Nanopore Identification\nof Polyglutamine Length via\n Cross-Slit Sensing

Nanopore sensing is now reshaping analytical proteomics\nwith its\nsimplicity, convenience, and high sensitivity. Determining the length\nof polyglutamine (polyQ) is crucial for the rapid screening of Huntington’s\ndisease. In this computational study, we present a cross-nanoslit\ndetection approach to determine the polyQ length, where the nanoslit\nis carved within a two-dimensional (2D) in-plane heterostructure of\ngraphene (GRA) and hexagonal boron nitride (hBN). We designed a heterostructure\nwith an hBN strip embedded in the graphene sheet. With such a design,\npolyQ peptides can spontaneously and linearly stretch out on the hBN\nstripe. By tuning the strength of an external in-plane electric field,\nmolecular transportation of polyQ peptides along the hBN stripe can\nbe effectively regulated. Subsequent cross-nanoslit motion can be\napplied to record time-dependent electric signals. The signal features\nare then utilized to train the machine learning classification models.\nThe machine-learning-assisted recognition enables accurate determination\nof the protein’s length. This nanoslit-sensing method may offer\n theoretical guidance on 2D heterostructure design for the detection\nof polyQ peptide lengths and rapid screening of protein-related diseases.