# Patent

## Title
Apparatus, systems and methods for processing and treating a biological fluid with light

## Abstract

Apparatus (10), systems and methods are disclosed for treating a biological fluid with light. A container (206) of biological fluid is introduced into a fluid treatment chamber (40) where it is contacted with light provided by one or more light sources (60, 70) in proximity to the fluid treatment chamber (40). A light sensing system (650) senses the intensity of illumination of the light. A radiometer (460) may be inserted into fluid treatment chamber (40) to calibrate the light sensing system (650). An electronic control system (600) utilizes an interface circuit board (606) to interface a computer circuit board (602) to a display panel (37), a user interface panel (39, 39a), a relay circuit board (640), light sensors 404 and various other sensors (649). A detector (385) senses agitating movement of a tray (90) that contains biological fluids. Methods include calibrating (781-785), sensing (770-773) and correcting (774-775) light intensity measurements, and determining the length of treatment (776) to reach a desired illumination dose. A radiometer (460) is equipped with a plurality of light sensors (469) disposed on both sides to measure light intensity in chamber (40) and to provide a reference for calibrating light sensing system (650).

## Background
CROSS-REFERENCE TO RELATED APPLICATIONS
This is a divisional patent application of patent application Ser. No. 10/269,409, filed on Oct. 11, 2002, now U.S. Pat. No. 7,068,361, which is a continuation-in-part of U.S. application Ser. No. 09/325,325, filed Jun. 3, 1999, now U.S. Pat. No. 6,565,802 B1.


BACKGROUND OF THE INVENTION
The present invention generally relates to apparatus, systems and methods for processing and treating biological fluids, such as blood and blood components. More particularly, the present invention relates to such apparatus, systems and methods having a light sensing system to measure the illumination intensity of a plurality of lamps, a radiometer with a plurality of light sensors that may be inserted into the apparatus to calibrate the light sensing system, an interface printed circuit board that interfaces a computer printed circuit board with the electronics and sensors of the apparatus, a sensor arrangement to detect the motion of an agitator for agitating the biological fluid, methods for calibrating, sensing and correcting light intensity measurements, a radiometer for accurately measuring light in the apparatus to provide a reference for calibrating the light sensing system, and methods for determining the length of treatment to reach a desired illumination dose by using the calibrated light sensing system.
Apparatus, methods and systems for treating biological fluids, such as blood and blood components, with light are well known. For example, U.S. Pat. No. 4,952,812, incorporated by reference herein, discloses an apparatus for treating unwanted white blood cells in platelet concentrate with ultraviolet radiation to limit the ability of white cells to trigger an immune reaction in a patient. To treat containers of platelet concentrate, the containers are placed on a slidable drawer that is introduced into a housing between facing arrays of lamps for irradiation from both sides of the container. During irradiation, the drawer (or a portion of the drawer) may be pivoted in a rocking motion to agitate the platelet concentrate.
U.S. Pat. No. 5,557,098, also incorporated by reference herein, discloses a system and apparatus for treating a biological fluid with light for the purpose of inactivating pathogens that may be present in the biological fluid. A slidable drawer is used to position the containers of biological fluid between facing arrays of light emitting diodes. Extended flaps on the containers, located outside the light field, are automatically punched to indicate different stages of the light treatment.
U.S. Pat. No. 6,245,570, which is also incorporated by reference herein, discloses apparatus and methods for treating a container of a blood product between two facing arrays of light. The container includes a light sensitive tape that changes color when exposed to ultraviolet light, thereby indicating when the treatment process is complete.
Still other apparatus and systems for treating biological fluid are disclosed in U.S. Pat. Nos. 4,726,949, 5,709,991, 6,433,343 and 6,190,609, all of which are incorporated by reference herein.
Prior art radiometers typically measure light intensity at a single point and from only one direction.
While the prior art apparatus, systems and methods have generally worked satisfactorily, there is a need for improved apparatus, systems and methods that provide, for example, improved reliability and accuracy, greater flexibility and efficiency, improved ease of use and serviceability, as well as enhanced tracking, record keeping and the like.
SUMMARY OF THE INVENTION
The following summary is intended as an overview of certain aspects of the present invention. It is not intended by this summary to limit or expand the scope of the claims, which define the scope of the present invention. The mention of certain features or elements in this summary does not mean that such elements or features are necessary to the use or practice of the invention in its broader or other aspects, or that such should be read into claims that do not expressly recite such feature or element. Conversely, the absence of any mention of certain elements or features is not intended to detract from the significance of such elements or features in those claims in which they are expressly included.
In one aspect, the present invention is embodied in an apparatus for treating a biological fluid in a fluid treatment chamber having a plurality of lamps and a light sensing system to determine the light intensity emitted from the plurality of lamps with the light intensity measurements corrected with previously determined calibration coefficients to provide a calibrated light intensity.
In another aspect, the present invention is embodied in a light sensing system for apparatus to treat a biological fluid in a fluid treatment chamber with at least one light source. The system includes at least one light sensor to sense the light level within the treatment chamber. The light sensor preferably provides an output frequency signal that is related to the sensed light intensity. This frequency signal is counted and analyzed to determine the light intensity in the treatment chamber. Multiple frequency signals from multiple sensors may be multiplexed prior to counting. The count of the frequency signals may be corrected with calibration coefficients that were determined in a prior calibration procedure.
In another aspect, the present invention is also embodied in an electronic control system for the biological fluid treatment apparatus with a computer circuit board and an interface circuit board to interface a display, an operator input device, the light sensing system, the lamp control system and a plurality of sensors and the like with the computer circuit board.
The present invention is also directed to methods for calibrating, sensing and correcting light intensity measurements. The methods also include determining the length of treatment of a biological fluid in order to reach a desired illumination dose.
In yet another aspect, the present invention is embodied in a radiometer with a plurality of light sensors disposed on at least one side, and preferably on opposite sides of the radiometer, to measure light intensity from at least one array of illumination sources. The radiometer is separately calibrated to provide accurate light measurements over a predetermined area of the treatment chamber, which measurements are used by a central processing unit of the apparatus to determine appropriate calibration coefficients for the light sensing system. Preferably, the radiometer simulates the dimensions and geometry of the product to be treated with light in the apparatus.



BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a perspective view of an apparatus for treating a biological fluid with light, embodying the present invention;
FIG. 2 is a perspective view of the apparatus of FIG. 1 showing the modular components of the apparatus separated;
FIG. 3 is a perspective view of the apparatus of FIG. 1 with the front access door open;
FIG. 4 is a perspective view of the apparatus of FIG. 1 with front, top and side panels removed;
FIG. 5 is a partially exploded view of the apparatus of FIG. 1;
FIG. 6 is a perspective view of a light drawer with a socket panel open;
FIG. 6A is an exploded view of the light drawer of FIG. 6.
FIG. 7 is a perspective view of a fluid container carrying tray;
FIG. 8 is a perspective view of the fluid carrying drawer with tray removed;
FIG. 8A is a partial side view of the drawer tilt knob and assembly of the fluid carrying drawer;
FIG. 8B is a modified partial side view of the drawer tilt knob and assembly of the fluid carrying drawer;
FIG. 9 is another perspective view, from the underside, of the fluid carrying drawer without the fluid container carrying tray;
FIG. 10 is a front view of the fluid carrying drawer with fluid carrying tray removed showing side-to-side oscillation of the tray;
FIG. 11 is a perspective view of a container marker assembly;
FIG. 11A is another perspective view, from the underside, of the container marker assembly;
FIG. 12 is an enlarged perspective view of an individual marking unit of the container marker assembly;
FIG. 13 is a perspective view of stacked apparatus embodying the present invention;
FIG. 14 is a block diagram of one embodiment of a control system for the apparatus of the present invention;
FIG. 14A is a perspective view of a light sensing device which may be used with the apparatus of FIG. 1;
FIG. 15 is a plan view of a disposable fluid processing set embodying the present invention;
FIG. 16 is a plan view of another disposable fluid processing set embodying the present invention;
FIG. 17 is a plan view of a disposable fluid processing set embodying the present invention in position for attachment with containers of a collected biological fluid;
FIG. 18 is a perspective view of a part of the disposable fluid processing set embodying the present invention that includes at least one container disposed within a holder;
FIG. 18A is a perspective view of an alternative embodiment of the holder in a closed position with containers disposed therein;
FIG. 18B is a perspective view of the holder of FIG. 18A in an open position but without container(s);
FIG. 18C is a perspective view of another alternative embodiment of a holder in an open position;
FIG. 18D is a perspective view of another alternative embodiment of a holder with the frame portions separated;
FIG. 19 is a flow chart showing the start-up phase of the control system for the present invention;
FIG. 20A is a flow chart showing the pretreatment phase of the control system for the present invention;
FIG. 20B is a continuation of the flow chart of FIG. 20A;
FIG. 21 is a flow chart showing the treatment phase of the control system for the present invention;
FIG. 21A is a flow chart showing the steps employed to measure the illumination intensity during the treatment phase of the apparatus of the present invention;
FIG. 21B is a flow chart showing the steps employed in calibrating the apparatus of the present invention to measure the illumination intensity in accordance with the present invention;
FIG. 22 is a flow chart showing the operator initiated instrument settings functions of the control system for the present invention;
FIG. 23 is a flow chart showing the diagnostic functions of the control system for the present invention;
FIG. 24 is a rear perspective view of one embodiment of the fluid-carrying drawer, fluid container carrying tray and an alternative embodiment of the agitation assembly;
FIG. 25 is a top view of the motor for moving the fluid-carrying drawer;
FIG. 26 is an exploded view of the drawer sub-assembly and fluid-carrying tray;
FIG. 27 is a perspective view of the fluid carrying drawer with the fluid carrying tray placed therein;
FIG. 28 is a perspective view from the underside, of the fluid carrying drawer without the fluid carrying tray;
FIG. 29 is a perspective view of an radiometer embodying the present invention;
FIG. 30 is a cross-sectional view, taken along section line 30-30 of the radiometer shown in FIG. 29;
FIG. 31 is an exploded view of the radiometer of FIG. 29;
FIG. 32 is a perspective view of the radiometer positioned within a compartment of the fluid container carrying tray;
FIG. 33 is a block diagram showing the preferred interconnections and relationships between the printed circuit boards that contain the electronic circuitry for the control system of the present invention;
FIG. 34 is a diagram of the lamps and the light sensing circuitry for the light sensing system of the present invention; and
FIG. 35 is an electrical schematic diagram of the light sensing circuitry.



