Laser Device for Treatment of Wounds

Abstract

The present invention relates to a device and a method for treatment or disinfection of a volume comprising bacteria in the vicinity of cells, such as a laser device and the use of the laser device for the treatment of wounds. In particular, it relates to the treatment of chronic wounds.

Claims

1. A device for treatment or disinfection of a volume comprising bacteria in the vicinity of cells, said device comprising: a. Means for generating a beam of electromagnetic radiation, said means preferably comprising a laser; b. Optionally means for spreading said beam of electromagnetic radiation, said means for spreading preferably comprising a diverging lens; c. Means for collimating said beam of electromagnetic radiation, said means for collimating preferably comprising a converging lens, thereby providing a beam of collimated electromagnetic radiation; d. Means for focusing said beam of collimated electromagnetic radiation, said means for focusing preferably comprising at least one focusing lens, wherein said means for focusing allows focusing said beam of collimated electromagnetic radiation in at least one focal volume inside said volume to be treated or disinfected; Wherein said device comprises means allowing changing the position of said at least one focal volume inside said volume to be treated or disinfected; and Wherein said device is adapted to allow eradicating or harming said bacteria with said electromagnetic radiation while leaving said cells substantially unharmed, by allowing said electromagnetic radiation to provide sufficient energy in said at least one focal volume to eradicate or harm said bacteria while providing insufficient energy to substantially harm said cells.

2. The device according to claim 1, wherein said means b. comprises a diverging or negative lens.

3. The device according to any of the preceding claims, wherein said means c. comprises a condenser lens or converging or positive lens or a collimator.

4. The device according to any of the preceding claims, wherein said means d. comprises a plurality of lenses, such as a micro array lens.

5. The device according to any of the preceding claims, wherein at least one of said means b., c., and d. allows changing the position of said focal volume inside said volume to be treated or disinfected.

6. The device according to any of the preceding claims, wherein said device comprises means for changing the distance between the means c. and the means d., thereby allowing changing the position of said focal volume inside said volume to be treated or disinfected.

7. The device according to any of the preceding claims, wherein said device comprises means for changing the position of said means d. with respect to said collimated electromagnetic direction in at least two independent directions, thereby allowing changing the position of said focal volume inside said volume to be treated or disinfected.

8. A device for treatment or disinfection of a volume comprising bacteria in the vicinity of cells, said device comprising: e. Means for generating collimated electromagnetic radiation; f. Means for focusing said collimated electromagnetic radiation, said means for focusing preferably comprising at least one focusing optical lens, wherein said means for focusing allows focusing said electromagnetic radiation in at least one focal volume inside said volume to be treated or disinfected; Wherein said device comprises means allowing changing the position of said at least one focal volume inside said volume to be treated or disinfected; and Wherein said device is adapted to allow eradicating or harming said bacteria with said electromagnetic radiation while leaving said cells substantially unharmed, by allowing said electromagnetic to provide sufficient energy in said at least one focal volume to eradicate or harm said bacteria while providing insufficient energy to substantially harm said cells.

9. The device according to any of the preceding claims, wherein said focal volume has a volume of 1-10.000 m.sup.3, preferably 2-5000 m.sup.3, more preferred 3-3000 m.sup.3, preferably 5-2000 m.sup.3, more preferred 10-1000 m.sup.3, preferably 20-500 m.sup.3, more preferred 30-400 m.sup.3, preferably 50-200 m.sup.3, more preferred about 100 m.sup.3.

10. The device according to any of the preceding claims, wherein said focal volume has a volume of at least 1 m.sup.3, preferably at least 2 m.sup.3, more preferred at least 3 m.sup.3, preferably at least 5 m.sup.3, more preferred at least 10 m.sup.3, preferably at least 20 m.sup.3, more preferred at least 50 m.sup.3, preferably at least 100 m.sup.3, more preferred at least 200 m.sup.3, preferably at least 300 m.sup.3, more preferred at least 500 m.sup.3, preferably at least 1000 m.sup.3, more preferred at least 2000 m.sup.3.

