Electrochemical detection of single molecules using abiotic nanopores having electrically tunable dimensions

Abstract

A barrier structure for use in an electrochemical stochastic membrane sensor for single molecule detection. The sensor is based upon inorganic nanopores having electrically tunable dimensions. The inorganic nanopores are formed from inorganic materials and an electrically conductive polymer. Methods of making the barrier structure and sensing single molecules using the barrier structure are also described.

The invention claimed is: 
     
       1. A barrier structure, the barrier structure comprising:
 a. a first chamber;   b. a second chamber;   c. a barrier separating the first chamber and the second chamber, wherein the barrier comprises at least one electroactive nanopore structure joining the first chamber and the second chamber, wherein the at least one electroactive nanopore structure comprises:
 i. a wall defining a electroactive nanopore connecting the first chamber and the second chamber and having an electrically tunable diameter; 
 ii. a first electrode pair disposed in the wall, wherein electrodes of the first electrode pair are disposed at opposite ends of the electroactive nanopore, and wherein a first voltage across the first electrode pair attracts a plurality molecules to the electroactive nanopore and drives the plurality of molecules through the electroactive nanopore; and 
 iii. a second electrode pair disposed in the wall between the first electrode pair; and 
 iv. a conductive polymer disposed over an electrode of the second electrode pair, wherein the conductive polymer is responsive to a second voltage across the second electrode pair and is capable of expansion or contraction in response to the second voltage, and wherein the expansion decreases the electrically tunable diameter and the contraction increases the electrically tunable diameter; and 
   d. at least one power supply electrically coupled to the first electrode pair and the second electrode pair, wherein the at least one power supply provides the first voltage across the first electrode pair and the second voltage across the second electrode pair.   
     
     
       2. The barrier structure according to  claim 1 , further including a current measuring device for measuring a current flowing between the first electrode pair, wherein the current corresponds to a predetermined molecular species. 
     
     
       3. The barrier structure according to  claim 2 , wherein the barrier structure forms a portion of a sensor. 
     
     
       4. The barrier structure according to  claim 1 , wherein each of the electrodes of the first electrode pair and the second electrode pair comprises one of platinum, gold, graphite, a metal alloy, and combinations thereof. 
     
     
       5. The barrier structure according to  claim 1 , wherein the first electrode pair and the second electrode pair are separated by an insulating material. 
     
     
       6. The barrier structure according to  claim 1 , wherein the insulating material comprises at least one of a glass, a metal oxide, a non-conductive polymer, and combinations thereof. 
     
     
       7. The barrier structure according to  claim 1 , wherein the conductive polymer is one of polypyrrole, polyaniline, and combinations thereof. 
     
     
       8. The barrier structure according to  claim 1 , wherein the barrier structure forms a portion of one of a valve structure and a membrane structure. 
     
     
       9. The barrier structure according to  claim 1 , wherein the at least one power supply includes a DC power supply. 
     
     
       10. An electroactive nanopore structure, the electroactive nanopore structure comprising:
 a. a wall defining a electroactive nanopore having a first open end and a second open end and having a electrically tunable diameter;   b. a first electrode pair disposed in the wall, wherein electrodes of the first electrode pair are disposed at opposite ends of the electroactive nanopore, and wherein a first voltage across the first electrode pair attracts a plurality molecules to the electroactive nanopore and drives the plurality of molecules through the electroactive nanopore; and   c. a second electrode pair disposed in the wall between the first electrode pair; and   d. a conductive polymer disposed over an electrode of the second electrode pair, wherein the conductive polymer is responsive to a second voltage across the second electrode pair and is capable of expansion or contraction in response to the second voltage, and wherein the expansion decreases the electrically tunable diameter and the contraction increases the electrically tunable diameter.   
     
     
       11. The electroactive nanopore according to  claim 10 , wherein each of the electrodes of the first electrode pair and the second electrode pair comprises one of platinum, gold, graphite, a metal alloy, and combinations thereof. 
     
     
       12. The electroactive nanopore structure according to  claim 10 , wherein the first electrode pair and the second electrode pair are separated by an insulating material. 
     
     
       13. The electroactive nanopore structure according to  claim 10 , wherein the insulating material comprises a glass, a metal oxide, a non-conductive polymer, and combinations thereof. 
     
     
       14. The electroactive nanopore structure according to  claim 10 , wherein the conductive polymer is one of polypyrrole, polyaniline, and combinations thereof. 
     
     
       15. The electroactive nanopore structure according to  claim 10 , wherein the electroactive nanopore structure forms a portion of one of a valve structure, a sensor, and a membrane structure. 
     