DETAILED DESCRIPTION
For purposes of illustration, the various aspects of the present invention will be described, in large part, in connection with their preferred embodiments. However, it should be recognized that the apparatus, systems and methods embodying the different aspects of the present invention are not limited to the specific details described herein.
An apparatus for treating a biological fluid is generally shown in FIGS. 1-14 and is referred to herein generally as light box 10. Light box 10 may be used for treating a variety of materials for a variety of purposes.
Light box 10 is particularly useful in the treatment of biological fluids. As used herein, biological fluid refers to any fluid that is found in or that may be introduced into the body including, but not limited to, blood and blood products. As used herein “blood product” refers to whole blood or a component of whole blood such as red blood cells, white blood cells, platelets, plasma or a combination of one or more of such components that have been separated from whole blood.
One specific, non-limiting use of light box 10 is in the treatment of a blood product that has been combined with a photochemical agent for activation when subjected to light. Such photochemical agents are used, for example, in the inactivation of viruses, bacteria, white blood cells and other contaminants (collectively referred to herein as “pathogens”). In pathogen inactivation applications, the activated agent inactivates pathogens that may be present in a blood product.
Typically, the biological fluid to be treated is introduced into a fluid treatment chamber within light box 10 in flexible, plastic, sterilizable, translucent, biologically compatible containers. In accordance with aspects of the present invention, the containers may be integrally connected to other containers and plastic tubing useful in the processing of the biological fluid both before and after the treatment provided by light box 10. Examples of the disposable processing set and its components are shown in FIGS. 15-18. The light box, the disposable processing set and the methods of using them are described in more detail below.
a. Light Box
As shown in FIG. 1, light box 10 includes a housing 12 defined by top panel 14, bottom panel 16, front and rear panels 17, and side panels 18. Housing 12 is supported by feet 13 attached to bottom panel 16 (FIG. 4). In a preferred embodiment, feet 13 are rubber or other elastomeric mounts. Side panels 18 may include handles 22 for grasping and transporting light box 10. An openable or removable door 24 in side panel 18 allows for access to the interior of light box 10 and, more specifically, the electronic components of light box 10, which are described in more detail below. Door 24 may be opened or removed by turning fasteners 25.
For convenience and efficiency, it is preferred that light box 10 be fairly compact. In one, non-limiting example, light box 10 may be approximately 100-120 cm wide, 20-100 cm deep and between approximately 30-40 cm high. A compact instrument allows, for example, for placement of a greater number of instruments per treatment center and/or may allow two or more instruments to be stacked on top of each other (as shown in FIG. 13), resulting in greater throughput of biological fluid per horizontal area or space (i.e. bench space, shelf space or the like).
Light box 10 may include a control module 26 and a fluid treatment module 28. As described in more detail below, control module 26 may include and/or house the command and control elements for the treatment of biological fluid. Fluid treatment module 28 houses the elements and components where fluid processing takes place.
Control module 26 and fluid treatment module 28 may be contained in the same housing but in a preferred embodiment, as shown in FIG. 2, they are readily separable modules. Control module 26 and fluid treatment module 28 are electrically and physically connected when light box 10 is in use, but may be separated as shown in FIG. 2. In one embodiment, control module 26 and fluid treatment module 28 are held together, in part, by a draw pin 30 (FIG. 4), which holds together interfitting parts of the modules. Alternatively, modules 26 and 28 may be held together by captive fasteners 31 (also shown in FIG. 4) with or without draw pin 30. Control module 26 and fluid treatment module 28 may be separated by removing draw pin 30 and/or turning of fasteners 31 shown in FIG. 4. Fasteners 31 may be accessed by removing door 24 (shown in FIG. 1) in side panel 18. Of course, other means of connecting and readily separating control and fluid treatment modules may be used, including, mating clips and slots on the facing panels of the control 26 and fluid treatment module 28.
Providing light box 10 in two readily separable modules 26 and 28 allows for easier access to the control and fluid treatment modules 26 and 28 and, generally, provides for easier serviceability of light box 10. For example, if off-site service is required for control module 26 only, that module can be removed without requiring removal and transport of the entire light box 10.
As shown in FIGS. 1 and 2, the exterior of control module 26 includes a control panel 32 located in the front of light box 10. Control panel 32 includes, a display screen 37 such as, but not limited to, an LCD display for providing graphical, textual and alphanumerical information to the operator regarding the treatment process. Also included within control panel 32 of control module 26 is a key pad 39 to allow operator control over the process and/or for data entry by the operator. A different keypad 39a is shown in FIG. 29, which is a four-by-four matrix with 10 numerical digits including the * and # functions, such as the keypads typically provided on telephones. Additional means of data entry are provided by bar code reader scanner 41 which, when not in use, rests in slot 43 or a scanner holder. A trough 45 may be provided for the coiled cable of bar code reader 41. Alternatively, coiled cable of bar code reader/scanner 41 may be routed through the rear of scanner holder 43. Control panel may also include the on/off switch 35 for light box 10.
The interior components of control module 26 are generally shown in FIG. 4. Control module 26 will typically include a programmable microprocessor for operation of light box 10 including central processing unit 27 and memory devices such as random access memory (RAM) and EPROMS for the system program storage and non-volatile memory for back-up data storage. Control module 26 may further include an isolation transformer 29 for converting an AC input voltage to a DC control system voltage and for maintaining leakage current within acceptable limits for medical devices. Other components within control module 26 may include power supply 167, input/output board 33 and a power inlet module 34, filtered pass through 34b for use with an external light intensity sensing device and filtered output pass through 34a. 
Control module 26 may be adapted for connection to external components such as a printer 500 (FIG. 14) through parallel and/or serial ports 612, 613 and/or 616 (FIG. 33) (such as to a label printer through a serial port), or to a computer printed circuit board (PCB) 602 or, for example, to an Ethernet port 621. Computer PCB 602 can receive data from the several instruments, allowing the operator at a treatment center to retrieve information regarding the several procedures. As will be appreciated by one of ordinary skill, control module 26 may also include other components such as additional printed circuit boards shown in FIG. 33. While FIG. 14 illustrates one embodiment of an electronic control system to light box 10, the preferred embodiment is illustrated in FIGS. 33-35, which are discussed in detail below.
Turning now to the fluid treatment module 28, as shown in FIGS. 1-3, fluid treatment module 28 includes front door 36 which when opened, allows for introduction and removal of the biological fluid into a fluid treatment chamber, as described in more detail below. The front panel 17 of fluid treatment module 28 may also be opened to allow for fuller access to the interior of fluid treatment module. As shown in FIG. 3, panel 17 may include fasteners 17a and ball detents which, when turned, allow front panel 17 to be opened or removed.
FIGS. 4 and 5 generally show the interior of fluid treatment module 28 with at least top panel 14 and front panel 17 removed. As best seen in FIG. 5, fluid treatment module 28 includes an interior framework 38 that defines, in part, a fluid treatment chamber 40 and light chambers 42 and 44 for housing light sources (described in more detail below). The framework 38 may typically be constructed of any sturdy material which will allow light box 10 to support one or more additional light boxes as generally shown in FIG. 13. A preferred material is aluminum and, in particular, Aluminum 6061 hardened to T-6 or Aluminum 5052/H32.
Returning to FIG. 5, the light chambers 42 and 44 are located above and below fluid treatment chamber 40 to provide two-sided illumination of the biological fluid. Of course, it will be appreciated that light box 10 may include a single light chamber, placed in close proximity to fluid treatment chamber or two or more light chambers disposed around a fluid treatment chamber in other than “top and bottom” positions.
As shown in FIGS. 3 through 5, fluid treatment chamber 40 is adapted to receive fluid carrying drawer 50. Light chambers 42 and 44 are adapted to receive light drawers 60 and 70. Fluid treatment module 28 may, optionally, further include a container marker assembly 74 shown, for example, in FIG. 5. Marker assembly 74 may carry one or more markers 76a-76d for marking containers, before and/or after treatment, as will be discussed in more detail below.
Turning more specifically to a description of fluid carrying drawer 50, as shown in FIG. 13, fluid carrying drawer 50 allows for introduction of biological fluid into fluid treatment chamber 40. Fluid carrying drawer 50 may be moveable, either manually or automatically, into and out of fluid treatment chamber 40. Where manual movement of fluid carrying drawer 50 is required, drawer 40 may include handle 80. In one embodiment, movement of fluid carrying drawer 50 is facilitated by slides 82 on either or both sides of drawer 50, which are disposed within rails 86 of framework 38, as best seen in FIGS. 8, 9 and 13. Alternatively, fluid carrying drawer 50 may include rollers or other devices that allow for movement of drawer 50 into and out of fluid treatment chamber 40.
For ease of loading and unloading containers of biological fluid, fluid carrying drawer 50 preferably includes a pivot mount that permits the drawer to be tilted downwardly when fully withdrawn. The ability to tilt drawer 50 downwardly may be particularly useful for loading containers of fluid in the upper light boxes where two or more light boxes are stacked on top of each other, as shown in FIG. 13. In one embodiment, fluid carrying drawer 50 may be hingedly attached to framework 38 so that when fluid carrying drawer 50 is fully opened and is outside of housing 12, front edge of drawer 50 may be tilted downwardly at, for example, a 20-45° angle, and preferably a 30° angle.
To allow tilting of fluid carrying drawer, light box 10 may include spring loaded tilt knob 83 which, when pulled, releases fluid carrying drawer 50 and allows it to be tilted in the manner described above. More specifically, as shown in FIG. 8A, tilt knob 83 is connected to rod 82a which is attached to slide 82 (FIG. 9). The end of rod 82a is coupled to pivot member 83a, which is connected to ring 83b attached to drawer 50. Rod 82a further includes a spring 82c and spring stops 82d. When the end of rod 82a is coupled to pivot member 83a, movement of ring 83b is prevented (as shown in FIG. 8A). However, when knob 83 is pulled, (as shown in FIG. 8B) rod 82a is uncoupled from pivot member 83a, allowing ring to rotate relative to pivot member 83a and, thereby, allowing drawer 50 to be tilted downwardly, as shown in FIG. 13.
Alternatively, light box 10 and more specifically, fluid-carrying drawer 50, may include release button 300 which, when pressed, allows drawer 50 to be downwardly tilted in the manner shown in FIGS. 26-28. As shown in FIGS. 27-28, button 300 actuates rod 302, which is attached to bell crank 304. As rod 302 is moved forward, bell crank 304 pivots around cylinder 306. The pivoting of bell crank 304 pulls rod 308, thereby disengaging latch pawl 310 from its fixed position on the internal framework of light box 10 (not shown). With latch pawl 310 disengaged, fluid-carrying drawer 50 may be tilted downwardly for ease of loading of the biological fluid containers as generally shown in FIG. 13.
Returning to FIGS. 8-9, fluid carrying drawer 50 is generally open and includes a central cavity 88 to allow for placement of a container-carrying tray 90 shown in FIG. 7. Container carrying tray 90 may be integral with fluid carrying drawer 50, although, a removable non-integrated tray 90 may be preferable for easier container loading and/or tray cleaning.
During treatment of the biological fluid, it may be desirable that the fluid within fluid carrying drawer 50 be continuously or periodically agitated to provide mixing of the biological fluid and ensure that substantially all of the biological fluid is sufficiently and uniformly exposed to light and/or any photochemical agent. Accordingly, fluid carrying drawer 50 may be attached to means for agitating the biological fluid.
As shown in FIGS. 9 and 10, fluid carrying drawer 50 may include an agitation assembly that, for example, provides side-to side oscillation of tray 90. Agitation assembly may include a pair of fixed lower rails 95b that extend front to back within light chamber. Upper rails 95a are attached to the lower rails by pivotally attached link arms 93a and 93b. The link arms allow side-to-side motion of the upper rails 95a. To provide oscillation, an electrical motor 92 is attached to lower rail 95b. Motor 92 rotates a cam 97a. Cam 97a may be an L-shaped crank or bracket attached to roller 97. Roller 97 is captured between parallel walls 97b depending from upper rail 95a. As crank 97a causes roller 97 to orbit around the motor 92 axis, roller slides fore and aft and up and down between walls 97b, imparting side-to-side motion of upper rail 95a. 
Alternatively, as shown in FIG. 24, the agitation assembly may include I-shaped legs 320. As shown in FIG. 24, the bottom flared portions of legs 320 are affixed to lower rods 322 which are, in turn, affixed to the floor of the fluid treatment module 26. The top flared portions of legs 320 are fixed to plate 324, which receives fluid-carrying drawer 50 (and tray 90), as shown in FIG. 24.
Yoke 326 is fixed to and depends from one side of plate 324. Yoke 326 includes a gap 328 that receives roller 330 of motor 334. As shown in FIG. 25, motor 334 includes a central shaft 336, which receives a cam 338. Cam 338 may be an L-shaped crank or bracket. Shaft 340 of cam 338 receives roller 330. As shown in FIG. 25, roller 330 is offset from shaft 336 by a predetermined distance.
As will be appreciated by those of skill in the art, rotation of cam 338 causes an eccentric motion and movement of roller 330. Specifically, roller 330 slides fore and aft and up and down and moves yoke 326 accordingly, resulting in side-to-side movement of fluid-carrying tray 90.
In one embodiment, roller 330 is offset from shaft 336 by a distance of anywhere between 0.5 and 1 inch and, more preferably, 0.75 inches. This results in a total displacement of fluid-carrying tray 90 of approximately 1.5 inches.
