Organo luminescent semiconductor nanocrystal probes for biological applications and process for making and using such probes

• US 6,699,723 B1
• Filed: 05/24/2001
• Issued: 03/02/2004
• Est. Priority Date: 11/25/1997
• Status: Expired due to Term

• Current Assignee: Regents of the University of California (University of California)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Weiss, Shimon, Alivisatos, Paul, Bruchez, Marcel Jr.
• Primary Examiner(s): Chin, Christopher L.
• Application Number:
  US09/865,130
• Time in Patent Office: 1,013 Days
• Field of Search: 424/9.32, 424/9.34, 424/9.341, 424/9.36, 428/402, 428/402.24, 428/403, 428/404, 428/405, 428/406, 436/172, 436/173, 436/518, 436/524, 436/525, 436/527
• US Class Current: 436/518
• 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: G01N 33/54373 involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings
• CPC Class Codes: G01N 33/588 with semiconductor nanocrystal label, e.g. quantum dots
• 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

A semiconductor nanocrystal compound is described capable of linking to an affinity molecule. The compound comprises (1) a semiconductor nanocrystal capable of emitting electromagnetic radiation and/or absorbing energy, and/or scattering or diffracting electromagnetic radiation—when excited by an electromagnetic radiation source or a particle beam; and (2) at least one linking agent, having a first portion linked to the semiconductor nanocrystal and a second portion capable of linking to an affinity molecule. The compound is linked to an affinity molecule to form a semiconductor nanocrystal probe capable of bonding with a detectable substance. Subsequent exposure to excitation energy will excite the semiconductor nanocrystal in the probe, causing the emission of electromagnetic radiation. Further described are processes for respectively: making the semiconductor nanocrystal compound; making the semiconductor nanocrystal probe; and using the probe to determine the presence of a detectable substance in a material.

Claims

1. A luminescent semiconductor nanocrystal probe, comprising:

a) a water-soluble semiconductor-nanocrystal comprising;

i) a core comprising a first semiconductor material; and

ii) a core-overcoating shell comprising a second semiconductor material;

b) a linking agent comprising a first portion and a second portion, wherein said first portion is linked to said water-soluble semiconductor nanocrystal; and

c) an affinity molecule linked to said second portion of said linking agent.

2. The probe of claim 1, wherein said first semiconductor material is a II-VI semiconductor or a III-V semiconductor.

3. The probe of claim 2, wherein said first semiconductor material is a II-VI semiconductor.

4. The probe of claim 2, wherein said first semiconductor material is a III-V semiconductor.

5. The probe of claim 3, wherein said first semiconductor material is MgS, MgSe, MgTe, CaS, CaSe, CaTe, SrS, SrSe, SrTe, BaS, BaSe, BaTe, ZnS, ZnSe, ZnTe, CdS, CdSe, CdTe, HgS, HgSe, or HgTe.

6. The probe of claim 4, wherein said first semiconductor material is GaAs, InGaAs, InP, or InAs.

7. The probe of claim 1, wherein said second semiconductor material is a II-VI semiconductor or a III-V semiconductor.

8. The probe of claim 7, wherein said second semiconductor material is a II-VI semiconductor.

9. The probe of claim 7, wherein said second semiconductor material is a III-V semiconductor.

10. The probe of claim 8, wherein said second semiconductor material is MgS, MgSe, MgTe, CaS, CaSe, CaTe, SrS, SrSe, SrTe, BaS, BaSe, BaTe, ZnS, ZnSe, ZnTe, CdS, CdSe, CdTe, HgS, HgSe, or HgTe.

11. The probe of claim 9, wherein said second semiconductor material is GaAs, InGaAs, InP, or InAs.

12. The probe of claim 1, wherein said first semiconductor material is CdSe and said second semiconductor material is ZnS.

13. The probe of claim 1, wherein said linking agent comprises a thiol moiety.

14. The probe of claim 13, wherein said linking agent further comprises an alkyl group.

15. The probe of claim 14, wherein said alkyl group is a propyl group.

16. The probe of claim 1, wherein said linking agent is chosen from N-(3-aminopropyl)-3-mercapto-benzamide, 3-aminopropyl-trimethoxysilane, 3-mercaptopropyl-trimethoxysilane, 3-maleimidopropyl-trimethoxysilane, and 3-hydrazidopropyl-trimethoxysilane.

17. The probe of claim 1, wherein said nanocrystal compound further comprises a glass coating on said shell.

18. The probe of claim 17, wherein said glass coating comprises a polymeric oxide.

19. The probe of claim 18, wherein said polymeric oxide is chosen from an oxide of silicon, an oxide of boron, an oxide of phosphorus, and a mixture thereof.

20. The probe of claim 18, wherein said glass coating further comprises metal silicate, a metal borate or a metal phosphate.

21. The probe of claim 17, wherein said linking agent is chosen from N-(3-aminopropyl)-3-mercapto-benzamide, 3-aminopropyl-trimethoxysilane, 3-mercaptopropyl-trimethoxysilane, 3-maleimidopropyl-trimethoxysilane, and 3-hydrazidopropyl-trimethoxysilane.

22. The probe of claim 1, wherein said affinity molecule is chosen from an antibody, a nucleic acid, a protein, a polysaccharide and a small molecule.

23. The probe of claim 1, wherein said affinity molecule is chosen from avidin, streptavidin, biotin and anti-digoxiginen.

24. The probe of claim 1, wherein said affinity molecule is streptavidin.

25. The probe of claim 1, wherein said linking agent is 3-mercaptopropyl-trimethoxysilane and said affinity molecule is chosen from avidin, streptavidin, biotin and anti-digoxiginen.

26. The probe of claim 1, wherein said linking agent is 3-mercaptopropyl-trimethoxysilane and said affinity molecule is streptavidin.

27. The probe of claim 1, wherein said shell epitaxially surrounds said core.