11. The device according to any of the preceding claims, wherein said focal volume has a volume of less than 5000 m.sup.3, preferably less than 3000 m.sup.3, more preferred less than 2000 m.sup.3, preferably less than 1000 m.sup.3, more preferred less than 500 m.sup.3, preferably less than 300 m.sup.3, more preferred less than 200 m.sup.3, preferably less than 100 m.sup.3, more preferred less than 50 m.sup.3, preferably less than 30 m.sup.3, more preferred less than 20 m.sup.3, preferably less than 10 m.sup.3, more preferred less than 5 m.sup.3.

12. The device according to any of the preceding claims, wherein the focus depth is 0.5-500 m, preferably 2-200 m, more preferred 3-100 m, preferably 5-50 m, more preferred 10-20 m.

13. The device according to any of the preceding claims, wherein the focus spot is an area of 0.05-100 m.sup.2, preferably 0.1-50 m.sup.2, more preferred 0.2-20 m.sup.2, preferably 0.5-10 m.sup.2, more preferred 1-5 m.sup.2.

14. The device according to any of the preceding claims, wherein said volume to be treated or disinfected comprises at least part of a wound, such as a chronic wound.

15. The device according claim 14, wherein said device has access to 3D information about the distribution of said wound in the tissue thereby allowing focusing the electromagnetic radiation inside said wound.

16. The device according to any of the preceding claims, wherein said device further comprises means for moving said volume to be treated or disinfected with respect to said focal volume thereby changing the position of said focal volume with respect to said volume to be treated or disinfected.

17. The device according to any of the preceding claims, wherein said device further comprises means for keeping said volume to be treated or disinfected in a fixed position with respect to said device.

18. The device according to any of the preceding claims, wherein said device allows changing the position of said focal volume inside said volume to be treated or disinfected in a helical and/or zigzag pattern.

19. The device according to any of the preceding claims, wherein said device allows changing the position of said focal volume, allowing said focal volume to travel in lines through said volume to be treated or disinfected with a determined spacing between said lines.

20. The device according to claim 19, wherein said determined spacing is 1-200 m, preferably 2-100 m, more preferred 3-50 m, preferably 5-40 m, more preferred 10-30 m, preferably 15-25 m, more preferred about 20 m.

21. The device according to any of the preceding claims, wherein said electromagnetic radiation has a wavelength of 100-3000 nm, preferably 200-2500 nm, more preferred 300-2000 nm, preferably 500-1500 nm, more preferred 700-1400 nm, preferably 800-1300 nm, more preferred 900-1200 nm, preferably 1000-1125 nm, more preferred 1025-1100 nm, preferably 1050-1080 nm, more preferred 1060-1070 nm, preferably about 1064 nm.

22. The device according to any of the preceding claims, wherein said device allows said electromagnetic radiation to be provided as electromagnetic pulses.

23. The device according to claim 22, wherein said electromagnetic pulses have duration of 0.01-1000 ns, more preferred 0.05-100 ns, preferably 0.1-20 ns, more preferred 0.5-10 ns, preferably 1-8 ns, more preferred 2-6 ns, preferably 3-5 ns, more preferred about 4 ns.

24. The device according to claim 22 or 23, wherein the electromagnetic pulses have duration sufficient to eradicate or harm bacteria while having duration insufficient to substantially harm cells.

25. The device according to any of the claims 22-24, wherein each of said electromagnetic pulses provides an amount of energy of 1-10.000 nJ, preferably 5-5.000 nJ, more preferred 10-2500 nJ, preferably 20-1000 nJ, more preferred 30-500 nJ, preferably 40-100 nJ, more preferred about 50 nJ in each of said at least one focal volume.

