Methods for uniformly treating biological samples with electromagnetic radiation

• US 20050202395A1
• Filed: 03/14/2005
• Published: 09/15/2005
• Est. Priority Date: 03/15/2004
• Status: Active Grant

• Current Assignee: Terumo BCT Biotechnologies, LLC (Terumo Corporation)
• Original Assignee: Terumo BCT Biotechnologies, LLC (Terumo Corporation)
• Inventors: Edrich, Richard Alan, Antwiler, Glen Delbert, Goodrich, Laura
• Granted Patent: US 8,296,071 B2
• Time in Patent Office: Days
• US Class Current: 435/2
• CPC Class Codes: A61L 2/0005 for pharmaceuticals, biologicals or living parts
• CPC Class Codes: A61L 2/0011 using physical methods
• CPC Class Codes: A61L 2/0082 using chemical substances
• CPC Class Codes: A61L 2/08 Radiation
• CPC Class Codes: A61L 2/084 Visible light
• CPC Class Codes: A61L 2/085 Infrared radiation
• CPC Class Codes: A61L 2/10 Ultraviolet radiation
• CPC Class Codes: A61L 2202/22 Blood or products thereof
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

Methods, devices and device components are presented for uniformly treating fluids undergoing mixing with electromagnetic radiation. In one aspect, the present invention provides methods of treating a fluid undergoing continuous fluid mixing wherein net radiant energies necessary to provide uniform treatment of the fluid samples with electromagnetic radiation are calculate on the basis of the volume, mass or mixing rate of the fluid or any combination of these variables. In another aspect, the present invention provides algorithms for determining net radiation energies, radiant powers, and/or illumination times necessary for providing uniform treatment of fluid samples. The present invention provides methods for uniformly reducing pathogens in biological fluids, including blood and blood components.

Claims

1. A method for reducing pathogens in a fluid, said method comprising the steps of:

providing the fluid held in an at least partially transparent container, wherein the fluid comprises particles;

determining the volume of the fluid;

mixing the fluid held in the at least partially transparent container;

calculating a net radiant energy for reducing said pathogens in the fluid using the volume determined for the fluid; and

providing electromagnetic radiation having said net radiant energy to the fluid, thereby generating a photoreactive layer in the fluid wherein said electromagnetic radiation interacts with said particles; and

wherein mixing the fluid in said container transports the particles through the photoreactive layer, thereby reducing pathogens in the fluid.

2. The method of claim 1 wherein the calculated net radiant energy is proportional to the volume of the fluid.

3. The method of claim 1 wherein the calculated net radiant energy is related to the volume of the fluid in a substantially linear manner.

4. The method of claim 1 wherein the calculated net radiant energy is determined using the expression:

5. The method of claim 4 wherein the volume of the fluid is a value selected from the range of values of about 200 ml to about 400 ml and wherein said first constant (Z) is equal to about 6.24 J cm⁻

3, and said second constant (b) has a value equal to about 0.

6. The method of claim 1 wherein the calculated net radiant energy is related to the volume of said fluid in a manner selected from the groups consisting of:

a substantially logarithmic manner;

a substantially quadratic manner; and

a substantially exponential manner.

7. The method of claim 1 wherein said step of determining the volume of the fluid comprises the steps of:

measuring the mass of the fluid; and

dividing said mass of the fluid by the density of the fluid, thereby determining the volume of the fluid;

8. The method of claim 1 wherein said step of mixing the fluid held in the at least partially transparent container transports the entire volume of the fluid through said photoreactive layer, thereby reducing pathogens throughout the entire volume of the fluid.

9. The method of claim 1 further comprising the step of adding a photosensitizer to the fluid, and wherein said step of determining the volume of the fluid comprises determining the volume of the fluid having said photosensitizer.

10. The method of claim 9 wherein said photosensitizer is 7, 8-dimethyl-10-ribityl isoalloxazine.

11. The method of claim 1 wherein substantially all of said particles are exposed to equivalent effective net radiant energies.