     
       16. A stochastic sensor structure, the stochastic sensor structure comprising:
 a. a first chamber;   b. a second chamber;   c. a barrier separating the first chamber and the second chamber, wherein the barrier comprises at least one electroactive nanopore structure joining the first chamber and the second chamber, wherein the at least one electroactive nanopore structure comprises:
 i. a wall defining a electroactive nanopore connecting the first chamber and the second chamber and having a electrically tunable diameter; 
 ii. a first electrode pair disposed in the wall, wherein electrodes of the first electrode pair are disposed at opposite ends of the electroactive nanopore, and wherein a first voltage across the first electrode pair attracts a plurality molecules to the electroactive nanopore and drives the plurality of molecules through the electroactive nanopore; and 
 iii. a second electrode pair disposed in the wall between the first electrode pair; and 
 iv. a conductive polymer disposed over an electrode of the second electrode pair, wherein the conductive polymer is responsive to a second voltage across the second electrode pair and is capable of expansion or contraction in response to the second voltage, and wherein the expansion decreases the electrically tunable diameter and the contraction increases the electrically tunable diameter; 
   d. at least one power supply electrically coupled to the first electrode pair and the second electrode pair, wherein the at least one power supply provides the first voltage across the first electrode pair and the second voltage across the second electrode pair; and   e. a current measuring device for measuring a current flowing between the first electrode pair, wherein the current corresponds to a predetermined molecular species.   
     
     
       17. A method of making a electroactive nanopore structure, wherein the electroactive nanopore structure comprises: a wall defining a electroactive nanopore having a first open end and a second open end and having a electrically tunable diameter; a first electrode pair having electrodes disposed at opposite ends of the electroactive nanopore; a second electrode pair comprising a second anode and a second cathode disposed in the wall between the first electrode pair; and a conductive polymer disposed over an electrode of the second electrode pair; the method comprising the steps of:
 a. providing a template comprising a strip of photocurable polymer;   b. depositing alternating layers of conductive material and insulating material over the template, wherein the alternating layers form the first electrode pair and the second electrode pair, and wherein electrodes of the first electrode pair and the second electrode pair are separated by at least one layer of insulating material;   c. removing the template to form the electroactive nanopore; and   d. depositing the conductive polymer on the electrode of the second electrode pair to form the electrically tunable diameter.   
     
     
       18. The method according to  claim 17 , wherein the step of depositing alternating layers of conductive material and insulating material over the template comprises:
 a. depositing a first conductive layer over the template;   b. depositing a first insulating layer over the first conductive layer;   c. depositing a second conductive layer over the first insulating layer;   d. depositing a second insulating layer over the second conductive layer;   e. depositing a third conductive layer over the second conductive layer, wherein the second conductive layer and the third conductive layer form the second electrode pair;   f. depositing a third insulating layer over the third conductive layer; and   g. depositing a fourth conductive layer over the third conductive layer, wherein the first conductive layer and the fourth conductive layer form the first electrode pair.   
     
     
       19. The method according to  claim 17 , wherein at least one of the first conductive layer, the first insulating layer, the second conductive layer, the second insulating layer, the third conductive layer, the third insulating layer, and the fourth conductive layer is deposited by energetic neutral beam lithography/epitaxy. 
     
     
       20. The method according to  claim 17 , wherein the step of depositing the conductive polymer comprises electrochemically depositing the conductive polymer onto at least one of the second anode and the second cathode. 
     
     
       21. The method according to  claim 17 , wherein the template further comprises a cylinder having a diameter that is substantially equal to the electrically tunable diameter of the electroactive nanopore, wherein the cylinder comprises the photcurable polymer. 
     
     
       22. The method according to  claim 17 , wherein the step of removing the template to form the electroactive nanopore comprises drilling through the alternating layers of conductive material and insulating material with a focused ion beam to form the electroactive nanopore. 
     
     
       23. A method of sensing the presence of an analyte molecule, the method comprising the steps of:
 a. providing a sensor structure, the sensor structure comprising a sampling chamber, a collection chamber, and a separation structure separating the sampling chamber and the collection chamber, wherein the separation structure includes a electroactive nanopore structure comprising: a wall defining a electroactive nanopore connecting the sampling chamber and the collection chamber and having a electrically tunable diameter; a first electrode pair having electrodes disposed at opposite ends of the electroactive nanopore; a second electrode pair disposed in the wall between the first electrode pair; and a conductive polymer disposed over an electrode of the second electrode pair;   b. providing the analyte molecule to the sampling chamber;   c. passing the analyte molecule from the sampling chamber into the electroactive nanopore; and   d. measuring a current across the first electrode pair, wherein the current is indicative of the presence of the analyte molecule.   
     
