Challenging Nanopores with Analyte Scope and Environment

Nanopores are nanofluidic channels formed through thin membranes that can deliver standout single-molecule and single-particle sensing capabilities. Analytical targets include small molecules and nanoparticles, and the DNA, protein, and glycan biopolymers underpinning genomics, proteomics, and glycomics. Detection-notably even in the simplest implementation, resistive-pulse sensing-does not inherently require sample labeling and, thus, offers the potential for general sensing utility combined with the prospective benefits of reduced sample processing requirements. A key pursuit for biopolymer sensing is the characterization of monomer sequence. This review article will provide an overview of the use of nanopores for general chemical sensing and -omics-related applications, writ-large. The broad analyte scope provides fertile ground for a discussion of principles governing nanopore sensing and considerations useful for guiding nanopore development. For nanopores to be effective in the face of broad analyte scope, stringent requirements on analytical performance must be met within the particular analyte class without sacrificing the operational flexibility necessary to be responsive across classes presenting very different physical and chemical challenges. These sample-driven challenges provide a unifying framework for discussing aspects of nanopore fabrication, properties, and integration; sensing paradigms, performance, and prospects; fundamental electrokinetic and interfacial phenomena; and practical challenges facing the use and further development of nanopore devices.