Nano-scale biosensors

1. A device, comprising:

a thermally responsive, electrically insulating substrate;

at least one heating element; and

a first detecting unit, comprising:

a first electrode and a second electrode separated by a nanogap; and

a plurality of first aptamer probes attached to said substrate in said nanogap.

2. A device of claim 1 ,

wherein said first aptamer probes are single-stranded or double-stranded nucleic acids and have the same nucleic acid sequence.

3. A device of claim 1 ,

wherein each of said first aptamer probes comprises:

a first nucleic acid portion in a hairpin loop formation;

wherein said first nucleic acid portion comprise a spacer, a loop, and a stem region, said stem region being double-stranded; and

a second nucleic acid portion in a linear formation;

wherein said second nucleic acid portion is single stranded and is attached to said substrate; and

wherein said second nucleic acid portion is complementary to at least a portion of said spacer in said first nucleic acid portion; and

wherein each of said first aptamer probes has the same nucleic acid sequence.

4. A device of claim 1 ,

wherein said plurality of first aptamer probes form a self-assembled monolayer.

5. A device of claim 1 ,

wherein said thermally responsive, electrically insulating substrate is silicon, silicon dioxide, polydimethylsiloxane, or a combination thereof.

6. A device of claim 1 ,

wherein said thermally responsive, electrically insulating substrate is nano-textured.

7. A device of claim 1 , further comprising:

a plurality of additional heating elements capable of forming a temperature gradient.

8. A device of claim 1 ,

wherein said heating element is embedded in said substrate.

9. A device of claim 1 ,

wherein said heating element comprises gold.

10. A device of claim 1 ,

wherein said first detecting unit is located on the surface of said substrate.

11. A device of claim 1 ,

wherein said first and second electrodes comprise a metal selected from the group consisting of gold, silver, titanium, copper, or a combination thereof.

12. A device of claim 1 ,

wherein said nanogap is formed by focused ion beam scratching followed by electromigration.

13. A device of claim 1 ,

wherein said nanogap is about 10 nm to about 500 nm.

14. A device of claim 1 ,

wherein said first aptamer probes are covalently attached to said substrate.

15. A device of claim 1 , further comprising:

a plurality of second detecting units, comprising:

a first electrode and a second electrode separated by a nanogap; and

a plurality of second aptamer probes attached to said substrate in said nanogap.

16. A device of claim 15 ,

wherein said second aptamer probes are double-stranded nucleic acids and have the same nucleic acid sequence;

wherein said second aptamer probes are the same or different from said first aptamer probes in said first detecting unit; and

wherein said second aptamer probes are the same or different from other second aptamer probes in said plurality of second detecting units.

17. A device of claim 15 ,

wherein each of said second aptamer probes comprises:

a first nucleic acid portion in a hairpin loop formation;

wherein said first nucleic acid portion comprise a spacer, a loop, and a stem region, said stem region being double-stranded; and

a second nucleic acid portion in a linear formation;

wherein said second nucleic acid portion is single stranded and is attached to said substrate; and

wherein said second nucleic acid portion is complementary to at least a portion of said spacer in said first nucleic acid portion; and

wherein said second aptamer probes are the same or different from said first aptamer probes in said first detecting unit; and

wherein said second aptamer probes are the same or different from other second aptamer probes in said plurality of second detecting units.

18. A device of claim 1 , further comprising:

a plurality of microfluidic channels; and

an optional cover.

19. A device of claim 1 ,

wherein said at least one heating element is located in a first layer; and

wherein said first electrode and said second electrodes are located in a second layer.

20. A system, comprising:

a device of claim 1 ; and

an electrical reading device for interrogating said device;

wherein said electrical reading device is optionally portable.

21. A method for detecting hybridization of a target, comprising:

providing a device, comprising:

a thermally responsive, electrically insulating substrate;

at least one heating element; and

a first detecting unit, comprising:

a first electrode and a second electrode separated by a nanogap; and

a plurality of first aptamer probes attached to said substrate in said nanogap;

providing a solution comprising said target under hybridizing conditions;

wherein said target is a protein or a cell; and

wherein said target hybridizes at least some of said first aptamer probes;

applying a voltage drop across said electrodes; and

measuring a change in conductivity, resistivity, capacitance, or impedance across said electrodes at known locations to determine specific binding of said target to said first aptamer probes.

22. A method of claim 21 ,

wherein said target is a protein target;

wherein said protein target is optionally tagged with a nanoparticle selected from the group consisting of a metal, semiconductor, magnetic colloidal particle, or a combination thereof; and

wherein said first aptamer probes are double-stranded nucleic acids and have the same nucleic acid sequence.

23. A method of claim 21 ,

wherein said target is a cell target; and

wherein each of said first aptamer probes comprises:

a first nucleic acid portion in a hairpin loop formation;

wherein said first nucleic acid portion comprise a spacer, a loop, and a stem region, said stem region being double-stranded; and

a second nucleic acid portion in a linear formation;

wherein said second nucleic acid portion is single stranded and is attached to said substrate; and

wherein said second nucleic acid portion is complementary to at least a portion of said spacer in said first nucleic acid portion; and

wherein each of said first aptamer probes has the same nucleic acid sequence.

24. A method of claim 21 , further comprising:

washing to remove unhybridized components from said detecting unit.

25. A method of claim 21 , further comprising:

heating said device to remove said hybridized targets from said aptamer probe to permit recycling of said detecting unit.

26. A method of claim 21 , further comprising:

forming a temperature gradient to focus said target at said detecting unit.

27. A method of claim 21 , further comprising:

reversing the polarity of said voltage drop to remove unbound components or nonspecifically bound components from said detecting unit.