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Nanopore transduction detection offers prospects for highly sensitive and discriminative biosensing. The NTD “Nanoscope” functionalizes a single nanopore with a channel current modulator that is designed to transduce events, such as binding to a specific target. Nanopore event transduction involves single‐molecule biophysics, engineered information flows, and nanopore cheminformatics. In the NTD functionalization the transducer molecule is drawn into the channel by an applied potential but is too big to translocate, instead becoming stuck in a bistable capture such that it modulates the channel’s ion‐flow with stationary statistics in a distinctive way. If the channel modulator is bifunctional in that one end is meant to be captured and modulated while the other end is linked to an aptamer or antibody for specific binding, then we have the basis for a remarkably sensitive and specific biosensing capability.
In the NTD Nanoscope experiments [2] , the molecular dynamics of a (single) captured non‐translocating transducer molecule provide a unique stochastic reference signal with stable statistics on the observed, single‐molecule blockaded channel current, somewhat analogous to a carrier signal in standard electrical engineering signal analysis. Discernible changes in blockade statistics, coupled with SSA signal processing protocols, enable the means for a highly detailed characterization of the interactions of the transducer molecule with binding targets (cognates) in the surrounding (extra‐channel) environment.