Nano-scale bridge biosensors

1. A device, comprising:

an electrically-insulating substrate; and

a first detecting unit, comprising:

a source electrode disposed on said electrically-insulating substrate;

a drain electrode; and

a dielectric layer having a substantially uniform thickness and at least one exposed side;

wherein said dielectric layer is disposed between said source electrode and said drain electrode;

wherein said dielectric layer is contiguous with said drain electrode;

wherein said source electrode, said drain electrode and said dielectric layer are self aligned on said at least one exposed side of said dielectric layer;

a first self-assembling monolayer attached to and in contact with said at least one exposed side of said dielectric layer;

a second self-assembling monolayer attached to and in contact with said source electrode and said drain electrode;

wherein said second self-assembling monolayer has a polarity different than the polarity of said first self-assembling monolayer; and

at least one capture unit, comprising:

a nanoparticle; and

a plurality of first single-stranded oligonucleotides attached to said nanoparticle;

wherein said first single-stranded oligonucleotides have a first nucleotide sequence complementary to a portion of a first oligonucleotide target; and

wherein said capture unit is located on said exposed side of said dielectric layer and is substantially centered between said source electrode and said drain electrode.

2. A device of claim 1 , further comprising:

a plurality of second detecting units, each second detecting unit comprising:

a source electrode disposed on said electrically-insulating substrate;

a drain electrode; and

a dielectric layer having a substantially uniform thickness and at least one exposed side;

wherein said dielectric layer is disposed between said source electrode and said drain electrode;

wherein said dielectric layer is contiguous with said drain electrode;

wherein said source electrode, said drain electrode and said dielectric layer are self aligned on said at least one exposed side of said dielectric layer;

a first self-assembling monolayer attached to and in contact with said at least one exposed side of said dielectric layer;

a second self-assembling monolayer attached to and in contact with said source electrode and said drain electrode;

wherein said second self-assembling monolayer has a polarity different than the polarity of said first self-assembling monolayer; and

at least one capture unit, comprising:

a nanoparticle; and

a plurality of at least one second single-stranded oligonucleotides attached to said nanoparticle;

wherein said at least one second single-stranded oligonucleotides have a second nucleotide sequence complementary to a portion of a second oligonucleotide target;

wherein said capture unit is located on said exposed side of said dielectric layer and is substantially centered between said source electrode and said drain electrode;

wherein said second nucleotide sequences are the same or different from said first nucleotides sequences in said first detecting unit; and

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

3. A device of claim 1 ,

wherein said nanoparticle is a metal, semiconductor, or magnetic colloidal particle.

4. A device of claim 1 ,

wherein said electrically-insulating substrate is silicon, silicon dioxide, or a combination thereof.

5. A device of claim 4 ,

wherein said electrically-insulating substrate comprises more than one layer.

6. A device of claim 1 ,

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

7. A device of claim 1 , further comprising:

a plurality of microfluidic channels; and

an optional cover.

8. A device of claim 1 ,

wherein said source electrode, said drain electrode and said dielectric layer are self aligned on said at least one exposed side of said dielectric layer in a vertical dimension.

9. A device, comprising:

an electrically-insulating substrate; and

a first detecting unit, comprising:

a source electrode disposed on said electrically-insulating substrate;

a drain electrode; and

a dielectric layer having a substantially uniform thickness and at least one exposed side;

wherein said dielectric layer is disposed between said source electrode and said drain electrode;

wherein said source electrode, said drain electrode and said dielectric layer are in the same plane;

a first self-assembling monolayer attached to and in contact with said dielectric layer;

a second self-assembling monolayer attached to and in contact with said source electrode and said drain electrode;

wherein said second self-assembling monolayer has a polarity different than the polarity of said first self-assembling monolayer; and

at least one capture unit, comprising:

a nanoparticle; and

a plurality of first single-stranded oligonucleotides attached to said nanoparticle;

wherein said first single-stranded oligonucleotides have a first nucleotide sequence complementary to a portion of a first oligonucleotide target; and

wherein said capture unit is located on said dielectric layer and is substantially centered between said source electrode and said drain electrode.

