Single Nucleotide Polymorphism Detection via Cheminformatics Analysis of Nanopore-Blockades Engineered for Event Transduction.

The nanopore transduction detector is a unique platform for detection and analysis of single molecules. Proof-of-Concept experiments indicate a promising approach to single nucleotide polymorphism (SNP) detection in a clinical environment, via use of the channelblockade signals produced by engineered eventtransducers. The transducer molecule is a bi-functional molecule; one end is captured in the nanopore channel while the other end is outside the channel. This extrachannel end is engineered to bond to a specific target: the analyte being measured. When the outside portion is bound to the target, the molecular changes (conformational and charge) and environmental changes (current flow obstruction geometry and electro-osmotic flow) result in a change in the channel-binding kinetics of the portion that is captured in the channel. This change of kinetics generates a change in the channel blockade current which is engineered to have a signal unique to the target molecule; the transducer molecule is, thus, a bi-functional molecule which is engineered to produce a unique signal change upon binding to its cognate. This provides the basis for a highly sensitive and accurate biosensor.