Light box 10 may include one or more light sources, preferably disposed above and below fluid treatment chamber 50. For ease of serviceability, such as lamp replacement, it is preferable that the light source(s) be readily accessible. As used herein, “readily accessible” means that access to the light source can be quickly and easily had without the use of, for example, a screwdriver or other tools. For example, in one embodiment, it may be desirable that the light source be either partially or completely removable from the housing 12 and/or fluid treatment module 28. The light source(s) may be accessible through any one of the front, side, top or bottom panels. In one embodiment, the light sources are housed in light drawers 60 and 70. As shown in FIG. 5, when front panel 17 and/or door 36 are removed or opened, light drawers may be moveable (or even completely removable) into and out of fluid treatment module 28. Light drawers 60 and 70 may include slides 99 (FIG. 6) attached to the bottom surface of drawers 60 and 70. Slides 99 rest and move on brackets 96 and slide mounting blocks 98 of framework 38 as shown in FIG. 5. Light drawers 60 and 70 may also include handles 84 for grasping during insertion and removal.
As shown in FIGS. 6, light drawer 60 and/or 70 may be divided into two or more chambers 101 and 103 separated by dividing wall 102. Dividing wall 102 minimizes light from one light chamber of radiating into the other light chamber. This ensures that the light emitted from each lamp or lamp array and contacting the biological fluid is substantially constant. In addition, each of the lamp arrays within light chambers 101 and 103 may be independently monitored and controlled from control module 26. Thus, when one array of lamps is turned off, the other array of lamps may remain on. As described in more detail below, this may be particularly useful where two or more containers of biological fluid requiring different levels of treatment are being treated.
Each of light chambers 101 and 103 of light drawer 60 or 70 is generally defined by four sidewalls 105a-d and a bottom wall 107. Walls 105a-d and 107 may be made of or coated with a reflective material to maximize the amount of light delivered to the biological fluid. In one specific embodiment, where the light source provides light in the ultraviolet A (UVA) range, walls 105a-d and 107 may be made of a highly reflective aluminum to provide substantial reflection of UVA light. Such a material is sold under the name 1500 G-2 and is available from ALANOD of Ennepetal, Germany.
The light sources suitable for use in the present invention may include any light source that is capable of providing light of a particular wavelength and intensity for treating a particular biological fluid. For example, light sources capable of providing white light, red light, infrared, ultraviolet A and/or B light may be used. Light drawers 60 and 70 may include a single lamp or an array of multiple lamps 100. In one embodiment, light source may include standard fluorescent lamps or bulbs capable of providing light of a wavelength in the UVA (ultraviolet A) range. Such lamps may be obtained from Sankyo Denki of Japan under the product code BL352. Light drawers 60 and 70 may further, optionally, include fans 109 for cooling lamps 100 and, more specifically, ends of lamps 100 at or near the lamp filaments.
As shown in FIG. 6, the ends of lamps 100 are inserted into sockets 104 housed on socket panel 106. Socket panel may also serve as a printed circuit board. Socket panel, 106 may be hinged and openable to allow for easy access to lamps 100, easy insertion and removal of lamps 100, and in general, easier serviceability of light drawers 60 and 70.
As shown in FIG. 5, a portion of fluid treatment chamber 40 and, for that matter, fluid carrying drawer 50, are separated from light drawers 60 and 70 by glass plates 110. As shown in FIG. 5, upper glass plate 110 rests on framework 38 and is, generally, held in place by clamps 112 and 114. A lower glass plate 110 separating a portion of fluid carrying drawer 50 from lower light drawer 70 may also be included. Glass plates 110 are substantially translucent to light of the wavelengths used for the treatment of biological fluid. Preferably, glass plates 110 may also filter unwanted light. Alternatively, a separate filter may be provided for placement between the light source and the fluid treatment chamber 40. In one specific embodiment, where treatment of a biological fluid with UVA light is desired, glass plate 110 may be substantially translucent to ultraviolet light within the range to 320-400 nm, but not translucent to light of a wavelength of less than about 320 nm. Such glass plates are commercially available from Schott Glass of Yonkers, N.Y. under the product designation B-270.
As set forth above, fluid treatment module 28 may optionally further include marker assembly 74. Marker assembly 74 may include one or more markers 76a-76d for marking containers within fluid treatment chamber. One or more markers 76 may be provided to mark containers at different stages of the treatment. Markers 76a-d may be punches for punching holes into a portion of the container such as the container flap as described in U.S. Pat. No. 5,557,098, which is incorporated by reference. Alternatively, and more preferably, markers may be stampers for stamping designated portions of a container with ink. Such markers are commercially available from Trodat of Wels, Austria under the product name Printy 4911.
As shown in FIG. 11, marker assembly 74 may include a plurality of markers 76a-d for marking a plurality of containers during different stages of the light treatment. Markers 76a-d may be attached to a bracket 78, which includes a slide 114. Slide 114 is suspended from and movable within track 116 which is attached to the interior framework 38 of light box 10. Thus the entire assembly 74 can be withdrawn from fluid treatment module 28 for reinking, replacement of markers 76 or for general servicing as shown in FIG. 5.
As shown in FIG. 12, each individual marker unit includes a marker drive motor 120 that moves markers 76 up and down through gear 122, gear 124, lead screw 128, lead nut 126, bracket 130 and spring 132. Movement of gears 122 and 124 actuates movement of lead screw 128 and causes downward and/or upward movement of lead nut 126, bracket 130 and consequently marker 76.
Fluid treatment module 28 includes blower 134 which provides air flow into fluid treatment chamber 40 and fluid containers and thus, provides for temperature control of fluid treatment chamber 40 (FIG. 5). Blower 134 receives ambient air through an opening in bottom wall 16 located below blower 134. Blower 134 may be provided with a filter to prevent dust from entering fluid treatment module 26. In addition to providing air to fluid treatment chamber 50, air from blower 134 may also pass through opening 136 of fluid treatment module 28 and a perforation or opening 136a in control module 26, as seen, for example in FIGS. 2 and 4. In addition, fluid treatment module 26 may be provided with an air flow sensor for monitoring air movement. As shown in FIG. 5, sensor 135 may be located at blower 134 or in close proximity thereto in fluid treatment module 26. A temperature sensor 135 disposed in light box 10 senses the ambient temperature. Thus, if the ambient temperature rises above a predetermined threshold temperature, such as may occur if blower 134 fails, the treatment procedure will be terminated and the container of biological fluids will be marked or identified as unusable.
Returning to the fluid treatment module 28 and more specifically fluid carrying drawer 50, as shown in FIGS. 5 and 13, fluid carrying drawer 50 may include a tray 90 for holding one or more containers of biological fluid. Tray 90, shown in FIG. 7, may be placed within the cavity 88 of the fluid carrying drawer 50 (FIG. 8). In one embodiment, tray 90 may be made of a molded plastic material. Where the biological fluid is treated from two sides, the molded plastic material should be sufficiently translucent to the light provided by the lamps 100. Suitable materials for tray 90 include acrylic polymers such as polymethyl methacrylate (PMMA) or members of the polyolefin family such as methylpentene copolymer. Such materials are available from many sources including CYRO Industries of Rockaway, N.J. under the product name ACRYLITE® OP4 or from Mitsui Plastics of White Plains, N.Y. under the name TPX.
Where one or more containers are to be treated, tray 90 may be divided into a first portion 180 and a second portion 182 separated by dividing wall 184. As shown in FIG. 27, at least a portion of dividing wall 184 may be made of or covered with a reflective material of the type described above. In a preferred embodiment, the portion of dividing wall that separates first compartments 188 (described below) is reflective. A reflective divider provides improved and more uniform distribution of light to the fluid containers. As shown in FIG. 7, tray 90 may include retaining tabs 186 for placing a slit or other aperture of a biological fluid container 206 over tab 186 to limit movement of the container within tray 90 and ensure that the container is substantially within the field of light provided by the light source. The volume of tray 90 should be sufficient to hold at least the entire volume of biological fluid contained within the containers so as to minimize the risk that, in the event of container leakage, liquid will overflow and contact the electrical and mechanical components of light box 10, even during agitation.
Where the biological container is part of an integrated fluid processing set, tray 90 may be compartmentalized to provide separate compartments for the container undergoing treatment on the one hand, and the remainder or a portion of the remainder of the disposable processing set, on the other hand. As shown for example, in FIG. 7, first portion 180 and second portion 182 each include a first compartment 188 and second compartment 190 separated by discontinuous wall 192. First compartment 188 may hold a container of biological fluid 206 and the second compartment may hold the remaining components of the fluid processing set. A slot in the wall 192 accommodates the tubing that connects container 206 with the remainder of the disposable processing set. The slot may also assist in limiting movement of container 206 within tray 90. Tray 90 or second compartment 190 of tray may further include container retaining tabs or pegs 193 to hold in place the containers in the second compartment and/or limit movement of such containers within tray 90. Alternatively, pegs 193 may be located on drawer 50, as shown in FIG. 26.
When the tray 90 with disposable processing set is introduced into fluid treatment chamber 50, container 206 within a first compartment 188 is positioned substantially within the field of light provided by the light source. The remainder of the disposable processing set and/or containers within a second compartment 190 are outside the field light, preferably held in place by tray cover 380, described below. In the embodiment where marker assembly 74 is provided, containers within second compartment 190 are aligned substantially with marker assembly 74 as shown in FIGS. 4 and 5. Thus, the status of the treatment may be indicated on the other containers of the processing set within the second compartment 190 by markers 76a-d. 
In an embodiment where the light box does not include a marker assembly, drawer 50 may include a cover 380 of the type shown in FIGS. 26-28. Cover 380 holds in place containers within second compartment 190. As shown in FIG. 28, cover 380 may be hingedly attached to drawer 50 and flipped over compartments 190 prior to the illumination process.
As shown in FIG. 28, cover 380 may include latch 382 for securing cover 380 to dividing wall 184 of tray 90. Cover 380 may also include a plurality of apertures 384 aligned with bag placement sensors (described below). Cover 380 can be made of any suitable material which is not translucent to light from light sources. Preferably, cover 380 is made of aluminum.
Light box 10 may include sensors for detecting different conditions during the pretreatment and treatment processes. The sensors relay signals to the microprocessor of the light box 10 that is housed within control module 26. As shown for example in FIG. 14, sensors (e.g., 404, 430) send signals through the sensor input/output board 33 which translates the signal into a format that is understandable by microprocessor 160. The computer alerts the operator, either by an audible alarm or a message on the display screen 37. The operator may, in response to the alarm or message, take action through keypad 39. Alternatively, in response to certain alarm conditions, the control system may be preprogrammed to automatically take action; such as terminate treatment, if necessary.
For example, light box 10 may include internal light intensity sensors 404 for measuring the intensity of light provided by the lamps 100 to fluid treatment chamber 50. In the event that the light intensity provided by lamps 100 is insufficient for the desired treatment, sensors 404 send signals through input/output board 33 (FIG. 14) to microprocessor 160 as described above.
In one embodiment, light intensity sensors 404 may be located within the light chambers 101 and 103 of light drawers 60 and 70 (FIG. 6). In one embodiment, light drawer 60 and/or 70 include a light intensity sensor subassembly 402 on the underside of drawer 60 and/or 70. As shown in FIG. 6a, subassembly 402 includes two or more sensors 404 attached thereon and placed within sensor windows 406 located in the bottom wall 107 of drawers 60 and/or 70. Sensor windows 406 allow light from lamps 100 to pass through and contact sensors 404. Sensors 404 may include or be used with one or more filters to filter out unwanted light. More specifically, where light box 10 is used to activate a photochemical agent, it may be desirable that the filters used in association with sensors 404 have a maximum sensitivity in the wavelength range that substantially matches the wavelength range within which the particular photochemical agent is most effectively activated (i.e., the “action curve”). This allows sensors 404 to detect the effectiveness of photochemical activation. Sensors 404 are available, for example, from Micropac Industries, Inc. of Garland, Tex. under part number 61120. Filters are available from a variety of sources such as Schott Technical Glass of Duryea, Pa.
A fluid carrying drawer sensor 144 may be included for monitoring the position of fluid carrying drawer within fluid treatment chamber 40. Fluid carrying drawer positioning sensor 144 ensures that the drawer 50 is in a fully closed position and therefore, that containers of biological fluid are substantially within the field of light provided by lamps 100. If the drawer is not in a fully closed position, sensor 144 sends a signal to the microprocessor, alerting the operator and preventing treatment from proceeding.
Light box 10 may, optionally, further include temperature sensors 145 for either directly or indirectly monitoring and measuring the temperature within fluid treatment chamber 40. Temperature sensor may be disposed within the fluid treatment chamber 40 or, as shown in FIGS. 4 and 5, may be disposed on the exterior of light box 10 to measure the ambient temperature of the outside environment. For example, ambient temperature sensor 145 may be located anywhere on the surface of light box 10. In one embodiment, as shown in FIGS. 1 and 2, ambient temperature sensor 145 is placed at or near control module 26. Ambient temperature sensor 145 provides an indication of the air temperature being delivered to fluid treatment chamber by blower 134. In the event that the temperature falls outside of a predetermined temperature range, the ambient temperature sensor sends a signal to the microprocessor as generally described above, which alerts the operator that the temperature is approaching or has exceeded its limit. Accordingly, the operator and/or instrument may take further action.
Additional sensors may be provided, including a sensor for monitoring the agitation provided by the agitation assembly. In an embodiment of light box 10 that includes marker sub-assembly 74, sensor 430 may be attached to marker subassembly 74, as shown in FIG. 11A, and measures movement of the agitation assembly described above. In an embodiment where light box 10 does not include marker sub-assembly 74, sensor 430 may be attached to marker subassembly 74 In one embodiment, sensor 430 may include an infrared source such as, but not limited to a light emitting diode (LED) or laser that contacts a selected reflective portion of the agitation assembly. If sensor 430 does not detect reflection or does not detect reflection at the predetermined frequency, it signals the microprocessor accordingly.
