Abstract:
An apparatus for irradiating blood or blood products, preferably with ultra violet or visible light, to reduce contaminants in the blood or blood products. A removable radiometer having light integrating chambers detects the light intensity, allowing the radiation characteristics of the apparatus to be calibrated. A control circuit uses the measurements to control the delivery of an effective dose of illumination to blood or blood products in a bag or container. One or more light integrating optical chambers in the radiometer allow a single light sensor to sense light across an entire field. Thermistors in the irradiating apparatus or the radiometer or both sense the temperature of photo sensors. The control circuit compensates for temperature-dependant variations in the output of the photo sensors.

Description:
This application describes an apparatus for irradiating blood or blood products, preferably with ultra violet or visible light, to reduce contaminants in the blood or blood products. A removable radiometer having light integrating chambers detects the light intensity, allowing the radiation characteristics of the apparatus to be calibrated. A control circuit uses the measurements to control the delivery of an effective dose of illumination to blood or blood products in a bag or container. One or more light integrating chambers in the radiometer allow a single light sensor to sense light across an entire field. 
     BACKGROUND 
     Contamination of whole blood or blood products with infectious microorganisms such as HIV, hepatitis and other viruses and bacteria present a serious health hazard for those who must receive transfusions of whole blood or administration of various blood products or blood components such as platelets, red cells, blood plasma, Factor VIII, plasminogen, fibronectin, anti-thrombin III, cryoprecipitate, human plasma protein fraction, albumin, immune serum globulin, prothrombin complex plasma growth hormones, and other components isolated from blood. Blood screening procedures may miss pathogenic contaminants, and sterilization procedures which do not damage cellular blood components but effectively inactivate all infectious viruses and other microorganisms have not heretofore been available. 
     In some circumstances, certain blood components may themselves be harmful to the desired blood product. For example, white blood cells, which are part of the donor&#39;s immune system, may cause an adverse reaction in the recipient of a red blood cell product. Many white cells are separated by centrifugation from the desired red blood cells, but some usually remain mixed with the red blood cells. The undesired white blood cells may be considered a “contaminant” or “pathogen” with respect to the desired relatively pure red blood cell product. The white blood cells may be inactivated in the same manner as an infectious virus or microorganism. 
     The use of pathogen inactivating agents include certain photo sensitizers, or compounds which absorb light of defined wavelengths and transfer the absorbed energy to an energy acceptor, have been proposed for inactivation of microorganisms found in blood products or fluids containing blood products. Such photo sensitizers may be added to the fluid containing blood or blood products and irradiated. 
     The photo sensitizers which may be used in this invention include any photo sensitizers known to the art to be useful for inactivating microorganisms. A “photo sensitizer” is defined as any compound which absorbs radiation at one or more defined wavelengths and subsequently utilizes the absorbed energy to carry out a chemical process. Examples of photo sensitizers which may be used for the reduction of pathogens in blood or blood products include porphyrins, psoralens, dyes such as neutral red, methylene blue, acridine, toluidines, flavine (acriflavine hydrochloride) and phenothiazine derivatives, coumarins, quinolones, quinones, and anthroquinones. 
     A number of systems and methods for irradiating pathogens in a fluid with light either with or without the addition of a photo sensitizer are known in the art. For example, U.S. Pat. No. 5,762,867 is directed toward a system for activating a photoactive agent present in a body fluid with light emitting diodes (LEDs). 
     U.S. Pat. No. 5,527,704 is directed toward an apparatus containing LEDs used to activate a fluid containing methylene blue. 
     U.S. Pat. No. 5,868,695 discloses using LEDs having a red color and emitting light at a wavelength of 690 nm in combination with benzoporphrin derivative photo sensitizers to inactivate red blood cells. As taught in this patent, at a wavelength of 690 nm, red blood cells are essentially transparent to radiation, and as such, the benzoporphorin derivatives absorb radiation at this wavelength to become activated. Also disclosed in this patent is the use of LEDs having a blue color and emitting light at a peak wavelength of 425 mn to inactivate platelets. 