26. The device according to any of the claims 22-25, wherein each of said electromagnetic pulses provides an amount of energy of less than 10.000 nJ, preferably less than 5.000 nJ, more preferred less than 2500 nJ, preferably less than 1000 nJ, more preferred less than 500 nJ, preferably less than 100 nJ, more preferred about less than 50 nJ in each of said at least one focal volume.

27. The device according to any of the claims 22-26, wherein said device allows providing said electromagnetic pulses with a frequency of 1-100 kHz, more preferred 5-50 kHz, preferably 10-40 kHz, more preferred 15-30 kHz, preferably about 20 kHz.

28. The device according to any of the claims 22-25, wherein the electromagnetic pulses are focused inside said volume to be treated or disinfected with a distance of 1-200 m, preferably 2-100 m, more preferred 3-50 m, preferably 5-40 m, more preferred 10-30 m, preferably 15-25 m, more preferred about 20 m between said pulses.

29. The device according to any of the preceding claims, wherein said volume to be treated or disinfected has a surface, and wherein said at least one focal volume is at least a distance of 1 m, more preferred at least 2 m, preferably at least 5 m, more preferred at least 10 m, preferably at least 20 m, more preferred at least 50 m, preferably at least 100 m, more preferred at least 200 m, from said surface.

30. The device according to any of the preceding claims, wherein said volume to be treated or disinfected has a surface, and wherein said at least one focal volume is a distance of 1-500 m, more preferred 5-300 m, preferably 10-200 m, more preferred 40-100 m, from said surface.

31. The device according to any of the preceding claims, wherein the focal length is 1-100 mm, more preferred 2-50 mm, preferably 3-30 mm, more preferred 4-20, preferably 5-10 mm.

32. A use of a device according to any of the preceding claims for treatment or prophylaxis.

33. The use according to claim 32, wherein the subject is human or animal, preferably a mammal.

34. The use according to any of the claims 32-33, wherein said volume to be treated or disinfected is part of the body, such as a limb, a leg or an arm.

35. The use according to any of the claims 32-34, for topical use.

36. The use according to any of the claims 32-35, for non-invasive use.

37. The use according to any of the claims 32-36, for use without medicaments.

38. A use of a device according to any of the preceding device claims for in-vitro or non-medical purposes, such as cosmetic purposes.

39. A method for the treatment or disinfection of a volume comprising bacteria in the vicinity of cells, said method comprising transmitting electromagnetic radiation to at least one focal volume inside said volume to be treated or disinfected by allowing said electromagnetic to provide sufficient energy in said at least one focal volume to eradicate or harm said bacteria while providing insufficient energy to substantially harm said cells.

40. The method according to claim 39, wherein said volume to be treated or disinfected has a surface, and wherein said at least one focal volume is at least a distance of 1 m, more preferred at least 2 m, preferably at least 5 m, more preferred at least 10 m, preferably at least 20 m, more preferred at least 50 m, preferably at least 100 m, more preferred at least 200 m, from said surface.

41. The method according to any of the claims 39-40, wherein said volume to be treated or disinfected has a surface, and wherein said at least one focal volume is a distance of 1-500 m, more preferred 5-300 m, preferably 10-200 m, more preferred 40-100 m, from said surface.

42. The method according to any of the claims 39-41, wherein said electromagnetic radiation is generated by a laser.

43. The method according to claim 42, wherein said laser is operated in a continuous or pulsed mode.

44. The method according to any of the claims 39-43, wherein said at least one focal volume is moved within said volume to be treated or disinfected with a velocity allowing said electromagnetic to provide sufficient energy in said at least one focal volume to eradicate or harm said bacteria while providing insufficient energy to substantially harm said cells.

45. The method according to any of the preceding claims, wherein said volume to be treated or disinfected comprises at least part of a wound, such as a chronic wound.

46. The method according claim 45, wherein said the electromagnetic radiation is focused inside said wound.

47. The method according to any of the preceding claims, wherein said method comprises changing the position of said focal volume inside said volume to be treated or disinfected in a helical and/or zigzag pattern.