A preferred embodiment of a motion sensor arrangement for the agitator system is illustrated in FIG. 27. This agitator motion sensor includes a light emitter 386, such as a lamp, a light emitting diode, a laser diode, or the like, disposed on one side of tray 90. An aperture 388 is defined through one edge of cover 380 and a light detector 385, such as a photo-diode, photo-transistor, photo-multiplier tube, or the like, is disposed on the opposite side of cover 380 from the light emitter 386. When aperture 388 is in alignment with light emitter 386 and with light detector 385, a brief electronic pulse will be generated by light detector 385 when light is transmitted through aperture 388 to light detector 385. Based upon the rate of pulses, the speed of agitation can be determined or confirmed. Also, if no pulses are received, it can be assumed that the agitator system is not in motion.
Light box 10 may also include a sensor 440 to detect whether the front door of the light box is closed during treatment. Door sensor may be a magnetic switch that detects contact between door 36 and magnetic plate 441 shown in FIG. 3. Also, plunger switch 36a (FIG. 4) is pressed when door 36 is closed. If door 36 is open, plunger switch 36a serves as an electrical cut off. If, the door is open, the system will not permit the treatment to proceed. Alternatively, light box 10 may include a door lock 388. Door lock 388 may include a solenoid that establishes contact with a pin on door 36 and ensures that door 36 remains locked during treatment.
Light box 10 may also include sensors 450 for determining whether containers are in position for marking by markers 76. In the embodiment wherein light box 10 includes marker sub-assembly 74, shown in FIG. 11A, sensors 450 may be attached to markers 76 and may include optical receivers aligned with light emitting diodes (LED) (not shown) typically located below fluid carrying tray 90. The labels of containers placed within the second compartment 190 of tray 90 or a holder or organizer used to hold together containers in compartment 190, prevent optical receiver 450 from receiving the LED signal, indicating the presence of a container. Conversely, if sensor 450 receives the signal, this indicates that no container is present and the marker will not be activated. In addition, each marker 76a-d may include a microswitch (shown as 470 in FIG. 14) to detect whether movement of the marker has occurred and to prevent mechanical failure or damage to the parts that make up the marker.
Returning to FIG. 27, in an embodiment where light box 10 does not include marker sub-assembly 74, a pair of light emitters 383 and 384 may be disposed on one side of an edge of cover 380. A pair of light detectors 381 and 382 may be disposed on an opposite side of the edge of cover 380. A pair-of apertures 387 and 389 is defined through the edge of tray 90. When a container is present, light from light emitters 383 and 384 is obstructed from passing through apertures 387 and 388 to light detectors 381 and 382. However, when no container is present, light will pass through one or both of apertures 387 and 389, and corresponding light detectors 381 and/or 382 will generate a signal. Any such signals indicate that no container is present and the instrument will either alert the operator and/or terminate further processing.
The electronic circuitry, generally designated 600, for controlling light box 10 is illustrated in block diagram format in FIG. 33. A computer printed circuit board (PCB) 602 preferably includes a 486DX4 compatible central processing unit (CPU), or microprocessor, 603 typically operating at 100 MHz, or more, to provide, and to service, a multiplicity of functions. A DRAM module 604 provides memory for CPU 603, which may be, by way of example, about 32 Megabytes. Flash memory may be added to a compact flash socket 605. Preferably, about 32 Megabytes of flash memory is provided. VGA BIOS 606 is programmable to support displays on display screen 37 on control panel 32 (FIGS. 1 and 2). A VGA port 607 provides video information to display screen 37 on control panel 32 via output lines 608. A PC/104 port provides an ISA Bus 610 for transferring information to and from computer PCB 602.
Four RS232 compatible ports 612 through 615 provide serial information transfer, such as from bar code reader 41. One of the RS232 ports is configurable as an RS 485 port, if desired. Port 615 is at the rear panel of the light box 10, and ports 612 and 613 are spares. For example, one of spare ports 612 or 613 may be used for a label printer. A printer port 618 on computer PCB 602 is brought out to the back panel of light box 10 as a port 619 for connection to a printer. Similarly, an Ethernet port 620 on computer PCB 602 is provided as an Ethernet port 621 on the back panel. Computer PCB 602 is preferably an off-the-shelf computer board, such as that commercially available from Ampro Computers, Inc., San Jose, Calif. under part number LB3-486e. More information about this and comparable computer PCBs is available at internet site www.ampro.com, which is incorporated herein in by reference in its entirety.
An interface PCB 606 directly or indirectly interfaces computer PCB 602 with most of the other electrical apparatus, such as lamps, sensors, displays and so forth. Interface PCB 606 is subdivided into several portions. An LCD portion 624 receives video and control signals from computer PCB via lines 608 and provides control signals to a back light inverter (BLI) PCB 626 to control and to supply power for the backlighting of display panel 37. LCD portion 624 also supplies video and control signals, and power, via lines 627 to display panel 37. A keypad and LED portion 630 receives inputs from keypad 39 at the user interface 32, and sends such inputs to computer PCB 602 via ISA bus 610.
A light sensor portion 634 of interface PCB 606 bi-directionally communicates with a relay PCB 640 via a plurality of lines 635 to provide control output signals and to receive sensor input signals. A miscellaneous sensors portion 636 and a relay control portion 637 bi-directionally communicate with relay PCB 640 via a plurality of lines 638 to provide control output signals and to receive sensor input signals.
Interface PCB 606 also supplies operating power to the other PCBs. Interface PCB 606 receives +5 Vdc and +12 Vdc at a connector 622 and +24 Vdc at a connector 623, all from a power supply 167. Relay PCB 640 is supplied with +5 Vdc and +24 Vdc on certain of lines 638, front panel user interface 37 is supplied with +5 Vdc on one of lines 627, BLI PCB 626 is supplied with +5 Vdc on one of lines 625 and computer PCB is supplied with +5 Vdc and +12 Vdc on certain of lines 610, all from interface PCB 606. In addition, relay PCB 640 directly receives 240 Vac from the power supply 167 at a connector 641 to supply power to the shaker motor 92.
Relay PCB 640 controls the application of power to upper lamp ballasts 645 and lower lamp ballasts 646, such as with electronic relays located on relay PCB 640, to supply operating power to upper lamps 100 and to lower lamps 100 under the influence of control signals from light sensor interface 634 on interface PCB 606. Light sensor circuitry shown in FIG. 34 is disposed on upper and lower light sensor PCBs 643 and 644 and provides signals to relay PCB 640 that are indicative of the intensity of illumination provided by the upper and lower lamps, respectively. Relay PCB 640 also controls the application of power to shaker motor 647 and blower fan 648, such as with electronic relays, in accordance with control signals from relay control interface 637 on interface PCB 606. Relay PCB 640 routes signals from door solenoid 648 and miscellaneous sensors 649 to miscellaneous sensors interface 636 on interface PCB 606.
As previously explained, light box 10 has two light chambers 42 and 43 for treating biological fluids in either or both chambers. Two light arrays consisting of four lamps 100 are disposed in an upper position and in a lower position in each chamber for a total of 16 lamps, as seen in FIG. 34. A light sensing system, for sensing the intensity of the illumination from lamps 100, is generally designated 650. Disposed adjacently to the upper lamp arrays in chambers 42 and 43 is upper light sensor PCB 643. Lower light sensor PCB 644 is similarly adjacently disposed to lower light arrays. Light sensors 404 are positioned on upper and lower light sensor PCBs 643 and 644, respectively, between pairs of lamps 100 such that each sensor monitors the illumination level of two adjacent lamps. In this respect, each light sensor is preferably located midway between a pair of monitored lamps 100. Light sensors 404 provide a frequency output generally in the range of 10 Hz to 1 MHz depending upon the sensed irradiation level. In this application, sensors 404 preferably operate near a mid-range, such as in about the 1 KHz to 100 KHz range, for example.
Circuitry associated with each upper or lower light sensor PCB 643 or 644, and which constitutes a portion of light sensing system 650, is shown in greater detail in FIG. 35. The frequency outputs from upper light sensors 404 are sent to a pair of multiplexers 651 and 652. Multiplexer 652 is a secondary or redundant multiplexer that is used to confirm that data received from multiplexer 651 is accurate. A test circuit 654 consists of an oscillator 655 that has its frequency divided by a divider 656 to provide three test or reference frequencies on three lines 657, which are provided as inputs to multiplexers 651 and 652. For example, these test frequencies may be about 230 KHz, 115 KHz and 57.5 KHz. The power supply +5 Vdc is also provided as an input to multiplexers 651 and 652 to monitor the power supply for any undesired noise that could interfere with the signals from the light sensors. Three address selection lines 658, including A0, A1 and A2, are used to cause multiplexers 651 or 652 to alternately sample one of the outputs from the four light sensors, one of the three test frequencies or the power supply voltage. For example, the sampling periods may be about 15 milliseconds. These address selection bits on lines 658 are generated by a programmable logic device (PLD) 680 on interface PCB 606 and supplied to upper light sensor PCB by lines 669 and to lower light sensor PCB by lines 668. Lower light sensors 404, multiplexers 660 and 661 and test circuit 662 on lower light sensor PCB 644 operate similarly to the corresponding elements described on upper light sensor PCB 643 to provide a second multiplexed frequency signal.
The outputs of multiplexers 652 and 660 are routed to a frequency counter 670 on interface PCB 606 via lines 665 and 664. The outputs of multiplexers 651 and 661 are routed to frequency counter 671 also on interface PCB 606 via lines 667 and 666. Counters 670 and 671 are commercially available from Intel Corporation, Santa Clara, Calif. under part number 8254. PLD 680 selects data from frequency counter 670 by a chip selection line 681 or from frequency counter 671 by a chip selection line 682. Frequency counters 670 and 671 and PLD 680 share a common data bus 683 for the transfer of data therebetween. PLD 680 thus receives counts from counters 670 and 671 that represent the frequencies received by these counters from multiplexers 651, 652, 660 and 661 which, in turn, represent the illumination levels from all 16 of the lamps 100 in light box 10. PLD 680 provides this lamp illumination data to computer PCB 602 on data busses 687 and 688. PLD 680 essentially acts as a conduit for the count information from counters 670 and 671 to computer PCB 602, provides buffering of these count signals and provides chip select functions to select counter 670 or 671. Counters 670 and 671 can issue interrupt requests to PLD 680 on lines 684 and 685, respectively. PLD 680 can also issue interrupt requests to computer PCB 602 on a line 686 and control signals are received by PLD 680 from computer PCB 602 on one or more lines 689. PLD 680 is commercially available, for example, from Altera Corporation of San Jose, Calif. under part number EPM7128S.
Sensor read software 690 enables CPU 603 on computer PCB 602 to read the data sent from PLD 680 on data busses 687 and 688. Independent illumination software 691 monitors the data for any malfunction or irregularity. For example, if the illumination data from any light sensor 404 is below a defined threshold level, one of the lamps 100 may have failed or is providing insufficient illumination. In this instance, a message will be displayed on display 37 to replace one or more lamps 100.
Energy measurement software 692 measures the illumination level supplied by lamps 100, as by analyzing the frequency counts from PLD 480, and then essentially integrating the measured illumination level over time until the predetermined illumination dose for the biological fluid being treated in light box 10 is reached. Software 692 may recalculate the light intensities about every second, for example. Frequent recalculations are preferred because the light intensity from lamps 100 changes with temperature. Based upon these continuous recalculations of light intensity, energy measurement software 692 also determines the current illumination dose that the biological fluid has been subjected to since the initiation of treatment. Software 692 is essentially integrating the light intensity in real time to determine the current illumination dose. Software 692 can similarly estimate how much additional time is required, based upon currently measured light intensities, to reach the desired illumination dose. Upon reaching the dosage entered by the user at the beginning of treatment, software 692 causes illumination to cease and the user is advised that treatment is completed.
Software 692 also preferably constantly monitors the count of the test frequencies 657 because these frequencies are known and the count results will confirm the signal paths and counting accuracy with respect to the frequency signals from light sensors 404. The redundant light sensing channel provided by secondary multiplexers 652 and 661 are also preferably monitored to confirm the accuracy of information received from primary multiplexers 651 and 660. If the frequency count data received from primary multiplexers 651 and 660 are not within a certain tolerance with the data received from secondary multiplexers 652 and 661, an error message will be supplied to the user, as on display 37. When the predetermined illumination dose is reached, energy measurement software 692 terminates illumination in light box 10.
In addition, a portable and attachable light intensity sensing, verification and calibration device or radiometer 460 may be provided to verify light intensity provided by light box 10 and for calibration of light box 10. Radiometer 460 may be adapted for placement within fluid treatment chamber 40 for measuring the energy dose delivered to the biological fluid. More specifically, radiometer 460 may be adapted for placement within the fluid container carrying tray 90. In one embodiment, radiometer 460 may be adapted for placement within a compartment of tray 90 such as first compartment 188 of tray 90.
As shown in FIG. 14A, radiometer 460 may include a support 465 having a top surface 467 and a bottom surface 468. Support 465 is typically a printed circuit board. One or more sensors 469 are electrically and physically connected to support 465. Additionally, as best seen in FIG. 31, support 465 also includes data port 512.
It is known that a light source may not always uniformly emit light. For example, depending on the age of the lamp, the intensity of light emitted from one part of the lamp may not be the same as the intensity emitted from another part of the lamp. Accordingly, in a preferred embodiment, as shown in FIG. 14A, radiometer 460 may include a plurality of sensors 469 spaced across the top and/or bottom surface(s) to receive light from different points on one or more lamps. Also, sensors 469 may be placed on one side of support 465, but preferably are placed on both the top surface 467 and the bottom surface 468. Top and bottom placement of sensors 469 is particularly preferred where radiometer 460 is used to measure light provided by two facing light sources, such as the two arrays of lamps 100 in one of the embodiments of light box 10.