     U.S. Pat. No. 5,658,722 discloses irradiating platelets using UVA1 light having an emission peak near 365 nm. This patent teaches that damage to platelets is caused by short UVA&lt;345 nm, and unlike the present invention, calls for removing UVA wavelengths below 345 nm. 
     Use of light which is variably pulsed at a wavelength of 308 nm without the addition of a photo sensitizer to inactivate virus in a washed platelet product is taught in an article by Prodouz et al. (Use of Laser-UV for Inactivation of Virus in Blood Products; Kristina Prodouz, Joseph Fratantoni, Elizabeth Boone and Robert Bonner; Blood, Vol 70, No. 2). This article does not teach or suggest the addition of a photo sensitizer in combination with light to kill viruses. 
     U.S. Pat. No. 6,843,961 is directed toward the reduction of pathogens which may be present in blood or blood products using light having peak wavelengths in combination with an endogenous photo sensitizer. 
     Whether or not a photo sensitizer is used, it is important that the dosage of radiation delivered to the blood or blood component be accurately controlled. Proper calibration of the irradiation apparatus is, therefore, necessary. 
     SUMMARY OF THE INVENTION 
     The present invention provides an apparatus for irradiating a fluid containing blood products and pathogens, including a radiometer for accurate calibration of delivered radiation. The apparatus comprises treatment chamber having at least one radiation emitting source emitting radiation; a support platform for holding the fluid containing blood cells or blood components to be irradiated; a control unit for controlling the radiation emitting source; and a removable radiometer in electrical communication with the control unit, the radiometer comprising a first optical chamber having a aperture for receiving at least some of the radiation and a photo sensor responsive to the received radiation in the optical chamber. The optical chamber may comprise an elongated cavity or cylinder, with an aperture shaped as a slot extending parallel to a long dimension of the optical chamber. This aperture might be covered by or filled with a light transmitting material such as quartz glass. An inner surface of the optical chamber may be “optically rough”, producing a diffuse or lambertion reflection. The inner surface may be coated with or made from TEFLON™ or other suitable material. 
     The photo sensor may be coupled to a thermistor through a heat sink. The output of the photo sensor may be correlated to a detected temperature, whereby a more accurate measurement of illumination may be obtained. 
     In a further aspect of the invention related to an illuminator, a photo sensor in the illuminator responds to radiation emitted by the radiation source and communicates a signal to the control unit. A thermistor detects temperature changes and communicates a signal to the control unit, which correlates the photo sensor signal with respect to the temperature signal. It has been found that the photo sensor signal is a function both of received light and of temperature, and that actual illumination can be more accurately controlled if the illuminator senses the temperature of the photodiode. Further, the illuminator may comprise a plurality of light sources and a plurality of photo diodes, at least some of the photodiodes being mounted in a heat sink. The thermistor may be coupled to the heat sink. 
     In another aspect of the invention the radiometer may further comprise a first integrating chamber coupled to the first optical chamber by an opening, which may be a second slot. The second slot may be generally perpendicular to the first slot with respect to an axis of symmetry of the first optical chamber. Where there are two or more coupled optical chambers, the sensor is preferably in the last chamber, for example, in the first integrating chamber. 
     In a further aspect of the invention, the sensor is recessed away from an inner surface of the optical chamber. This may eliminate the use of a baffle. The recess may be “apodized”, that is, optically sharp corners or discontinuities may be removed. The sensor may be mounted diametrically across the first optical chamber from the second slot. 
     The apparatus may also have a second radiation emitting source emitting radiation, wherein the radiometer is mounted between the first radiation emitting source and the second radiation emitting source. The radiometer may further comprise a second optical chamber having a third aperture for receiving at least some of said radiation from the second radiation source and a second photo sensor responsive to the radiation received in the third optical chamber. 
     In another embodiment of the invention, the apparatus comprises a first integrating chamber coupled to the first optical chamber by an opening and a second integrating chamber coupled to the second optical chamber by another opening. The optical chambers may be parallel, elongated cylinders having substantially parallel longitudinal axes of symmetry and the apertures and the openings may be slots, the slots being substantially parallel to the axes of symmetry. 
