Chemical functionalization of solid-state nanopores and nanopore arrays and applications thereof
Chemical functionalization of solid-state nanopores and nanopore arrays and applications thereof. Nanopores are extremely sensitive single-molecule sensors. Recently, electron beams have been used to fabricate synthetic nanopores in thin solid-state membranes with sub-nanometer resolution. A new class of chemically modified nanopore sensors are provided with two approaches for monolayer coating of nanopores by: (1) self-assembly from solution, in which nanopores −10 nm diameter can be reproducibly coated, and (2) self-assembly under voltage-driven electrolyte flow, in which 5 nm nanopores may be coated. Applications of chemically modified nanopore are provided including: the detection of biopolymers such as DNA and RNA; immobilizing enzymes or other proteins for detection or for generating chemical gradients; and localized pH sensing.
1. A device comprising:
a solid-state membrane, the membrane having a nanometer-scale thickness, the membrane having an aperture with at least one surface that forms a nanopore open to two opposite sides of the membrane, wherein at least a portion of an analyte is capable of passing through the nanopore,
wherein an organic chemical coating comprising a self-assembled monolayer is disposed inside the walls of the nanopore, and
wherein the organic chemical coating modifies at least one surface characteristic of the nanopore without specific binding between the analyte and the nanopore wherein the at least one surface characteristic of the nanopore coating includes at least one of concavity, surface charge, polarity, pH sensitivity, hydrophobicity, and functionality, to control the rate of passage of the analyte through the nanopore.
2. The device of claim 1 , wherein the organic chemical coating disposed inside the walls of the nanopore on the surface of the aperture comprises a layer substantially conformal to the walls of the nanopore.
3. The device of claim 2 , wherein the organic chemical coating has a selected thickness and distribution.
4. The device of claim 3 , wherein the selected thickness of the organic chemical coating is less than or equal to approximately 2.5 nanometers.
5. The device of claim 1 , wherein the organic chemical coating comprises an epoxy, a methoxyethylene glycol, an amine, a carboxylic acid, or an aldehyde.
6. The device of claim 1 , wherein the organic chemical coating comprises a methoxyethelyne glycol-terminated silane monolayer.
7. The device of claim 6 , wherein the organic chemical coating comprises a reactive monolayer forming covalent bonds with the inside walls of the nanopore.
8. The device of claim 1 , wherein the organic chemical coating comprises a substantially uniform layer of chain molecules.
9. The device of claim 8 , wherein the organic chemical coating comprises a substantially uniform layer of chain molecules of organosilanes.
10. The device of claim 1 , wherein the membrane has a thickness of about 5 nanometers and about 100 nanometers.
11. The device of claim 1 , wherein the nanopore has a thickness from about 5 nanometers to about 20 nanometers.
12. The device of any one of claims 1 , 10 , and 11 , wherein the nanopore has a diameter of about 1 nanometer to about 10 nanometers.
13. The device of claim 1 , further comprising a protein or protein channel attached to the organic chemical coating.
14. The device of claim 13 , wherein the protein is an enzyme.
15. The device of claim 13 , wherein the protein channel is an alpha-hemolysin channel.
16. The device of claim 1 , wherein the analyte is a biopolymer.
17. The device of claim 16 , wherein the biopolymer is selected from the group consisting of single-stranded DNA, double-stranded DNA, and RNA.