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Machine translation
1. (WO2016210386) BIOMOLECULAR SENSORS AND METHODS
Note: Text based on automatic Optical Character Recognition processes. Please use the PDF version for legal matters

CLAIMS

What is claimed is:

1. A sensor comprising:

a first contact coupled to a first electrode;

a second contact coupled to a second electrode;

a sensor gap defined between one of the first contact and the first electrode and one of the second contact and the second electrode; and

a bridge molecule comprising a first end and a second end;

wherein the bridge molecule is a biopolymer bridge molecule; and

wherein the bridge molecule is coupled to the first contact at the first end and is coupled to the second contact at the second end.

2. A sensor comprising:

a first electrode overlying a substrate surface;

a second electrode overlying the substrate surface;

a sensor gap defined between the first electrode and the second electrode; and a bridge molecule comprising a first end and a second end;

wherein the sensor gap comprises a sensor gap dimension of between about 5 nm and about 30 nm; and

wherein the bridge molecule is coupled to the first contact at the first end and coupled to the second contact at the second end.

3. The sensor as in claims 1 or 2, wherein the first end comprises a first self-assembling anchor and the second end comprises a second self-assembling anchor.

4. The sensor of claim 2, wherein the bridge molecule comprises chemically synthesized bridge molecule.

5. The sensor of claim 2, wherein the bridge molecule comprises a biopolymer bridge molecule.

6. The sensor as in claims 1 or 2, wherein the bridge molecule comprises an end-to-end length configured to approximate the sensor gap dimension.

7. The sensor as in claims 1 or 4, wherein the biopolymer bridge molecule comprises a nucleic acid duplex.

8. The sensor of claim 7, wherein the nucleic acid duplex comprises one of a DNA

duplex, a DNA-RNA hybrid duplex, a DNA-PNA hybrid duplex, a PNA-PNA duplex, and a DNA-LNA hybrid duplex.

9. The sensor of claim 8, wherein the nucleic acid duplex further comprises an internal biotin-modified nucleotide.

10. The sensor as in any one of claims 1-9, wherein the bridge molecule is configured to self-assemble to the first contact and the second contact to produce a bridge molecule conformation when a fluid medium comprising the bridge molecule is contacted with one of the first contact and the second contact.

11. The sensor of any one of claims 1-10, further comprising a probe, wherein the probe is configured to attach to the bridge molecule by a self-assembling linker, and wherein the probe is configured to engage a single target molecule.

12. The sensor of claim 11, wherein the target molecule comprises a plurality of target molecules features, each target molecule feature having a discrete position, including a first target molecule feature at a first position, a second target molecule feature at a second position, and an nth target molecule feature at an nth position.

13. The sensor of claim 12, wherein the probe is an enzyme configured to engage the target molecule during a reaction in a solution comprising a plurality of different target molecules, wherein the reaction comprises a time period t, and wherein contacting the target molecule produces a plurality of conformation changes in the enzyme in response to the plurality of target molecule features, wherein each of the plurality of configuration changes modulates an electrical current in the sensor to produce a signal feature.

14. A method comprising:

providing a sensor according to any of claims 1-13;

contacting a nucleic acid template with a probe, wherein the probe is coupled to a bridge molecule comprising a portion of the sensor, and wherein the probe comprises a polymerase;

applying an electrical potential to the sensor;

providing a nucleotide base mix;

performing, by the polymerase, an incorporation event comprising incorporation of a nucleotide from the nucleotide base mix into a synthesized nucleic acid;

detecting a signal produced by the incorporation event.

15. The method of claim 14, further comprising a series of incorporation events

performed in a time period t, wherein the series of incorporation events produces a

signal trace comprising a sequence of signal features, each signal feature corresponding to one of the series of incorporation events.

16. The method of claim 15, wherein the method distinguishes a first signal feature produced in response to an unmodified template nucleotide and a second signal feature produced in response to a modified template nucleotide.

17. A method of manufacturing a biomolecular sensing device comprising:

forming a first electrode and a second electrode on a substrate surface, wherein the first electrode and the second electrode are separated by an electrode gap;

placing a first contact on the first electrode and a second contact on the second electrode, wherein the first contact and the second contact are separated by a contact gap; and

attaching a bridge molecule to the first contact and the second contact.

18. The method of claim 17, wherein attaching the bridge molecule to the first contact and the second contact comprises a self-assembly step.

19. The method of claim 17, wherein the electrode gap and the contact gap are between about 5 nm and about 30 nm.

20. The method of claim 17, further comprising fabricating an integrated circuit

electronically coupled to the first electrode and the second electrode,

21. The method of claim 20, wherein the integrated circuit, the first electrode, and the second electrode are fabricated using a CMOS fabrication method.

22. The method of claim 17, wherein the first and second contact are fabricated using a CMOS fabrication method.