Radiometer 460 is preferably calibrated with a precision light source in accordance with NIST standards. As seen in FIG. 29, a bar code 506 may be placed on the edge of one of the halves 504. Bar code 506 preferably contains information on the identity of each radiometer, such as a unique identifying number or a serial number. Also preferably included in bar code 506 are the calibration coefficients determined during the most recent calibration of radiometer 460 for each of the sensors 469, and an expiration date by which radiometer 460 will need to be recalibrated. For example, the expiration date may be one year from the date of the most recent calibration. Thus, reading of bar code 506 by bar code reader 41 will provide CPU 603 with information on the identity of radiometer 460, the calibration coefficients associated with that particular radiometer, and the date by which radiometer 460 needs to be recalibrated.
Support 465 is preferably housed in cover 501. As shown in FIG. 31, cover 501 may be made of two halves 503 and 504 that are attached together. Cover 501 may include a label 506 (FIG. 29) displaying a unique bar code for each radiometer 460. As further shown in FIG. 31, radiometer also includes intermediate panels or substrates 508 and 510. Cover halves 503 and 504 and substrates 508 and 510 may be made of any hard, commercially available molded plastic. A preferred material is a terpolymer of acrylonitrile, butyldiene and styrene (ABS). Slots in cover 501 and substrates 508 and 510 are provided to accommodate sensors 469.
A connector cable 516, as shown in FIG. 32, is attached to radiometer 460 for electrical connection to light box 10 and, for example, to port 461 (FIG. 5). This allows radiometer 460 to transmit data to the computer PCB 602 (FIG. 33) of light box 10, which system provides information to the operator and/or automatically takes action based on the transmitted data. Radiometer 460 may also include a slit 472 (FIG. 29) for placement over tab 186 (FIG. 7) in tray 90 of light box 10.
Sensors 469 are generally any device that is capable of detecting light of selected wavelengths. These sensors are preferably robust such that they reproducibly detect the appropriate wavelengths accurately. In one embodiment, these sensors may comprise a plurality of optical fibers that absorb the selected wavelengths and channel the light into an appropriate detector. Such optical fibers can be configured to appropriate dimensions to represent the dimensions over which the light delivery is to be measured. An advantage of this configuration is that the optical fibers can cover a large percentage of the area over which the light delivery is to be measured. In the preferred sensor embodiment, as represented in FIG. 14A, sensors 469 in radiometer 460 are preferably the same type of sensor as sensors 404 in light sensing system 650. Of courses, sensors 404 and 469 need to be capable of detecting, light of the desired wavelengths. Sensors 469 may also include or be used with filters to filter out unwanted light as substantially described above.
When used in connection with light box 10, it is preferred that the dimensions and geometry of radiometer 460 be substantially equivalent to the dimensions of the fluid-filled containers used with light box 10. Accordingly, it is preferred that the light sensing area of radiometer 460 have a height, a width and a thickness substantially equal to such filled containers. A radiometer with dimensions substantially equal to the fluid-filled container provides a reliable approximation of the energy being delivered to the fluid and of the effectiveness of the treatment.
As set forth above, radiometer 460 may be used for light intensity verification by, for example, the operator and for calibration of light box 10 generally and more specifically, of internal light sensors 404. In accordance with the method of using radiometer 460 for light intensity verification, the operator may place radiometer 460 in first compartment 188 of tray 90, as shown in FIG. 32. Connector cable 516 may be pressed into strain relief tabs 474 within light box 10 (FIG. 8) or, more preferably, thread through slot 390 in drawer 50, as shown in FIG. 32. The fluid carrying drawer 50 is inserted into fluid treatment chamber 40 and door 36 is closed. Lamps 100 are turned on and the light delivered is measured by sensors 469 in radiometer 460. Specifically, the light measured by sensors 469 is processed by the system's microprocessor 603 on computer PCB 602 to provide a calibrated reading of the energy being provided to the fluid treatment chamber 40. For example, microprocessor 603 may use the calibrated readings of the light levels from each sensor 649 of radiometer 460 to calculate a calibration coefficient for light levels sensed by each sensor 404 on upper and lower light sensor PCBs 643 and 644. Thereafter, energy measurement software 692 (FIG. 34) associated with microprocessor 603 can apply these calibration coefficients to the illumination measurements from light sensors 404 to provide corrected light level measurements that will approximate those measured by radiometer 640. The flow chart in FIG. 21A also provides information about the processes of determining the light intensity and determining the treatment time.
The operator can monitor the output of lamps 100 and determine any diminishment in the lamp output by comparing the reading to a pre-set acceptable energy dose range. In addition, the readings provided by sensors 469 are also compared to the readings provided by sensors 404 to detect any diminished sensing capability of sensors 404. The process may be repeated with the other first compartment 188.
Thus, for example if the energy dose measured by radiometer 460 is substantially equal to the energy dose detected by sensors 404, but is outside the pre-set dose range, this may be an indication that the output of lamps 100 has diminished and that lamps 100 may have to be replaced. Alternatively, if the energy dose as measured by radiometer 460 is substantially equal to the expected pre-set dose of the instrument, but both are different from the energy dose as measured by sensors 404, this may be an indication that sensing capability of sensors 404 has diminished. Finally, if the dose as measured by sensors 404 is substantially equal to the expected pre-set dose, but different than the energy dose as measured by radiometer 460, this may indicate that the sensing capability of radiometer 460 has diminished. Radiometer 460 may also be used to calibrate light box 10. Radiometer 460 itself may be calibrated against a standard (e.g. a standard from the National Institute for Standards and Technology or NIST), or by using an independent calibration system that has been calibrated to NIST standards.
Of course, it will be appreciated that radiometer 460 may have utility in other applications and is not limited to use in the apparatus or methods of the present invention. Indeed, radiometer 460 may be used whenever light is to be measured over an extended surface area or from opposite directions. Radiometer 460 also has utility where it is desired to average light intensity measurements over a surface area, including non-planar surfaces. It will be readily appreciated that radiometer 460 could be configured with complex, non-planar surfaces, if so desired.
The components of the fluid treatment module 28 including the agitator assembly, the light sources, the blower, the marker subassembly are powered by power supplies in an alternative embodiment of the electronic control system shown in FIG. 14. In FIG. 14, the letter “n” represents the number of electrical or mechanical components such as sensors, lamps, ballasts etc. For example, power supplies (ballasts) 166 power lamps 100 and are controlled by relay board and isolation transformer 29. Shaker motor 92 is powered through relay board and isolation transformer 29. Additional power supply 168 supplies power for the blower 134, light drawer fans 109, and drive motors 120 for markers 76a-d and door lock 480. Preferably, the power supply for powering these components may be approximately 24 volts DC. Power supply for powering shaker motor may be 230V AC. Power supply 167 may supply +5 and +12 volts DC to, for example, computer board 160.
Finally, light box 10 includes a programmable computer software-based control system 600 to control the operation of light box 10 that has already been described with reference to FIGS. 33-35. The control system 600 is further generally and diagrammatically depicted in FIGS. 19-23 and is described in greater detail in connection with the description of the method of processing and treating a biological fluid which follows the description of the disposable processing set provided below.
b. Disposable Processing Set
Disposable processing sets useful with light box 10 are shown in FIGS. 15-18. Typically, the disposable processing set will include two or more plastic containers integrally connected by plastic tubing. At least one of the containers should be suitable for holding the biological fluid during light treatment. The other container should be suitable for storage of the biological fluid after treatment. As described in more detail below, the disposable processing set may be joined with containers of biological fluid, and the fluid may be transferred to containers of the disposable processing set. Further details about these disposable processing sets are described in the U.S. patent application entitled “Fluid Processing Sets and Organizers for the Same,” bearing Attorney Docket No. F8-5459CIP, filed Oct. 11, 2002, and incorporated herein by reference, in it entirety.
One embodiment of a disposable fluid processing set 200 is shown in FIG. 15. Processing set 200 includes a container 202, a container 206, a container 210 and a container 214. The containers may be integrally interconnected with tubing segments as generally shown and described in detail below. The sizes and internal volumes of containers 202, 206, 210 and 214 may vary depending on the biological fluid being processed. In a non-limiting example, container 202 may be capable of holding approximately 5-30 ml of fluid, containers 206 and 210 approximately 1000 ml and container 214 between approximately 1000-1500 ml. Of course, other desirable sizes and volumes may be used and are within the scope of the present invention.
Where the disposable processing set is used in or as part of a pathogen inactivation treatment, container 202 may include, for example, a photochemical agent which is mixed with the biological fluid. Examples of such photochemical agents include psoralen compounds described in U.S. Pat. No. 5,709,991 and compounds from the family of phenothiazine dyes such as, but not limited to, methylene blue and riboflavin. Container 202 may be made of any material suitable for holding such photochemical agents. One such material may be a blend of ethylene polypropylene, polyamide and a block copolymer of ethylene and butylene with terminal blocks of polystyrene. Containers made of such material are available from Baxter Healthcare Corporation under the name PL2411. Container 202 includes a tubing segment 203 extending therefrom and having a sealed end 204. A second tubing 205 extending from container 202 is integrally connected to container 206. In another embodiment, the photochemical agent may be contained or predisposed within container 206, thereby eliminating the need for a separate container 202 for holding the photochemical agent. In still another embodiment, the photochemical agent may be combined with the biological fluid prior to joinder to the disposable processing set. For example, the photochemical agent may be included in a container 201 used to hold the biological fluid collected from a donor (FIG. 17).
Container 206 is preferably a container suitable for holding the biological fluid during light treatment. Accordingly, it is desirable that container 206 be made of a clear, durable, thermoplastic material that is translucent to light of the selected wavelength and sterilizable by known forms of sterilization including steam sterilization, gamma and electron beam radiation. For example, where the blood product to be treated includes blood platelets or blood plasma and the treatment is to be with light in the UVA range, container is made of a material that is substantially translucent to UVA light and remains stable after sterilization. Such materials may include polyvinyl chloride, but more preferably, may be blends of thermoplastic polymers and copolymers, including general purpose polymers, elastomers and the like. One such material includes the block copolymer described above which includes a central block of ethylene and butylene and terminal blocks of polystyrene. Block copolymers of the type described above are available from the Shell Chemical Company under the name KRATON. The block copolymer may be blended with other polymers such as ultra low-density polyethylene (ULDPE) and ethylene vinyl acetate (EVA). Containers made of the blended material are available from Baxter Healthcare Corporation of Deerfield, Ill. under the name PL-2410. Other thermoplastic materials may also be suitable for container 206, including materials including KRATON, EVA, and polypropylene. A container made from such material is also available from Baxter Healthcare Corporation under the name PL-732. Still other suitable materials for container 206 include fluoropolymers such as polytetrafluoroethylene (PTFE), PFA or copolymers including such fluoropolymers.
Container 206 further includes a slit 207 which, as described above, may be placed over retaining tab 186 in tray 90. Container 206 includes a tubing segment 208 which may be integrally connected to a container 210.
In the pathogen inactivation of biological fluid, container 210 may, for example, include an adsorbent material 211 for removing excess photochemical agent or the byproducts of the photoactivation process. The adsorbent material may be contained in a semi-permeable pouch, preferably affixed to the container walls or portions thereof within the interior chamber of container 210. The interior chamber of container 210 has a volume sufficient to hold the biological fluid from container 206. Such a container and the adsorbent material are disclosed in more detail in copending patent application entitled “Plastic Containers Having Inner Pouches and Methods for Making Such Containers” which is being filed simultaneously herewith in the names of Mahmood Mohiuddin, George D. Cimino and Derek J. Hei, and is incorporated by reference in its entirety. Materials such as those used in the PL-2410 and PL-732 containers described above are suitable for use in container 210.
Container 210 may also include a time-sensitive tape 209. Tape 209 changes color with time, thus informing the operator if the biological fluid has contacted the adsorbent material for a sufficient period of time. Container 210 may be integrally connected by tubing segment 211 to another container 214 which may be suitable for storage of the biological fluid. As shown in FIG. 15, the portion of tubing segment 211 that communicates with the interior of container 210 may include a filter 211a to capture loose particles of adsorbent, if any.
Container 214 may include and/or be capable of receiving a label 216 which may carry bar codes 222 or other indicia that provide information about the biological fluid. For example, bar codes 222 may identify the donor, the product, the lot number of the biological fluid, expiration date and the like. Container 214 may include additional bar codes or indicia 224 which are used to provide information regarding the status or progress of the fluid treatment (described in more detail below). Container 214 may also include a slit 226 and/or apertures 228, 230 for placement over corresponding pegs (193) on tray 90. Materials such as those described above are suitable for use in container 214. Container 214 may also include sampling pouches 214a and access ports 214b to allow for fluid access during later transfusion, as will be recognized by those of ordinary skill.
