Nanopore based sequencer
View Patent ↗The present invention is directed to systems, devices and methods for identifying biopolymers, such as strands of DNA, as they pass through a constriction such as a carbon nanotube nanopore. More particularly, the invention is directed to such systems, devices and methods in which a newly translocated portion of the biopolymer forms a temporary electrical circuit between the nanotube nanopore and a second electrode, which may also be a nanotube. Further, the invention is directed to such systems, devices and methods in which the constriction is provided with a functionalized unit which, together with a newly translocated portion of the biopolymer, forms a temporary electrical circuit that can be used to characterize that portion of the biopolymer.
1. A method of sequencing a target molecule, the method comprising:
providing an apparatus including:
a substrate;
a first electrode passing through at least a portion of the substrate, the first electrode including a nanopore and configured to permit the translocation of a target molecule therethrough, the first electrode including a first recognition element connected to an end thereof;
a second electrode supported by the substrate and disposed in a fixed relationship with respect to said first electrode, the second electrode forming a first gap with the first electrode, the second electrode including a second recognition element connected to an end thereof; and
an electrical circuit configured to detect, upon passage of the target molecule past said gap, an electrical current between the first electrode and the second electrode; and
a first chamber and a second chamber, the first chamber being located on a first side of the device and the second chamber being located on a second side of the device;
introducing a target molecule into the second chamber;
electrophoresing the target molecule so that it translocates through the nanopore; and
detecting an electrical current passing through the first electrode, the first recognition element, the target molecule, the second recognition element, and the second electrode.
2. The method of claim 1 , wherein the first and second recognition elements are the same.
3. The method of claim 1 , each of the first recognition element and the second recognition element configured to recognize a plurality of target molecules, the first recognition element and the second recognition element further configured to form a set of hydrogen bonds with each target molecule.
4. The method of claim 1 , wherein at least one of the first recognition element and the second recognition element includes thiobenzoic acid.
5. The method of claim 1 , wherein the target molecule is a DNA molecule.
6. The method of claim 1 , the detecting the electrical current including detecting switching between two levels of the electrical current.
7. The method of claim 1 , further comprising identifying, based on the electrical current, the target molecule.
8. The method of claim 1 , further comprising identifying, based on the time-varying magnitude of the electrical current, the target molecule.
9. The method of claim 1 , wherein at least one of the first recognition element and the second recognition element includes 4-(mercaptomethyl)-1H-imidazole-2-carboxamide.
10. The method of claim 1 , wherein at least one of the first recognition element and the second recognition element includes 5-(2-aminoethyl)-1H-imidazole-2-carboxamide.
11. The method of claim 1 , wherein the universal base reader includes thiobenzoic acid.