Meta Logos Systems, LLC

The Nanopore Detector (ND)

A nanopore detector consists of a nanometer-scale channel that connects two chambers of electrolyte solution, allowing an electrochemical circuit to be completed as long as the (single) channel is not blocked. If the channel is blocked part-way by a nanometer-scale molecule (everything of interest), then one can obtain a highly sensitive channel current blockade signal of that molecule. The most common scenario is a channel signal that provides a multi-level channel current blockade due to translation of a polymeric molecule with nanometer-scale cross-section (e.g., ssDNA). that has variability along its length (e.g., the familiar encoding on the DNA in terms of a sequence of {A,C,G,T}). DNA sequencing can be done with a nanopore detector in other words (see Oxford Nanopore Technologies for further details).

The Nanopore Transduction Detector (NTD)

From a biophysics and electrical engineering signal analysis perspective, the optimal use of the single channel current blockade is not via translocation of molecules. Instead, the entire blockade dynamic range is utilized by seeking channel-capture modulators with large modulations, and the modulatory signal itself, provided by a ‘captured’ molecule in the channel, has an entirely different biophysical basis allowing incredibly higher pattern recognition capabilities. An example transduction molecule studied is a DNA hairpin molecule, that upon ‘capture’ by its dsDNA end (but too big to translocate) creates a modulatory signal. The signal is modulatory because the ‘captured’ DNA hairpin molecule has more than one capture state. The modulation in the levels of channel current blockade then correspond to the switching between these bound states with incredibly precise tracking on the transitions between those bound-states/blockades. This means that in the electrical signal domain we have the trivial task of extracting bound-state lifetime information and state-transition information, which provides an incredibly precise ‘fingerprint’ for the blockading molecule.. This provides the basis for a novel functionalization of the ND via introduction of bifunctional modulator molecules: one function to be captured by the channel at one end and provide a modulatory signal, and another function, at the non-captured end, to have a binding moiety for a target molecule of interest. The measurable effect of such binding on the channel modulation signal provides the basis for a very sensitive biosensor (for anything, according to the bifunctional molecule used).