10. A system, comprising:

a device of claim 1 ; and

a plurality of nanoparticle reporter conjugates;

wherein said nanoparticle reporter conjugates comprise at least one nanoparticle and a single-stranded oligonucleotide complementary to at least a portion of said first oligonucleotide target different than said portion complementary to said first nucleotide sequence; and

wherein said nanoparticle is a metal, semiconductor, or magnetic colloidal particle.

11. A system, comprising:

a device of claim 2 ; and

a plurality of first nanoparticle reporter conjugates; and

a plurality of at least one second nanoparticle reporter conjugates;

wherein said first nanoparticle reporter conjugates comprise at least one nanoparticle and a single-stranded oligonucleotide complementary to at least a portion of said first oligonucleotide target different than said portion complementary to said first nucleotide sequence;

wherein said nanoparticle in said first nanoparticle reporter conjugate is a metal, semiconductor, or magnetic colloidal particle;

wherein said at least one second nanoparticle reporter conjugates comprise at least one nanoparticle and a single-stranded oligonucleotide complementary to at least a portion of said at least one second oligonucleotide target different than said portion complementary to said at least one second nucleotide sequence;

wherein said nanoparticle in said at least one second nanoparticle reporter conjugate is a metal, semiconductor, or magnetic colloidal particle;

wherein said second nanoparticle reporter conjugates are the same or different from said first nanoparticle reporter conjugates; and

wherein said second nanoparticle reporter conjugates are the same or different from said other second nanoparticle reporter conjugates.

12. A system of claim 10 , further comprising:

an electrical reading device for interrogating said device.

13. A system of claim 12 ,

wherein said electrical reading device is portable.

14. A method for detecting nucleic acid hybridization, comprising:

providing a device of claim 1 ;

passivating said first self-assembling monolayer;

providing a solution comprising at least one buffer and single-stranded oligonucleotide target under hybridizing conditions;

wherein said single-stranded oligonucleotide target hybridizes a portion of said first nucleotide sequence thereby leaving an unhybridized portion of said single-stranded oligonucleotide target;

providing a plurality of first nanoparticle reporter conjugates under hybridizing conditions;

wherein said first nanoparticle reporter conjugates comprise at least one nanoparticle and an oligonucleotide complementary to said unhybridized portion of said single-stranded oligonucleotide target;

wherein said nanoparticle in said first nanoparticle reporter conjugate is a metal, semiconductor, or magnetic colloidal particle;

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 perfect complementarity of said oligonucleotide target to said first oligonucleotide sequence.

15. A method of claim 14 ,

wherein said measuring step measures an increase in conductivity across said electrodes at known locations to determine perfect complementarity of said oligonucleotide target to said first oligonucleotide sequence.

16. A method of claim 14 ,

wherein said single-stranded oligonucleotide target is prepared by heating a solution comprising double-stranded oligonucleotide target.

17. A method of claim 14 , further comprising:

washing to remove unhybridized components from said detecting unit.

18. A method of claim 14 , further comprising:

heating a solution comprising double stranded oligonucleotide target to form said solution comprising single-stranded oligonucleotide target.

19. A method for detecting nucleic acid hybridization, comprising:

providing a device of claim 2 ;

passivating said first self-assembling monolayer;

providing a solution comprising at least one buffer and single-stranded oligonucleotide target under hybridizing conditions;

wherein said single-stranded oligonucleotide target hybridizes a portion of said at least one second nucleotide sequence thereby leaving an unhybridized portion of said single-stranded oligonucleotide target;

providing a plurality of at least one second nanoparticle reporter conjugates under hybridizing conditions;

wherein said second nanoparticle reporter conjugates comprise at least one nanoparticle and an oligonucleotide complementary to said unhybridized portion of said single-stranded oligonucleotide target;

wherein said nanoparticle in said second nanoparticle reporter conjugate is a metal, semiconductor, or magnetic colloidal particle;

wherein said second nanoparticle reporter conjugates are the same or different from said first nanoparticle reporter conjugates;

wherein said second nanoparticle reporter conjugates are the same or different from said other second nanoparticle reporter conjugates;

wherein said measuring step is carried out in parallel or sequentially for said first detecting unit and said plurality of said additional detecting units.

