Tunneling Approach

“…Under experimental conditions, "ionic blockade height" is reported to be superior to traditional features like dwell time. 43,44 Hence, molecular conductance combined with ionic blockade height and ionic current mean could be more advantageous features for the classification of nucleotides.…”

“…The classification results signify that, by employing the SVC rbf ML classifier model with the graphene nanopore, the nucleotide sequence of an unknown long DNA stand can be identified with optimized accuracy only considering their unlabeled transmission readout. Under experimental conditions, “ionic blockade height” is reported to be superior to traditional features like dwell time. , Hence, molecular conductance combined with ionic blockade height and ionic current mean could be more advantageous features for the classification of nucleotides.…”

Polarization Induced Electro-Functionalization of Pore Walls: A Contactless Technology

“…However, crystalline atomically thin 2D materials have been developed and integrated as membranes for nanopores. Among others, we may mention 2D materials such as graphene [70,71], molybdenum disulfide (MoS 2 ) [72], heterostructure of graphene and MoS 2 [73], boron nitride (BN) [74], and tungsten disulfide (WS 2 ) [75]. Despite their advantages of very low thicknesses, these 2D materials suffered from several drawbacks that prevented their implementation for DNA sequencing, among which were noise upon sensing and mechanical fluctuations [54,69].…”

Highly accurate random DNA sequencing using inherent interlayer potential traps of bilayer MoS2nanopores

“…There are limited number of studies on single nucleotide sensing using 1-layer thick MoS2 nanopores [33][34][35][36][37] . Single nucleotide detection from homogenous polynucleotide strands has been demonstrated by 1-layer thick MoS2 nanopores at a concentration of 5 µg ml -1 with 100 mM KCl solution 14 .…”