Biological applications of quantum dots

• US 6,855,551 B2
• Filed: 04/12/2001
• Issued: 02/15/2005
• Est. Priority Date: 09/18/1998
• Status: Expired due to Term

• Current Assignee: Massachusetts Institute of Technology
• Original Assignee: Massachusetts Institute of Technology
• Inventors: Mikulec, Frederic V., Bawendi, Moungi G., Sundar, Vikram C.
• Primary Examiner(s): Chin, Christopher L.
• Application Number:
  US09/832,959
• Publication Number:
  US 20010023078A1
• Time in Patent Office: 1,405 Days
• Field of Search: 436/518, 436/523, 436/524, 436/525, 436/527, 436/136, 436/173, 424/9.32, 424/9.34, 424/9.341, 424/9.36, 428/402, 428/402.24, 428403-406, 435/6
• US Class Current: 436/6
• CPC Class Codes: B82Y 15/00 Nanotechnology for interacting, sensing or actuating, e.g. quantum dots as markers in protein assays or molecular motors
• CPC Class Codes: C12Q 1/6844 Nucleic acid amplification reactions
• CPC Class Codes: C12Q 1/6869 Methods for sequencing
• CPC Class Codes: C12Q 2563/113 the label being electroactive, e.g. redox labels
• CPC Class Codes: C12Q 2563/155 Particles of a defined size, e.g. nanoparticles
• CPC Class Codes: G01N 33/532 Production of labelled immunochemicals
• CPC Class Codes: G01N 33/533 with fluorescent label
• CPC Class Codes: G01N 33/54373 involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings
• CPC Class Codes: G01N 33/582 with fluorescent label
• CPC Class Codes: G01N 33/588 with semiconductor nanocrystal label, e.g. quantum dots
• CPC Class Codes: G06K 19/06046 Constructional details
• CPC Class Codes: Y10S 977/924 using nanostructure as support of dna analysis
• CPC Class Codes: Y10T 428/2982 Particulate matter [e.g., sphere, flake, etc.]
• CPC Class Codes: Y10T 428/2989 Microcapsule with solid core [includes liposome]
• CPC Class Codes: Y10T 428/2991 Coated
• CPC Class Codes: Y10T 428/2993 Silicic or refractory material containing [e.g., tungsten oxide, glass, cement, etc.]
• CPC Class Codes: Y10T 428/2995 Silane, siloxane or silicone coating
• CPC Class Codes: Y10T 428/2996 Glass particles or spheres
• CPC Class Codes: Y10T 436/24 Nuclear magnetic resonance, electron spin resonance or other spin effects or mass spectrometry

Abstract

The present invention provides a composition comprising fluorescent semiconductor nanocrystals associated to a compound, wherein the nanocrystals have a characteristic spectral emission, wherein said spectral emission is tunable to a desired wavelength by controlling the size of the nanocrystal, and wherein said emission provides information about a biological state or event.

Claims

1. A method of detecting biological moieties comprising:

providing a plurality of compositions capable of characteristic spectral emissions, the composition comprising a compound and a semiconductor nanocrystal associated with the compound, wherein each of the members of the plurality is characterized in that;

the nanocrystal of the member of the plurality has an emission spectrum distinct from the other members of the plurality and a quantum yield of greater than 10% in water, and

the compound of the member of the plurality has a corresponding biological moiety distinct from other biological moieties in the sample;

allowing a sample containing or suspected of containing one or more biological moieties to interact with the compositions; and

monitoring the spectral emission of each interaction between each composition and each biological moiety of the sample, wherein the interaction between the biological moiety and the composition comprises a noncovalent interaction.

2. The method of claim 1, wherein the compound comprises a molecular complex with a molecule associated with the nanocrystal complexed to a second molecule that interacts with the biological moiety.

3. The method of claim 1, wherein each interaction between each composition and each biological moiety of the sample are monitored substantially simultaneously.

4. The method of claim 1, wherein the spectral emission provides information about a biological state or event.

5. The method of claim 4, wherein the spectral emission provides information about the amount of biological moiety in the sample.

6. The method of claim 4, wherein the spectral emission provides information about the presence of the biological moiety in the sample.

7. The method of claim 1, wherein the semiconductor nanocrystal is water-soluble.

8. The method of claim 1, wherein the semiconductor nanocrystal comprises a core comprising a semiconductor material, and a layer overcoating the core comprising a semiconductor material.

9. The method of claim 1, wherein the spectral emission is tunable to a desired wavelength by controlling the size of the nanocrystal.

