Carbon nanotube molecular labels

• US 6,821,730 B2
• Filed: 11/09/2001
• Issued: 11/23/2004
• Est. Priority Date: 11/09/2001
• Status: Active Grant

• Current Assignee: Intel Corporation
• Original Assignee: Intel Corporation
• Inventors: Hannah, Eric C.
• Primary Examiner(s): Ponnaluri, Padmashri
• Assistant Examiner(s): TRAN, MY CHAU T
• Application Number:
  US09/991,610
• Publication Number:
  US 20040110128A1
• Time in Patent Office: 1,110 Days
• Field of Search: 435/3, 435/4, 435/6, 435/7.1, 435/7.92, 435/174, 435/180, 435/287.1, 435/287.2, 436/518, 436/528, 436/524, 436/536
• US Class Current: 435/6.11
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• CPC Class Codes: C12Q 1/6816 characterised by the detection means C12Q1/6804 takes precedence
• CPC Class Codes: C12Q 2563/155 Particles of a defined size, e.g. nanoparticles
• CPC Class Codes: G01N 33/582 with fluorescent label
• CPC Class Codes: Y10S 977/746 Modified with biological, organic, or hydrocarbon material
• CPC Class Codes: Y10S 977/924 using nanostructure as support of dna analysis
• CPC Class Codes: Y10S 977/951 Laser

Abstract

The methods and compositions disclosed herein concern highly diverse, novel labels comprising carbon nanotubes of discrete lengths and/or diameters. In certain embodiments, the nanotube labels may be attached to oligonucleotide or similar probes for use in DNA sequencing. Upon excitation, for example by an electron beam or UV laser, the carbon nanotubes exhibit distinguishable emission spectra. The nanotube labels are not limited to DNA sequencing, but rather are of use in any application where large numbers of distinguishable labels are desirable. Novel methods for production of carbon nanotubes and apparatus for detection of nanotubes are also disclosed herein.

Claims

1. A method of identifying one or more nucleic acids comprising:

a) obtaining a probe for each nucleic acid to be identified;

b) attaching at least one carbon nanotube to each probe;

c) hybridizing the probes to the nucleic acids;

d) exciting the nanotubes; and

e) detecting the emission spectra of the excited nanotubes wherein the emission spectra are correlated with the probes hybridized to one or more nucleic acids.

2. The method of claim 1, wherein the nanotubes are excited with an ultraviolet (UV) laser or an electron beam.

3. The method of claim 2, further comprising identifying one or more peaks in the optical emission spectrum of each nanotube.

4. The method of claim 3, further comprising determining the wavelength of each peak.

5. The method of claim 1, wherein at least one probe is attached to at least two nanotubes.

6. The method of claim 1, wherein the nanotubes are single wall carbon nanotubes.

7. The method of claim 1, wherein nanotubes attached to different probes exhibit distinguishable emission spectra.

8. The method of claim 1, wherein the probes are oligonucleotides, chemically modified oligonucleotides, oligonucleotide analogs or peptide nucleic acids.

9. The method of claim 8, wherein the probes comprise all possible nucleotide sequences for a probe of defined length.

10. The method of claim 9, wherein the probe length is selected from the group consisting of 4, 5, 6, 7 and 8 nucleotides.

11. The method of claim 8, wherein at least one probe is attached to at least two nanotubes.

12. The method of claim 8, wherein the probes comprise random nucleotide sequences.

13. The method of claim 8, wherein the probes comprise at least one constant nucleotide.

14. The method of claim 8, wherein the probe length is selected from the group consisting of 4, 5, 6,7, 8, 9, 10, 11, 12, 13, 14 and 15 nucleotides.

15. The method of claim 8, wherein the probe length is greater than 15 nucleotides.

16. The method of claim 1, further comprising identifying the probes that hybridize with the nucleic acid.

17. The method of claim 1, wherein the nucleic acids are attached to a substrate.

18. The method of claim 17, wherein the substrate is a chip.

19. The method of claim 16, further comprising identifying the sequence of probes that are hybridized with the nucleic acid.

20. The method of claim 19, further comprising moving the hybridized nucleic acid past a detector, wherein the hybridized probes move past the detector in a linear sequence.

21. The method of claim 20, wherein the hybridized nucleic acid moves past the detector in a microchannel or microcapillary.

22. The method of claim 19, further comprising separating unhybridized probes from probes hybridized to the nucleic acid.