(Invited) Electrochemistry Confined Nanopore: Design and Application in Single Molecule Sensing

Abstract

Single-molecule sensing is key to deep understanding of elemental biological processes and complex bioreactions. Nanopore-based single-molecule method, a unique technique based on the modulation in ionic current, provides a high temporal-spatial resolution for single molecule sensing. To achieve a high selectivity and sensitivity of biological nanopore, the modification of specific group presenting in the whole region of Aerolysin nanopore was successfully designed, and every single molecule forms a whole sensing interface.1,2 As a reasonable model, a single membrane protein which is assembled from several monomers is regarded as a single molecule interface Therefore, the side chain of every single amino acid groups could be designed respectively by single site mutation.3 The single molecule interface has been achieved in biological nanopore sensors. A single membrane protein molecule could be regarded as a single molecule interface. Single molecule interface facilities the design of single sensing zone which ensures high spatial- and temporal resolution towards single molecule analysis. The single-site modification along the single molecule interface manipulates each site of interface for the precise responses which meet the multiple sensing requirement. More importantly, single molecule interface provides a confinement for the single molecule reaction which offers the possibility to study reaction kinetics in high temporal resolution. These advances provide a new concept in designing advanced sensors. Moreover, by combining with other single molecule methods such as fluorescence or plasmonic technology, it is possible to construct an integrated single molecule interface for multi-element readouts, which is expected to further provide the rich structural information of a single molecule. Figure 1. Single-molecule music. A single-molecule interface likes a tuba. As each molecule flows through the single-molecule interface, one can control the ‘button’ along the ‘tuba’ to organize a beautiful rhythm for single-molecule music. Keywords: Nanopore; Aerolysin nanopore, Single biomolecule interface, Site Mutation, Single molecule sensing.