Microtomy-Fabricated Two-Dimensional Nano-slits Enable Single Molecule Biosensing

Abstract

Nanofluidic devices have emerged as a powerful sensor for single-molecule studies. Among these, biological nanopores have demonstrated remarkable capabilities, ranging from detecting epigenetic modifications in DNA and showing promising results for developing protein sequencing technology. Despite extensive research, solid-state counterparts, such as solid-state nanopores and nano-slits, have not achieved comparable success. Unlike biological nanopores, where bacterial proteins can spontaneously insert into lipid membranes to create thousands of atomically identical copies, solid-state counterparts lack a similarly straightforward and scalable fabrication method. This inability to consistently produce multiple devices with the same precision in dimensions as biological systems remains a significant barrier to their academic and industrial adoption and applications in molecular sensing. Towards this direction, we show the potential of ultramicrotomy based fabrication of atomically smooth two-dimensional (2D) nanocapillaries and its applications in biosensing. This precise and straightforward method enabled the sustainable production of several hundred molybdenum disulfide-based 2D nano-slits with identical cross-sectional dimensions and tunable lengths from layered crystals. Here, we demonstrated DNA sensing with these 2D nano-slits using the resistive ionic current blockade technique. This robust microtomy technique accelerates production from a single device over 2–3 weeks to hundreds of identical nano-slit biosensors in parallel within the same period. In addition to 1/f noise analysis, these MoS2 nano-slits reveal diverse topological local conformations of DNA during translocation.