WO2016064945A1 - Systems and methods for pathogen inactivation in blood using uv irradiation while minimizing heat transfer thereto - Google Patents
Systems and methods for pathogen inactivation in blood using uv irradiation while minimizing heat transfer thereto Download PDFInfo
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
- A61M1/36—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
- A61M1/3681—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits by irradiation
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2/00—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
- A61L2/0005—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor for pharmaceuticals, biologicals or living parts
- A61L2/0011—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor for pharmaceuticals, biologicals or living parts using physical methods
- A61L2/0029—Radiation
- A61L2/0047—Ultraviolet radiation
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
- A61M1/36—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
- A61M1/3681—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits by irradiation
- A61M1/3683—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits by irradiation using photoactive agents
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01J—MEASUREMENT OF INTENSITY, VELOCITY, SPECTRAL CONTENT, POLARISATION, PHASE OR PULSE CHARACTERISTICS OF INFRARED, VISIBLE OR ULTRAVIOLET LIGHT; COLORIMETRY; RADIATION PYROMETRY
- G01J5/00—Radiation pyrometry, e.g. infrared or optical thermometry
- G01J5/02—Constructional details
- G01J5/06—Arrangements for eliminating effects of disturbing radiation; Arrangements for compensating changes in sensitivity
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01K—MEASURING TEMPERATURE; MEASURING QUANTITY OF HEAT; THERMALLY-SENSITIVE ELEMENTS NOT OTHERWISE PROVIDED FOR
- G01K13/00—Thermometers specially adapted for specific purposes
- G01K13/02—Thermometers specially adapted for specific purposes for measuring temperature of moving fluids or granular materials capable of flow
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/10—Inactivation or decontamination of a medicinal preparation prior to administration to an animal or a person
- A61K41/17—Inactivation or decontamination of a medicinal preparation prior to administration to an animal or a person by ultraviolet [UV] or infrared [IR] light, X-rays or gamma rays
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2/00—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
- A61L2/02—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor using physical phenomena
- A61L2/08—Radiation
- A61L2/10—Ultra-violet radiation
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2202/00—Aspects relating to methods or apparatus for disinfecting or sterilising materials or objects
- A61L2202/20—Targets to be treated
- A61L2202/22—Blood or products thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
- A61M1/36—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
- A61M1/3621—Extra-corporeal blood circuits
- A61M1/3622—Extra-corporeal blood circuits with a cassette forming partially or totally the blood circuit
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M2202/00—Special media to be introduced, removed or treated
- A61M2202/04—Liquids
- A61M2202/0413—Blood
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M2205/00—General characteristics of the apparatus
- A61M2205/05—General characteristics of the apparatus combined with other kinds of therapy
- A61M2205/051—General characteristics of the apparatus combined with other kinds of therapy with radiation therapy
- A61M2205/053—General characteristics of the apparatus combined with other kinds of therapy with radiation therapy ultraviolet
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01J—MEASUREMENT OF INTENSITY, VELOCITY, SPECTRAL CONTENT, POLARISATION, PHASE OR PULSE CHARACTERISTICS OF INFRARED, VISIBLE OR ULTRAVIOLET LIGHT; COLORIMETRY; RADIATION PYROMETRY
- G01J5/00—Radiation pyrometry, e.g. infrared or optical thermometry
- G01J5/02—Constructional details
- G01J5/06—Arrangements for eliminating effects of disturbing radiation; Arrangements for compensating changes in sensitivity
- G01J2005/065—Arrangements for eliminating effects of disturbing radiation; Arrangements for compensating changes in sensitivity by shielding
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01K—MEASURING TEMPERATURE; MEASURING QUANTITY OF HEAT; THERMALLY-SENSITIVE ELEMENTS NOT OTHERWISE PROVIDED FOR
- G01K13/00—Thermometers specially adapted for specific purposes
- G01K13/02—Thermometers specially adapted for specific purposes for measuring temperature of moving fluids or granular materials capable of flow
- G01K13/026—Thermometers specially adapted for specific purposes for measuring temperature of moving fluids or granular materials capable of flow of moving liquids
Definitions
- the present relates to systems and methods for the UV-irradiation of a biological fluid for the purposes of reduction of pathogens therein. While the primary object of the invention is to treat blood, blood-based products and synthetic blood substitutes, the concepts of the present invention may be used for treating other fluids such as those encountered in beverage industries including dairy, distilling and brewing, as well as in water treatment industries including sewerage and purification systems. Other uses of the invention contemplate treating blood from a subject and returning the blood to the subject after completion of the treatment.
- pathogens is used broadly for the purposes of the present invention to include a variety of harmful microorganisms such as bacteria, fungi, viruses (including among others a human immunodeficiency virus, a hepatitis A, B and C virus, an influenza virus, a hemorrhagic fever virus such as Ebola virus etc.), parasites, molds, yeasts and other similar organisms which may be found in human or non-human blood and products derived from blood, as well as various other body fluids such (as for example milk) and synthetic fluids manufactured for use as replacements for any such body fluids or components thereof.
- harmful microorganisms such as bacteria, fungi, viruses (including among others a human immunodeficiency virus, a hepatitis A, B and C virus, an influenza virus, a hemorrhagic fever virus such as Ebola virus etc.), parasites, molds, yeasts and other similar organisms which may be found in human or non-human blood and products derived from blood, as
- UVC Short wavelengths ultraviolet light
- UVC penetration is very limited due to absorption of UV irradiation by the red cells.
- all attempts to use UV irradiation for sterilizing whole blood or red cells have been unsuccessful so far.
- UV irradiation source should not be too powerful nor may the fluid be exposed to the UV radiation for too long, if one is to avoid damaging the components of the biological fluid.
- sufficient UVC energy needs to be transmitted to the blood flow to assure substantial reduction and effective elimination of the pathogens. This balance is critical in achieving desired effectiveness of UVC treatment.
- UV irradiation In addition to mixing, a sufficient intensity of the UV irradiation needs to be provided by a source of UV irradiation.
- Traditional devices used as such source include low pressure and medium pressure mercury UV lamps, amalgam UV lamps, arc UV lamps, fluorescent UV lamps, halogen UV lamps, and xenon UV lamps.
- Such lamps have a number of disadvantages when used directly for the purposes of the present invention as they produce low level of UV output given the energy requirements, have large size, fragile and if broken represent an environmental hazard of mercury contamination.
- traditional UV lamps produce UV output over a broad range of UV wavelengths, some of which may be harmful to the biological fluid.
- the system of the invention is designed for inactivation of pathogens in the biological fluid such as a unit of whole blood suitable for transfusion.
- the system includes a novel exposure chamber comprising a source of UV irradiation and a closely positioned adjacent flow path configured to expose the biological fluid to UV irradiation.
- the source of UV irradiation may be configured to emit ultraviolet light in the UVC range of wavelengths.
- UVC light may be used with a predetermined peak wavelength from about 250 nm to about 270 nm.
- the system may include a pump such as a roller pump or a centrifugal pump to propagate biological fluid such as whole blood through a UV-transparentflow path of the exposure chamber, for example in a serpentine-shaped tube.
- the flow path may include one or more static mixer elements to cause intermittent or continuous mixing of the biological fluid during its propagation through the flow path.
- the flow path may be configured for exposure of the fluid to UVC irradiation from a suitable source such as one or several UV lamps or a plurality of UV emitting diodes (UV LEDs). UV exposure of the biological fluid may be conducted at an appropriately high power density that allows sufficient UVC dose to be impinged on the fluid - such that sufficient inactivation of pathogens takes place. The treated fluid may then be propagated out of the exposure chamber and collected in a new storage bag and the disposable flow path may be discarded after use.
- a suitable source such as one or several UV lamps or a plurality of UV emitting diodes (UV LEDs).
- UV exposure of the biological fluid may be conducted at an appropriately high power density that allows sufficient UVC dose to be impinged on the fluid - such that sufficient inactivation of pathogens takes place.
- the treated fluid may then be propagated out of the exposure chamber and collected in
- the novel portion of the system includes provisions for separation of the flow path from the UV irradiation source by a layer of fluid known to absorb at least some and preferably a substantial portion of infra-red radiation emanating from the source of UV irradiation, ambient light or any other light sources to which the flow path is exposed to.
- a layer of fluid known to absorb at least some and preferably a substantial portion of infra-red radiation emanating from the source of UV irradiation, ambient light or any other light sources to which the flow path is exposed to.
- Such layer may be positioned between the flow path and the source of UV irradiation for the purposes of reducing or preventing heat transfer to the biological fluid from the source of UV irradiation.
- a UV-transparent jacket surrounding the flow path is provided and the IR-absorbing fluid is circulated therethrough.
- Introducing the IR-absorbing fluid at a temperature lower than that of the biological fluid allows the system to both absorb the IR irradiation (to prevent it from reaching the biological fluid) as well as cool the biological fluid to counteract energy absorption resulting from exposure to UV irradiation.
- FIGURE 1 is a general schematic view of the system of the invention used to treat a subject
- FIGURE 2 is a general schematic view of the system of the invention used to treat a unit of collected donor blood
- FIGURE 3 is a general schematic view of the components of the system of the invention.
- FIGURE 4 shows a serpentine flow path;
- FIGURE 5 shows one embodiment of the jacket containing IR-absorbing fluid surrounding the serpentine flow path of the system in which the direction of IR-absorbing fluid propagating through the jacket is perpendicular to the direction of biological fluid propagating through the serpentine flow path;
- FIGURE 6 shows another embodiment of the jacket containing IR-absorbing fluid in which the direction of IR-absorbing fluid propagating through the jacket is parallel to the direction of biological fluid propagating through the serpentine flow path;
- FIGURE 7 shows yet another embodiment of the jacket which surrounds the flow path and in which the direction of IR-absorbing fluid propagating therethrough is opposite to the direction of biological fluid propagating through the serpentine flow path;
- FIGURE 8 is a side view of the key elements of the system of the invention.
- FIGURE 9 is a top view of the same;
- FIGURE 10 is a side view of an alternate configuration of the system of the invention.
- FIGURE 11 is a graph showing various wavelengths of the UV lamp output prior to utilization of the IR-absorbent layer.
