ABSTRACT
Emerging from the broad diversity of nanoscale-sensing platforms, nanopores are single-molecule (SM) sensors in a class of their own, capable of detection, analysis, and the manipulation of single molecules with high throughput. Much like gel electrophoresis, where the native electric charge of biomolecules is used to move the molecule in the direction of an external electrical eld, in the nanopore technique, electrical force is used to thread biomolecules through a narrow nanopore constriction. Nanopores o er an unparalleled set of advantages over other single-molecule sensing methodologies: (1) Biomolecules can be detected without chemical or radioactive labeling, thus enabling the development of extremely low-cost and rapid diagnostic tools. (2) High analyte sensitivity can be achieved, as nanomolar concentrations are routinely su cient. In conjunction with advances in nano uidics, nanopore sensors integrated with sub-μL cells are extremely well suited for the ampli cation-free detection of trace samples. (3) Nanopores are a unique force apparatus for the analysis of biomolecular interactions, in that the immobilization of the molecules onto surfaces or beads is not required. (4) Finally, sensing using nanopores does not require making or breaking chemical bonds, and thus the technique is nondestructive. Despite the great utility of this technique for current and future applications, its underlying principles are simple, borrowing from the resistive sensing principles developed by Coulter in the 1950s (Coulter, 1953). In this chapter, we provide a detailed overview of the experimental
aspects of the nanopore technique. We highlight its short-term and long-term prospects, and describe the progress made thus far with natural and synthetic pores for single-biomolecule detection and analysis. We nally discuss future possible directions of nanopore sensing, and the potential impacts of the technique on biophysics and biomedical research.