20. A process for preparing a nano-scale bridging biosensor, comprising:

forming a device, comprising:

an electrically-insulating substrate; and

a first detecting unit, comprising:

a source electrode disposed on said electrically-insulating substrate;

a drain electrode; and

a dielectric layer having a substantially uniform thickness and at least one exposed side;

a first self-assembling monolayer attached to and in contact with said at least one exposed side of said dielectric layer;

a second self-assembling monolayer attached to and in contact with said source electrode and said drain electrode;

wherein said second self-assembling monolayer has a polarity different than the polarity of said first self-assembling monolayer;

wherein said dielectric layer is disposed between said source electrode and said drain electrode;

wherein said dielectric layer is contiguous with said drain electrode; and

wherein said source electrode, said drain electrode and said dielectric layer are self aligned on said at least one exposed side of said dielectric layer;

providing on said exposed side of said dielectric layer and substantially centered between said source electrode and said drain electrode at least one capture unit, said capture unit comprising:

a nanoparticle; and

a plurality of first single-stranded oligonucleotides attached to said nanoparticle; and

wherein said first single-stranded oligonucleotides have a first nucleotide sequence complementary to a portion of a first oligonucleotide target; and

passivating said first self-assembling monolayer.

21. A process of claim 20 ,

wherein said first single-stranded oligonucleotides are attached to said nanoparticle prior to attachment of said capture unit to said exposed side of said dielectric layer.

22. A process of claim 20 ,

wherein said first single-stranded oligonucleotides are attached to said nanoparticle subsequent to attachment of said capture unit to said exposed side of said dielectric layer.

23. A process of claim 20 ,

wherein said self-assembling monolayer is passivated.

24. A device, comprising:

an electrically-insulating substrate; and

a first detecting unit, comprising:

a source electrode disposed on said electrically-insulating substrate;

a drain electrode; and

a dielectric layer having a substantially uniform thickness and at least one exposed side;

wherein said dielectric layer is disposed between said source electrode and said drain electrode;

wherein said dielectric layer is contiguous with said drain electrode;

wherein said source electrode, said drain electrode and said dielectric layer are self aligned on said at least one exposed side of said dielectric layer;

a first self-assembling monolayer attached to and in contact with said at least one exposed side of said dielectric layer;

a second self-assembling monolayer attached to and in contact with said source electrode and said drain electrode;

wherein said second self-assembling monolayer has a polarity different than the polarity of said first self-assembling monolayer; and

at least one capture unit, comprising:

a nanoparticle; and

a plurality of first antibodies attached to said nanoparticle;

wherein said first antibody have affinity to a portion of a first polypeptide target; and

wherein said capture unit is located on said exposed side of said dielectric layer and is substantially centered between said source electrode and said drain electrode.

25. A method of detecting protein-antibody interaction, comprising:

providing a device of claim 24 ;

passivating said first self-assembling monolayer;

providing a solution comprising at least one buffer and polypeptide target under binding conditions;

wherein a portion of said polypeptide target binds said first antibody;

providing a plurality of first nanoparticle reporter conjugates under hybridizing conditions;

wherein said first nanoparticle reporter conjugates comprise at least one nanoparticle and a second antibody capable of binding the unbound portion of said polypeptide target;

wherein said nanoparticle in said first nanoparticle reporter conjugate is a metal, semiconductor, or magnetic colloidal particle;

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 perfect binding of said polypeptide target to said first antibody.