- FIGURE 12 is a graph showing remaining wavelengths after passing the output of a UV lamp through a layer of an IR-absorbing fluid.
- UV irradiation is used generally in this description to encompass various techniques of exposing biological fluids including blood to UV light for therapeutic purposes, such techniques are also known under other names including Ultraviolet Blood Irradiation, Photoluminescence, Ultra Violet Photoluminescence, Photo-oxidation Therapy, Ultraviolet Blood Irradiation, Hematogenous Oxygenation Therapy, and Extracorporeal Photophoresis.
- Fig. 1 shows a general illustration of the method and the system for treating blood.
- the method of the invention comprises a step of irradiating a biological fluid such as blood with UV light through a layer of IR- absorbing fluid in order to intercept IR exposure of the biological fluid and therefore prevent its unwanted heating.
- the method may be accomplished by using the system of the present invention for treating a subject in order to reduce his or her blood-borne pathogen count or for another useful purpose.
- pathogens or harmful microorganisms may be susceptible to the UV irradiation (and in particular UVC irradiation) and therefore the system of the invention may be used to remove these pathogens from the blood stream.
- pathogens may include bacteria, fungi, viruses, parasites, molds, yeasts and other similar organisms. UVC light is known to disrupt the DNA or RNA of such pathogens and therefore eradicate them.
- viruses may be reduced or eliminated from the blood stream or in donor blood by the present invention.
- Non-limiting examples of such viruses include the following: Adeno-associated virus, Aichi virus, Australian bat lyssavirus, BK polyomavirus, Banna virus, Barmah forest virus, Bunyamwera virus, Bunyavirus La Crosse, Bunyavirus snowshoe hare, Cercopithecine herpesvirus, Chandipura virus, Chikungunya virus, Cosavirus A, Cowpox virus, Coxsackievirus, Crimean-Congo hemorrhagic fever virus, Dengue virus, Dhori virus, Dugbe virus, Duvenhage virus, Eastern equine encephalitis virus, Ebola virus, Echovirus, Encephalomyocarditis virus, Epstein-Barr virus, European bat lyssavirus, GB virus C/Hepatitis G virus, Hantaan virus, Hendra virus, Hepatitis A virus, Hepatitis A virus
- Louis encephalitis virus Tick-borne powassan virus, Torque teno virus, Toscana virus, Uukuniemi virus, Vaccinia virus, Varicella-zoster virus, Variola virus, Venezuelan equine encephalitis virus, Vesicular stomatitis virus, Western equine encephalitis virus, WU polyomavirus, West Nile virus, Yaba monkey tumor virus, Yaba-like disease virus, Yellow fever virus, Zika virus and synthetic viruses.
- Blood borne bacteria that can be reduced or eradicated by the present invention include at least the following: Acetobacter aurantius, Acinetobacter baumannii, Actinomyces israelii, Agrobacterium radiobacter, Agrobacterium tumefaciens, Anaplasma, Anaplasma phagocytophilum, Azorhizobium caulinodans, Azotobacter vinelandii, Bacillus anthracis, Bacillus brevis, Bacillus cereus, Bacillus fusiformis, Bacillus licheniformis, Bacillus megaterium, Bacillus mycoides, Bacillus stearothermophilus, Bacillus subtilis, Bacteroides fragilis, Bacteroides gingivalis, Bacteroides melaninogenicus (aka Prevotella melaninogenica), Bartonella henselae, Bartonella quintana, Bordetella, Bordetella bronchiseptica, Bordetell
- Non-limiting examples of blood borne parasites that may be eradicated using the methods and the systems of the invention include Plasmodium, Trypanosoma cruzi, Babesia microti, and Leishmania.
- Such pathogens may be present in the blood stream of the subject as a result of a natural transmission such as between humans, between animals or across species, as well as a result of contamination or a deliberate biological agent attack.
- the blood treatment of the subject may be conducted once or repeated from time to time, such as every 10 min, 30 min, 1 hour, 2 hours, 3 hours, 6 hours, 12 hours, 24 hours, 48 hours, 72 hours, 96 hours, weekly, bi-weekly, monthly or on any other schedule prescribed by a physician.
- UV irradiation of blood may be conducted for a number of other therapeutic purposes, such as the following:
- UV irradiation may not kill every pathogen in the body directly. Rather UV exposure transmits energy to the blood that empowers a strong biochemical response thereto, including stabilization of white blood cells, and increasing cell membrane permeability (which may enhance the body's ability to produce antibodies) Furthermore, the debris from dead pathogens may stimulate the immune response further against even the most stubborn pathogens;
- Oxygen in the blood has a powerful effect, helping to eradicate not only pathogens, but it also creates an environment in which yeasts, fungi, and cancer cells cannot exist;
- UV irradiation of blood may be used as treatment for a number of ailments including Inflammatory conditions (for example Acute thrombophlebitis, Fibrositis, Bursitis, Nephritis, Iritis, uveitis, Cholecystitis, Pancreatitis, Rheumatoid arthritis), Circulatory conditions (for example Varicose and diabetic ulcers, Peripheral vascular disease, Gangrene, Vascular headaches), and other conditions (for example Non-healing Wounds and Fractures, Pemphigus, Emphysema, Adjunctive cancer treatment).
- Inflammatory conditions for example Acute thrombophlebitis, Fibrositis, Bursitis, Nephritis, Iritis, uveitis, Cholecystitis, Pancreatitis, Rheumatoid arthritis
- Circulatory conditions for example Varicose and diabetic ulcers, Peripheral vascular disease
- blood from a subject may be withdrawn using a traditional venous or arterial catheter and directed towards the system of the invention. After treatment, blood may be returned to the subject. In some embodiments, removal, treatment and return of blood may be conducted at the same time. In other embodiments, a predetermined volume of blood may be withdrawn, treated and then returned to the subject, such volume may be 20 cc, 30 cc, 50 cc, 75 cc, 100 cc, 150 cc, 200 cc, 250 cc, 300 cc, 400 cc, 500 cc, 600 cc, 750 cc or any other volume therebetween.
- blood may be subjected to at least the following two steps:
- Exposure to UV light may be achieved while minimizing heat transfer to the blood by the source of UV irradiation - by separating the blood from UV source using a layer of IR-absorbing fluid.
- the details of separating blood from UV source by a layer of IR-absorbing fluid to prevent the unwanted IR irradiation from reaching the biological fluid are described below.
- the method may further include active cooling of blood to maintain its temperature within a desirable temperature range, which may be selected to prevent its degradation and thermal damage to any of its components.
- Other elements and components may be included in the circuit for treating blood such as additional or intermediate storage bags, gas bubble traps, various sensors such as fluid pressure, UV intensity monitor/sensor, flow, and temperature sensors, additional blood pumping devices, filters, etc.
- Fig .2 shows one example of how blood (such as freshly collected donor blood) contained in the storage bag 102 may be withdrawn into the system 100 of the present invention, treated to expose the blood to UV irradiation and then placed into another bag 132 for subsequent processing, separation into components, immediate use for another subject and/or storage.
- blood such as freshly collected donor blood
- FIG. 3 shows a general block-diagram of the system 100 of the invention.
- a fluid supply source 102 may be used to draw the biological fluid from.
- such fluid supply source may be a unit of blood collected from a donor, for example.
- Biological fluid may be drawn from or gravity-fed into a pump 104 suitable for the purposes of pumping the biological fluid.
- a variety of pumps may be used for the purposes of the present invention.
- a biocompatible atraumatic pump may be used such as a suitable peristaltic pump, centrifugal pump, diaphragm pump or another blood- compatible pump.
- the pump 104 may be controlled by a pump controller 108, which in turn may be operable by a central control unit 106, which in turn may be driven by a microprocessor to automate at least some or most operations of the system 100.
- the pump controller 108 may be operated to cause the pump 104 to propagate the biological fluid through the exposure chamber of the system 100 with a desired constant or variable rate.
- the central control unit 106 may be further equipped with computer memory to store the preferred modes of operation, accumulate usage data, record alert conditions, etc.
- the biological fluid may be pumped by the pump 104 from the fluid supply 102 through the optional flow sensor 110 (operably connected to the pump controller 108), and further through an optional inlet pressure sensor 112 and an optional inlet temperature sensor 114 prior to entering the exposure chamber, which includes a fluid flow path 124 described in greater detail below with reference to Fig. 4.
- a source of UV irradiation 120 may be used to provide UV irradiation suitable for reducing pathogens in the biological fluid while in the exposure chamber.
- a plurality of UV irradiation lamps or lights may form together the combined source of UV irradiation 120. Utilizing such plurality of lamps or lights as opposed to a single lamp or light allows a more uniform UV exposure over a greater portion or preferably the entire fluid flow path 124.
- the UV irradiation source 120 may be operated by a UV light source driver 118, which in turn may be controlled by the UV source control circuit 116 operable by the central control unit 106.
- a layer of IR-absorbing fluid 150 may be placed between the source of UV irradiation 120 and the flow path 124 to preclude or at least reduce exposure of the flow path to IR irradiation.
- the biological fluid may be directed through an optional outlet temperature sensor 128 towards the outlet fluid collection element 132, such as a blood collection bag for example.
- Additional elements of the system 100 may include a biological fluid temperature control system 122, which may be operably connected to the inlet temperature sensor 114 and the outlet temperature sensor 128 to detect a potential increase in fluid temperature above a predetermined safe threshold. Such temperature increase may be caused by too much energy passed into the biological fluid from the source of UV irradiation 120, deliberate decrease of pump flow or by an inadvertent slow-down of the pump 104 causing an increase in residence time of the biological fluid while inside the flow path 124.
- the optional fluid temperature control system 122 may be connected to the central control unit 106 and used to at least trigger an alarm.
- the system 122 may be used to activate or regulate (increase or decrease) the active cooling of the flow path 124 and the biological fluid contained therein so as to maintain its temperature within allowable safe limits.
- the cooling of the UV irradiation source 120 and/or the flow path 124 may be accomplished in a number of known ways. Passive cooling may be accomplished by using a heat sink or by providing passive vents to expose the outer surfaces of the flow path to atmosphere. Active air cooling may be accomplished by providing one or more fans 130 or other cooling devices such as Peltier coolers thermally coupled to the heat sink, wherein such cooling devices may be activated upon either the biological fluid or a source of UV irradiation 120 reaching an upper limit of their respectfully allowable safe temperatures.