     These and other features of the invention will be apparent from the following detailed description, taken with reference to the accompanying drawings. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  is a cross-sectional view of a treatment chamber in an illuminator which may be used in the present invention. 
         FIG. 2  is a cross-sectional view of another treatment chamber. 
         FIG. 3  is a perspective view of an irradiation apparatus or illuminator containing a treatment chamber. 
         FIG. 4  is a top plan view of elements of a treatment chamber, with a calibration radiometer. 
         FIG. 5  is a cross-sectional plan view of the elements of  FIG. 4 , taken along line  5 - 5  of  FIG. 4 . 
         FIG. 6  is a cross-sectional plan view of the elements of  FIG. 4 , taken along line  6 - 6  of  FIG. 4 . 
         FIG. 7  is a perspective view of a radiometer. 
         FIG. 8  is a further perspective view of the radiometer of  FIG. 7 . 
         FIG. 9  is an exploded perspective view of a four-chamber radiometer. 
         FIG. 10  is a schematic diagram of an amplifier for use in the radiometer. 
     
    
    
     DETAILED DESCRIPTION 
     The term “blood product” as used herein includes all blood constituents or blood components and therapeutic protein compositions containing proteins derived from blood as described above. Fluids containing biologically active proteins other than those derived from blood may also be treated by the methods and devices of this invention. 
     Photo sensitizers may include compounds which preferentially adsorb to nucleic acids, thus focusing their photodynamic effect upon microorganisms and viruses with little or no effect upon accompanying cells or proteins. Other types of photo sensitizers are also useful in this invention, such as those using singlet oxygen-dependent mechanisms. 
     Most preferred are endogenous photo sensitizers. The term “endogenous” means naturally found in a human or mammalian body, either as a result of synthesis by the body or by ingestion as an essential foodstuff (e.g. vitamins) or formation of metabolites and/or byproducts in vivo. Examples of such endogenous photo sensitizers are alloxazines such as 7,8-dimethyl-10-ribityl isoalloxazine (riboflavin), 7,8,10-trimethylisoalloxazine (lumiflavin), 7,8-dimethylalloxazine (lumichrome), isoalloxazine-adenine dinucleotide (flavine adenine dinucleotide [FAD]), alloxazine mononucleotide (also known as flavine mononucleotide [FMN] and riboflavine-5-phosphate), vitamin Ks, vitamin L, their metabolites and precursors, and napththoquinones, naphthalenes, naphthols and their derivatives having planar molecular conformations. The term “alloxazine” includes isoalloxazines. Endogenously-based derivative photo sensitizers include synthetically derived analogs and homologs of endogenous photo sensitizers which may have or lack lower (1-5) alkyl or halogen substituents of the photo sensitizers from which they are derived, and which preserve the function and substantial non-toxicity thereof. When endogenous photo sensitizers are used, particularly when such photo sensitizers are not inherently toxic or do not yield toxic photoproducts after photo radiation, no removal or purification step is required after decontamination, and a treated product can be directly returned to a patient&#39;s body or administered to a patient in need of its therapeutic effect without any further required processing. Using endogenous photo sensitizers to inactivate pathogens in a blood product are described in U.S. Pat. Nos. 6,843,961, 6,258,577 and 6,277,337, herein incorporated by reference in their entirety to the amount not inconsistent. In U.S. Pat. No. 6,843,961, the photo sensitizer used in the examples is 7,8-dimethyl-10-ribityl isoalloxazine (riboflavin). Non-endogenous photo sensitizers based on endogenous structures, such as those described in U.S. Pat. No. 6,268,120, may also be used in the present invention, and is incorporated by reference herein. Upon exposure of the photo sensitizer to light of a particular wavelength, the photo sensitizer will absorb the light energy, causing photolysis of the photo sensitizer and any nucleic acid bound to the photo sensitizer. 
