Methods and kits for early stage caries detection

• US 20080038686A1
• Filed: 04/13/2007
• Published: 02/14/2008
• Est. Priority Date: 04/18/2006
• Status: Abandoned Application

• Current Assignee: President and Fellows of Harvard College (Harvard Corporation)
• Original Assignee: President and Fellows of Harvard College (Harvard Corporation)
• Inventors: Nagai, Shigemi
• Application Number:
  US11/787,158
• Publication Number:
  US 20080038686A1
• Time in Patent Office: Days
• US Class Current: 433/29
• CPC Class Codes: A61B 5/0088 for oral or dental tissue

Abstract

Methods and kits are provided for identifying very early stage carious lesions using a detectable probe that binds to the lesion.

Claims

1. A method for detecting an early stage dental caries in a subject, the method comprising:

contacting a caries lesion which is at an early stage, selectively binding an optically detectable probe to the caries; and

detecting the caries having bound probe using an optical device.

2. The method according to claim 1, wherein detecting the selective binding further comprises a step selected from the group of:

contacting a tooth with a fluorescent probe, wherein the fluorescent probe is selected from the group of tetracycline, Hylight Fluor, Qdot, Indocyanine Green, Doxorubicin, Riboflavin, Chlorophyll, and Porphyrin, and illuminating the tooth at an excitation wavelength, wherein diagnosing is detecting a area of light emission at an emission wavelength;

contacting the tooth with the probe, wherein the probe is luciferase and further contacting the tooth with luciferin and ATP, wherein diagnosing is detecting a area of bioluminenesce;

contacting the tooth with a colloidal gold, wherein diagnosing is detecting a area of absorbance of near infra red (NIR) light;

contacting the tooth with a quantum dot composition probe, wherein diagnosing is detecting fluorescence or fluorescence-detected dichroism;

contacting a tooth with a probe that is a conjugate of a quantum dot composition, wherein the conjugate is attached to a second agent selected from the group of a tetracycline, bismuth, a colloidal gold or the like, followed by detecting fluorescence or fluorescence-detected dichroism; and

contacting a tooth with colloidal gold, wherein diagnosing is detecting fluorescence with a HiLyte Fluor 750 hydrazide.

3. The method according to claim 1, wherein the early stage caries is prior to cavitation or advanced demineralization.

4. The method according to claim 2, wherein detecting the caries is observing by photometry.

5. The method according to claim 2, wherein the caries with selectively bound tetracycline probe is observing a white spot.

6. The method according to claim 2, wherein the caries with the selectively bound quantum dot probe is a spot of enamel-translucent fluorescence.

7. The method according to claim 3, wherein a gray, silver, white or translucent spot is diagnosed on the surface of enamel, or within an underlayer of about 50 to about 100 micrometer of the surface.

8. The method according to claim 1, wherein the caries is interproximal.

9. The method according to claim 1, wherein prior to contacting, interproximal regions are accessed by at least one method selected from the group of:

inserting a spacer; and

delivering the probe into the interproximal area using a metal or plastic strip containing the probe.

10. The method according to claim 9, wherein the conjugate comprises a quantum dot composition or a HiLyte Fluor 750 hydrazide.

11. The method according to claim 9, wherein the colloidal gold comprises gold nanoshell particles.

12. The method according to claim 9, wherein the tetracycline fluorescence probe comprises at least one of chlortetracycline, oxytetracycline, and doxycycline.

13. The method according to claim 9, wherein a duration of contacting is at least about 20 seconds, at least about 40 seconds, or at least about 60 seconds.

14. The method according to claim 4, wherein an area having a gray, silver, white or translucent spot is an indication of a location of the caries.

15. The method according to claim 4, wherein a size of an area having a gray, silver, white or translucent spot is an indication of an extent of the caries.

16. The method according to claim 1, wherein the optical device is a hand-held intra-oral optical device.

17. The method according to claim 4, wherein fluorescence is detected using a device selected from the group consisting of an ultra-violet lamp or a hand-held intra-oral probe attachment, which connects to a spectrophotometer.

18. The method according to claim 1, further comprising prior to contacting, detecting a presence of an auto-fluorescence.

19. The method according to claim 1, further comprising curing the detected caries by remineralization.

20. The method according to claim 1, wherein the subject is a mammal.

21. The method according to claim 1, wherein the subject is a human.

22. The method according to claim 1, further comprising preparing a photographic image of an area of the caries with bound probe.

23. The method according to claim 1, further comprising remineralizing the caries lesion, wherein the caries lesion is monitored, and is prevented or reduced.

