Methods and systems for characterizing a polymer

• US 20050136408A1
• Filed: 12/19/2003
• Published: 06/23/2005
• Est. Priority Date: 12/19/2003
• Status: Abandoned Application

• Current Assignee: Agilent Technologies, Inc.
• Original Assignee: Agilent Technologies, Inc.
• Inventors: Tom-Moy, May, Myerholtz, Carl, Pittaro, Richard J.
• Application Number:
  US10/741,119
• Publication Number:
  US 20050136408A1
• Time in Patent Office: Days
• US Class Current: 435/6
• CPC Class Codes: C12Q 1/6816 characterised by the detection means C12Q1/6804 takes precedence
• CPC Class Codes: C12Q 1/6874 involving nucleic acid arrays, e.g. sequencing by hybridisation
• CPC Class Codes: C12Q 2563/155 Particles of a defined size, e.g. nanoparticles
• 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

Abstract

Methods and systems for characterizing a polymer in a sample are provided. In the subject methods, a sample that includes a polymer labeled with at least one nanoparticle is contacted with a nanopore under conditions so that the polymer translocates through the nanopore. A signal is read from the nanopore to characterize the translocated polymer. The subject systems include a nanopore device and a polymer that is labeled with at least one nanoparticle. Also provided is programming stored on a computer-readable medium for use in practicing the subject methods. Kits for use in practicing the subject methods are also provided.

Claims

1. A method of characterizing a polymer in a sample, said method comprising:

(a) contacting said sample comprising said polymer with a nanopore under conditions so that said polymer translocates through said nanopore, wherein said polymer is labeled with at least one nanoparticle label; and

(b) reading a signal from said nanopore to characterize said polymer in said sample.

2. The method of claim 1, wherein said at least one nanoparticle label is chosen from gold, silver, copper, tin, titanium, iron, cobalt, aluminum, zinc, bismuth, zirconia, cerium, magnesium, copper oxide, tin oxide, titanium dioxide, indium tin oxide, antimony tin oxide, barium titanate and calcium oxide.

3. The method of claim 1, wherein said at least one nanoparticle label has a diameter that ranges from about 0.5 nm to about 35 nm.

4. The method of claim 2, wherein said polymer is labeled with a plurality of said nanoparticle labels.

5. The method of claim 4, wherein all of said nanoparticle labels produce the same detectable signal.

6. The method of claim 4, wherein two or more of said nanoparticle labels produce different detectable signals.

7. The method of claim 6, wherein said polymer is a nucleic acid that comprises at least two different types of sub-units and each different sub-unit is labeled with a different type of nanoparticle label.

8. The method of claim 1, wherein said at least one nanoparticle label is a conductive nanoparticle label.

9. The method of claim 1, wherein said at least one nanoparticle label is a semiconductive nanoparticle label.

10. The method of claim 1, wherein said at least one nanoparticle label is a magnetic nanoparticle label.

11. The method of claim 1, wherein said reading step comprises observing the tunneling current effect of said translocation.

12. The method of claim 1, wherein said reading step comprises observing the resonance tunneling current effect of said translocation.

13. The method of claim 1, wherein said reading step comprises observing the ionic current effect of said translocation.

14. The method of claim 1, wherein said reading step comprises observing the change in magnetic susceptibility.

15. The method of claim 1, wherein said method is a method of sequencing a nucleic acid.

16. The method of claim 1, wherein said method is a method of detecting polymorphisms in a nucleic acid.

18. The system of claim 16, wherein said polymer is labeled with a plurality of nanoparticle labels.

19. The system of claim 18, wherein all of said nanoparticle labels produce the same detectable signal.

20. The system of claim 18, wherein two or more of said nanoparticle labels produce different detectable signals.

21. The system of claim 20, wherein said polymer comprises at least two different types of sub-units and each different type of sub-unit is labeled with a different nanoparticle label, wherein each different nanoparticle label produces a different detectable signal.

22. The system of claim 17, further comprising a computer readable medium comprising programming for characterizing a polymer according to the method of claim 1.

28. A computer-readable medium comprising programming for characterizing a polymer according to claim 1.

29. A kit for use in the characterization of a polymer in a sample, said kit comprising:

(a) at least one nanoparticle label that is conductive, semiconductive, magnetic or a combination of two or more thereof; and

(b) instructions for using said at least one nanoparticle label in a method according to claim 1.

30. The kit of claim 29, wherein said kit comprises a plurality of different types of nanoparticle labels.

31. The kit of claim 29, wherein said kit further includes an algorithm recorded on a computer-readable medium for practicing some or all of the method according to claim 1.

17. A system for characterizing a polymer in a sample, said system comprising:

(a) a nanopore device; and

(b) a polymer that is labeled with at least one nanoparticle label.

23. The system of claim 17, wherein said nanopore device is capable of producing ionic current.

24. The system of claim 17, wherein said nanopore device is capable of producing electron tunneling current.

25. The system of claim 17, wherein said nanopore device is capable of producing resonant electron tunneling current.

26. The system of claim 17, wherein said nanopore device is capable of producing a magnetic circuit.

27. The system of claim 17, wherein said polymer is a nucleic acid.