10. The method of claim 1, wherein monitoring the spectral emission occurs in assays selected from the group consisting of:

immunochemistry, immunocytochemistry, immunobiology, immunofluorescence, DNA sequence analysis, fluorescence resonance energy transfer, flow cytometry, fluorescence activated cell sorting, diagnostics in biological systems, and high-throughput screening.

11. The method of claim 1, wherein the noncovalent interaction comprises hydrophobic interaction, hydrophilic interaction, electrostatic interaction, van der Waals interaction, or magnetic interaction.

12. The method of claim 1, wherein the biological moiety comprises a small molecule.

13. The method of claim 1, wherein the biological moiety comprises a protein, peptide or antibody.

14. The method of claim 1, wherein the biological moiety comprises a nucleic acid.

15. The method of claim 14, wherein the nucleic acid comprises DNA or RNA.

16. The method of claim 1, wherein the biological moiety comprises an amino acid.

17. The method of claim 1, wherein the biological moiety comprises a ligand.

18. The method of claim 1, wherein the biological moiety comprises an antigen.

19. The method of claim 1, wherein the biological moiety comprises a cell.

20. The method of claim 1, wherein the biological moiety comprises a subcellular organelle.

21. A method of detecting biological moieties comprising:

providing a plurality of compositions capable of characteristic spectral emissions, the composition comprising a compound and a semiconductor nanocrystal associated with the compound, wherein each of the members of the plurality is characterized in that;

the nanocrystal of the member of the plurality has an emission spectrum distinct from the other members of the plurality, and

the compound of the member of the plurality has a corresponding biological moiety distinct from other biological moieties in the sample and is associated with the nanocrystal by a ligand having at least one linking group for attachment to the nanocrystal spaced apart from a hydrophilic group by an alkyl or alkenyl group;

allowing a sample containing or suspected of containing one or more biological moieties to interact with the compositions; and

monitoring the spectral emission of each interaction between each composition and each biological moiety of the sample, wherein the interaction between the biological moiety and the composition comprises a noncovalent interaction.

22. The method of claim 21, wherein the hydrophilic group is selected from the group consisting of carboxylic acid, carboxylate, sulfonate, hydroxide, alkoxide, ammonium, phosphate, and phosphonate.

23. The method of claim 21, wherein each interaction between each composition and each biological moiety of the sample are monitored substantially simultaneously.

24. The method of claim 21, wherein the spectral emission provides information about a biological state or event.

25. The method of claim 21, wherein the semiconductor nanocrystal is water-soluble.

26. The method of claim 21, wherein the semiconductor nanocrystal comprises a core comprising a semiconductor material, and a layer overcoating the core comprising a semiconductor material.

27. The method of claim 21, wherein the biological moiety comprises a small molecule.

28. The method of claim 21, wherein the biological moiety comprises a protein, peptide or antibody.

29. The method of claim 21, wherein the biological moiety comprises a nucleic avid.

30. The method of claim 29, wherein the nucleic acid comprises DNA or RNA.

31. The method of claim 21, wherein the biological moiety comprises an amino acid.

32. The method of claim 21, wherein the biological moiety comprises a ligand.

33. The method of claim 21, wherein the biological moiety comprises an antigen.

34. The method of claim 21, wherein the biological moiety comprises a cell.

35. The method of claim 21, wherein the biological moiety comprises a subcellular organelle.

36. The method of claim 21, wherein the spectral emission is tunable to a desired wavelength by controlling the size of the nanocrystal.

37. The method of claim 21, wherein monitoring the spectral emission occurs in assays selected from the group consisting of:

immunochemistry, immunocytochemistry, immunobiology, immunofluorescence, DNA sequence analysis, fluorescence resonance energy transfer, flow cytometry, fluorescence activated cell sorting, diagnostics in biological systems, and high throughput screening.

38. The method of claim 21, wherein the spectral emission is tunable to a desired wavelength by controlling the size of the nanocrystal.

39. The method of claim 21, wherein monitoring the spectral emission occurs in assays selected from the group consisting of:

immunochemistry, immunocytochemistry, immunobiology, immunofluorescence, DNA sequence analysis, fluorescence resonance energy transfer, flow cytometry, fluorescence activated cell sorting, diagnostics in biological systems, and high throughput screening.

40. The method of claim 21, wherein the noncovalent interaction comprises hydrophobic interaction, hydrophilic interaction, electrostatic interaction, van der Waals interaction, or magnetic interaction.