Biospecific contrast agents

• US 20040023415A1
• Filed: 03/05/2003
• Published: 02/05/2004
• Est. Priority Date: 03/05/2002
• Status: Abandoned Application

• Current Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Original Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Inventors: Korgel, Brian A., Richards-Kortum, Rebecca, Sokolov, Konstantin, Ellington, Andrew D.
• Application Number:
  US10/382,136
• Publication Number:
  US 20040023415A1
• Time in Patent Office: Days
• US Class Current: 436/518
• CPC Class Codes: A61B 5/0059 using light, e.g. diagnosis by transillumination, diascopy, fluorescence A61B5/0093, A61B5/1455, A61B5/02416 and A61B5/0261 take precedence
• CPC Class Codes: A61B 5/411 Detecting or monitoring allergy or intolerance reactions to an allergenic agent or substance
• CPC Class Codes: A61B 5/415 the glands, e.g. tonsils, adenoids or thymus
• CPC Class Codes: A61B 5/416 the spleen
• CPC Class Codes: A61B 5/418 lymph vessels, ducts or nodes
• CPC Class Codes: A61K 49/00 Preparations for testing in vivo
• CPC Class Codes: A61K 49/0017 Fluorescence in vivo
• CPC Class Codes: A61K 49/0058 Antibodies
• CPC Class Codes: A61K 49/0067 quantum dots, fluorescent nanocrystals
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• 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: G01N 33/587 Nanoparticles
• CPC Class Codes: G01N 33/588 with semiconductor nanocrystal label, e.g. quantum dots

Abstract

Methods and apparatuses for detecting a condition of a sample (including cervical cancers and pre-cancers) through reflectance and/or fluorescence imaging. A sample is obtained. One or more metallic nanoparticles and/or one or more quantum dots are obtained. The one or more metallic nanoparticles and/or one or more quantum dots are coupled to one or more biomarkers of the sample that are associated with the condition. A reflectance and/or fluorescence image of the sample is then taken. The image(s) exhibit characteristic optical scattering from the one or more metallic nanoparticles and/or characteristic fluorescence excitation from the one or more quantum dots to signal the presence of the one or more biomarkers. In this way, the condition can be readily screened or diagnosed.

Claims

1. A contrast agent for reflectance imaging comprising one or more metallic nanoparticles configured to couple to one or more specific biomarkers of a sample and to exhibit characteristic optical scattering when subjected to reflectance imaging.

2. The contrast agent of claim 1, wherein the one or more metallic nanoparticles comprise gold.

3. The contrast agent of claim 1, wherein the one or more metallic nanoparticles comprise silver.

4. The contrast agent of claim 1, wherein the one or more metallic nanoparticles are configured to couple to a molecular probe that couples to the one or more specific biomarkers.

5. The contrast agent of claim 4, wherein the one or more biomarkers comprise cancerous or pre-cancerous biomarkers.

6. The contrast agent of claim 1, the contrast agent being a contrast agent for detecting a condition of a sample in vivo through reflectance imaging.

7. A contrast agent for detecting cervical cancer or pre-cancer in vivo through reflectance imaging, comprising one or more metallic nanoparticles configured to couple to one or more cancerous or pre-cancerous biomarkers of a sample and to exhibit characteristic optical scattering when subjected to reflectance imaging.

9. A contrast agent for detecting cervical cancer or pre-cancer in vivo through fluorescence imaging, comprising one or more quantum dots configured to couple to one or more cancerous or pre-cancerous biomarkers of a sample and to exhibit characteristic fluorescence excitation when subjected to fluorescence imaging.

10. A method, comprising:

administering to a tissue a metallic nanoparticle coupled to a probe molecule; and

forming an in vivo reflectance image of the tissue.

11. The method of claim 10, the metallic nanoparticle comprising gold.

12. The method of claim 10, the metallic nanoparticle comprising silver.

13. A method for enhanced reflectance imaging, comprising:

obtaining a sample;

coupling one or more metallic nanoparticles to the sample; and

generating a reflectance image of the sample, the image exhibiting characteristic optical scattering from the one or more metallic nanoparticles.

14. The method of claim 13, wherein the sample comprises a biological sample.

15. The method of claim 14, wherein the sample comprises cervical tissue.

16. The method of claim 14, wherein the sample comprises one or more unpurified human fluids.

17. The method of claim 16, wherein the one or more fluids comprise whole blood, serum, or urine.

18. The method of claim 13, wherein the coupling comprises coupling the one or more metallic nanoparticles to a molecular probe that couples to one or more biomarkers of the sample.

