Permanent, removable tissue markings
View Patent ↗The present invention provides microparticles that create permanent tissue markings, such as tattoos, designed in advance for change and/or removal on demand, as well as methods for implanting the microparticles in tissue and changing and/or removing the resulting markings. Colored microparticles are constructed with specific electromagnetic absorption and/or structural properties that facilitate changing and/or removing tissue markings made using the microparticles by applying specific energy (such as electromagnetic radiation from a laser or flash-lamp) to the tissue marking site.
1. A tissue marking ink comprising:
a particle comprising a thermolabile chromophore that becomes invisible upon heating by application of a specific energy; and
a carrier.
2. The ink of claim 1 , wherein the particle further comprises a component in contact with the chromophore that indirectly heats the chromophore upon application of the specific energy.
3. The ink of claim 1 , wherein the particle further comprises a thermally initiated activator mixed into the chromophore that releases free radicals upon heating by application of the specific energy.
4. The ink of claim 1 , wherein the specific energy is electromagnetic radiation.
5. The ink of claim 1 , wherein the specific energy is infrared or near-infrared radiation.
6. The ink of claim 1 , wherein the appearance of the chromophore changes when the specific energy is applied once.
7. The ink of claim 1 , wherein the chromophore has an average particle size of less than about 50 nm.
8. The ink of claim 1 , wherein the chromophore changes from an initial color to a different color upon exposure of the particle to the specific energy.
9. The ink of claim 1 , wherein the particle further comprises:
an indispersible, biologically inert coating; and
a core enveloped within the coating, wherein the core comprises the chromophore.
10. The ink of claim 9 , wherein the coating comprises a metal oxide, silica, glass, fluorocarbon resin, organic polymer, wax, or a combination thereof.
11. The ink of claim 9 , wherein the coating is substantially visibly transparent and absorbs near-infrared radiation.
12. The ink of claim 9 , wherein multiple cores are enveloped within the coating of a single particle.
13. The ink of claim 9 , wherein the chromophore is detectable through the coating.
14. The ink of claim 9 , wherein the coating comprises from about 10 to about 95 percent of the volume of the particle.
15. The ink of claim 1 , wherein the particle is from about 50 nm to about 100 microns in size.
16. The ink of claim 1 , wherein the particle is from about 15 nm to about 500 nm in size.
17. The ink of claim 1 , wherein the particle is less than about 50 nm in size.
18. The ink of claim 1 , wherein the particle is less than about 5 nm in size.
19. The ink of claim 1 , wherein the carrier comprises at least one of alcohol, water, or glycerin.
20. A method of applying a tissue marking, the method comprising:
providing the tissue marking ink of claim 1 ; and
implanting said ink into a tissue to form a tissue marking,
wherein the chromophore becomes invisible upon exposure to a specific energy when the ink is within the tissue.
21. The method of claim 20 , wherein the specific energy is electromagnetic radiation.
22. The method of claim 20 , wherein the specific energy is infrared or near-infrared radiation.
23. A method for altering a tissue marking implanted in tissue, wherein the tissue marking comprises the ink of claim 1 , wherein the chromophore that becomes invisible upon heating by application of a specific energy when the ink is within the tissue, the method comprising exposing the tissue marking to the specific energy for a sufficient time to render the chromophore substantially invisible.
24. The method of claim 23 , wherein the specific energy is electromagnetic radiation.
25. The method of claim 23 , wherein the specific energy is infrared or near-infrared radiation.
26. A tissue marking ink comprising a particle, wherein the particle comprises polymethylmethacrylate (PMMA) and an iron oxide absorption component, wherein the particle ruptures upon exposure to a specific energy when the particle is within a tissue.
27. The tissue marking ink of claim 26 , further comprising a chromophore.
28. The tissue marking ink of claim 27 , wherein the chromophore is a Food and Drug Administration (FDA)-approved dye.
29. The tissue marking ink of claim 27 , wherein the chromophore is selected from the group consisting of phthalocyanine dyes, cyanine dyes, and pyrylium dyes.
30. The tissue marking ink of claim 27 , wherein the chromophore is carbon black.
31. The tissue marking ink of claim 27 , wherein the chromophore is selected from the group consisting of rifampin, β-carotene, tetracycline, indocyanine green, Evan's blue, and methylene blue.
32. The tissue marking ink of claim 27 , wherein the chromophore is selected from the group consisting of FD&C Blue No. 2, FD&C Blue No. 1 (Brilliant Blue FCF), FD&C Green No. 3 (Fast Green FCF), FD&C Red No. 3 (Erythrosine), FD&C Red No. 40 (ALLURA™ Red AC), FD&C Yellow No. 5 (Tartrazine), and FD&C Yellow No. 6 (Sunset Yellow FCF).
33. The tissue marking ink of claim 27 , wherein the chromophore is a soluble inorganic salt selected from the group consisting of copper sulfate, Cu(NH 3 ) 2+ , MnO 4 , NiCl 2 , CrO 4 , and Cr 2 O 7 2− .
34. The tissue marking ink of claim 27 , wherein the chromophore is white.
35. The tissue marking ink of claim 27 , wherein the chromophore is yellow.
36. The tissue marking ink of claim 27 , wherein the chromophore is blue.
37. The tissue marking ink of claim 27 , wherein the chromophore is green.
38. The tissue marking ink of claim 27 , wherein the chromophore is red.
39. The tissue marking ink of claim 26 , wherein the particle is less than about 5 microns in diameter.
40. The tissue marking ink of claim 26 , wherein the particle is in the nanometer size range.
41. The tissue marking ink of claim 26 , wherein the particle is suspended in a liquid carrier.
42. The tissue marking ink of claim 41 , wherein the carrier comprises alcohol, water, or glycerin, or any combination thereof.
43. The tissue marking ink of claim 26 , wherein the specific energy is laser radiation.
44. A method of applying a tissue marking, the method comprising:
providing the tissue marking ink of claim 26 ; and
implanting the particle into a tissue to form a tissue marking.
45. A method for rendering undetectable a tissue marking implanted in tissue, the tissue marking comprising a particle comprising polymethylmethacrylate (PMMA), an iron oxide absorption component, and a chromophore, wherein the particle is rendered undetectable upon exposure to a specific energy when the particle is within a tissue, the method comprising exposing the tissue marking to the specific energy for a sufficient time to render the particle undetectable.
46. The method of claim 45 , wherein the specific energy is laser radiation.