     
       24. The method according to  claim 23 , wherein the step of passing the analyte from the sampling chamber into the electroactive nanopore comprises applying a first voltage across the first electrode pair, wherein the first voltage is sufficient to cause the analyte to migrate from the sampling chamber through the electroactive nanopore structure to the collection chamber. 
     
     
       25. The method according to  claim 23 , further including the step of increasing or decreasing the electrically tunable diameter of the electroactive nanopore. 
     
     
       26. The method according to  claim 23 , wherein the step of increasing or decreasing the electrically tunable diameter of the electroactive nanopore comprises applying a second voltage across the second electrode pair, wherein the second electrode voltage causes the conductive polymer to either expand or contract. 
     
     
       27. A method of controlling flow of a fluid between a first chamber and a second chamber, the method comprising:
 a. providing a barrier structure, wherein the barrier structure includes at least one electroactive nanopore structure, wherein the at least one electroactive nanopore structure comprises: a wall defining a electroactive nanopore connecting the first chamber and the second chamber and having a electrically tunable diameter; a first electrode pair disposed in the wall and having electrodes disposed at opposite ends of the electroactive nanopore; a second electrode pair disposed in the wall between the first electrode pair; and a conductive polymer disposed over an electrode of the second electrode pair;   b. providing the fluid to the first chamber;   c. passing the fluid from the first chamber into the electroactive nanopore; and   d. increasing or decreasing the electrically tunable diameter of the electroactive nanopore to control the flow of the fluid through the electroactive nanopore to the second chamber.   
     
     
       28. The method according to  claim 27 , wherein passing the fluid from the first chamber into the electroactive nanopore comprises applying a first voltage across the first electrode pair, wherein the first voltage is sufficient to cause the fluid to migrate from the first chamber through the electroactive nanopore structure to the second chamber. 
     
     
       29. The method according to  claim 27 , wherein the step of increasing or decreasing the electrically tunable diameter of the electroactive nanopore comprises applying a second voltage across the second electrode pair, wherein the second electrode voltage causes the conductive polymer to either expand or contract, and wherein expansion of the conductive polymer increases the electrically tunable diameter and contraction of the conductive polymer decreases the electrically tunable diameter. 
     
     
       30. A nanopore structure comprising
 a nanopore having an opening and a wall defining the nanopore, wherein the opening has an electrically tunable diameter,   a first electrode pair disposed in the wall,   a second electrode pair disposed in the wall between the first electrode pair,   a polymer disposed over an electrode of the second electrode pair, wherein the opening is an opening through the polymer,   wherein each of the electrodes of the first electrode pair and the second electrode pair comprises one of platinum, gold, graphite, a metal alloy, and combinations thereof.   
     
     
       31. A nanopore structure comprising
 a nanopore having an opening and a wall defining the nanopore, wherein the opening has an electrically tunable diameter,   a first electrode pair disposed in the wall,   a second electrode pair disposed in the wall between the first electrode pair,   a polymer disposed over an electrode of the second electrode pair, wherein the opening is an opening through the polymer,   wherein the polymer comprises a conductive polymer.   
     
     
       32. The nanopore structure of claim 31, wherein the conductive polymer is one of polypyrrole, polyaniline, and combinations thereof. 
     
     
       33. A nanopore structure comprising
 a nanopore having an opening and a wall defining the nanopore, wherein the opening has an electrically tunable diameter,   a first electrode pair disposed in the wall,   a second electrode pair disposed in the wall between the first electrode pair,   a polymer disposed over an electrode of the second electrode pair, wherein the opening is an opening through the polymer,   wherein the first electrode pair and the second electrode pair are separated by an insulating material.   
     
     
       34. The nanopore structure of claim 33, wherein the insulating material comprises at least one of a glass, a metal oxide, a non-conductive polymer, and combinations thereof. 
     
     
       35. The nanopore structure of claim 31, wherein the conductive polymer is capable of expansion or contraction in response to a voltage. 
     
     
       36. The nanopore structure of claim 31, wherein the conductive polymer is responsive to a voltage across the second electrode pair. 
     
     
       37. The nanopore structure of claim 35, wherein the expansion decreases the electrically tunable diameter and the contraction increases the electrically tunable diameter. 
     
     
       38. A nanopore structure comprising
 a nanopore having an opening and a wall defining the nanopore, wherein the opening has an electrically tunable diameter,   a first electrode pair disposed in the wall,   a second electrode pair disposed in the wall between the first electrode pair,   a polymer disposed over an electrode of the second electrode pair, wherein the opening is an opening through the polymer,   wherein the polymer is configured to change at least one dimension in response to an electrical stimulus.