- Liquid cooling systems may also be provided as an alternative to air cooling. Such liquid cooling systems may include circulation of a cooling liquid in thermal contact with the source of UV irradiation 120 and / or the fluid flow path 124.
- the safe upper temperature limit for the biological fluid may be set at 42 degrees C.
- the upper safe temperature limit may selected to be about 50 degrees C (ideal operating temperature may be about room temperature, or 20 to 25 degrees C while the maximum allowable temperature may not be above 100 degrees C - higher operating temperature caused a significant reduction in UV output).
- the cooling elements of the system may be activated for the entire duration of UV irradiating the biological fluid or for a portion thereof.
- the cooling elements may be activated on a predefined intermittent schedule or based on the feedback from the temperature sensors 114 and 128 or the optional temperature sensors 126 configured to detect the temperature of the source of UV irradiation 120.
- the layer of IR-absorbing fluid may by itself be used to both absorb the undesirable IR irradiation and cool the biological fluid while in the exposure chamber - as described in greater detail below.
- Fig.4 shows a side view of the flow path 124, which may be selected to be sufficiently long to provide for sufficient UV exposure for the biological fluid propagating therethrough.
- the length of the flow path may vary from about 0.1 meter to about 20 meters. In embodiments, the length of the flow path may depend on the diameter thereof, the rate of biological fluid flow, the intensity of UV irradiation, the desired efficacy of pathogen reduction ("log kill" limit) and other factors.
- the length of the flow path 124 may be selected to be from about 4 meters to about 20 meters. In embodiments, the length of the flow path may be selected to be about 4 meters, about 6 meters, about 8 meters, about 10 meters, about 12 meters, about 14 meters, about 16 meters, about 18 meters, about 20 meters or any length in-between these numbers.
- the cross-sectional shape of the flow path 124 may be selected to be flat, oval, or round.
- the flat shape may be selected to have a wide portion thereof to be exposed to the source of UV irradiation 124 so as to maximize the exposure of the biological fluid to UV light.
- the internal diameter of the flow path 124 may be selected to be from about 1 mm to about 15 mm. In embodiments, the internal diameter of the flow path 124 may be selected to be about 1 mm, about 2 mm, about 3 mm, about 4 mm, about 5 mm, about 6 mm, about 7 mm, about 8 mm, about 10 mm, about 12 mm, about 15 mm or any diameter in-between these numbers. [0058] To provide a substantial length of the flow path in a small package, various methods of folding the flow path 124 into a compact structure may be used. One such method is to form the flow path in a serpentine shape as shown in Fig.
- the serpentine- shaped flow path 124 may be formed along a single flat plane so as to allow its exposure on both sides to the sources of UV irradiation 120 as described below. Alternatively, the serpentine shape may be wrapped about a centrally-placed source of UV irradiation 120 or otherwise presented in a compact way to make the entire system easy to use and transport.
- all or some elements of the system 100 which are in direct contact with the biological fluid may be made disposable or reusable.
- only the flow path 124 may be made disposable.
- the flow path 124 along with the tubing for the peristaltic pump 104 as well as the necessary sensors or sensor access points may all be formed as a disposable cassette or a cartridge for easy handling before, during and after use.
- Such disposable cassette may have provisions to "plug into” the rest of the system including reusable UV irradiation source 120, the active portion (rollers) of the pump 104, and all the elements of the above described control system. Once assembled, the disposable portion of the system 100 may be attached at the inlet to the source 102 of biological fluid and at the outlet to the fluid collection element 132.
- the serpentine-shaped flow path 124 may be made from a UV-transparent material such as glass, and in particular quartz glass.
- the flow path may be formed from plastics such as organic polymers, co-polymers and the like such as but not limited to cellulose products, PTFE, FEP, PVC and PE. In general, these materials have UV transmission properties in the range from 30 to 95% for a typical wall thickness, which may generally be between about 0.3 mm and about 4 mm.
- Helical flow mixers may be installed along a portion or the entire length of the flow path 124. Such mixers may be used to cause propagating biological fluid to undergo intense mixing so as to expose all elements thereof to the outside surface and subsequently to UV irradiation.
- the present invention uses a layer of IR-absorbing fluid positioned between the source of UV irradiation 120 and the flow path 124 containing the biological fluid.
- the layer design and the choice of the fluid may be made to assure at least substantial or preferably complete passing of the UV light therethrough in the desired therapeutic range such as UVC light.
- the IR-absorbing fluid may be selected to absorb at least 50% or preferably the entire light energy in the IR wavelength spectra so as to prevent it from reaching the biological fluid.
- Non-limiting examples of such IR-absorbing fluid include various liquids and gases such as carbon dioxide, water vapor, methane, nitrous oxide, and ozone. Carbone dioxide may be particularly useful as it is readily available, safe, and can be harmlessly discharged into atmosphere in small quantities needed for the purposes of the present invention.
- Fig. 5 shows an example of the flow path 124 surrounded by a UV-transparent jacket 150 containing an IR-absorbing fluid, such as carbon dioxide.
- the jacket may completely surround the flow path 124 to place the IR-absorbing fluid in close thermal contact with the exterior of the flow path 124 as seen in Fig. 5 or may be placed to separate the flow path 124 from the source of UV irradiation 120 on one side thereof.
- the UV-transparent jacket 150 may be made from the same material as the flow path 124, such as glass, and in particular quartz glass.
- the jacket 150 may be formed from plastics such as organic polymers, co-polymers and the like, for example cellulose products, PTFE, FEP, PVC and PE.
- the thickness of the layer of IR-absorbing fluid may be selected to absorb at least a substantial portion of IR irradiation, such as over 50% thereof or greater. Depending on the choice of the UV irradiation source 120 and the choice of the IR-absorbing fluid, the thickness of its layer may be selected to be anywhere from about 1 ⁇ 4 of an inch to 3 inches. In embodiments, the thickness of the IR-absorbing fluid may be about 1 ⁇ 4 of an inch, about 1 / 2 of an inch, about 3 ⁇ 4 of an inch, about 1 inch, about 1.5 inches, about 2 inches, about 2.5 inches, about 3 inches or any suitable thickness inbetween.
- a left manifold 154 with a plurality of nozzles 155 and a right manifold 156 with a plurality of nozzles 157 Either one or both manifolds may be used to inject the IR-absorbing fluid into the jacket 150 so as to envelope the flow path 124 and separate thereof from the source of UV irradiation 120.
- One or more pressure relief valves 152 may also be included to be a part of the jacket.
- the IR-absorbing fluid may be introduced through one of the manifolds 154 or 156 so it passes through the jacket 150 in a direction perpendicular to that of the flow of the biological fluid through the flow path 124 - in the design shown in Fig.
- IR-absorbing fluid flows laterally while the biological fluid is propagated vertically. After passing over the biological fluid, the IR-absorbing fluid may be collected using the opposite manifold 156 or 154. After collecting, the IR-absorbing fluid may be reintroduced on the opposite side of the jacket 150 and reused. In some embodiments, the IR-absorbing fluid may be cooled or otherwise conditioned after each passage over the fluid flow path 124. Active circulation of the IR-absorbing fluid over the flow path 124 may be used to accomplish two purposes: absorb IR irradiation and cool the flow path 124. In that case, the temperature of the IR-absorbing fluid introduced into the jacket 150 may be selected to be below that of the biological fluid inside the flow path 124.
- the IR-absorbing fluid may be injected into the jacket 150 and kept in a static state under constant pressure for the duration of the procedure.
- the IR-absorbing fluid may be pressurized so as to increase its density. This may be particularly advantageous in the case of a gas used for such purpose, in particular using carbon dioxide.
- Such IR-absorbing gas may be pressurized to be above atmospheric pressure by about 1 ATM, about 10 ATM, about 20 ATM, about 30 ATM, about 50 ATM, about 75 ATM, about 100 ATM, about 150 ATM or any suitable pressure inbetween.
- the pressurized IR-absorbing fluid such as compressed carbon dioxide may be introduced into the jacket 150 from one or more pressurized canisters 159 through one or both manifolds 154 and 156 and allowed to be vented to atmosphere through the relief valves 152 during the procedure.
- Canisters 159 may contain the IR-absorbing gas at high pressures that may exceed 100 ATM.
- the opening level of pressure relief for the valves 152 may be selected to be below the pressure of gas introduced into the jacket 150 and may range from atmospheric pressure to any pressure listed above up to about 150 ATM.
- One advantage of this approach is a natural cooling effect occurring once the pressurized gas enters a lower pressure environment of the jacket 150. Reduction of gas pressure leads to a drop of its temperature, which may by itself be sufficient to cool the flow path 124 and maintain the temperature of the biological fluid therein at safe levels.
- the flow of IR-absorbing fluid may be arranged to be in a direction other than that of the biological fluid circulating in the flow path 124.
- Fig. 5 shows an example when the direction of the IR- absorbing fluid is perpendicular to the direction of the biological fluid.
- Fig. 6 shows a configuration of the system in which the direction of flow of the IR-absorbing fluid is along the direction of flow of the biological fluid along some portions of the flow path 124 and opposite in some other portions of the flow path 124.
- Fig. 7 shows yet another configuration of the system in which the serpentine-shaped flow path 124 is enclosed in a respectively larger size serpentine-shaped channel for IR-absorbing fluid.
- the direction of flow of both fluids may be selected to be opposite to each other so as to maximize the heat exchange therebetween.
- Fig. 8 shows a side view of one embodiment of the system in which the flow path 124 is separated from sources of UV irradiation 120 located on both sides thereof by a layer of IR-absorbing fluid 150.
- Fig. 9 shows a top view of the same showing a plurality of spaced apart UV lights 120 located on both sides of the flow path 124.
- Fig. 10 shows yet another alternative arrangement in which the action of absorbing IR is separated from the action of cooling the biological fluid.