12. The method of claim 1 wherein the fluid is a biological fluid.

13. The method of claim 12 wherein said biological fluid is selected from the group consisting of:

whole blood;

a blood component;

a red blood cell-containing blood component;

a plasma-containing blood component;

a platelet-containing blood component;

a white blood cell-containing blood component;

a solution containing one or more proteins derived from blood; and

a peritoneal solution.

14. The method of claim 1 wherein said electromagnetic radiation provided to the fluid has wavelengths in the ultraviolet region of the electromagnetic spectrum.

15. The method of claim 1 wherein said electromagnetic radiation provided to the fluid has wavelengths in the visible region of the electromagnetic spectrum.

16. The method of claim 1 wherein said step of mixing the fluid held in the at least partially transparent container comprises agitating the fluid held in the at least partially transparent container.

17. The method of claim 1 wherein the electromagnetic radiation having said net radiant energy is provided to the fluid by providing a selected radiant power for a selected illumination period.

18. A method for reducing pathogens in a fluid, said method comprising the steps of:

providing the fluid held in an at least partially transparent container, wherein the fluid comprises particles;

mixing the fluid held in the at least partially transparent container at a selected mixing rate;

calculating a net radiant energy for reducing said pathogens in the fluid using the selected mixing rate of the fluid; and

providing electromagnetic radiation having said net radiant energy to the fluid, thereby generating a photoreactive layer in the fluid wherein said electromagnetic radiation interacts with said particles; and

wherein mixing the fluid in said container transports said particles through said photoreactive layer, thereby reducing pathogens in the fluid.

19. The method of claim 18 wherein the calculated net radiant energy is inversely related to said selected mixing rate.

20. The method of claim 18 wherein substantially all of said particles are exposed to equivalent effective net radiant energies.

21. The method of claim 18 wherein said step of mixing the fluid held in the at least partially transparent container at a selected mixing rate comprises agitating the fluid held in the at least partially transparent container.

22. The method of claim 18 wherein said step of mixing the fluid held in the at least partially transparent container transports the entire volume of the fluid through said photoreactive layer, thereby reducing pathogens throughout the entire volume of the fluid.

23. The method of claim 18 further comprising the step of adding a photosensitizer to the fluid.

24. The method of claim 18 wherein said photosensitizer is 7, 8-dimethyl-10-ribityl isoalloxazine.

25. A method for uniformly treating a plurality of fluid samples with electromagnetic radiation, said method comprising the steps of:

providing said plurality of fluid samples, wherein each fluid sample comprises particles;

providing each of the fluid samples held in at least partially transparent containers;

determining the volumes of each of the fluid samples held in at least partially transparent containers;

mixing each of the fluid samples held in the at least partially transparent containers;

calculating net radiant energies for each of the fluid samples using the volumes determined for each of the fluid samples;

providing electromagnetic radiation having said net radiant energies to each of the fluid samples, thereby generating photoreactive layers in each of the fluid samples, wherein said electromagnetic radiation interacts with said particles in photoreactive layers of each fluid sample; and

wherein mixing the fluid samples transports said particles through said photoreactive layers, thereby uniformly treating the plurality of fluid samples with electromagnetic radiation.

26. The method of claim 25 wherein the calculated net radiant energies provided to each of the fluid samples are related to the volumes of each of the fluid samples in a substantially linear manner.

27. The method of claim 25 wherein said step of mixing each of the fluid sample held in at least partially transparent containers transports the entire volumes of the fluid samples through said photoreactive layers, thereby reducing pathogens throughout the entire volumes of the fluid samples.

28. The method of claim 25 wherein the calculated net radiant energies provided to each fluid sample are provided by the expression:

29. The method of claim 28 wherein the volumes of the fluid samples are selected from the range of values of about 200 ml to about 400 ml and wherein said first constant (Z) is equal to about 6.24 J cm⁻

3, and said second constant (b) has a value equal to about 0.

30. The method of claim 25 wherein substantially all of said particles comprising all of the fluid samples are exposed to equivalent effective net radiant energies.