     Microorganisms or pathogens which may be eradicated or inactivated using pathogen inactivation agents or photo sensitizers include, but are not limited to, viruses (both extra-cellular and intracellular), bacteria, bacteriophages, fungi, blood-transmitted parasites, and protozoa. Exemplary viruses include acquired immunodeficiency (HIV) virus, hepatitis A, B and C viruses, sinbis virus, cytomegalovirus, vesicular stomatitis virus, herpes simplex viruses, e.g. types I and II, human T-lymphotropic retroviruses, HTLV-III, lymphadenopathy virus LAV/IDAV, parvovirus, transfusion-transmitted (TT) virus, Epstein-Barr virus, and others known to the art. Bacteriophages include Φ X174, Φ 6, λ, R17, T 4 , and T 2 . Exemplary bacteria include but are not limited to  P. aeruginosa, S. aureus, S. epidermis, L. monocytogenes, E. coli, K. pneumonia  and  S. marcescens.    
     The fluid to be pathogen inactivated has the photo sensitizer added thereto, and the resulting fluid mixture may be exposed to photo radiation of the appropriate peak wavelength and amount to activate the photo sensitizer, but less than that which would cause significant non-specific damage to the biological components or substantially interfere with biological activity of other proteins present in the fluid. Accurate control of the amount of radiation delivered to the fluid is, therefore, important. 
     The term peak wavelength as defined herein means that the light is emitted in a narrow range centered around a wavelength having a particular peak intensity. Visible light for pathogen reduction may be centered around a wavelength of approximately 470 nm, and having a maximum intensity at approximately 470 nm. In another embodiment, the light may be centered around a narrow range of UV light at an approximate wavelength of 302 nm, and having a maximum intensity at approximately 302 nm. The term light source or radiation source as defined herein means an emitter of radiant energy, and may include energy in the visible and/or ultraviolet range, as further described below. 
     The photo sensitizer may be added directly to the fluid to be pathogen inactivated, or may be flowed into the photo-permeable container separately from the fluid being treated, or may be added to the fluid prior to placing the fluid in the photo-permeable treatment container. The photo sensitizer may also be added to the photo-permeable container either before or after sterilization of the treatment container. 
     The fluid containing the photo sensitizer may also be flowed into and through a photo-permeable container for irradiation, using a flow through type system. Alternatively, the fluid to be treated may be placed in a photo-permeable container which is agitated and exposed to photo radiation for a time sufficient to substantially inactivate the microorganisms, in a batch-wise type system. 
     The term “container” refers to a closed or open space, which may be made of rigid or flexible material, e.g., may be a bag or box or trough. The container may be closed or open at the top and may have openings at both ends, e.g., may be a tube or tubing, to allow for flow-through of fluid therein. A cuvette has been used to exemplify one embodiment of the invention involving a flow-through system. Collection bags, such as those used with the Trima® and/or Spectra™ apheresis systems of Gambro, Inc., (f/k/a Cobe Laboratories, Inc., Lakewood, Colo., USA), have been used to exemplify another embodiment involving a batch-wise treatment of the fluid. 
     The term “photo-permeable” means the material of the treatment container is adequately transparent to photo radiation of the proper wavelength for activating the photo sensitizer. In a flow-through system, the container has a depth (dimension measured in the direction of the radiation from the photo radiation source) sufficient to allow photo radiation to adequately penetrate the container to contact photo sensitizer molecules at all distances from the light source and ensure inactivation of pathogens in the fluid to be decontaminated, and a length (dimension in the direction of fluid flow) sufficient to ensure a sufficient exposure time of the fluid to the photo radiation. The materials for making such containers, as well as the depths and lengths of the containers may be easily determined by those skilled in the art, and together with the flow rate of fluid through the container, the intensity of the photo radiation and the absorptivities of the fluid components, e.g., plasma, platelets, red blood cells, will determine the amount of time the fluid should be exposed to photo radiation. The container used may be any container known in the art for holding fluid to be irradiated, including, but not limited to blood bags, cuvettes and tubing. One example, not meant to be limiting which may be used as the container is an Extended Life Platelet (ELP) bag available from Gambro BCT, Inc. Another example of a suitable container is the Sangewald bag (available from Sangewald Verpackungen GmbH &amp; Co. KG). 
     After treatment, the blood or blood product may be stored for later delivery to a patient, concentrated, infused directly into a patient or otherwise processed for its ultimate use. 