- a layer of cooling fluid or gas 160 may be positioned in close thermal contact with the exterior of the flow path 124 which the layer of IR-absorbing fluid 150 may be positioned outside the cooling layer 160 but still between the flow path 124 and the source of UV irradiation 120 so as to preclude the IR portion of light irradiation emanating from the source 120 from reaching the biological fluid inside the flow path 124.
- the cooling fluid may be circulated using the system 122 as described in greater detail above.
- the system of the invention may be operated in the following way.
- Initial supply of the biological fluid may be positioned in the fluid supply source 102.
- the entire fluid-contacting circuit as described above may be primed or filled with inert gas, carbon dioxide, saline or the biological fluid itself may be pumped therethrough by the pump 104.
- the processing of the biological fluid may then be initiated by activating the source of UV irradiation 120 and the pump 104.
- the biological fluid While in the flow path 124, the biological fluid may be protected from overheating by the layer of IR- absorbing fluid as described above.
- Fig. 11 shows a typical example of spectra coming out of a UV lamp.
- a broad range of wavelengths are emanated by the lamp including a strong IR presence in the range over 700 nm.
- the desired wavelength range for the purposes of reducing pathogens is quite narrow - from about 250 nm to about 270 nm. All other wavelengths cause heating of the biological fluid when absorbed by it and in that sense are believed to be undesirable.
- IR-absorbing fluid in this case CO2
- Fig. 12 shows an exemplary spectra of the same UV lamp after passing through a layer of CO2. As can be seen, almost the entire portion of the IR spectra is no longer visible in Fig. 12, indicating that the biological fluid is no longer exposed thereto.
- any two components so associated may also be viewed as being “operably connected”, or “operably coupled”, to each other to achieve the desired functionality, and any two components capable of being so associated may also be viewed as being “operably couplable”, to each other to achieve the desired functionality.
- operably couplable include but are not limited to physically mateable and/or physically interacting components and/or wirelessly interactable and/or wirelessly interacting components and/or logically interacting and/or logically interactable components.
Abstract
The systems and methods for pathogen reduction in donor blood operates by exposure of blood to UVC irradiation. Unwanted wavelengths of light, mostly in the infrared spectra, may be precluded from reaching blood by providing a layer of IR-absorbing fluid positioned between blood and the source of UV irradiation, whereby minimizing energy absorption and heating of blood. Some embodiments further disclose a system configured to utilize the same IR-absorbing fluid to actively cool blood by flowing along the flow path thereof.
Description
Systems and Methods for Pathogen Inactivation in Blood Using UV Irradiation While Minimizing
Heat Transfer Thereto
BACKGROUND OF THE INVENTION
[001] The present relates to systems and methods for the UV-irradiation of a biological fluid for the purposes of reduction of pathogens therein. While the primary object of the invention is to treat blood, blood-based products and synthetic blood substitutes, the concepts of the present invention may be used for treating other fluids such as those encountered in beverage industries including dairy, distilling and brewing, as well as in water treatment industries including sewerage and purification systems. Other uses of the invention contemplate treating blood from a subject and returning the blood to the subject after completion of the treatment.
[002] The term "pathogens" is used broadly for the purposes of the present invention to include a variety of harmful microorganisms such as bacteria, fungi, viruses (including among others a human immunodeficiency virus, a hepatitis A, B and C virus, an influenza virus, a hemorrhagic fever virus such as Ebola virus etc.), parasites, molds, yeasts and other similar organisms which may be found in human or non-human blood and products derived from blood, as well as various other body fluids such (as for example milk) and synthetic fluids manufactured for use as replacements for any such body fluids or components thereof.
[003] Blood transfusion in developed countries is very safe with regard to avoidance of transmitting of an infectious disease. This is primarily achieved by donor exclusion using questionnaires and screening for pathogens presence by means of serological methods and direct testing for nucleic acids. Despite these practices, there remains a risk of transmission of pathogens with the transfusion of cellular components of blood (such as red cells and platelets for example). This is at least in part because current screening tests leave a window of time after infection and before their sensitivity allows for detection of pathogens. In addition, screening does not takes place for rarely occurring pathogens or as yet unknown transmissible pathogens (Soland, E.M. et al. J. Am. Med. Assoc. 21 A: 1368-1373 (1995); Schreiber, G.B. et al. New Engl. J. Med. 334: 1685-1690 (1996); Valinsky, J.E. In: Blood Safety and Surveillance, Linden, J.V. and Bianco, C, Eds., Marcel Dekker, NY, 2001 , pp. 185-219).
[004] The use of pathogen reduction technologies has the potential of eliminating the remaining risks of transmission of infectious disease as a result of blood transfusion. Various approaches have been used to sterilize blood components (Ben-Hur, E. and B. Horowitz AIDS 10: 1183-1190 (1996); Ben-Hur, E. and R.P.
Goodrich, In: Photodynamic Inactivation of Microbial Pathogens, Hamblin, M.R. and J. Gori, Eds. RSC Publishing, UK, 2011 , pp. 233-263). The most promising methods are photochemical ones, two of which were approved by regulatory agencies for pathogen reduction in platelet concentrates. The Intercept method employs a psoralen and UVA light (Lin, L. et al. Transfusion 37: 423-435 (1997)) and the Mirasol method uses riboflavin and UVA+UVB light (Goodrich, R.P. et al. Transfusion Apheresis Sci. 35: 5-17 (2006)).
[005] Short wavelengths ultraviolet light (UVC, 180-290 nm) is a known sterilizing agent that targets the nucleic acids of microorganisms (Setlow, R.B. and J.K. Setlow Proc. Natl. Acad. USA 48: 1250-1253 (1962)). It has been used for pathogen reduction in optically-transparent biological fluids such as plasma (Chin, S. et al. Blood 86: 4331-4336 (1995)) and is being studied also in platelet concentrates (Bashir, S. et al. Transfusion 53: 990-1000 (2013)). However, in opaque biological fluids such as red cell concentrates as well as in whole blood, UVC penetration is very limited due to absorption of UV irradiation by the red cells. As a result, all attempts to use UV irradiation for sterilizing whole blood or red cells have been unsuccessful so far.
[006] Therefore, there is a need for an effective system and method for reducing pathogens in a biological fluid such as blood.
[007] Attempts to irradiate blood or other opaque biological fluids with UV light have been described before. The exposure of a biological fluid to UV irradiation can result in damage to various components of the biological fluid, for example enzymes and other functional proteins. Therefore, the UV irradiation source should not be too powerful nor may the fluid be exposed to the UV radiation for too long, if one is to avoid damaging the components of the biological fluid. On the other hand, sufficient UVC energy needs to be transmitted to the blood flow to assure substantial reduction and effective elimination of the pathogens. This balance is critical in achieving desired effectiveness of UVC treatment.
[008] To ensure that substantially all of the fluid receives a sufficient dose of UV radiation, it has been found that intensive mixing of the fluid to be treated during UV irradiation increases the efficiency of the irradiation process. A variety of devices that include static mixers placed in the fluid flow pathway have been proposed such as those described in US Pat. Nos.6312593; 7175808; US Pat. Application Publications 2004/0039325; 2006/0270960; or PCT publications W01997046271 ; WO2000020045.
[009] In addition to mixing, a sufficient intensity of the UV irradiation needs to be provided by a source of UV irradiation. Traditional devices used as such source include low pressure and medium pressure mercury UV lamps, amalgam UV lamps, arc UV lamps, fluorescent UV lamps, halogen UV lamps, and xenon UV lamps. Such lamps have a number of disadvantages when used directly for the purposes of the present invention
as they produce low level of UV output given the energy requirements, have large size, fragile and if broken represent an environmental hazard of mercury contamination. In addition, traditional UV lamps produce UV output over a broad range of UV wavelengths, some of which may be harmful to the biological fluid.
[0010] There is a need for a new exposure chamber and a new system for reducing pathogens in a biological fluid with improved source of UV irradiation and specifically with the ability to provide high intensity of UV light in a small physical size. There is also a need for a new source of UV irradiation to provide efficacious UV irradiation at desired peak wavelength with low energy consumption.
SUMMARY OF THE INVENTION
[0011] Accordingly, it is an object of the present invention to overcome these and other drawbacks of the prior art by providing a novel systems and methods for reduction of pathogens in a biological fluid by exposing the fluid to a sufficient dose of UVC irradiation but without damaging of other blood elements caused by absorption of IR spectra of wavelengths leading to excessive heating thereof.
[0012] It is a further object of the present invention to provide novel systems for reduction of pathogens in the biological fluid having sufficient UVC irradiation intensity to treat opaque biological fluids such as whole blood and blood products.
[0013] It is yet another object of the invention to provide extracorporeal systems and methods for reducing pathogen level in a blood of a subject suffering from a condition associated with a presence of blood-borne pathogens.
[0014] It is yet another object of the present invention to provide novel systems and method for treating donor blood prior to its further processing, separation into individual components and storage.
[0015] The system of the invention is designed for inactivation of pathogens in the biological fluid such as a unit of whole blood suitable for transfusion. The system includes a novel exposure chamber comprising a source of UV irradiation and a closely positioned adjacent flow path configured to expose the biological fluid to UV irradiation. The source of UV irradiation may be configured to emit ultraviolet light in the UVC range of wavelengths. In embodiments, UVC light may be used with a predetermined peak wavelength from about 250 nm to about 270 nm. The system may include a pump such as a roller pump or a centrifugal pump to propagate biological fluid such as whole blood through a UV-transparentflow path of the exposure chamber, for example in a serpentine-shaped tube. The flow path may include one or more static mixer elements to cause intermittent or continuous mixing of the biological fluid during its propagation through the flow path. The flow path may be configured for exposure of the fluid to UVC irradiation from a suitable source such as
one or several UV lamps or a plurality of UV emitting diodes (UV LEDs). UV exposure of the biological fluid may be conducted at an appropriately high power density that allows sufficient UVC dose to be impinged on the fluid - such that sufficient inactivation of pathogens takes place. The treated fluid may then be propagated out of the exposure chamber and collected in a new storage bag and the disposable flow path may be discarded after use.
