Photoeradication of microorganisms with pulsed purple or blue light

• US 10,639,498 B2
• Filed: 04/18/2018
• Issued: 05/05/2020
• Est. Priority Date: 05/26/2016
• Status: Active Grant

• Current Assignee: San Diego State University (SDSU) Research Foundation
• Original Assignee: CareWear Corp.
• Inventors: Enwemeka, Chukuka S., Castel, John C.
• Primary Examiner(s): Cleveland, Timothy C
• Application Number:
  US15/955,773
• Publication Number:
  US 20180280723A1
• Time in Patent Office: 748 Days
• CPC Class Codes: A23L 3/26 by irradiation without heating
• CPC Class Codes: A61B 2017/00057 Light
• CPC Class Codes: A61L 2/08 Radiation
• CPC Class Codes: A61L 2/084 Visible light
• CPC Class Codes: A61L 2/16 using chemical substances
• CPC Class Codes: A61L 2202/11 Apparatus for generating biocidal substances, e.g. vaporisers, UV lamps
• CPC Class Codes: A61N 2005/0628 including a radiation sensor
• CPC Class Codes: A61N 2005/0632 Constructional aspects of the apparatus
• CPC Class Codes: A61N 2005/0651 Diodes
• CPC Class Codes: A61N 2005/0653 Organic light emitting diodes
• CPC Class Codes: A61N 2005/0663 Coloured light
• CPC Class Codes: A61N 5/0616 Skin treatment other than tanning
• CPC Class Codes: A61N 5/0624 for eliminating microbes, germs, bacteria on or in the body

Abstract

The present invention is directed to a system and method for photoeradication of microorganisms from a target. A light source is configured to irradiate the target with purple or blue light in a pulsed mode of irradiation at an average irradiance that preferably ranges from 0.1 mW/cm² to 20 mW/cm². An electronic circuit is configured to control the light source in accordance with an irradiation schedule that includes a plurality of irradiation sessions. The light source is controlled to provide the purple or blue light at a radiant exposure that preferably ranges from 0.5 J/cm² to 60 J/cm² during each of the irradiation sessions. The irradiation sessions are provided at a plurality of time intervals so as to cause photoeradication of all or a portion of the microorganisms.

Claims

1. A method for photoeradication of microorganisms from a target, the method comprising:

obtaining test data for each of a plurality of experiments, wherein each experiment comprises irradiating test microorganisms with a sequence of light pulses having a plurality of pulse parameters and a wavelength that ranges from 380 nm to 500 nm, wherein the pulse parameters comprise a peak irradiance for each of the light pulses, a pulse duration for each of the light pulses, and an off time between each two adjacent light pulses, and wherein the test data comprises a survival rate for the test microorganisms after irradiation with the light pulses;

analyzing the test data to identify the pulse parameters that result in a survival rate for the test microorganisms of between 0% and 50%; and

irradiating the microorganisms of the target with the light pulses having the identified pulse parameters in accordance with an irradiation schedule.

2. The method of claim 1, wherein the peak irradiance of the light pulses ranges from 0.3 mW/cm² to 60 mW/cm², the pulse duration of the light pulses ranges from 5 microseconds to 1,000 microseconds, and the off time between the light pulses ranges from 10 microseconds to 1 second.

3. The method of claim 2, wherein the light pulses are provided at a duty factor that ranges from 20% to 33% and a pulse repetition rate that ranges from 33 kHz to 40 kHz.

4. The method of claim 1, wherein the irradiation schedule comprises a plurality of irradiation sessions wherein the irradiation sessions are timed to a depletion and recovery cycle of a photoactive molecule associated with the microorganisms in which the irradiation sessions occur during a depletion stage of the photoactive molecule and the recovery periods occur during a recovery stage of the photoactive molecule.

5. The method of claim 4, wherein the microorganisms comprise Propionibacterium acnes and the photoactive molecule comprises porphyrin.

6. The method of claim 1, wherein the target comprises one of a region of skin, a tissue or a wound infected by the microorganisms so as to cause a bacterial infection.

7. The method of claim 1, wherein the target comprises an environment contaminated with the microorganisms.

8. The method of claim 1, wherein the target comprises food contaminated with the microorganisms.

25. The method of claim 1, further comprising:

determining a depletion and recovery cycle of the photoactive molecule comprising (a) a depletion stage in which the photoactive molecule decreases to a lower level during irradiation of the test microorganisms and (b) a recovery stage in which the photoactive molecule increases to an upper level with no irradiation of the test microorganisms; and

wherein the irradiation schedule comprises a plurality of irradiation sessions separated by one or more recovery periods, and wherein the irradiation sessions are timed to the depletion and recovery cycle of the photoactive molecule in which the irradiation sessions occur during the depletion stage of the photoactive molecule and the recovery periods occur during the recovery stage of the photoactive molecule.