48. The method according to any of the preceding claims, wherein said method comprises changing the position of said focal volume, allowing said focal volume to travel in lines through said volume to be treated or disinfected with a determined spacing between said lines.

49. The method according to claim 48, wherein said determined spacing is 1-200 m, preferably 2-100 m, more preferred 3-50 m, preferably 5-40 m, more preferred 10-30 m, preferably 15-25 m, more preferred about 20 m.

50. The method according to any of the preceding claims, wherein said electromagnetic radiation has a wavelength of 100-3000 nm, preferably 200-2500 nm, more preferred 300-2000 nm, preferably 500-1500 nm, more preferred 700-1400 nm, preferably 800-1300 nm, more preferred 900-1200 nm, preferably 1000-1125 nm, more preferred 1025-1100 nm, preferably 1050-1080 nm, more preferred 1060-1070 nm, preferably about 1064 nm.

51. The method according to any of the preceding claims, wherein said electromagnetic radiation is provided as electromagnetic pulses.

52. The method according to claim 51, wherein said electromagnetic pulses have duration of 0.1-20 ns, more preferred 0.5-10 ns, preferably 1-8 ns, more preferred 2-6 ns, preferably 3-5 ns, more preferred about 4 ns.

53. The method according to claim 51 or 52, wherein the electromagnetic pulses have duration sufficient to eradicate or harm bacteria while having duration insufficient to substantially harm cells.

54. The method according to any of the claims 51-53, wherein each of said electromagnetic pulses provides an amount of energy of 1-10.000 nJ, preferably 5-5.000 nJ, more preferred 10-2500 nJ, preferably 20-1000 nJ, more preferred 30-500 nJ, preferably 40-100 nJ, more preferred about 50 nJ in each of said at least one focal volume.

55. The method according to any of the claims 51-54, wherein each of said electromagnetic pulses provides an amount of energy of less than 10.000 nJ, preferably less than 5.000 nJ, more preferred less than 2500 nJ, preferably less than 1000 nJ, more preferred less than 500 nJ, preferably less than 100 nJ, more preferred about less than 50 nJ in each of said at least one focal volume.

56. The method according to any of the claims 51-55, wherein said electromagnetic pulses are provided with a frequency of 1-100 kHz, more preferred 5-50 kHz, preferably 10-40 kHz, more preferred 15-30 kHz, preferably about 20 kHz.

57. The method according to any of the claims 51-56, wherein the electromagnetic pulses are focused inside said volume to be treated or disinfected with a distance of 1-200 m, preferably 2-100 m, more preferred 3-50 m, preferably 5-40 m, more preferred 10-30 m, preferably 15-25 m, more preferred about 20 m between said pulses.

58. The method according to any of the preceding claims, wherein said focal volume is moved around in said volume to be treated or disinfected, thereby providing treatment and/or disinfection of all or substantially all of said volume to be treated or disinfected.

59. The method according to any of the preceding claims, wherein said focal volume is moved around multiple times in said volume to be treated or disinfected in multiple passes.

60. The method according to any of the preceding claims, wherein the contents of said volume comprising bacteria in the vicinity of cells is substantially solid or non-liquid or non-fluid.

Description

FIGURES

[0118] FIG. 1 shows a schematic view of a device for treatment or disinfection of a volume comprising bacteria in the vicinity of cells according to an embodiment of the invention. The device comprises a diverging lens (104) for spreading the electromagnetic radiation (102) provided by a laser (not shown), and a converging lens acting as a collimator (106) for the electromagnetic radiation, and thereby providing a beam of collimated electromagnetic radiation (107). A micro array lens (108) focuses the collimated electromagnetic radiation in a focal volume (110) inside the volume subjected to treatment or being disinfected, where the focal length (112) is the distance between the micro array lens and the focus point (111) at the center of the focal volume (110). The device allows changing the distance between the converging lens (106) and the micro array lens (108), i.e. along the axis indicated with z, as well as the position of the micro array lens in the x-y plane, thereby changing the position of the focal volume (110) inside the volume comprising bacteria.