In an alternative embodiment, disposable processing set may include a single container for housing the adsorbent material of container 210 and for storing the biological fluid, thereby combining the functions of container 210 and 214 described above.
The disposable processing set 200 described herein may further include frangible members 230(a-c) disposed within tubing segments as shown in FIG. 15. Frangible members 230 are broken at the appropriate time to establish fluid communication between the containers of the processing set 200. Such frangible connectors are described in detail in U.S. Pat. No. 4,294,297 which is incorporated by reference herein. Tubing segments of disposable processing set 200 may further include indicators 234a and 234b on the tubing to indicate proper positioning of the disposable processing set within the tray 90 (as will be described more detail below) and/or to serve as indicators of where tubing is to be severed and sealed. In one embodiment, indicators 234 may be plastic rings disposed around tubing segments. Of course, other tubing indicating means may be used.
Another embodiment of a fluid processing set is shown in FIG. 16. In FIG. 16, disposable processing set 240 also includes a container 242 which carries a photochemical agent, a container 244 which holds the biological fluid during light treatment, a container 246 which includes an adsorbent material for removing excess photochemical agent and/or the byproducts of the photoactivation process, and a container 248 suitable for storage of the biological fluid. Container 248 is adapted to receive label 249 with bar codes or other indicia and may include additional indicia 251 including, for example, additional bar codes as substantially described above.
In contrast to the container 210 of the earlier described embodiment, container 246 is a flow through device which includes adsorbent material 212 but does not include a chamber for holding the biological fluid for any significant period of time. Such flow through devices are described in International Publication No. WO 96/40857, which is incorporated by reference herein. Disposable processing set 240 may further include an air reservoir 256 and air sink 258. Air reservoir 256 provides air to help expel biological fluid from container 244 and air sink 258 receives excess air expelled from storage container 248 after processing. Air reservoir 256 and air sink 258 may be made of any suitable biocompatible material, including the materials described above. Likewise, the containers of disposable processing set 240 may also be made from the materials generally described above. Preferably, container 256 is substantially impermeable to air.
As in the embodiment of FIG. 15, the containers of disposable processing set 240 shown in FIG. 16 may be integrally interconnected by tubing segments 243, 245 and 247. Tubing segments may further include frangible members 249(a-c) for opening fluid communication between the containers.
Disposable processing set 200 (or 240) is typically provided to the user in a sealed package in a manner that is easy for the user to unpack and use. For example, upon opening the package, it is preferred that the container to be used first in the fluid processing be located near the top of the package. For example, in the processing set 200 shown in FIG. 15, container 202 would be located near the top of the package, followed by container 206, followed by the remainder of the disposable processing set that includes containers 210 and 214. In addition, if disposable processing set includes container 202, (or 242 in the embodiment of FIG. 16) at least such container should include a separate and additional light impermeable overwrap to protect the contents (i.e. the photochemical agent) from exposure to light which could result in premature activation of the photochemical agent. In one embodiment, the light impermeable overwrap may be permanently sealed to the outer walls of container 202.
In a preferred embodiment, containers 210 and 214 may be contained within or held together by a holder. Holder may be any device such as a clamp that holds together containers 210 and 214. The holder may be integral with the disposable processing set or may be provided separately.
More preferably, holder 260, shown in FIGS. 17-18, may be a receptacle or other shell-like holding device. In one embodiment, holder 260 may include a bottom wall 262 which separates the containers 210 and 214 from container 206. In a preferred embodiment, holder 260 may have sidewalls 262 and 264, a back wall 268 and includes a substantially open front portion as shown in FIGS. 17-18. In addition, bottom wall 262 may include a slot 263 to accommodate tubing that connects containers of disposable processing set 200. Holder 260 may also include additional side openings 265 (shown, for example, in FIG. 17) for holding tubing segments of container 202 prior to unpackaging of the disposable processing set. Holder 260 may be made of any suitable material such as but not limited to plastic or cardboard. Preferably, holder 260 is made of a moldable plastic material that may be sterilizable and impact resistant.
Alternative embodiments of holder 260 are shown in FIGS. 18A-18D. As shown in FIGS. 18A-18C, holder may include two frame or partial frame portions 600 and 602. Frame portions 600 and 602 may be joined and include hinge 604 as shown in FIGS. 18B and 18C. Alternatively, frame members 600 and 602 may be completely separable as shown in FIG. 18D. Frame portions 600 and 602 include means for securing together the frame portions such as mating slots 605 and pins or lugs 606 as shown. Holder 260 shown in FIGS. 18A-18D includes a central opening 608 to allow the label of a container placed within holder 260 to be exposed to the outside environment to allow scanning by, for example, a bar code reader and/or marking by markers 76 as described below.
In one embodiment, container 210 is placed in the front portion of holder 260, such that a label to be applied to the container 210 and other indicia on the container itself are exposed to the outside environment through the open portion of holder 260 as shown in FIG. 17. For purposes of illustration, in FIGS. 17-18, label is shown as applied to container 214. In one embodiment container 214 may not include label at the time of use and a label may be transferred to container 214 from a container of biological fluid. Alternatively, container 214 may include a label and an additional label may be transferred from a container of biological fluid. In any event, container 214 may be folded in half (or tri-folded) with container 210 (also folded) placed behind container 214. In addition, folded container 214 may be lightly spot welded at its ends to keep the container folded and improve handleability of the container. The weld should be sufficiently strong to keep container 214 in a folded position, but not so strong that undue force applied by the user would be required to disconnect the welded ends. Spot welded ends of container 210 should release when tugged gently by the user.
Methods of Processing and Treating Fluid
The method of processing fluid using disposable processing set 200 (or 240) and treating a biological fluid with light in, for example, light box 10 will now be described. Although the following description will be provided in the context of processing the biological fluid for subsequent inactivation of pathogens in the biological fluid, it should be understood that many of the steps described below may also be carried out in other fluid processing and treating methods that do not involve pathogen inactivation. The following description will be provided using the disposable processing set of FIG. 15 as an example, although it will be understood that the description may also apply to other processing sets, such as the set of FIG. 16.
In accordance with the method of processing a biological fluid such as blood using the processing set 200, a container of collected blood or biological fluid is provided. Although the method of collection is beyond the scope of the present application, representative methods of collecting blood products include the automated and manual centrifugal processing, separation and collection of blood products, membrane separation of blood products and the like. One example of a centrifugal blood processing system is the AMICUS® Separator sold by Baxter Healthcare Corporation.
Regardless of the collection method, containers of the collected blood product will typically bear a label that includes information identifying the donor, the blood product and lot numbers. Most typically, such information is presented in the form of one or more bar codes on the label, which can be scanned and read by bar code reader, such as bar code reader 41 of light box 10. Such labels may be removable and transferable to container 214 of the disposable processing set 200.
Typically, the collection container will include a tubing segment extending therefrom. Accordingly, tubing from the collection container 201 and tubing segment 203 from the disposable processing set 200 are brought together and joined in a sterile manner, as shown generally in FIG. 17. A device that is useful for the sterile joinder of tubing portions is available from Terumo Corporation of Japan and sold under the name Terumo SCD. This device heat seals two opposing tubing portions in a sterile manner. The heat from the heat sealing kills any bacteria from the outside environment that may enter or reside in the tubing segments, thereby preserving the sterility of the entire processing set. Of course, any method and apparatus for joining two tubing segments while maintaining sterility may be used.
Once tubing segments have been joined, frangible member 230a is broken to provide an open flow path from the collection container 201 to the container 206 (FIG. 15). Photochemical agent from container 202 is also allowed to flow into container 206. After fluid transfer to container 206, tubing segment may be severed and sealed and the portion of the disposable processing set that included container 202 and the collection container(s) 201 are discarded. Indicator 234a provides a reference point as to where the tubing is to be severed. It is preferable that the indicator be placed as close as possible to the container 206 so that most of the biological fluid is retained within container 206 where it is most likely to be mixed and treated.
Before or after placement of the disposable processing set in tray 90, operator may scan the label and other container indicia with bar code reader 41. Bar codes 222 on the main container label 216 or the container itself provide the instrument with information regarding the biological fluid to be treated. Based on the data, the light treating instrument or operator prescribes the light dosage and then calculates the duration of the treatment.
Container 206 of disposable processing set 200 is typically placed in first compartment of tray 90. Slit 207 in container 206 is placed over retaining tab 186 in first compartment 188 and holder 260 with containers placed therein is placed within the second compartment 190 of tray 90. Slits and/or apertures in container 216 are likewise placed over retaining tabs or pegs 193 in second compartment 190. Tubing connecting container 206 with container 210 (and/or 214) may be pressed into the slot in wall 192. It is preferable that the tubing be positioned parallel to the direction of the side-to-side oscillation provided by the agitator assembly described above. This further ensures that any fluid within tubing segment 208 is also mixed. Indicator 234b not only serves as a reference point for severance of the tubing but also serves as a reference point for container placement by ensuring that substantially the entire container and biological fluid therein is within the field of light. The indicator has a diameter greater than the width of the slot.
Once the containers are in their respective compartments of tray 90, fluid carrying drawer 50 is closed. As set forth above, plunger switch 36a (FIG. 4) is pressed when door 36 is closed. If door 36 is open, plunger switch 36a serves as an electrical cut off. If, the door is open, the system will not permit the treatment to proceed.
Light box 10 includes a programmable computer software-based control system to control the operation of light box 10. The control system is generally and diagrammatically depicted in FIGS. 19-23. As shown in FIGS. 19-23, the, system tests, monitors and controls various aspects of the light box 10 and treatment operation such as the start up, container loading, container treatment and container unloading stages of the light box operation. The control system allows the operator to take action or advises the operator of the treatment status through either an alphanumeric or a graphical user interface displayed on screen 37. The various functions may be initiated by the operator through control panel or automatically by the control system itself.
For example as shown in FIG. 19, after the operator has turned on the instrument (step 700), the control system will initiate a series of steps including checking for file system integrity 700a, loading the software 700b, displaying the graphical user interface (GUI) screen 701, and continuing to initialize 702 the light box 10 until a screen is generated requesting the user to log in 703. After the user logs in, the main menu 704 is displayed. The operator may then select from the series of available functions 705 including the treatment function 706, the print function 707 or the illuminate settings 708. Alternatively, the operator may choose the exit function 712 to exit the system. Diagnostic checks 710 may also be selected and performed, typically by a service technician.
If the treatment function 706 in FIG. 19 is selected, the control system, through the programmed software will automatically determine if treatment is appropriate 713 and more particularly, if light box 10 is prepared for treatment as shown in FIG. 20A. Thus, for example, if the system detects a failure in the light source, or a failure in one of the sensors or other equipment, an error message 714 will be displayed and the user will be requested to press the enter 714a option. Treatment will then not be enabled and will not proceed until the condition is remedied. If treatment is enabled however, the system will then determine if treatment was otherwise cancelled 715. If not, the system will prompt the operator to input the container (i.e. biological fluid) information 716. Container information may be input manually or by scanning bar codes 222 on, for example, container 214 shown in FIG. 15. The system again determines if the treatment process has been cancelled. If the data from the bag information entry in step 716 is valid at step 718, the system proceeds to the next function or phase as generally shown in FIG. 20B.
As shown in FIG. 20B, the control system displays additional options for the operator to select at step 719. For example, the operator may proceed to treatment of the container, request treatment of a second container or cancel the operation entirely as shown at step 720. At step 719, the user may elect to return or to enter the next selection. If “Bag 2” option is selected at step 719a, the operator is again requested to input container information at step 722 and the system will repeat the steps generally described above before commencing the treatment process at step 724a. If treatment on a single container is to be performed, the operator selects the treatment function at step 324, which is described in more detail below. When the treatment process at step 724 is finished, the system prompts the user for another treatment. If another treatment is selected at step 726, the system returns to point A in FIG. 20A to input the new bag information, step 716, and to determine if the new bag information is valid, step 718, while continuing to permit treatment to be cancelled at steps 715 and 717.
After containers have been placed into tray 90, to commence treatment the system activates the light source(s) 100, shaker motor 92 and fans as shown in step 728 of FIG. 21. The instrument may display, for verification by the operator, information regarding the fluid to be treated and the treatment process generally, as at step 730. For example, in one embodiment, the instrument may display, the predetermined target dose of energy to be applied to containers, the selected treatment time and a running value of the dosage percent being applied to the biological fluid during the treatment as shown in step 730. Treatment will continue unless terminated by the operator or automatically terminated by the instrument in response to an alarm condition.