19. The method of claim 18, wherein the one or more biomarkers comprise cancerous or pre-cancerous biomarkers.

20. The method of claim 19, further comprising forming a diagnosis of the sample based upon the reflectance image.

21. The method of claim 13, wherein the one or more metallic nanoparticles comprise gold.

22. The method of claim 13, wherein the one or more metallic nanoparticles comprise silver.

23. The method of claim 13, wherein the generating the image is performed in vivo.

24. The method of claim 13, wherein the generating the image is performed in vitro.

25. A method for detecting a condition of a sample through reflectance imaging, comprising:

obtaining a sample;

obtaining one or more metallic nanoparticles;

coupling the one or more metallic nanoparticles to one or more biomarkers of the sample that are associated with the condition; and

generating a reflectance image of the sample, the image exhibiting characteristic optical scattering from the one or more metallic nanoparticles to signal a presence of the one or more biomarkers.

26. The method of claim 25, wherein generating the image is performed in vivo.

27. The method of claim 25, wherein the sample comprises cervical tissue.

28. The method of claim 25, wherein the sample comprises one or more unpurified human fluids.

29. The method of claim 28, wherein the one or more fluids comprise whole blood, serum, or urine.

30. A method for detecting cervical cancer or pre-cancer through reflectance imaging, comprising:

obtaining a sample;

obtaining one or more metallic nanoparticles;

coupling the one or more metallic nanoparticles to one or more biomarkers of the sample that are associated with the cervical cancer or pre-cancer; and

generating a reflectance image of the sample, the image exhibiting characteristic optical scattering from the one or more metallic nanoparticles to signal a presence of the one or more biomarkers.

31. The method of claim 30, wherein generating the image is performed in vivo.

32. A method for detecting a condition of a sample through fluorescence imaging, comprising:

obtaining a sample;

obtaining one or more quantum dots;

coupling the one or more quantum dots to one or more biomarkers of the sample that are associated with the condition; and

generating a fluorescence image of the sample, the image exhibiting characteristic fluorescence excitation from the one or more quantum dots to signal a presence of the one or more biomarkers.

33. The method of claim 32, wherein generating the image is performed in vivo.

34. The method of claim 32, wherein the sample comprises cervical tissue.

35. The method of claim 32., wherein the sample comprises one or more unpurified human fluids.

36. The method of claim 35, wherein the one or more fluids comprise whole blood, serum, or urine.

37. A method for detecting cervical cancer or pre-cancer through fluorescence imaging, comprising:

obtaining a sample;

obtaining one or more quantum dots;

coupling the one or more quantum dots to one or more biomarkers of the sample that are associated with the cervical cancer or pre-cancer; and

generating a fluorescence image of the sample, the image exhibiting characteristic fluorescence excitation from the one or more quantum dots to signal a presence of the one or more biomarkers.

38. The method of claim 37, wherein generating the image is performed in vivo.

39. A method for detecting a condition of a sample through a combination of reflectance and fluorescence imaging, comprising:

obtaining a sample;

obtaining one or more metallic nanoparticles and one or more quantum dots;

coupling the one or more metallic nanoparticles and one or more quantum dots to one or more biomarkers of the sample that are associated with the condition; and

generating a reflectance and fluorescence image of the sample, the image exhibiting characteristic optical scattering from the one or more metallic nanoparticles and characteristic fluorescence excitation from the one or more quantum dots to signal a presence of the one or more biomarkers.

40. The method of claim 39, wherein generating the image is performed in vivo.

41. The method of claim 39, wherein the sample comprises cervical tissue.

42. The method of claim 39, wherein the sample comprises one or more unpurified human fluids.

43. The method of claim 42, wherein the one or more fluids comprise whole blood, serum, or urine.

44. A method for detecting cervical cancer or pre-cancer through a combination of reflectance and fluorescence imaging, comprising:

obtaining a sample;

obtaining one or more metallic nanoparticles and one or more quantum dots;

coupling the one or more metallic nanoparticles and one or more quantum dots to one or more biomarkers of the sample that are associated with the cervical cancer or pre-cancer; and

generating a reflectance and fluorescence image of the sample, the image exhibiting characteristic optical scattering from the one or more metallic nanoparticles and characteristic fluorescence excitation from the one or more quantum dots to signal a presence of the one or more biomarkers.

45. The method of claim 44, wherein generating the image is performed in vivo.