       FIG. 1  shows, in a cross-sectional view, the inside of a radiation or treatment chamber of one type of apparatus that may be used in the present invention. The treatment chamber shown in  FIG. 1  may be used in batch-wise systems, however, it should be noted that similar elements may also be used in flow-through systems. It should be noted that throughout the description of the invention, like elements have been given like numerals. The apparatus  10 , used for inactivating a fluid which may contain pathogens, consists of an radiation chamber  12  having at least one source of radiation  14 . In one preferred embodiment ( FIG. 1 ), the radiation chamber may contain a second source of radiation  16 . A single light source, as shown in  FIG. 2 , may also be used. Each radiation source  14  and  16  respectively, is depicted as including a plurality of discrete radiation-emitting elements  18 ,  30 . The radiation chamber  12  further consists of a support platform  20  for supporting a fluid container  22  containing the fluid to be irradiated, and a control unit  24 . 
     As introduced above, two sources of radiation are shown within radiation chamber  12 . Radiation source  14  may be located along the top portion of the radiation chamber  12  above the container  22 , which holds or contains the fluid to be irradiated, while radiation source  16  may be located along the bottom portion of the radiation chamber  12  below the container  22 . Although not shown, radiation sources may also be located along some or all of the sides of the radiation chamber  12  perpendicular to the container  22 . The radiation chamber  12  may alternatively contain a single radiation source at any location within the radiation chamber  12  and still comply with the spirit and scope of the present invention. 
     The upper radiation source  14  includes an upper support substrate  36  supporting a plurality of discrete radiation emitting elements or discrete light sources (see discrete source  18  as one example) mounted thereon. As further depicted in  FIG. 1 , the lower radiation source  16  includes a lower support substrate  28  which also supports a plurality of discrete radiation emitting elements or discrete light sources (see discrete source  30  as another example). Lower support substrate  28  preferably runs parallel to support platform  20 . The support substrates  36 ,  28  may be substantially flat as shown, or may be in an arcuate shape, or may be in a shape other than arcuate, without departing from the spirit and scope of the invention. 
     The support substrate may or may not have reflective surfaces. In a further alternative configuration, the reflective surface may not contain any light sources. Such a reflective surface containing no light sources (not shown) may be located within the radiation chamber  12  on a side opposite from the radiation source. The support platform  20  may have a reflective surface  32 . This reflective surface  32  on support platform  20  may be in place of, or may be in addition to another reflective surface within the radiation chamber. There may also be no reflective surfaces at all within the radiation chamber. 
     In any of these reflective surface embodiments, the reflective surface may be coated with a highly reflective material which serves to reflect the radiation emitted from the lights back and forth throughout the treatment chamber until the radiation is preferably completely absorbed by the fluid being irradiated. The highly reflective nature of the reflective surface reflects the emitted light back at the fluid-filled bag or container  22  with minimum reduction in the light intensity. 
     In  FIG. 1 , support platform  20  is positioned within the radiation chamber  12 . The support platform  20  may be located substantially in the center of the radiation chamber (as shown in  FIG. 1 ), or may be located closer to either the top portion or the bottom portion of the treatment chamber. The support platform  20  supports the container  22  containing the fluid to be irradiated. Additionally or alternatively, the platform  20  may be made of a photo-permeable material to enable radiation emitted by the lights to be transmitted through the platform and penetrate the fluid contained within the container  22 . The platform may also be a wire or other similar mesh-like material to allow maximum light transmissivity therethrough. 