26. The method of claim 25, wherein the light is provided at a radiant exposure that ranges from 3.6 J/cm² to 20 J/cm² during each of the irradiation sessions.

9. A method for photoeradication of microorganisms from a target, the method comprising:

irradiating the target with purple or blue light in a pulsed mode of irradiation during each of a plurality of irradiation sessions, wherein the light comprises a plurality of light pulses each of which excites a photoactive molecule present in the microorganisms and wherein an off time between the light pulses enables return of the photoactive molecule to a ground state to thereby create an oxidation reaction that produces free radicals which destroy a cellular structure of the microorganisms, wherein the light pulses are provided at a dose controlled by feedback from a photo sensor during each of the irradiation sessions, wherein the photo sensor detects light emitted by the photoactive molecule during irradiation of the microorganisms, wherein each of the irradiation sessions is terminated when the detected light reaches a predetermined lower level, and wherein the microorganisms are intermittently irradiated to determine when the detected light returns to a predetermined upper level upon which a next of the irradiation sessions is initiated.

10. The method of claim 9, wherein the light has a wavelength that ranges from 380 nm to 500 nm.

11. The method of claim 9, wherein the microorganisms comprise Propionibacterium acnes and the photoactive molecule comprises porphyrin.

12. The method of claim 9, wherein the target comprises one of a region of skin, a tissue or a wound infected by the microorganisms so as to cause a bacterial infection.

13. The method of claim 9, wherein the target comprises an environment contaminated with the microorganisms.

14. The method of claim 9, wherein the target comprises food contaminated with the microorganisms.

15. A method for photoeradication of microorganisms from a target, the method comprising:

determining a plurality of pulse parameters for a sequence of light pulses having a wavelength that ranges from 380 nm to 500 nm, wherein the pulse parameters comprise (a) a peak irradiance and a pulse duration for each of the light pulses that are selected to enable excitation of a photoactive molecule present in the microorganisms and (b) an off time between each two adjacent light pulses that is selected to enable return of the photoactive molecule to a ground state to thereby create an oxidation reaction that produces free radicals which destroy a cellular structure of the microorganisms;

determining an irradiation schedule for application of the light pulses having the pulse parameters during each of a plurality of irradiation sessions separated by one or more recovery periods, wherein the irradiation sessions are timed to target the microorganisms at a specified time during a replication cycle of the microorganisms; and

irradiating the microorganisms of the target with the light pulses having the pulse parameters in accordance with the irradiation schedule.

16. The method of claim 15, wherein the pulse parameters and the irradiation schedule result in a survival rate for the microorganisms of less than 50%.

17. The method of claim 15, wherein the pulse parameters and the irradiation schedule result in a survival rate for the microorganisms of less than 10%.

18. The method of claim 15, wherein the pulse parameters and the irradiation schedule result in a survival rate for the microorganisms of 0%.

19. The method of claim 15, wherein the light has an average irradiance that ranges from 0.1 mW/cm² to 20 mW/cm² and is provided at a radiant exposure that ranges from 0.5 J/cm² to 60 J/cm² during each of the irradiation sessions.

20. The method of claim 15, wherein the light pulses are provided at a fixed dose during each of the irradiation sessions.

21. The method of claim 15, wherein the microorganisms comprise Propionibacterium acnes and the photoactive molecule comprises porphyrin.

22. The method of claim 15, wherein the target comprises one of a region of skin, a tissue or a wound infected by the microorganisms so as to cause a bacterial infection.

23. The method of claim 15, wherein the target comprises an environment contaminated with the microorganisms.

24. The method of claim 15, wherein the target comprises food contaminated with the microorganisms.

27. The method of claim 15, further comprising:

determining a depletion and recovery cycle of the photoactive molecule comprising (a) a depletion stage in which the photoactive molecule decreases to a lower level during irradiation of the microorganisms and (b) a recovery stage in which the photoactive molecule increases to an upper level with no irradiation of the microorganisms; and

wherein the irradiation sessions are timed to the depletion and recovery cycle of the photoactive molecule in which the irradiation sessions occur during the depletion stage of the photoactive molecule and the recovery periods occur during the recovery stage of the photoactive molecule.

28. The method of claim 15, wherein the light is provided at a radiant exposure that ranges from 3.6 J/cm² to 20 J/cm² during each of the irradiation sessions.