31. The method of claim 25 wherein said step of determining the volumes of each of the fluid samples comprises the steps of:

measuring the masses of each of the fluid samples; and

dividing the masses of each of the fluid samples by estimates of the densities of each of the fluid samples, thereby determining the volumes of each of the fluid samples.

32. The method of claim 25 wherein said step of mixing each of the fluid samples comprises agitating each of the fluid samples held in at least partially transparent containers.

33. A method for uniformly treating a plurality of fluid samples with electromagnetic radiation, said method comprising the steps of:

providing said plurality of fluid samples, wherein each fluid sample comprises particles;

providing each of the fluid samples held in at least partially transparent containers;

mixing each of the fluid samples held in at least partially transparent containers at selected fluid mixing rates;

calculating net radiant energies for each of the fluid samples using the selected fluid mixing rates for each of the fluid samples;

providing electromagnetic radiation having said net radiant energies to each of the fluid samples, thereby generating photoreactive layers in each of the fluid samples, wherein said electromagnetic radiation interacts with said particles in photoreactive layers of the fluid samples; and

wherein mixing the fluid samples transports said particles through said photoreactive layers, thereby uniformly treating the plurality of fluid samples with electromagnetic radiation.

34. The method of claim 33 wherein the calculated net radiant energies are inversely related to said selected mixing rates.

35. The method of claim 33 wherein substantially all of said particles comprising all of the fluid samples are exposed to equivalent effective net radiant energies.

36. The method of claim 33 wherein said step of mixing each fluid sample held in at least partially transparent containers transports the entire volumes of the fluid samples through said photoreactive layers, thereby reducing pathogens throughout the entire volumes of the fluid samples.

37. The method of claim 33 wherein said step of mixing each of the fluid samples held in at least partially transparent containers at selected fluid mixing rates comprises agitating each of the fluid samples held in at least partially transparent containers.

38. A system for reducing pathogens in a volume of a fluid comprising particles, said system comprising:

a partially transparent container for holding the fluid;

a means for mixing the fluid at a selected mixing rate;

a light source controller for determining a net radiant energy for reducing pathogens in the fluid, wherein said light source controller calculates said net radiant energy based on the volume of the fluid, the selected mixing rate or both, wherein said light source controller generates an output signal corresponding to said calculated net radiant energy; and

a source of electromagnetic radiation operationally connected to said light source controller for receiving the output signal corresponding to said calculated net radiant energy, and for exposing the fluid to electromagnetic radiation having said net radiant energy thereby generating a photoreactive layer in the fluid wherein said electromagnetic radiation interacts with said particles;

whereby mixing of the fluid circulates said particles through the photoreactive layer, thereby reducing pathogens in the volume of the fluid.

39. The system of claim 38 wherein the light source controller executes an algorithm that determines the net radiant energy, and wherein the net radiant energy is substantially linearly related to the volume of the fluid by operation of the algorithm.

40. The system of claim 39 wherein said algorithm determines the net radiant energy using the expression:

41. The method of claim 40 wherein the volume of the fluid is a value selected from the range of values of about 200 ml to about 400 ml and wherein said first constant (Z) is equal to about 6.24 J cm⁻

3, and said second constant (b) has a value equal to about 0.

42. The system of claim 38 wherein the light source controller executes an algorithm that determines the calculated net radiant energy, and wherein the net radiant energy is inversely related to the mixing rate of the fluid by operation of the algorithm.

43. The system of claim 38 further comprising a means of determining the volume of the fluid.

44. The system of claim 38 wherein the means for mixing the fluid at a selected mixing rate is an agitator operationally connected to said partially transparent container.

45. The system of claim 38 wherein mixing the fluid held in the at least partially transparent container transports the entire volume of the fluid through said photoreactive layer, thereby reducing pathogens throughout the entire volume of the fluid.

46. The system of claim 38 wherein substantially all of said particles comprising the fluid are exposed to equivalent effective net radiant energies.

47. The system of claim 38 wherein said source of electromagnetic radiation provides electromagnetic radiation having wavelengths in the ultraviolet region of the electromagnetic spectrum, visible region of the electromagnetic spectrum or both to the fluid.