[0119] FIG. 2 is a schematic representation of the movement of the focal volume inside the xyz volume. The device allows changing the position of the focal volume in a helical pattern (214), where the preferred distance between the lines in the z direction is 20 m (216). The electromagnetic radiation may operated in a continuous (218) or pulsed mode (220), wherein the pulses have duration sufficient to eradicate or harm the bacteria while having duration insufficient to substantially harm the cells.

[0120] FIG. 3 is a schematic view along the z-axis within the area of a micro array lens (308) according to an embodiment of the invention. Collimated electromagnetic radiation (not shown) is passed through the lens (308). The focal volume (310) is the area of the focal spot times the focus depth (322), where the area of the focal spot is calculated as (.sub.0).sup.2 if circular, and the focus depth is calculated as two times the Rayleigh length, Z.sub.R. The Rayleigh length, Z.sub.R, is calculated as Z.sub.R=(.sub.0).sup.2/ where the beam waist (324), .sub.0, is the radius of the area of the focal spot, and is the wavelength of the electromagnetic radiation.

[0121] FIG. 4 is a photograph of the device for treatment or disinfection of a volume comprising bacteria in the vicinity of cells according to an embodiment of the invention. The photograph shows a leg fixed to the device, but any infected part of the body of humans or animals is contemplated to be fixed with respect to the device.

[0122] All cited references are incorporated by reference.

[0123] The accompanying Figures and Examples are provided to explain rather than limit the present invention. It will be clear to the person skilled in the art that aspects, embodiments, claims and any items of the present invention may be combined.

[0124] Unless otherwise mentioned, all percentages are in weight/weight. Unless otherwise mentioned, all measurements are conducted under standard conditions (ambient temperature and pressure).

EXAMPLES

Example 1

[0125] Purpose: To identify the relative amount of energy required for killing a vital E. coli (Escherichia coli) cell and a vital human fibroblast cell, respectively.

[0126] Method: Human fibroblast cells and E. coli cells were stained with SYTO 9 dye and propidium iodide. A sample was prepared by mixing stained human fibroblast cells, stained E. coli cells and low-melt agarose, providing embedment of cells in the low-melt agarose. A drop was taken from the sample and placed on a glass slide. The glass slide was placed under a conventional confocal microscope equipped with a 405-nm laser. Using a standard confocal setup, a UV ablation method was utilized to selectively induce cellular death and to visualize single-cell responses in a dose-dependent manner. Vital cells were identified as being green, whereas non-vital (dead) cells were identified as being red. A vital E. coli cell was identified and the 405-nm laser was engaged. The 405-nm laser intensity was initially set low and the laser intensity was increased until one E. coli cell was killed using one laser pulse. Afterwards, starting from the laser intensity sufficient to kill one E. coli cell, the intensity was decreased until one E. coli cell was no longer killed using one laser pulse. For each new laser intensity a new E. coli cell was identified and used. The procedure was repeated for human fibroblast cells. The applied laser power output is instrument-specific and will differ for every confocal setup, but may be adjusted as described here to achieve the desired effect. Subsequently the identified effect or power setting may be used to eradicate or harm bacteria with the electromagnetic radiation while leaving cells substantially unharmed.

[0127] Results: Using the 405-nm laser, E. coli cells were generally killed when applying laser intensities of 35% of full power with one single laser pulse, whereas human fibroblast cells in general required laser intensities of 100% of full power at least 50 times in order to kill the cells.

[0128] Conclusion: The amount of energy required for killing an E. coli cell is considerably less that the amount of energy required for killing a human fibroblast cell, likely in the order of about 1000 times less.