[0016] The novel portion of the system includes provisions for separation of the flow path from the UV irradiation source by a layer of fluid known to absorb at least some and preferably a substantial portion of infra-red radiation emanating from the source of UV irradiation, ambient light or any other light sources to which the flow path is exposed to. Such layer may be positioned between the flow path and the source of UV irradiation for the purposes of reducing or preventing heat transfer to the biological fluid from the source of UV irradiation. In other embodiments, a UV-transparent jacket surrounding the flow path is provided and the IR-absorbing fluid is circulated therethrough. Introducing the IR-absorbing fluid at a temperature lower than that of the biological fluid allows the system to both absorb the IR irradiation (to prevent it from reaching the biological fluid) as well as cool the biological fluid to counteract energy absorption resulting from exposure to UV irradiation.
BRIEF DESCRIPTION OF THE DRAWINGS
[0017] Subject matter is particularly pointed out and distinctly claimed in the concluding portion of the specification. The foregoing and other features of the present disclosure will become more fully apparent from the following description and appended claims, taken in conjunction with the accompanying drawings. Understanding that these drawings depict only several embodiments in accordance with the disclosure and are, therefore, not to be considered limiting of its scope, the disclosure will be described with additional specificity and detail through use of the accompanying drawings, in which:
[0018] FIGURE 1 is a general schematic view of the system of the invention used to treat a subject;
[0019] FIGURE 2 is a general schematic view of the system of the invention used to treat a unit of collected donor blood;
[0020] FIGURE 3 is a general schematic view of the components of the system of the invention; [0021] FIGURE 4 shows a serpentine flow path;
[0022] FIGURE 5 shows one embodiment of the jacket containing IR-absorbing fluid surrounding the serpentine flow path of the system in which the direction of IR-absorbing fluid propagating through the jacket
is perpendicular to the direction of biological fluid propagating through the serpentine flow path;
[0023] FIGURE 6 shows another embodiment of the jacket containing IR-absorbing fluid in which the direction of IR-absorbing fluid propagating through the jacket is parallel to the direction of biological fluid propagating through the serpentine flow path;
[0024] FIGURE 7 shows yet another embodiment of the jacket which surrounds the flow path and in which the direction of IR-absorbing fluid propagating therethrough is opposite to the direction of biological fluid propagating through the serpentine flow path;
[0025] FIGURE 8 is a side view of the key elements of the system of the invention; [0026] FIGURE 9 is a top view of the same;
[0027] FIGURE 10 is a side view of an alternate configuration of the system of the invention;
[0028] FIGURE 11 is a graph showing various wavelengths of the UV lamp output prior to utilization of the IR-absorbent layer; and
[0029] FIGURE 12 is a graph showing remaining wavelengths after passing the output of a UV lamp through a layer of an IR-absorbing fluid.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT OF THE INVENTION
[0030] The following description sets forth various examples along with specific details to provide a thorough understanding of claimed subject matter. It will be understood by those skilled in the art, however, that claimed subject matter may be practiced without one or more of the specific details disclosed herein. Further, in some circumstances, well-known methods, procedures, systems, components and/or circuits have not been described in detail in order to avoid unnecessarily obscuring claimed subject matter. In the following detailed description, reference is made to the accompanying drawings, which form a part hereof. In the drawings, similar symbols typically identify similar components, unless context dictates otherwise. The illustrative embodiments described in the detailed description, drawings, and claims are not meant to be limiting. Other embodiments may be utilized, and other changes may be made, without departing from the spirit or scope of the subject matter presented here. It will be readily understood that the aspects of the present disclosure, as generally described herein, and illustrated in the figures, can be arranged, substituted, combined, and designed in a wide variety of different configurations, all of which are explicitly contemplated and make part of this disclosure.
[0031] The definition of the terms "IR" or "infra-red" range of wavelengths used for the purposes of the present invention is somewhat broader than the classic definition of IR and includes a wavelength range from about 700 nm to about 1100 nm. The term "about" is used here and throughout the rest of this description to denote a deviation from the cited value by plus or minus 20 percent.
[0032] The term "UV irradiation" is used generally in this description to encompass various techniques of exposing biological fluids including blood to UV light for therapeutic purposes, such techniques are also known under other names including Ultraviolet Blood Irradiation, Photoluminescence, Ultra Violet Photoluminescence, Photo-oxidation Therapy, Ultraviolet Blood Irradiation, Hematogenous Oxygenation Therapy, and Extracorporeal Photophoresis.
[0033] Fig. 1 shows a general illustration of the method and the system for treating blood. The method of the invention comprises a step of irradiating a biological fluid such as blood with UV light through a layer of IR- absorbing fluid in order to intercept IR exposure of the biological fluid and therefore prevent its unwanted heating. The method may be accomplished by using the system of the present invention for treating a subject in order to reduce his or her blood-borne pathogen count or for another useful purpose.
[0034] As mentioned above, a number of pathogens or harmful microorganisms may be susceptible to the UV irradiation (and in particular UVC irradiation) and therefore the system of the invention may be used to remove these pathogens from the blood stream. Such pathogens may include bacteria, fungi, viruses, parasites, molds, yeasts and other similar organisms. UVC light is known to disrupt the DNA or RNA of such pathogens and therefore eradicate them.
[0035] A variety of viruses may be reduced or eliminated from the blood stream or in donor blood by the present invention. Non-limiting examples of such viruses include the following: Adeno-associated virus, Aichi virus, Australian bat lyssavirus, BK polyomavirus, Banna virus, Barmah forest virus, Bunyamwera virus, Bunyavirus La Crosse, Bunyavirus snowshoe hare, Cercopithecine herpesvirus, Chandipura virus, Chikungunya virus, Cosavirus A, Cowpox virus, Coxsackievirus, Crimean-Congo hemorrhagic fever virus, Dengue virus, Dhori virus, Dugbe virus, Duvenhage virus, Eastern equine encephalitis virus, Ebola virus, Echovirus, Encephalomyocarditis virus, Epstein-Barr virus, European bat lyssavirus, GB virus C/Hepatitis G virus, Hantaan virus, Hendra virus, Hepatitis A virus, Hepatitis B virus, Hepatitis C virus, Hepatitis E virus, Hepatitis delta virus, Herpes simplex virus, Herpes zoster virus, Horsepox virus, Human adenovirus, Human astrovirus, Human coronavirus, Human cytomegalovirus, Human enterovirus 68, 70, Human herpesvirus 1 , Human herpesvirus 2, Human herpesvirus 6, Human herpesvirus 7, Human herpesvirus 8, Human immunodeficiency virus, Human papillomavirus 1 , Human papillomavirus 2, Human papillomavirus 16, 18, Human parainfluenza, Human parvovirus B19, Human respiratory syncytial virus, Human rhinovirus, Human
SARS coronavirus, Human spumaretrovirus, Human T-lymphotropic virus, Human torovirus, Influenza A virus, Influenza B virus, Influenza C virus, Isfahan virus, JC polyomavirus, Japanese encephalitis virus, Junin arenavirus, Kl Polyomavirus, Kunjin virus, Lagos bat virus, Lake Victoria marburgvirus, Langat virus, Lassa virus, Lordsdale virus, Louping ill virus, Lymphocytic choriomeningitis virus, Machupo virus, Mayaro virus, MERS coronavirus, Measles virus, Mengo encephalomyocarditis virus, Merkel cell polyomavirus, Mokola virus, Molluscum contagiosum virus, Monkeypox virus, Mononucleosis virus, Mumps virus, Murray valley encephalitis virus, New York virus, Nipah virus, Norwalk virus, O'nyong-nyong virus, Orf virus, Oropouche virus, Pichinde virus, Poliovirus, Punta toro phlebovirus, Puumala virus, Rabies virus, Rift valley fever virus, Rosavirus A, Ross river virus, Rotavirus A, Rotavirus B, Rotavirus C, Rubella virus, Sagiyama virus, Salivirus A, Sandfly fever Sicilian virus, Sapporo virus, SARS virus, Semliki forest virus, Seoul virus, Simian foamy virus, Simian virus 5, Sindbis virus, Southampton virus, St. Louis encephalitis virus, Tick-borne powassan virus, Torque teno virus, Toscana virus, Uukuniemi virus, Vaccinia virus, Varicella-zoster virus, Variola virus, Venezuelan equine encephalitis virus, Vesicular stomatitis virus, Western equine encephalitis virus, WU polyomavirus, West Nile virus, Yaba monkey tumor virus, Yaba-like disease virus, Yellow fever virus, Zika virus and synthetic viruses.
