Solid-state nanopore sensing: the next workhorse of biophysical characterization

Abstract

Nanopore sequencing has entered the mainstream, with DNA and RNA sequencing now possible on portable, user-friendly devices. In the wake of these successes, the attention of the nanopore community has turned toward the challenge of de novo protein sequencing. Biological nanopores are primed to take on this task and have thus taken center stage. Here we draw focus back toward solid-state nanopores. We argue that these size-tunable and easily functionalized pores are key to studying the macromolecular superstructures inherent to natural and synthetic biochemical systems. While sequencing is undoubtedly a worthy goal, we advocate for the use of nanopores in new applications, toward understanding the supramolecular chemistry at the heart of biology and beyond. With ongoing improvements in hardware, nanopore functionalization and experimental design, new avenues for nanopore sensing are continually arising. Looking forward, we anticipate opportunities for solid-state nanopores in drug screening, protein engineering and synthetic self-assembled systems. This Perspective discusses opportunities and challenges of using solid-state nanopores for broader biophysical characterization.