     The support platform  20  is preferably capable of movement in multiple directions within the radiation chamber  12 . One type of agitation system used might be similar to the Helmer flatbed agitation system available from Helmer Corp. (Noblesville, Ind., USA). This type of agitator provides to and fro motion. Other types of agitators may also be used to provide a range of motion to the fluid contained within the container  22 . For example, the support platform might be oriented in a vertical direction with the light substrates  36  and  28  also oriented in a vertical direction. The support platform  20  may alternatively rotate in multiple possible directions within the radiation chamber in varying degrees from between 0° to 360°. Support platform  20  may also oscillate back and forth, or side to side along the same plane. As a further alternative, one or more of the light sources may also move in a coordinated manner with the movement of the support platform. Such oscillation or rotation would enable the majority of the photo sensitizer and fluid contained within the container  22  to be exposed to the light emitted from each of the discrete radiation sources (e.g. discrete sources  18  and  30 ), by continually replacing the exposed fluid at the light-fluid interface with fluid from other parts of the bag not yet exposed to the light. Such mixing continually brings to the surface new fluid to be exposed to light. The movement of both the support platform  20  and/or the radiation sources  14  and  16  may be controlled by control unit  24 . The control unit  24  may also control the rate of light emission. 
     In a preferred embodiment each discrete light source  18  and  30  emits a peak wavelength of light to irradiate the fluid contained in bag  22 . The peak wavelength of light emitted by each discrete light source is selected to provide irradiation of a sufficient intensity to activate both the photo sensitizer in a pathogen inactivation process as well as to provide sufficient penetration of light into the particular fluid being irradiated, without causing significant damage to the blood or blood components being irradiated. The preferred photo sensitizer is riboflavin. To irradiate a fluid containing red blood cells and riboflavin, it is preferred that each discrete light source  18  and  30  be selected to emit light at a peak wavelength of about 302 nm. Alternatively, 470 nm light might be used. The 470 nm of light is close to the optimal wavelength of light to both photolyse riboflavin, and also to enable significant penetration of the fluid containing red blood cells by the light. 
     If desired, the light sources  18  and  30  may be light emitting diodes and might be pulsed. Pulsing the light may be advantageous because the intensity of light produced by the light sources may be increased dramatically if the lights are allowed to be turned off and rested between light pulses. Pulsing the light at a high intensity also allows for greater depth of light penetration into the fluid being irradiated, thus allowing a thicker layer of fluid to be irradiated with each light pulse. 
     The light sources  18  as shown in  FIG. 3 , may be fluorescent or incandescent tubes, which stretch the length of the irradiation chamber, or may be a single light source which extends the length and width of the entire chamber (not shown). LEDs may also be used in this embodiment. As shown in  FIG. 3 , the support platform  20  may be located within and/or forming part of a drawer  34 . The support platform  20  may contain gaps  36  or holes or spaces within the platform  20  to allow radiation to penetrate through the gaps directly into the container  22  containing fluid to be irradiated. 
     A cooling system may also optionally be included. Air cooling using at least one fan  38  may be preferred but it is understood that other well-known systems can also be used. Although not shown in  FIG. 3 , the method may also include the use of temperature sensors and other cooling mechanisms where necessary to keep the temperature below temperatures at which desired proteins and blood components in the fluid being irradiated are damaged. Preferably, the temperature is kept between about 0° C. and about 45° C., more preferably between about 4° C. and about 37° C., and most preferably about 28° C. 
     The present invention includes a removable radiometer  40  that has the general shape of a blood bag  22 . When placed on the support platform  20  and electrically connected to the controller  24 , the radiometer  40  detects the intensity of incident light, preferably ultraviolet light, thereby allowing for calibration of the apparatus  10 . Once calibrated, the controller  24  will be able to adjust exposure time and light intensity to deliver a desired dose of radiation to a blood bag and its contents. As shown in  FIGS. 4 ,  5  and  6 , the support platform or platen  20  carries the radiometer  40  backwards and forwards parallel to the ultraviolet florescent light sources  18 . The stroke distance allows the sensing apparatus (described below) of the radiometer to “view” the light sources  18 ,  30 . Each of the light sources  18 ,  30  has an associated photo sensor  42 ,  44  ( FIG. 6 ) in electrical communication with the controller  24 . During calibration, the controller  24  correlates the signals from the photo sensors  42 ,  44  to the output of the radiometer  40 . When the radiometer  40  has been removed and replaced with a blood bag, the controller  24  will control the dose of radiation received by the blood bag based on the calibrated signals received from the photo sensors  42 ,  44 . 
