Controlled tunnel gap device for sequencing polymers
The invention includes compositions, devices, and methods for analyzing a polymer and/or polymer unit. The polymer may be a homo or hetero-polymer such as DNA, RNA, a polysaccharide, or a peptide. The device includes electrodes that form a tunnel gap through which the polymer can pass. The electrodes are functionalized with a reagent attached thereto, and the reagent is capable of forming a transient bond to a polymer unit. When the transient bond forms between the reagent and the unit, a detectable signal is generated and used to analyze the polymer.
1. A device for analyzing a polymer, said device comprising
(a) a first and second electrode that form a tunnel gap through which said polymer can pass; and
(b) a first reagent attached to the first electrode and a second reagent attached to the second electrode wherein the first and second reagents are each capable of forming a transient bond to a unit of the polymer, wherein a detectable signal is produced when the transient bond forms,
the first and second reagent being independently selected from the group consisting of mercaptobenzoic acid, 4-mercaptobenzcarbamide, imidazole-2-carboxide, and 4-carbamonylphenyldithiocarbamate.
2. The device of claim 1 , wherein the reagent and a width of the tunnel gap are configured to produce a specific detectable signal for each monomer of the polymer when the first and second reagents form the transient bond to said unit of the polymer.
3. The device of claim 1 , wherein the first and/or second electrode comprises gold, carbon, platinum, graphene, or titanium nitride.
4. The device of claim 1 , wherein the detectable signal produced is caused by the binding of only one unit of the polymer in the tunnel gap.
5. The device of claim 1 , wherein the tunnel gap has a width of about 1 to about 4 nm.
6. The device of claim 1 , wherein the first and second reagent are the same.
7. The device of claim 1 , wherein the transient bond is a hydrogen bond.
8. The device of claim 1 , wherein the first and second reagents comprise at least one hydrogen bond donor and at least one hydrogen bond acceptor in an aqueous solution.
9. The device of claim 1 , wherein the polymer is DNA or RNA and the unit is a nucleotide.
10. The device of claim 1 , wherein the unit is selected from the group consisting of A, C, T, G, and m C.
11. The device of claim 1 , further comprising
c) a first fluid reservoir and a second fluid reservoir separated by at least one nanopore through which the polymer may flow.
12. The device of claim 11 , further comprising a first driving electrode and a second driving electrode to apply an electrophoretic bias between the first fluid reservoir and the second fluid reservoir.
13. The device of claim 1 wherein the first and second electrodes are carbon nanotubes.
14. The device of claim 1 , wherein the transient bond is pi-stacking between aromatic groups in the reader molecule and aromatic groups in the analyte.
15. A device for slowing the speed with which an electrophoretically-driven polymer passes through a nanopore consisting of reagents that are chemically bonded to the inside of the pore and that form transient bonds with units of the polymer as they pass through the pore, the reagents including a first reagent and a second reagent independently selected from the group consisting of mercaptobenzoic acid, 4-mercaptobenzcarbamide, imidazole-2-carboxide, and 4-carbamonylphenyldithiocarbamate.