Functionalized fluorescent nanocrystals, and methods for their preparation and use

• US 7,368,086 B2
• Filed: 10/28/2005
• Issued: 05/06/2008
• Est. Priority Date: 10/29/2004
• Status: Active Grant

• Current Assignee: Life Technologies Corporation (Thermo Fisher Scientific Incorporated)
• Original Assignee: Invitrogen Corp. (Thermo Fisher Scientific Incorporated)
• Inventors: Naasani, Imad
• Primary Examiner(s): Le; Long V.
• Assistant Examiner(s): Jung; Unsu
• Application Number:
  US11/261,861
• Publication Number:
  US 20060216759A1
• Time in Patent Office: 921 Days
• Field of Search: 435/287.2, 435/287.9, 436/523, 436/525, 422/57, 422/82.05, 422/82.08, 977773- 74, 977/811, 977814-821, 977/830
• US Class Current: 422/82.08
• 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: C09K 11/025 non-luminescent particle coatings or suspension media
• CPC Class Codes: C09K 11/883 with zinc or cadmium
• CPC Class Codes: G01N 33/588 with semiconductor nanocrystal label, e.g. quantum dots
• CPC Class Codes: Y10S 977/773 Nanoparticle, i.e. structure having three dimensions of 100 nm or less
• CPC Class Codes: Y10S 977/792 Nucleic acid array, e.g. human genome array
• CPC Class Codes: Y10S 977/793 Protein array
• CPC Class Codes: Y10S 977/795 Composed of biological material
• CPC Class Codes: Y10S 977/811 Of specified metal oxide composition, e.g. conducting or semiconducting compositions such as ITO, ZnOx
• CPC Class Codes: Y10S 977/827 formed from hybrid organic/inorganic semiconductor compositions
• CPC Class Codes: Y10S 977/83 Inorganic core or cluster coated with organic or biological shell
• 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.]

Abstract

Functionalized fluorescent nanocrystal compositions and methods for making and using these compositions are disclosed. The compositions are fluorescent nanocrystals coated with at least one material. The coating material has chemical compounds or ligands with functional groups or moieties with conjugated electrons and moieties for imparting solubility to coated fluorescent nanocrystals in aqueous solutions. The coating material provides for functionalized fluorescent nanocrystal compositions which are water soluble, chemically stable, and emit light with a high quantum yield and/or luminescence efficiency when excited with light. The coating material may also have chemical compounds or ligands with moieties for bonding to target molecules and cells as well as moieties for cross-linking the coating. In the presence of reagents suitable for reacting to form capping layers, the compounds in the coating may form a capping layer on the fluorescent nanocrystal with the coating compounds operably bonded to the capping layer.

Claims

1. A functionalized fluorescent nanocrystal comprising:

a fluorescent nanocrystal; and

a coating material comprising gylcyl histidine and histidyl leucine.

2. The functionalized fluorescent nanocrystal of claim 1, wherein the fluorescent nanocrystal comprises a core and a shell.

3. The functionalized fluorescent nanocrystal of claim 1, wherein the fluorescent nanocrystal comprises a CdS, CdSe, or CdTe core.

4. The functionalized fluorescent nanocrystal of claim 1, wherein the fluorescent nanocrystal comprises a core and a ZnS, ZuSe, CdS, or CdSe shell.

5. The functionalized fluorescent nanocrystal of claim 1, wherein the fluorescent nanocrystal comprises a CdS or CdSe core, and a ZnS or ZuSe shell.

6. The functionalized fluorescent nanocrystal of claim 1, wherein the fluorescent nanocrystal comprises a CdSe core, and a ZnS shell.

7. The fluorescent nanocrystal of claim 1, wherein the fluorescent nanocrystal is a doped metal oxide nanocrystal.

8. The functionalized fluorescent nanocrystal of claim 1, characterized as emitting light with a quantum yield of greater than 10%.

9. The functionalized fluorescent nanocrystal of claim 1, characterized as emitting light with a quantum yield of greater than 30%.

10. The functionalized fluorescent nanocrystal of claim 1, characterized as emitting light with a quantum yield of greater than 50%.

11. The functionalized fluorescent nanocrystal of claim 1, characterized as emitting light with a quantum yield of greater than 70%.

12. The functionalized fluorescent nanocrystal of claim 1, characterized as being soluble in a fluid having a surface energy of greater than 35 dynes/cm.

13. The functionalized fluorescent nanocrystal of claim 1, characterized as being soluble in an aqueous solution.

14. The functionalized fluorescent nanocrystal of claim 1, further comprising a polynucleotide attached to the coating material.

15. The functionalized fluorescent nanocrystal of claim 1, further comprising a polynucleotide covalently attached to the coating material.

16. The functionalized fluorescent nanocrystal of claim 1, further comprising a biomolecule attached to the coating material, wherein the biomolecule is biotin, avidin, ConA, lectin, or IgG.

17. The functionalized fluorescent nanocrystal composition of claim 1, further comprising avidin attached to the coating material.

18. The functionalized fluorescent nanocrystal composition of claim 1, wherein the coating material is crosslinked with tris(hydroxy methyl) phosphine or beta-(tris(hydroxymethyl)phosphino) propionic acid.