[0036] Blood borne bacteria that can be reduced or eradicated by the present invention include at least the following: Acetobacter aurantius, Acinetobacter baumannii, Actinomyces israelii, Agrobacterium radiobacter, Agrobacterium tumefaciens, Anaplasma, Anaplasma phagocytophilum, Azorhizobium caulinodans, Azotobacter vinelandii, Bacillus anthracis, Bacillus brevis, Bacillus cereus, Bacillus fusiformis, Bacillus licheniformis, Bacillus megaterium, Bacillus mycoides, Bacillus stearothermophilus, Bacillus subtilis, Bacteroides fragilis, Bacteroides gingivalis, Bacteroides melaninogenicus (aka Prevotella melaninogenica), Bartonella henselae, Bartonella quintana, Bordetella, Bordetella bronchiseptica, Bordetella pertussis, Borrelia burgdorferi, Brucella, Brucella abortus, Brucella melitensis, Brucella suis, Burkholderia, Burkholderia mallei, Burkholderia pseudomallei, Burkholderia cepacia, Calymmatobacterium granulomatis, Campylobacter, Campylobacter coli, Campylobacter fetus, Campylobacter jejuni, Campylobacter pylori, Chlamydia, Chlamydia trachomatis, Chlamydophila, Chlamydophila pneumoniae (aka Chlamydia pneumoniae), Chlamydophila psittaci (aka Chlamydia psittaci), Clostridium, Clostridium botulinum, Clostridium difficile, Clostridium perfringens (aka Clostridium welchii), Clostridium tetani, Corynebacterium, Corynebacterium diphtheria, Corynebacterium fusiforme, Coxiella burnetii, Ehrlichia chaffeensis, Enterobacter cloacae, Enterococcus, Enterococcus avium, Enterococcus durans, Enterococcus faecalis, Enterococcus faecium, Enterococcus galllinarum, Enterococcus maloratus, Escherichia coli, Francisella tularensis, Fusobacterium nucleatum, Gardnerella vaginalis, Haemophilus, Haemophilus ducreyi, Haemophilus influenza, Haemophilus parainfluenzae, Haemophilus pertussis, Haemophilus vaginalis,
Helicobacter pylori, Klebsiella pneumonia, Lactobacillus, Lactobacillus acidophilus, Lactobacillus bulgaricus, Lactobacillus casei, Lactococcus lactis, Legionella pneumophila, Listeria monocytogenes, Methanobacterium extroquens, Microbacterium multiforme, Micrococcus luteus, Moraxella catarrhalis, Mycobacterium, Mycobacterium avium, Mycobacterium bovis, Mycobacterium diphtheria, Mycobacterium intracellulare, Mycobacterium leprae, Mycobacterium lepraemurium, Mycobacterium phlei, Mycobacterium smegmatis, Mycobacterium tuberculosis, Mycoplasma, Mycoplasma fermentans, Mycoplasma genitalium, Mycoplasma hominis, Mycoplasma penetrans, Mycoplasma pneumonia, Neisseria, Neisseria gonorrhoeae, Neisseria meningitides, Pasteurella, Pasteurella multocida, Pasteurella tularensis, Peptostreptococcus, Porphyromonas gingivalis, Prevotella melaninogenica (aka Bacteroides melaninogenicus), Pseudomonas aeruginosa, Rhizobium radiobacter, Rickettsia, Rickettsia prowazekii, Rickettsia psittaci, Rickettsia Quintana, Rickettsia rickettsii, Rickettsia trachomae, Rochalimaea, Rochalimaea henselae, Rochalimaea Quintana, Rothia dentocariosa, Salmonella, Salmonella enteritidis, Salmonella typhi, Salmonella typhimurium, Serratia marcescens, Shigella dysenteriae, Staphylococcus, Staphylococcus aureus, Staphylococcus epidermidis, Stenotrophomonas maltophilia, Streptococcus, Streptococcus agalactiae, Streptococcus avium, Streptococcus bovis, Streptococcus cricetus, Streptococcus faceium, Streptococcus faecalis, Streptococcus ferus, Streptococcus gallinarum, Streptococcus lactis, Streptococcus mitior, Streptococcus mitis, Streptococcus mutans, Streptococcus oralis, Streptococcus pneumonia, Streptococcus pyogenes, Streptococcus rattus, Streptococcus salivarius, Streptococcus sanguis, Streptococcus sobrinus, Treponema, Treponema pallidum, Treponema denticola, Vibrio, Vibrio cholera, Vibrio comma, Vibrio parahaemolyticus, Vibrio vulnificus, Wolbachia, Yersinia, Yersinia enterocolitica, Yersinia pestis, and Yersinia pseudotuberculosis.
[0037] Non-limiting examples of blood borne parasites that may be eradicated using the methods and the systems of the invention include Plasmodium, Trypanosoma cruzi, Babesia microti, and Leishmania.
[0038] Such pathogens may be present in the blood stream of the subject as a result of a natural transmission such as between humans, between animals or across species, as well as a result of contamination or a deliberate biological agent attack.
[0039] Importantly, just some reduction in the count of such pathogens and not its complete eradication may already be clinically useful in allowing the subject more time to upregulate its natural defenses. The blood treatment of the subject may be conducted once or repeated from time to time, such as every 10 min, 30 min, 1 hour, 2 hours, 3 hours, 6 hours, 12 hours, 24 hours, 48 hours, 72 hours, 96 hours, weekly, bi-weekly, monthly or on any other schedule prescribed by a physician.
[0040] In addition to reducing pathogens, UV irradiation of blood may be conducted for a number of other
therapeutic purposes, such as the following:
Energize or enhance the natural biochemical and physiological defenses of the body by introducing of ultraviolet energy into the blood stream. UV irradiation may not kill every pathogen in the body directly. Rather UV exposure transmits energy to the blood that empowers a strong biochemical response thereto, including stabilization of white blood cells, and increasing cell membrane permeability (which may enhance the body's ability to produce antibodies) Furthermore, the debris from dead pathogens may stimulate the immune response further against even the most stubborn pathogens;
Rapidly detoxify and relieve toxemia;
Increase venous blood oxygen in subjects with depressed blood oxygen values. Oxygen in the blood has a powerful effect, helping to eradicate not only pathogens, but it also creates an environment in which yeasts, fungi, and cancer cells cannot exist;
Reduce edema (swelling and water retention outside of the cells);
Stimulate red blood cell production;
Control nausea and vomiting.
[0041] In embodiments, UV irradiation of blood may be used as treatment for a number of ailments including Inflammatory conditions (for example Acute thrombophlebitis, Fibrositis, Bursitis, Nephritis, Iritis, uveitis, Cholecystitis, Pancreatitis, Rheumatoid arthritis), Circulatory conditions (for example Varicose and diabetic ulcers, Peripheral vascular disease, Gangrene, Vascular headaches), and other conditions (for example Non-healing Wounds and Fractures, Pemphigus, Emphysema, Adjunctive cancer treatment).
[0042] According to the invention, blood from a subject may be withdrawn using a traditional venous or arterial catheter and directed towards the system of the invention. After treatment, blood may be returned to the subject. In some embodiments, removal, treatment and return of blood may be conducted at the same time. In other embodiments, a predetermined volume of blood may be withdrawn, treated and then returned to the subject, such volume may be 20 cc, 30 cc, 50 cc, 75 cc, 100 cc, 150 cc, 200 cc, 250 cc, 300 cc, 400 cc, 500 cc, 600 cc, 750 cc or any other volume therebetween.
[0043] While in the system, blood may be subjected to at least the following two steps:
(a) Exposure to sufficient levels of UV irradiation in order to reduce pathogens therein - such as at a peak wavelength from about 250 nm to about 270 nm. Such exposure may be accomplished by propagating
the blood along a flow path in a vicinity of a suitable source of UV-irradiation using a suitable blood pump; and
(b) Exposure to UV light may be achieved while minimizing heat transfer to the blood by the source of UV irradiation - by separating the blood from UV source using a layer of IR-absorbing fluid.
[0044] The details of separating blood from UV source by a layer of IR-absorbing fluid to prevent the unwanted IR irradiation from reaching the biological fluid are described below. The method may further include active cooling of blood to maintain its temperature within a desirable temperature range, which may be selected to prevent its degradation and thermal damage to any of its components.
[0045] Other elements and components may be included in the circuit for treating blood such as additional or intermediate storage bags, gas bubble traps, various sensors such as fluid pressure, UV intensity monitor/sensor, flow, and temperature sensors, additional blood pumping devices, filters, etc.
[0046] The same or similar system may also be used for treating donor blood before its subsequent separation into various components and/or storage for use with another subject in the future. The requirements for pathogen reduction are much higher in this case but the general concept remains the same. Fig .2 shows one example of how blood (such as freshly collected donor blood) contained in the storage bag 102 may be withdrawn into the system 100 of the present invention, treated to expose the blood to UV irradiation and then placed into another bag 132 for subsequent processing, separation into components, immediate use for another subject and/or storage.
[0047] Fig. 3 shows a general block-diagram of the system 100 of the invention. A fluid supply source 102 may be used to draw the biological fluid from. As mentioned above, such fluid supply source may be a unit of blood collected from a donor, for example. Biological fluid may be drawn from or gravity-fed into a pump 104 suitable for the purposes of pumping the biological fluid. A variety of pumps may be used for the purposes of the present invention. In the case of processing blood or blood products, a biocompatible atraumatic pump may be used such as a suitable peristaltic pump, centrifugal pump, diaphragm pump or another blood- compatible pump. The pump 104 may be controlled by a pump controller 108, which in turn may be operable by a central control unit 106, which in turn may be driven by a microprocessor to automate at least some or most operations of the system 100. The pump controller 108 may be operated to cause the pump 104 to propagate the biological fluid through the exposure chamber of the system 100 with a desired constant or variable rate. The central control unit 106 may be further equipped with computer memory to store the preferred modes of operation, accumulate usage data, record alert conditions, etc.
[0048] The biological fluid may be pumped by the pump 104 from the fluid supply 102 through the optional flow sensor 110 (operably connected to the pump controller 108), and further through an optional inlet pressure sensor 112 and an optional inlet temperature sensor 114 prior to entering the exposure chamber, which includes a fluid flow path 124 described in greater detail below with reference to Fig. 4.
[0049] A source of UV irradiation 120 may be used to provide UV irradiation suitable for reducing pathogens in the biological fluid while in the exposure chamber. A plurality of UV irradiation lamps or lights may form together the combined source of UV irradiation 120. Utilizing such plurality of lamps or lights as opposed to a single lamp or light allows a more uniform UV exposure over a greater portion or preferably the entire fluid flow path 124. The UV irradiation source 120 may be operated by a UV light source driver 118, which in turn may be controlled by the UV source control circuit 116 operable by the central control unit 106. As described in further details below, a layer of IR-absorbing fluid 150 may be placed between the source of UV irradiation 120 and the flow path 124 to preclude or at least reduce exposure of the flow path to IR irradiation.
[0050] Following the exit from the flow path 124, the biological fluid may be directed through an optional outlet temperature sensor 128 towards the outlet fluid collection element 132, such as a blood collection bag for example.
[0051] Additional elements of the system 100 may include a biological fluid temperature control system 122, which may be operably connected to the inlet temperature sensor 114 and the outlet temperature sensor 128 to detect a potential increase in fluid temperature above a predetermined safe threshold. Such temperature increase may be caused by too much energy passed into the biological fluid from the source of UV irradiation 120, deliberate decrease of pump flow or by an inadvertent slow-down of the pump 104 causing an increase in residence time of the biological fluid while inside the flow path 124. In any case, the optional fluid temperature control system 122 may be connected to the central control unit 106 and used to at least trigger an alarm. In some embodiments, the system 122 may be used to activate or regulate (increase or decrease) the active cooling of the flow path 124 and the biological fluid contained therein so as to maintain its temperature within allowable safe limits.
