Synthesis of highly luminescent colloidal particles

• US 20100075437A1
• Filed: 09/21/2009
• Published: 03/25/2010
• Est. Priority Date: 08/17/2004
• Status: Active Grant

• Current Assignee: Life Technologies Corporation (Thermo Fisher Scientific Incorporated)
• Original Assignee: Life Technologies Corporation (Thermo Fisher Scientific Incorporated)
• Inventors: NAASANI, Imad
• Granted Patent: US 8,092,859 B2
• Time in Patent Office: Days
• US Class Current: 436/501
• 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: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• CPC Class Codes: C09K 11/02 Use of particular materials as binders, particle coatings or suspension media therefor
• CPC Class Codes: C09K 11/565 with zinc cadmium
• CPC Class Codes: C09K 11/883 with zinc or cadmium
• CPC Class Codes: C30B 29/605 Products containing multiple oriented crystallites, e.g. columnar crystallites
• CPC Class Codes: C30B 7/005 Epitaxial layer growth
• CPC Class Codes: G01N 33/588 with semiconductor nanocrystal label, e.g. quantum dots
• CPC Class Codes: Y10S 977/882 Assembling of separate components, e.g. by attaching
• CPC Class Codes: Y10S 977/896 Chemical synthesis, e.g. chemical bonding or breaking
• CPC Class Codes: Y10T 428/2991 Coated

Abstract

The present invention includes compositions and methods for their used wherein the compositions include clusters of coated fluorescent nanocrystals having a select size formed by controlled aggregation of individual coated nanocrystals.

Claims

1. A composition comprising an aggregate of nanocrystals;

wherein;

the nanocrystals comprise a coating layer;

the coating layer comprises one or more imidazole groups; and

the nanocrystals interact through the coating layer to form the aggregate.

2. The composition of claim 1, wherein the aggregate is cross linked.

3. The composition of claim 2, wherein a cross linking agent is used to cross link the aggregate.

4. The composition of claim 3, wherein the cross linking agent is tris(hydroxy methyl)phosphine.

5. The composition of claim 3, wherein the cross linking agent is beta-[tris(hydroxymethyl)phosphino]propionic acid.

6. The composition of claim 1, wherein the coating layer is bound to the nanocrystal by the one or more imidazole groups.

7. The composition of claim 1, wherein the aggregated nanocrystals are crosslinked by one or more organophosphine compounds.

8. The composition of claim 1, wherein the nanocrystals are luminescent.

9. The composition of claim 1, wherein the nanocrystals are fluorescent.

10. The composition of claim 1, wherein the aggregate is dispersed in an aqueous based solution.

11. The composition of claim 1, wherein the aggregate further comprises at least one functional group on the surface of the aggregate.

12. The composition of claim 1, wherein the aggregate further comprises a functional group selected from the group consisting of a hydroxyl, thiol, amino, acetylenic, carboxyl, ester, amide, dicarboxylic, carboxamide selenol, hydrazide, aldehyde and a combination thereof on the surface of the coated nanocrystal aggregate.

13. The composition of claim 1, wherein the nanocrystals are semiconductor core nanocrystals.

14. The composition of claim 1, wherein the nanocrystals are semiconductor core/shell nanocrystals.

15. The composition of claim 1, wherein the coating layer comprises histidine, carnosine, polyhistidine, polyimidazole, or glycyl histidine.

16. A composition comprising a nanocrystal aggregate and at least one affinity molecule;

wherein;

the aggregate comprises two or more coated nanocrystals;

the nanocrystals comprise a coating layer comprising one or more imidazole groups;

the nanocrystals interact through the coating layer to form the aggregate;

the aggregate comprises at least one functional group on its surface; and

the at least one affinity molecule is linked to the functional group.

17. The composition of claim 16, wherein the affinity molecule is selected from the group consisting of a polyclonal antibody, a monoclonal antibody, a peptide, an aptamer, a nucleic acid, a lectin, a lipid, a small organic molecule, a polysaccharide, avidin, neutravidin, streptavidin, an avidin derivative, biotin, a biotin derivative, and combinations thereof.

18. The composition of claim 16, wherein the affinity molecule is covalently linked to the functional group.

19. The composition of claim 16, wherein the functional group is selected from the group consisting of a hydroxyl, thiol, amino, acetylenic, carboxyl, ester, amide, dicarboxylic, carboxamide selenol, hydrazide, aldehyde and a combination thereof.

20. A composition comprising two to about twenty aggregated fluorescent semiconductor nanocrystals;

wherein;

the fluorescent nanocrystals comprise a coating layer;

the coating layer comprises one or more imidazole groups; and

the nanocrystals interact through their coating layers to form an aggregate, the aggregate being composed of from about two to about twenty fluorescent semiconductor nanocystals.

21. The composition of claim 20, wherein the nanocrystals are crosslinked by an organophosphine compound in the aggregate.

22. A method of preparing a nanocrystal aggregate, the method comprising:

contacting two or more nanocrystals in a solvent, the nanocrystals comprising a coating layer comprising at least one imidazole group; and

contacting the nanocrystals to prepare an aggregate of coated nanocystals.

23. The method of claim 22, further comprising controlling the aggregate size by modifying the solvent.

24. The method of claim 22, wherein the nanocrystals interact through their coating layers.

25. The method of claim 22, wherein the contacting step further comprises placing the two or more nanocrystals in a solvent mixture.

26. The method of claim 22, wherein the contacting step further comprises placing the two or more nanocrystals in an aqueous solvent mixture.

27. A method of detecting a target molecule in a sample, the method comprising:

providing a sample suspected of containing a target molecule;

providing one or more coated nanocrystal aggregates, said coated nanocrystal aggregates comprising a nanocrystal, an imidazole containing coating, and an affinity ligand having binding specificity for the target molecule;

contacting the sample and the aggregates to form a treated sample, wherein the aggregates form a complex with the target molecule;

exciting the complex with a wavelength of energy to form an excited complex;

and detecting the excited complex.

28. The method of claim 27, where the detecting step comprises detecting light emitted by the excited complex.

29. The method of claim 27, where the detecting step comprises using a Scintillation Proximity assay.

30. The method of claim 27, where the detecting step further comprises quantifying the amount of target molecule in the sample.

31. The method of claim 27, wherein the wavelength is less than about 500 nm.