     The photo sensors  42 ,  44  may be mounted in heat sinks  110 ,  112 . Thermistors  114 ,  116  detect the temperature of the photo sensors  42 ,  44  as represented by the temperature of the heat sinks  110 ,  112  and communicate a signal to the controller  24 . It has been found that the output signals of the photo sensors  42 ,  44  are dependant not only on the incident light received by a photo sensor, but also on temperature, that is, increased temperature will elevate the output of the photo sensor for the same intensity of incident light. With signals from both the thermistor and the photo sensor, the controller can more accurately control the dose of radiation received by the blood bag and its contents. 
     The radiometer  40  comprises at least one elongated, cylindrical optical chamber. If light is supplied solely from one side, for example, from the upper lamps  18 , a first or upward-opening optical chamber  46  may be provided, oriented generally perpendicularly to the tubes  18  and to a reciprocating movement of the platen  20 . An upper surface  48  of the radiometer  40  has a slot  50  parallel to the elongated axis of the optical chamber  46 , which allows light from the lamps  18  to enter the optical chamber. The edges  52  of the slot  50  are preferably chamfered to allow light from most of the length of the lamps to be received in the chamber  46 . Reciprocating movement of the platen  20  brings additional lengths of the lamps at each end into the view of the chamber  46 . Thus, the radiation received through the slot  50  approximates the radiation received by a blood sample and sample bag along a line at the position of the slot. Because the chamber “averages” the non-uniform light field emitted by the lamps  18 , the exposure on this line can be used to calculate the total exposure dose received by the sample. 
     An inner surface  54  of the optical chamber  46  is optically rough and coated with or made from a suitable substance such as TEFLON™ material, allowing light received in the chamber to reflect within the chamber in such a way that the light field becomes averaged at any point within the chamber. A single photo sensor  56 , mounted in the inner surface  54  perpendicularly from the slot  50 , can sense an intensity representative of the radiation being received along the entire length of the slot. Preferably, the photo sensor  50  is recessed away from the inner surface  54 , to reduce the likelihood of a beam of light or radiation from the lamps  18  falling directly on the photo sensor  56  without at least one reflection from the inner surface  54  of the chamber. Multiple photo sensors may also be used. 
     In an embodiment having a lower bank of lamps  30 , the radiometer  40  preferably has a second downward-opening optical chamber  58 . The second optical chamber  58  is oriented parallel to the first optical chamber  46  and also comprises a slot  60  in a lower surface  62  of the radiometer  40 , the slot  60  being parallel to the elongated axis of the second optical chamber  58 , but oriented in an opposite direction from the slot  50  in the first chamber  46 , which allows light from the lower lamps  30  to enter the second optical chamber  58 . The edges  64  of the slot  60  are preferably chamfered, as explained above, and reciprocating movement of the platen  20  brings additional lengths of the lower lamps at each end into the view of the lower chamber  58 . An inner surface  66  of the optical chamber  58  is optically rough and coated with or made from a suitable substance such as TEFLON™ material. As explained above, a single photo sensor  68 , mounted in the inner surface  66  perpendicularly from the slot  60 , is recessed away from the inner surface  66 . Although a single photo sensor in each optical chamber is preferred, a plurality of photo sensors could also be used. 