[0052] The cooling of the UV irradiation source 120 and/or the flow path 124 may be accomplished in a number of known ways. Passive cooling may be accomplished by using a heat sink or by providing passive vents to expose the outer surfaces of the flow path to atmosphere. Active air cooling may be accomplished by providing one or more fans 130 or other cooling devices such as Peltier coolers thermally coupled to the heat sink, wherein such cooling devices may be activated upon either the biological fluid or a source of UV irradiation 120 reaching an upper limit of their respectfully allowable safe temperatures. Liquid cooling systems may also be provided as an alternative to air cooling. Such liquid cooling systems may include
circulation of a cooling liquid in thermal contact with the source of UV irradiation 120 and / or the fluid flow path 124. When pumping blood or blood products, the safe upper temperature limit for the biological fluid may be set at 42 degrees C. For UVC irradiating LEDs, the upper safe temperature limit may selected to be about 50 degrees C (ideal operating temperature may be about room temperature, or 20 to 25 degrees C while the maximum allowable temperature may not be above 100 degrees C - higher operating temperature caused a significant reduction in UV output).
[0053] In embodiments, the cooling elements of the system (such as cooling fans 130) may be activated for the entire duration of UV irradiating the biological fluid or for a portion thereof. The cooling elements may be activated on a predefined intermittent schedule or based on the feedback from the temperature sensors 114 and 128 or the optional temperature sensors 126 configured to detect the temperature of the source of UV irradiation 120.
[0054] In further embodiments, the layer of IR-absorbing fluid may by itself be used to both absorb the undesirable IR irradiation and cool the biological fluid while in the exposure chamber - as described in greater detail below.
[0055] Fig.4 shows a side view of the flow path 124, which may be selected to be sufficiently long to provide for sufficient UV exposure for the biological fluid propagating therethrough. The length of the flow path may vary from about 0.1 meter to about 20 meters. In embodiments, the length of the flow path may depend on the diameter thereof, the rate of biological fluid flow, the intensity of UV irradiation, the desired efficacy of pathogen reduction ("log kill" limit) and other factors. In various embodiments, the length of the flow path 124 may be selected to be from about 4 meters to about 20 meters. In embodiments, the length of the flow path may be selected to be about 4 meters, about 6 meters, about 8 meters, about 10 meters, about 12 meters, about 14 meters, about 16 meters, about 18 meters, about 20 meters or any length in-between these numbers.
[0056] The cross-sectional shape of the flow path 124 may be selected to be flat, oval, or round. The flat shape may be selected to have a wide portion thereof to be exposed to the source of UV irradiation 124 so as to maximize the exposure of the biological fluid to UV light.
[0057] In case of a round cross-sectional shape, the internal diameter of the flow path 124 may be selected to be from about 1 mm to about 15 mm. In embodiments, the internal diameter of the flow path 124 may be selected to be about 1 mm, about 2 mm, about 3 mm, about 4 mm, about 5 mm, about 6 mm, about 7 mm, about 8 mm, about 10 mm, about 12 mm, about 15 mm or any diameter in-between these numbers.
[0058] To provide a substantial length of the flow path in a small package, various methods of folding the flow path 124 into a compact structure may be used. One such method is to form the flow path in a serpentine shape as shown in Fig. 4 with a well-defined inlet and outlet indicated by arrows in Fig. 4. The serpentine- shaped flow path 124 may be formed along a single flat plane so as to allow its exposure on both sides to the sources of UV irradiation 120 as described below. Alternatively, the serpentine shape may be wrapped about a centrally-placed source of UV irradiation 120 or otherwise presented in a compact way to make the entire system easy to use and transport.
[0059] In embodiments, all or some elements of the system 100 which are in direct contact with the biological fluid may be made disposable or reusable. In some embodiments, only the flow path 124 may be made disposable. In other embodiments, the flow path 124 along with the tubing for the peristaltic pump 104 as well as the necessary sensors or sensor access points may all be formed as a disposable cassette or a cartridge for easy handling before, during and after use. Such disposable cassette may have provisions to "plug into" the rest of the system including reusable UV irradiation source 120, the active portion (rollers) of the pump 104, and all the elements of the above described control system. Once assembled, the disposable portion of the system 100 may be attached at the inlet to the source 102 of biological fluid and at the outlet to the fluid collection element 132.
[0060] The serpentine-shaped flow path 124 may be made from a UV-transparent material such as glass, and in particular quartz glass. Alternatively, the flow path may be formed from plastics such as organic polymers, co-polymers and the like such as but not limited to cellulose products, PTFE, FEP, PVC and PE. In general, these materials have UV transmission properties in the range from 30 to 95% for a typical wall thickness, which may generally be between about 0.3 mm and about 4 mm.
[0061] Helical flow mixers may be installed along a portion or the entire length of the flow path 124. Such mixers may be used to cause propagating biological fluid to undergo intense mixing so as to expose all elements thereof to the outside surface and subsequently to UV irradiation.
[0062] To prevent the IR irradiation from reaching the biological fluid during UV exposure, the present invention uses a layer of IR-absorbing fluid positioned between the source of UV irradiation 120 and the flow path 124 containing the biological fluid. The layer design and the choice of the fluid may be made to assure at least substantial or preferably complete passing of the UV light therethrough in the desired therapeutic range such as UVC light. At the same time, the IR-absorbing fluid may be selected to absorb at least 50% or preferably the entire light energy in the IR wavelength spectra so as to prevent it from reaching the biological fluid. Non-limiting examples of such IR-absorbing fluid include various liquids and gases such as carbon dioxide, water vapor, methane, nitrous oxide, and ozone. Carbone dioxide may be particularly useful as it is
readily available, safe, and can be harmlessly discharged into atmosphere in small quantities needed for the purposes of the present invention.
[0063] Fig. 5 shows an example of the flow path 124 surrounded by a UV-transparent jacket 150 containing an IR-absorbing fluid, such as carbon dioxide. The jacket may completely surround the flow path 124 to place the IR-absorbing fluid in close thermal contact with the exterior of the flow path 124 as seen in Fig. 5 or may be placed to separate the flow path 124 from the source of UV irradiation 120 on one side thereof.
[0064] The UV-transparent jacket 150 may be made from the same material as the flow path 124, such as glass, and in particular quartz glass. Alternatively, the jacket 150 may be formed from plastics such as organic polymers, co-polymers and the like, for example cellulose products, PTFE, FEP, PVC and PE.
[0065] The thickness of the layer of IR-absorbing fluid may be selected to absorb at least a substantial portion of IR irradiation, such as over 50% thereof or greater. Depending on the choice of the UV irradiation source 120 and the choice of the IR-absorbing fluid, the thickness of its layer may be selected to be anywhere from about ¼ of an inch to 3 inches. In embodiments, the thickness of the IR-absorbing fluid may be about ¼ of an inch, about 1/2 of an inch, about ¾ of an inch, about 1 inch, about 1.5 inches, about 2 inches, about 2.5 inches, about 3 inches or any suitable thickness inbetween.
[0066] Shown in Fig. 5 is a left manifold 154 with a plurality of nozzles 155 and a right manifold 156 with a plurality of nozzles 157. Either one or both manifolds may be used to inject the IR-absorbing fluid into the jacket 150 so as to envelope the flow path 124 and separate thereof from the source of UV irradiation 120. One or more pressure relief valves 152 may also be included to be a part of the jacket. In embodiments, the IR-absorbing fluid may be introduced through one of the manifolds 154 or 156 so it passes through the jacket 150 in a direction perpendicular to that of the flow of the biological fluid through the flow path 124 - in the design shown in Fig. 5, IR-absorbing fluid flows laterally while the biological fluid is propagated vertically. After passing over the biological fluid, the IR-absorbing fluid may be collected using the opposite manifold 156 or 154. After collecting, the IR-absorbing fluid may be reintroduced on the opposite side of the jacket 150 and reused. In some embodiments, the IR-absorbing fluid may be cooled or otherwise conditioned after each passage over the fluid flow path 124. Active circulation of the IR-absorbing fluid over the flow path 124 may be used to accomplish two purposes: absorb IR irradiation and cool the flow path 124. In that case, the temperature of the IR-absorbing fluid introduced into the jacket 150 may be selected to be below that of the biological fluid inside the flow path 124.
[0067] Alternatively, the IR-absorbing fluid may be injected into the jacket 150 and kept in a static state under constant pressure for the duration of the procedure. In embodiments, the IR-absorbing fluid may be
pressurized so as to increase its density. This may be particularly advantageous in the case of a gas used for such purpose, in particular using carbon dioxide. Such IR-absorbing gas may be pressurized to be above atmospheric pressure by about 1 ATM, about 10 ATM, about 20 ATM, about 30 ATM, about 50 ATM, about 75 ATM, about 100 ATM, about 150 ATM or any suitable pressure inbetween.
[0068] In further embodiments, the pressurized IR-absorbing fluid such as compressed carbon dioxide may be introduced into the jacket 150 from one or more pressurized canisters 159 through one or both manifolds 154 and 156 and allowed to be vented to atmosphere through the relief valves 152 during the procedure. Canisters 159 may contain the IR-absorbing gas at high pressures that may exceed 100 ATM. The opening level of pressure relief for the valves 152 may be selected to be below the pressure of gas introduced into the jacket 150 and may range from atmospheric pressure to any pressure listed above up to about 150 ATM. One advantage of this approach is a natural cooling effect occurring once the pressurized gas enters a lower pressure environment of the jacket 150. Reduction of gas pressure leads to a drop of its temperature, which may by itself be sufficient to cool the flow path 124 and maintain the temperature of the biological fluid therein at safe levels.
[0069] In embodiments, the flow of IR-absorbing fluid may be arranged to be in a direction other than that of the biological fluid circulating in the flow path 124. Fig. 5 shows an example when the direction of the IR- absorbing fluid is perpendicular to the direction of the biological fluid. Fig. 6 shows a configuration of the system in which the direction of flow of the IR-absorbing fluid is along the direction of flow of the biological fluid along some portions of the flow path 124 and opposite in some other portions of the flow path 124. Fig. 7 shows yet another configuration of the system in which the serpentine-shaped flow path 124 is enclosed in a respectively larger size serpentine-shaped channel for IR-absorbing fluid. The direction of flow of both fluids may be selected to be opposite to each other so as to maximize the heat exchange therebetween.