24. The method according to claim 1, wherein the optically detectable probe is charged.

25. The method according to claim 2, wherein the fluorescent probe is a tetracycline, the wavelength for illuminating the tooth is about 350 to about 450 nm, and the wavelength for detecting its fluorescence is about 450 to about 600 nm.

26. The method according to claim 2, wherein the fluorescent probe is a Hilyte Fluor, the wavelength for illuminating the tooth is about 720 to about 750 nm, and the wavelength for detecting its fluorescence is about 750 to about 800 nm.

27. The method according to claim 2, wherein the fluorescence probe is a Qdot, the wavelength for illuminating the tooth is about 400 to about 750 nm, and the wavelength for detecting its fluorescence is about 750 to about 900 nm.

28. The method according to claim 2, wherein the fluorescence probe is an Indocyanine Green, the wavelength for illuminating the tooth is about 750 to about 800 nm, and the wavelength for detecting its fluorescence is about 820 to about 870 nm.

29. The method according to claim 2, wherein the fluorescence probe is a Doxorubicin, the wavelength for illuminating the tooth is about 400 to about 500 nm, and the wavelength for detecting its fluorescence is about 600 to about 700 nm.

30. The method according to claim 2, wherein the fluorescence probe is a Riboflavin, the wavelength for illuminating the tooth is about 400 to about 500 nm, and the wavelength for detecting its fluorescence is about 500 to about 700 nm.

31. The method according to claim 2, wherein the fluorescence probe is a Chlorophyll A, the wavelength for illuminating the tooth is about 600 to about 650 nm, and the wavelength for detecting its fluorescence is about 670 to about 900 nm.

32. The method according to claim 2, wherein the fluorescence probe is a Porphyrin, the wavelength for illuminating the tooth is about 550 to about 650 nm, and the wavelength for detecting its fluorescence is about 650 to about 750 nm.

33. The method according to claim 2, wherein the probe comprises a luciferase, luciferin and ATP, wherein wavelength for detecting its bioluminescence is about 600 to about 800 nm.

34. The method according to claim 2, wherein the probe is a colloidal gold, wherein the wavelength for detecting an area of its absorbance is about 500 to about 800 nm.

35. The method according to claim 2, wherein the probe is a bismuth, wherein the wavelength for detecting an area of its absorbance is about 500 to about 800 nm.

36. A kit for detecting early stage dental caries in a subject, the kit comprising a detectable probe that binds to the caries, the kit further comprising a container, and a positive control tooth sample having an early stage lesion.

38. The kit according to claim 36, further comprising instructions for use with an optical device.

39. The kit according to claim 36, wherein the fluorescent probe is a tetracycline or a tetracycline conjugate.

40. The kit according to claim 36, wherein the fluorescent probe selected from the group consisting of Indocyanine Green, Doxorubicin, Riboflavin, Chlorophyll, and Porphyrin.

50. The kit according to claim 36, wherein the probe is a unit dose.

37. A kit for detecting early stage dental caries in a subject, the kit comprising at least one probe selected from the group of:

colloidal gold;

a fluorescent probe; and

a bioluminescent;

wherein the probe binds selectively to the caries, the kit further comprising a container, and a positive control tooth sample having an early stage lesion.

41. A kit for detecting early stage dental caries in a subject, the kit comprising a detectable probe, an optical device, and a container.

42. The kit according to claim 41, further comprising a positive control tooth sample having an early stage lesion.

43. The kit according to claim 41, further comprising instructions for use.

44. The kit according to claim 41, wherein the optical device is at least one device selected from the group of:

a hand-held intra-oral light wave detection device, a camera, and a fiber optic optical device.

45. The kit according to claim 41, wherein the optical detection device further comprises an electromagnetic wavelength radiation emitter, wherein a wavelength is generated for excitation of fluorescent probes.

46. The kit according to claim 41, wherein the probe is at least one composition selected from the group of fluorescent compositions and bioluminescent compositions.

47. The kit according to claim 46, wherein the bioluminescent composition is at least one selected from the group of luciferase, luciferin, and a mixture thereof.

48. The kit according to claim 46, wherein the fluorescent probe is at least one composition selected from the group of Indocyanine Green, Doxorubicin, Riboflavin, Chlorophyll, and Porphyrin.

49. The kit according to claim 41, wherein the probe is at least one composition selected from the group of Qdot, colloidal gold, and bismuth.

51. The kit according to claim 41, wherein the kit further comprises an applicator for the probe.

52. The kit according to claim 51, wherein the applicator is at least one selected from the group of a spray, a soak in a bite wing plate, and a gel extruded from a compressible tube.