In one embodiment, container may be marked by markers 76 at the beginning of treatment and after treatment is completed. The marks made by marker 76 obliterate or otherwise masks the bar code, making it unreadable. Thus, a container with two masked bar codes 224 indicates that treatment has been successfully completed. On the other hand, if only one of the bar codes 224 has been masked, this serves as an indication that treatment was not successfully completed and the container may have to be discarded. Masking of bar codes 224 by markers 76 also ensures that a treated container will not be treated again.
During treatment, the system performs an energy calculation at step 732, which is computed by multiplying the light intensity sensor readings by preselected calibration factors, averaging the readings across the sensors in the same chamber and plane and adding the reading received for planes in the same chamber. The control system further verifies the treatment status at step 734. If treatment is completed at step 735, the system will check the keypad at step 735a and determine if the stop key was pressed at step 735b before turning off lamps 100 as shown at step 736.
The system may automatically update information on the lamp life as shown at step 737 and update container records at step 738. Control system may continue to power shaker motor 92 until terminated. The results are preferably transmitted to a microprocessor or central processing unit (CPU) 603 on computer board 602 (FIG. 33). After treatment, the system will prompt the operator to unload containers at step 742 and may prompt the user to perform another treatment, if desired, as at step 725 in FIG. 20B. The process may be repeated as generally described above.
The processes of determining the light intensity, determining the current energy dose and determining the treatment time based upon a predetermined or target energy dose is shown in the flow chart of FIG. 21A. This corresponds, in part, to the energy calculation step 732 in FIG. 21. It is assumed that treatment has been initiated at step 724, which also corresponds to steps 724 or 724a in FIG. 20B. When treatment is initiated, lamps 100 are illuminated at step 770. Light sensors 404 at step 771 make a measurement of the light intensity from lamps 100. Light sensors 404 convert the measured illumination level into a signal with a frequency that is related to the sensed light intensity at step 771. At step 772, the signals from each sensor 404 are combined by a multiplexer into a multiplexed frequency signal. At step 773, the frequencies of each sensor in the multiplexed signal are counted to provide a count that represents a composite of the illumination levels measured each for each light sensor. The count of the test frequency signals 657 is then checked at step 774 to determine the accuracy of the counted test frequency signals from step 773. Since the frequencies of test signals 657 are known, the count of these frequencies will confirm the accuracy of the information counted by the counter. This in turn, will determine the reliability of the count of the sensor signals from step 773. At step 775, the counts of the sensor signals from step 773, and the count of the test frequencies from step 774, are compared to corresponding counts from a secondary or redundant sensing circuit, to confirm that the counts from the primary sensing circuit are valid. At step 776, calibration coefficients are applied to each sensor count by CPU 603 to provide a corrected signal count. These calibration coefficients are defined during the calibration procedure, as will be explained below in FIG. 21B. With a corrected signal count, CPU 603 can determine the corresponding light intensity level in light box 10 at step 777. The light sensing system typically measures the light intensity about once every second. Using the corrected light intensity measurements, CPU 603 continuously updates the current energy dose that has been delivered to one or both of treatment chambers 42 and/or 44. Based upon the current energy dose and the current corrected illumination level, CPU can determine the remaining treatment time as well as the total treatment time, at step 779, needed to deliver the target dose, which was identified as one of the treatment parameters at step 730 in FIG. 21. When target dose is reached, treatment is terminated and illumination ceases, at step 779a. 
The process of calibrating the light box 10 with a pair of radiometers 460 is illustrated in FIG. 21B. The user first selects the calibration mode at step 780. Preferably, a bar code on radiometer 460 is first scanned to identify the radiometer being used at step 781. As previously explained this bar code identifies radiometer 460 by serial number or the like, provides calibration codes, such as for each sensor 469 in radiometer 460, and also provides an expiration date before which radiometer 460 will need recalibration. The radiometer calibration codes are provided to CPU 603 for use in correcting light intensity measurements made by the radiometer. The user then places radiometer 460 in one of the compartments of tray 90 such as the compartment that corresponds to first chamber 42 of light box 10, as in step 782. Preferably, the previously described agitator system is started so that the radiometer measures light intensities from lamps 100 as if radiometer 460 is a biological fluid under treatment. As previously described and as shown in FIG. 14A, radiometer 460 has eight light sensors 469 disposed on each side, with four sensors located near the corners and the remaining four sensors located more centrally between the four corners. Note that radiometer 460 will be measuring light intensity as actually received by a biological fluid after being filtered by any filters and as received after light transmission through tray 90 from the lower lamps 100. The light intensities measured by radiometer 460 are therefore more accurate than the light intensities measured by light sensors 404, which are disposed on the opposite sides of lamps 100 from radiometer 460. Radiometer 460 is thus able to more accurately measure light intensity in tray 90 where biological fluids are placed for treatment. It is therefore desirable to calibrate light sensing system 650 to measure light intensity received at tray 90 similarly to that measured by radiometer 460.
CPU 603 receives data from each sensor 469 in radiometer 640 to measure the light intensity in step 783. At the same time, CPU 603 receives data from both upper and lower light sensors 404 in step 784, which corresponds to steps 771-773 in FIG. 21A. In step 785, CPU 603 calculates a calibration coefficient for each sensor 404 based upon the corrected illumination intensity readings from radiometer 460 and the uncorrected illumination intensities from illumination sensing system 650.
Calibration coefficient or correction coefficient means any number or set of numbers that is used to correct measured illumination intensities to within a predefined tolerance of NIST standards. Thus, a general objective is to transfer the more accurate illumination measurement capabilities of the pre-calibrated radiometer 460 when disposed in treatment chambers 42 or 44 to the more remotely located light sensing system 650 such that light sensing system 650 will measure light intensities in chambers 42 and 44 in a manner similar to that of radiometer 460 when disposed therein. These calibration coefficients are preferably linear scaling factors that enable the light sensing system 650 to emulate the light measuring accuracy of radiometer 460 in the treatment chambers. These calibration coefficients, as determined in step 785, are temporarily stored in memory for future use.
At the conclusion of the calibration procedure with a first radiometer 460, the user will be prompted to again calibrate the first chamber 42 with a second radiometer 460. Use of a second radiometer is preferred to confirm the calibration results obtained from the first radiometer. The user scans a bar code on the second radiometer so that light box 10 can confirm that a different radiometer is being used. Steps 782-785 are repeated with the second radiometer. If the calibration results from the second radiometer at step 785 are within a certain tolerance, such as about 10 per cent, the calibration coefficient results are saved in memory, at step 787 for use in obtaining corrected light intensity measurements. If the results are not within the defined tolerance, it is assumed that one of the two radiometers is faulty and the user is instructed to return both radiometers for service. In this instance, none of the calibration coefficients is saved for use in calculating the light intensities, and the calibration coefficients from the last prior recalibration procedure continue to be used.
This ends the calibration procedure for the first compartment of the light box 10 at step 788, and steps 781-787 are preferably repeated to calibrate the light intensity measurements in the second compartment.
Treatment time and energy dosage will vary depending on the biological fluid to be treated. For example, the treatment time may be at least one minute but may also be less than one minute. Where light box 10 is used for the pathogen inactivation of biological fluid, the treatment may typically be anywhere between 1-30 minutes. For example, for the pathogen inactivation of blood platelets, treatment is, typically between 1-10 minutes, but more typically approximately 3-4 minutes. For the pathogen inactivation of blood plasma, treatment may also preferably be approximately 3-4 minutes.
Energy per unit area, or energy flux, is the product of power per unit area or, in the case of radiant flux, at the target, and the time of exposure. Accordingly, the amount of energy per unit area delivered to the target (for example, in one embodiment, the biological fluid) will vary with the duration of exposure and the irradiance—the radiant power per unit area incident on the target. In one embodiment the total radiant energy flux delivered may be between approximately 1-100 J/cm2 measured across a wavelength range of between approximately 300-700 nm. However, any useful wavelength that activates photochemical agents may be used. In general, light box 10 can be retrofitted for various illumination frequencies to illuminate treatment targets in treatment chamber 40, including those light frequencies outside of the range of 300-700 nm.
In another embodiment, where the light source provides light generally in the ultraviolet range, the total radiant energy flux delivered to the biological fluid may preferably be between 1-20 Joules/cm2 measured across a wavelength range of between approximately 320-400 nm. In one specific embodiment, the total radiant energy flux delivered to blood platelets or blood plasma may be between approximately 1-5 J/cm2 and more typically approximately 3-4 J/cm2 measured across a wavelength range of between approximately 320-400 nm. Preferably, the energy should not be outside the predetermined range in that excess heat generated within fluid treatment chamber 40 is to be avoided. For light treatment of blood platelets and blood plasma, for example, temperature within chamber 40 should typically not exceed 37 C. If an external temperature sensor of the type described above is used, the ambient temperature should be between 18-30 C.
During treatment, tray 90 is preferably agitated at a preset frequency. Of course, the frequency should not be so great so as to harm the biological fluid or components thereof. Typically, the tray 90 may be agitated between approximately 40-100 cycles/min and for blood platelets, more preferably, between approximately 40-80 cycles/per minute. A cycle is defined as one complete back and forth oscillation of drawer 80. Additionally, it may be desirable for agitation may continue for up to 30 minutes after blood platelets have been treated with the desired target light dose, i.e., after illumination in the light box 10 is terminated.
Once treatment has been successfully completed, fluid from container 206 may be transferred to container 210 by breaking frangible number 230b and opening the flow path between the containers 206 and 210 (FIG. 15). Once inside container 210, the biological fluid is allowed to contact the adsorbent material for a selected period of time. As noted above, in one embodiment, container 210 may also include time-sensitive tabs 209 that change color over time. This way, the operator will know if the container has been in contact with the adsorbent material for the appropriate period of time. The adsorbent material is selected to remove any residual photochemical agent or any by products of the photochemical process that may have been included in the biological fluid. The adsorbent material may include polystyrene beads or activated charcoal or other adsorbent material. Such materials are described in greater detail in International Publication No. WO 96/40857, incorporated by reference herein.
Alternatively, in the disposable processing set 240 shown in FIG. 16, the biological fluid may simply pass-through container 246 without residing for any significant time, within the container. The details of the removal process and materials used are described in the above-identified International Publication No. WO96/40857.
The residence time, if any, of the biological fluid in container 210 (or 246) will be anywhere between approximately 30 seconds and 7 days. In addition, during contact of the biological fluid with the adsorbent material of container 210, it may be desirable to shake or otherwise agitate container 210 to ensure maximum contact with the adsorbent material.
Regardless of which disposable set is used, after the required residence time, if any, the biological fluid may be transferred to container 214 (or 248 in FIG. 16) by breaking frangible member 230C where it may be stored prior to transfusion to a recipient. Label 216 (or 249) applied to storage container 214 (or 248) now carries identifying information regarding the donor and the fluid. Masked bar codes 224 (or 251) indicate successful treatment of the biological fluid and that no additional treatment is required. The container may be severed and sealed from the remaining portion of the disposable processing set as generally described above.
In addition to the treatment function generally described above and as generally depicted in FIG. 22, the control system may prompt the operator to perform other customer functions at steps 743, 744 and 744a, such as a system settings function at step 745 that allows the operator to set the date and time at step 748 and select the appropriate language at step 749. The control system also allows the operator to select certain container management functions such as auto-printing at step 751, a report printer at step 752, a label printer at step 753 or transmitting process reports to a data management system at step 754.
Alternatively, the diagnostics menu 755 shown in general in FIG. 23 may be selected. After waiting for the user to select an option at steps 756 and 756a, the user may select to see product data at step 757, initiate device tests at step 758, access service information at step 760 or initiate diagnostics at step 760. It will be appreciated that steps 757-759 may have sub-options like diagnostics step 760. Selecting diagnostics option 760 permits a maintenance person or supervisor to enter new operator ID information at step 762 to permit new persons to be authorized to operate light box 10, to over-write bag records at step 763, to reset lamp life information, as when lamps are replaced, at step 764 and to print a maintenance log at step 765.
It will be appreciated that various modifications of the embodiments and methods described herein may be made by those skilled in the art without departing from the scope of the present invention, which is set forth in the appended claims.