[0070] Fig. 8 shows a side view of one embodiment of the system in which the flow path 124 is separated from sources of UV irradiation 120 located on both sides thereof by a layer of IR-absorbing fluid 150. Fig. 9 shows a top view of the same showing a plurality of spaced apart UV lights 120 located on both sides of the flow path 124.
[0071] Fig. 10 shows yet another alternative arrangement in which the action of absorbing IR is separated from the action of cooling the biological fluid. To accomplish these objectives separately, a layer of cooling fluid or gas 160 may be positioned in close thermal contact with the exterior of the flow path 124 which the layer of IR-absorbing fluid 150 may be positioned outside the cooling layer 160 but still between the flow path 124 and the source of UV irradiation 120 so as to preclude the IR portion of light irradiation emanating from the source 120 from reaching the biological fluid inside the flow path 124. The cooling fluid may be circulated
using the system 122 as described in greater detail above.
[0072] In use, the system of the invention may be operated in the following way. Initial supply of the biological fluid may be positioned in the fluid supply source 102. The entire fluid-contacting circuit as described above may be primed or filled with inert gas, carbon dioxide, saline or the biological fluid itself may be pumped therethrough by the pump 104. The processing of the biological fluid may then be initiated by activating the source of UV irradiation 120 and the pump 104.
[0073] Pumping of the biological fluid through a serpentine-shaped flow path 124 causes it to be exposed to UV irradiation. Active mixing of the fluid is designed to bring pathogens to the surface of the flow and inactivate them by UV light. Flow mixing may be achieved by varying the flow through the pump 104 or by using static mixers in the flow path 124.
[0074] While in the flow path 124, the biological fluid may be protected from overheating by the layer of IR- absorbing fluid as described above.
Experiments and Examples
[0075] A series of tests has been conducted starting in spring of 2010 to analyze the spectra of wavelength emanating from various sources of UV irradiation. Fig. 11 shows a typical example of spectra coming out of a UV lamp. As seen in the figure, a broad range of wavelengths are emanated by the lamp including a strong IR presence in the range over 700 nm. As described earlier, the desired wavelength range for the purposes of reducing pathogens is quite narrow - from about 250 nm to about 270 nm. All other wavelengths cause heating of the biological fluid when absorbed by it and in that sense are believed to be undesirable.
[0076] Use of a layer of IR-absorbing fluid (in this case CO2) was evaluated for the purposes of shielding the biological fluid from the IR portion of the spectra. Fig. 12 shows an exemplary spectra of the same UV lamp after passing through a layer of CO2. As can be seen, almost the entire portion of the IR spectra is no longer visible in Fig. 12, indicating that the biological fluid is no longer exposed thereto.
[0077] The herein described subject matter sometimes illustrates different components or elements contained within, or connected with, different other components or elements. It is to be understood that such depicted architectures are merely examples, and that in fact many other architectures may be implemented which achieve the same functionality. In a conceptual sense, any arrangement of components to achieve the same functionality is effectively "associated" such that the desired functionality is achieved. Hence, any two components herein combined to achieve a particular functionality may be seen as "associated with" each other such that the desired functionality is achieved, irrespective of architectures or intermedial components.
Likewise, any two components so associated may also be viewed as being "operably connected", or "operably coupled", to each other to achieve the desired functionality, and any two components capable of being so associated may also be viewed as being "operably couplable", to each other to achieve the desired functionality. Specific examples of operably couplable include but are not limited to physically mateable and/or physically interacting components and/or wirelessly interactable and/or wirelessly interacting components and/or logically interacting and/or logically interactable components.
[0078] Although the invention herein has been described with respect to particular embodiments, it is understood that these embodiments are merely illustrative of the principles and applications of the present invention. It is therefore to be understood that numerous modifications may be made to the illustrative embodiments and that other arrangements may be devised without departing from the spirit and scope of the present invention as defined by the appended claims.
Claims
1 . A system for reducing pathogens in a biological fluid, the system comprising:
- a UV-transparent elongated serpentine-shaped flow path for the biological fluid to be pumped or gravity-fed therethrough from a fluid supply source towards a fluid collection element,
- a source of UV irradiation positioned in close proximity to said entire flow path so as to deliver UV irradiation to the biological fluid when propagated along at least a portion of said flow path, and
- a control system for energizing said source of UV irradiation and causing propagation of said biological fluid through said flow path from said fluid supply source towards said fluid collection element, and
- a UV-transparent jacket containing IR-absorbing fluid and surrounding said flow path, said jacket configured to pass through UV irradiation from said source of UV irradiation towards said fluid path while interrupting and absorbing IR irradiation emanating in a direction from said source of UV irradiation towards said fluid path,
wherein upon energizing of the source of UV irradiation by said control system, the biological fluid is irradiated by UV light while minimizing heat transfer thereto whereby causing reduction in said pathogens therein.
2. The system as in claim 1 , wherein said UV-transparent jacket is further utilized as a UV-transparent cooling system located in close contact with an exterior of said flow path, said cooling system is equipped with at least one temperature sensor of said biological fluid, said cooling system is configured to maintain said biological fluid temperature within a predefined range by circulating said IR-absorbing fluid.
3. A system for reducing pathogens in a biological fluid, the system comprising:
- a UV-transparent elongated serpentine-shaped flow path for the biological fluid to be pumped or gravity-fed therethrough from a fluid supply source towards a fluid collection element,
- a source of UV irradiation positioned in close proximity to said entire flow path so as to deliver UV irradiation to the biological fluid when propagated along at least a portion of said flow path,
- a UV-transparent jacket containing IR-absorbing fluid surrounding said flow path and separating thereof from said source of UV irradiation,
- a circulation system for propagating said IR-absorbing fluid through said UV-transparent jacket, and
- a control system configured to activate said source of UV irradiation, cause pumping or gravity-
feeding of said biological fluid through said flow path from said fluid supply source towards said fluid collection element, and operation of said circulation system, whereby upon activation of said control system, said biological fluid is exposed to UV irradiation to reduce pathogens therein while maintaining said biological fluid temperature within a predetermined range.
4. The system as in claim 3, wherein said IR-absorbing fluid is cooled prior to propagating through said UV- transparent jacket.
5. The system as in claim 3, wherein said IR-absorbing fluid is pressurized inside said UV-transparent jacket.
6. The system as in claim 3, wherein said IR-absorbing fluid is propagated in a direction other than that of the biological fluid propagating along said flow path.
7. The system as in claim 7, wherein said IR-absorbing fluid is propagated in a direction opposite or perpendicular to that of the biological fluid propagating along said flow path.
8. The system as in claim 3, wherein said source of UV irradiation is configured to emit ultraviolet light at a peak wavelength from about 250 nm to about 270 nm.
9. The system as in claim 3, wherein said source of UV irradiation comprises a plurality of spaced apart individual sources of UV irradiation positioned along said flow path and configured to provide uniform exposure to ultraviolet light for said biological fluid propagated through said flow path.
10. The system as in claim 10, wherein said source of UV irradiation is a UV lamp or at least one UV-emitting LED.
1 1 . The system as in claim 3, wherein said circulation system is configured to recycle and recirculate said IR-absorbing fluid through said UV-transparent jacket.
12. The system as in claim 13, wherein said circulation system comprises a cooling element configured to reduce the temperature of said IR-absorbing fluid prior to entry into said UV-transparent jacket.
13. A system for reducing pathogens in a biological fluid, the system comprising:
- a UV-transparent flow path for the biological fluid to be propagated therethrough,
- a source of UV irradiation positioned in close proximity to said flow path so as to deliver UV
irradiation to the biological fluid when propagated along at least a portion of said flow path,
- a UV-transparent jacket containing an IR-absorbing gas pressurized to be above atmospheric pressure, said IR absorbing gas surrounding said flow path to separate thereof from said source of UV irradiation, said IR-absorbing gas is selected from a group consisting of carbon dioxide, water vapor, methane, nitrous oxide, and ozone,
- a circulation system for propagating said IR-absorbing gas through said UV-transparent jacket, and
- a control system configured to activate said source of UV irradiation, cause propagation of said biological fluid through said flow path and operation of said circulation system, whereby upon activation of said control system, said biological fluid is exposed to UV irradiation to reduce pathogens therein while maintaining said biological fluid temperature within a predetermined range.
14. The system for reducing pathogens as in claim 13, wherein said circulation system comprising a canister for storing said IR-absorbing gas at a pressure higher than the pressure inside said UV-transparent jacket, whereby upon entry of said IR-absorbent gas from said canister into said UV-transparent jacket said IR-absorbing gas is expanded causing a reduction in temperature thereof below the temperature of the biological fluid.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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US14/521,398 | 2014-10-22 | ||
US14/521,398 US9265876B1 (en) | 2014-10-22 | 2014-10-22 | Systems and methods for pathogen inactivation in blood using UV irradiation while minimizing heat transfer thereto |
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CN111201201B (en) * | 2017-08-11 | 2022-12-02 | 埃奎森斯技术有限责任公司 | Irradiation device and method |
US10744246B2 (en) * | 2017-08-18 | 2020-08-18 | Heartware, Inc. | Therapeutic UV blood treatment in a blood pump |
EP3479849A1 (en) * | 2017-11-02 | 2019-05-08 | Justus-Liebig-Universität Gießen | Method and device for inactivating pathogens |
US11672898B2 (en) * | 2018-06-08 | 2023-06-13 | Oregon State University | Microfluidic removal of excess bilirubin from blood |
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US10894726B1 (en) | 2020-02-12 | 2021-01-19 | Aquisense Technologies, Llc | Water disinfecting module, systems and methods |
WO2021252685A1 (en) * | 2020-06-10 | 2021-12-16 | Ascepi Medical Group, Llc | Blood irradiation device and methods for treating viral infections using same |
CN114887087B (en) * | 2022-05-05 | 2023-08-18 | 上海甄徽网络科技发展有限公司 | Indoor mobile robot with ultraviolet disinfection function |
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US9265876B1 (en) | 2016-02-23 |
US9474844B1 (en) | 2016-10-25 |
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