Methods and device for biomolecule characterization

• US 7,744,816 B2
• Filed: 05/01/2002
• Issued: 06/29/2010
• Est. Priority Date: 05/01/2002
• Status: Expired due to Fees

• Current Assignee: Intel Corporation
• Original Assignee: Intel Corporation
• Inventors: Su, Xing, Berlin, Andrew A.
• Primary Examiner(s): ALEXANDER, LYLE
• Application Number:
  US10/138,157
• Publication Number:
  US 20030207326A1
• Time in Patent Office: 2,981 Days
• Field of Search: 422/58, 422/61, 422/99, 422/102, 422/104, 422/68.1, 422/82.01, 422/82.11, 436/164, 436/166, 436/149
• US Class Current: 422/68.1
• CPC Class Codes: C12Q 2563/179 the label being a nucleic acid
• CPC Class Codes: C12Q 2565/631 being a biochannel or pore
• CPC Class Codes: G01N 33/48721 Investigating individual macromolecules, e.g. by translocation through nanopores Coulter counters in general G01N15/12; fabrication methods for nanoscale apertures B81B1/00; sequencing of nucleic acids C12Q1/68
• CPC Class Codes: G01N 33/6803 General methods of protein analysis not limited to specific proteins or families of proteins

Abstract

The methods and apparatus 100, disclosed herein are of use for sequencing 150 and/or identifying 160 proteins 230, 310, polypeptides 230, 310 or peptides 230, 310. Proteins 230, 310 containing labeled amino acid residues may be synthesized and passed through nanopores 255, 330. A detector 257, 345 operably coupled to a nanopore 255, 330 may detect labeled amino acid residues as they pass through the nanopore 255, 330. Distance maps 140 for each type of labeled amino acid residue may be compiled. The distance maps 140 may be used to sequence 150 and/or identify 160 the protein 230, 310. In different embodiments of the invention, amino acid residues labeled with luminescent labels 235, 245 or nanoparticles 315 may be detected using photodetectors 257 or electrical detectors 345. Apparatus 100 of use for protein 230, 310 sequencing 150 and/or identification 160 are also disclosed herein.

Claims

1. An apparatus comprising:

a) at least one sub-device, each sub-device comprising a first chamber and a second chamber, said first and second chambers separated by sensor layers comprising a semiconductor material and having one or more nanopores therein, the first and second chambers of each sub-device in fluid communication through said one or more nanopores, wherein said nanopores are between 1 and 999 nm in diameter; and

b) one or more detectors comprising said sensor layers and configured to detect one or more analytes in the nanopores passing from said first chamber to said second chamber.

2. The apparatus of claim 1, further comprising an electrode in each first and second chambers, said electrodes operably coupled to a voltage regulator.

3. The apparatus of claim 1, further comprising a computer operably coupled to the one or more detectors.

4. The apparatus of claim 1, wherein the one or more detectors further comprise a photodetector, an electrical detector and/or a voltage detector.

5. The apparatus of claim 1, wherein said sensor layers comprise a support layer, a photon sensing layer and a light opaque layer.

6. The apparatus of claim 5, wherein said photon sensing layer is operably coupled to one or more photodetectors.

7. The apparatus of claim 6, further comprising a light source and an amplifier.

8. The apparatus of claim 1, wherein said sensor layers comprise at least one conducting layer and at least two insulating layers.

9. The apparatus of claim 8, wherein said conducting layer is operably coupled to one or more electrical detectors.

10. The apparatus of claim 1, wherein said nanopore is part of a nanotube or nanochannel.

11. The apparatus of claim 2, further comprising a computer operably coupled to said voltage regulator.

26. The apparatus of claim 1, further comprising a light source, wherein the one or more nanopores, the one or more detectors, and the light source are integrated on a single chip.

29. The apparatus of claim 1, wherein the one or more nanopores and the one or more detectors are incorporated into one or more micro-electro-mechanical systems.

32. The apparatus of claim 1, wherein the semiconductor material is selected from the group consisting of silicon, silicon nitride, germanium, gallium arsenide, a metal and a metal oxide.

12. An apparatus comprising:

a first chamber;

a second chamber;

sensor layers separating said first and second chambers, said sensor layers comprising a semiconductor material and including one or more nanopores extending through said sensor layers, said first and second chambers being in fluid communication through said one or more nanopores, wherein said nanopores are between 1 and 999 nm in diameter; and

one or more detectors comprising said sensor layers operably coupled to said sensor layers and configured to detect one or more analytes in the nanopores passing from said first chamber to said second chamber.

13. The apparatus of claim 12, wherein said one or more detectors further comprise a photodetector, an electrical detector and/or a voltage detector.

14. The apparatus of claim 12, further comprising a computer operably coupled to said one or more detectors.

15. The apparatus of claim 12, further comprising:

an electrode in each upper and lower chamber, and a voltage regulator operably coupled to said electrodes.

16. The apparatus of claim 12, wherein said sensor layers comprise a support layer, a photon sensing layer and a light opaque layer.

17. The apparatus of claim 16, wherein said photon sensing layer is operably coupled to one or more photodetectors.

18. The apparatus of claim 12, wherein said sensor layers comprise at least one conducting layer and at least two insulating layers.

19. The apparatus of claim 18, wherein said conducting layer is operably coupled to one or more electrical detectors.

20. The apparatus of claim 12, wherein said nanopores and/or sensor layers are coated with a Raman sensitive metal.

21. The apparatus of claim 12, wherein said nanopores comprise single ion channels.

25. The apparatus of claim 12, further comprising an electrode in each first and second chambers, said electrodes operably coupled to a voltage regulator.

27. The apparatus of claim 12, further comprising a light source, wherein the one or more nanopores, the one or more detectors, and the light source are integrated on a single chip.

30. The apparatus of claim 12, wherein the one or more nanopores and the one or more detectors are incorporated into one or more micro-electro-mechanical systems.

33. The apparatus of claim 12, wherein the semiconductor material is selected from the group consisting of silicon, silicon nitride, germanium, gallium arsenide, a metal and a metal oxide.

22. An apparatus comprising:

one or more first chambers in fluid communication with one or more second chambers via one or more nanopores, said one or more first chambers and said one or more second chambers separated by sensor layers comprising a semiconductor material and having said one or more nanopores therein, wherein said nanopores are between 1 and 999 run in diameter; and

one or more detectors comprising said sensor layers and configured to detect one or more analytes in the nanopores passing from said first chamber to said second chamber.

23. The apparatus of claim 22, further comprising a computer operably coupled to said-one or more detectors.

24. The apparatus of claim 22, further comprising:

an electrode in each first and second chambers, and a voltage regulator operably coupled to said electrodes.

28. The apparatus of claim 22, further comprising a light source, wherein the one or more nanopores, the one or more detectors, and the light source are integrated on a single chip.

31. The apparatus of claim 22, wherein the one or more nanopores and the one or more detectors are incorporated into one or more micro-electro-mechanical systems.

34. The apparatus of claim 22, wherein the semiconductor material is selected from the group consisting of silicon, silicon nitride, germanium, gallium arsenide, a metal and a metal oxide.