## Claims

1. Apparatus for treating a biological fluid comprising:
a fluid treatment chamber for receiving said biological fluid;
at least one light source with a plurality of lamps, said light source disposed either above or below said fluid treatment chamber;
a light sensing system with a plurality of light sensors for sensing the amount of light emitted by said plurality of lamps, wherein each light sensor of said plurality of light sensors is disposed adjacently to at least one of said plurality of lamps, and wherein each light sensor in the plurality of light sensors provides a signal consisting of a frequency that is related to the sensed light intensity; and
a first multiplexer to receive the frequency signals from each of the plurality of light sensors and to multiplex each of the frequency signals from the plurality of light sensors into a first multiplexed frequency signal that is related to the sensed light intensity.

2. The apparatus of claim 1 further comprising a first frequency counter to receive the first multiplexed signal and to count the frequencies in the first multiplexed frequency signal to provide a first counted output signal that is related to the sensed light intensity.

3. The apparatus of claim 2 further comprising:
a second multiplexer that also receives the plurality of signals from the plurality of light sensors and that multiplexes the plurality of signals from the light sensors into a second multiplexed frequency signal; and
a second frequency counter to receive the second multiplexed signal and to count the frequencies in the second multiplexed frequency signal to provide a second counted output signal representative of the amount of light emitted by the plurality of lamps, thereby enabling the light sensing system to confirm the accuracy of the first counted output signal.

4. The apparatus of claim 1 further comprising an oscillator that generates at least one test signal of a known frequency, said first multiplexer in communication with said oscillator to receive said at least one test signal and to multiplex said at least one test signal into said first multiplexed frequency signal.

5. The apparatus of claim 1 further comprising a power level input from a power source, said first multiplexer in communication with said power source to receive said power level input and to multiplex said power level input into said first multiplexed frequency signal.

6. The apparatus of claim 1 wherein said at least one light source further comprises:
a light source with two arrays, each array with a plurality of lamps, said light source having one array disposed above said fluid treatment chamber and having another array disposed below said fluid treatment chamber; and wherein said light sensing system further comprises
a light sensing system with a plurality of light sensors for sensing the amount of light emitted by each array, wherein each light sensor of said plurality of light sensors is disposed adjacently to at least one of said plurality of lamps in each array, and wherein each light sensor in the plurality of light sensors provides a signal consisting of a frequency that is related to the sensed light intensity; and
a first multiplexer to receive the frequency signals from each of the plurality of light sensors and to multiplex each of the frequency signals from the plurality of light sensors into a first multiplexed frequency signal that is related to the sensed light intensity.

7. The apparatus of claim 6 further comprising a first frequency counter to receive the first multiplexed signal and to count the frequencies in the first multiplexed frequency signal to provide a first counted output signal that is related to the sensed light intensity.

8. The apparatus of claim 7 further comprising:
a second multiplexer that also receives the plurality of signals from the plurality of light sensors and that multiplexes the plurality of signals from the light sensors into a second multiplexed frequency signal; and
a second frequency counter to receive the second multiplexed signal and to count the frequencies in the second multiplexed frequency signal to provide a second counted output signal representative of the amount of light emitted by the plurality of lamps, thereby enabling the light sensing system to confirm the accuracy of the first counted output signal.

9. The apparatus of claim 6 further comprising an oscillator that generates at least one test signal of a known frequency, said first multiplexer in communication with said oscillator to receive said at least one test signal and to multiplex said at least one test signal into said first multiplexed frequency signal.

10. The apparatus of claim 6 further comprising a power level input from a power source, said first multiplexer in communication with said power source to receive said power level input and to multiplex said power level input into said first multiplexed frequency signal.