     The radiometer  40  comprises an upper shell  71  and a lower shell  70 . The lower shell  70 , as shown in  FIG. 7  and  FIG. 8 , has a bottom surface  72  and a peripheral wall  74 , the peripheral wall having the general shape of a blood bag of a type that might be used in the illuminator  10 . The upper shell  71  has a top surface  48  and a mating peripheral wall  78  (see  FIG. 5  and  FIG. 6 ), adapted to fit against the peripheral wall  74  of the lower shell  70 . As explained above, first and second optical chambers  46 ,  58  are provided. These chambers  46 ,  58  comprise mating half-cylinders  80 ,  82  in the lower shell  70  and upper half-cylinders in the upper shell  71 . In the embodiment shown in  FIG. 7  and  FIG. 8 , the chambers  46 ,  58  are within an inner box  118  having a lower portion  120  and an upper portion  122 . Heat sinks  132 ,  134  cover the photo diodes  56 ,  68  on the outside of the box  118 . Thermistors  136 ,  138 , in thermal contact with the heat sinks  132 ,  134  respond to the temperature of the heat sinks, which is also representative of the temperature of the photo diodes  56 ,  68 . The output of the photodiodes is a function not only of the incident illumination, but also of the temperature of the photodiode. Thus, as the temperature of the photodiode increases, the output current of the photodiode will also rise, even if the illuminating radiation is constant. In order to provide an accurate measure of the illumination (as well as an accurate dose of radiation by the illuminator), the control circuit  24  compensates both for the temperature of the photodiodes in the radiometer during calibration and for the temperature of the photodiodes in the illuminator during viral inactivation. Electrical connecting wires (not shown) may pass through gaps  124 ,  126  between the shells  70 ,  71  and the box  118 , providing electrical connections between the photo diodes  56 ,  68 , amplifier circuits  128 ,  130 , thermistors  136 ,  138  and the control unit  24 . The wires pass as a cable through a block  140  ( FIG. 5 ), comprised of two mating halves  142 ,  144 , the lower half  142  of which is shown in  FIG. 7  and  FIG. 8 . Spring plates  146 ,  148  may be provided adjacent the block on both the lower shell  70  and the upper shell  71 , which may be engaged by a clamp (not shown) that holds a blood bag in position on the illuminator. 
     Each of the photo sensors  56 ,  68  is electrically coupled to transimpedance amplifiers  128 ,  130  respectively. The amplifiers  128 ,  130  are further electrically connected through a communications cable to the control unit  24 . Male and female plugs (not shown) may be provided so that the radiometer may be selectively coupled to the control unit  24  for calibrating the apparatus, and then removed for ordinary operation. As shown in  FIG. 11 , the transimpedance amplifiers comprise an operational amplifier  100  receiving input from a photo sensor  102 . The gain is controlled by both a manual variable resister  104  and a digital variable resister  106 . The signal is then fed to a second operational amplifier  108  before being conducted to the control unit  24 . It is anticipated that the variable resisters will be initially adjusted in comparison to a standardized light source, and would not need further adjustment when used in connection with a pathogen inactivation apparatus. 
     To calibrate a pathogen in activation apparatus, the radiometer  40  is substituted for a blood bag, and occupies the same location in the apparatus and has the same general shape as a blood bag containing blood or blood components. The radiometer would be electrically connected to the control unit  24  and exposed to radiation from the lamps  18 ,  30  for a selected period of time. Preferably, the platen  20  would also be agitated it the same manner as when a blood sample would be treated in the apparatus. The output of the radiometer provides a benchmark to the control unit  24  of exposure intensity per unit time, from which a desired dose of radiation can be calculated. After calibration of the apparatus, units of blood or blood components in appropriate translucent or transparent bags can be placed in the pathogen inactivation apparatus and exposed to controlled quantities of radiation. 
     Another embodiment of the radiometer  40 ′ is shown in  FIG. 9 . In this embodiment, the first optical chamber  46  is connected to a first elongated, cylindrical integrating chamber  84  through a third slot  86 . The walls of the first integrating chamber  84  are also optically rough and preferably made from TEFLON™ material or TEFLON-coated. In this embodiment, the photo sensor  56  is mounted in the inner wall  90  of the first integrating chamber, rather than in the inner wall of the first optical chamber. 
     Similarly, a second elongated, cylindrical integrating chamber  92  connects to the second optical chamber  58  through a fourth slot  94 . As above, the photo sensor  68  is mounted in the inner wall  96  of the second integrating chamber  92 , rather than in the inner surface  66  of the second optical chamber  58 . The inner wall  96  is also optically rough and preferably made from TEFLON™ material or TEFLON-coated. The additional first and second integrating chambers  84 ,  92  further integrate the received illumination, providing a more representative measurement at the respective photo sensors, but at the cost of a decrease in absolute intensity. 
     It will be apparent to those skilled in the art that various modifications and variations can be made to the structure and methodology of the present invention without departing from the scope or spirit of the invention. Rather, the invention is intended to cover modifications and variations provided they come within the scope of the following claims and their equivalents.