Abstract:
An apparatus and method for collecting whole blood and then separating it into components for subsequent use or storage. A self-contained bag set is used to collect the sample, which may then be placed into container adapted to fit into a centrifuge for separation of components. Each component is then sequentially extracted according to density, with a sensor present in the container to control the operation of valves directing the collection of each component. Each component may then be separated into its own storage container.

Description:
FIELD OF THE INVENTION  
         [0001]    The following invention relates generally to instrumentalities and methodologies in blood component separation techniques. More specifically, the instant invention is directed to a method and apparatus for collecting a blood sample and subsequently separating the collected sample into the blood components for individual storage or use.  
         BACKGROUND OF THE INVENTION  
         [0002]    Blood collection is always important, particularly in times of emergency (immediate use), but whole blood may only be stored for about 30 days before it is “outdated”. For long term storage, the ability to separate the whole blood into its major components (white blood cells, platelets, red blood cells and plasma) is of paramount importance because the long term storage conditions for each component is different in terms of temperature and storage media. The most important component separations occurring after collection is the separation of red blood cells (RBC), white blood cells (WBC), platelets, and plasma from one another. Within the WBC it is sometimes important to separate the granulocytes from the lymphocytes. After separation and extraction of particular components, a fraction of the blood may be returned to the patient.  
           [0003]    It is possible to separate the various components of whole blood either under or after centrifugation, due to their differing densities. Some prior art methods, such as that in U.S. Pat. No. 4,120,448, utilize a chamber connected to a centrifuge. The centrifuged blood separates in the chamber, and a plurality of collection means are positioned at various locations in the chamber corresponding to the areas where each component congregates, which is density-dependent.  
         SUMMARY OF THE INVENTION  
         [0004]    The present invention comprises a bag set that may be used to collect a whole blood sample from a source, then placed into a centrifuge for component separation. The whole blood collection bag, which contains an anticoagulant such as CPD, ACD or CPD-A, contains one outlet port connected to a plurality of component collection bags. Each component collection bag has a separate line leading from the whole blood collection bag, and each line can be clamped, tube-sealed and separated from the whole blood collection bag once a particular component bag has been filled.  
           [0005]    In practice, the blood is collected into the whole blood collection bag and the input line is clamped, sealed off, and separated from the whole blood collection bag. The whole blood collection bag hangs in a clamshell-style container that closely contacts the bag at the bottom end, and is adapted to fit in a centrifuge cup. The centrifuge is operated at varying G-forces to optimally separate the components. Once the components are separated in the whole blood collection bag, a driver motor is engaged to open a metering valve on the line leading from the collection bag to a bag that will contain the densest component. This allows the densest component to fill its particular storage bag.  
           [0006]    Complete collection of the first component is indicated by an optical sensor that is present in the clamshell container. The driver motor, directed by the sensor, automatically closes the metering valve on the line, terminating collection of that particular component. The driver motor then further engages the metering valve to allow collection of the next component through a second output line connecting the metering valve and the second storage bag. The process may sequentially continue until all desired components are collected in separate storage bags: red blood cells, white blood cells (lymphocytes and granulocytes), platelets, and plasma.  
           [0007]    Once collected, each storage bag may be sealed off and separated from the whole blood collection bag. Any necessary preservatives or additives may be introduced through the collection lines before processing or storing.  
         OBJECTS OF THE INVENTION  
         [0008]    Accordingly, it is a primary object of the present invention to provide a new and novel device and method for separating the components of whole blood for subsequent storage or use.  
           [0009]    It is a further object of the present invention to provide a device and method as characterized above in which separation may be accomplished entirely by machine during a single centrifugation run without the considerable handling and multiple centrifugation runs typically practiced in a blood bank.  
           [0010]    It is a further object of the present invention to provide a device and method as characterized above in which the separation apparatus is self-contained to simplify the operation.  
           [0011]    Viewed from a first vantage point, it is an object of the present invention to provide a bag set, comprising, in combination: a centrifuge bag leading to first and second bags; an inlet to allow blood into said centrifuge bag; conduits leading from said centrifuge bag to said red and white blood cell bags; and valve means operating under machine control to admit blood fractions to said first and second bags.  
           [0012]    Viewed from a second vantage point, it is an object of the present invention to provide a system for separating blood cells, comprising, in combination: a centrifuge; a bag set having plural interconnected bags; and a bag set container contoured to be received in said centrifuge, said container including means to selectively provide access between bags within said bag set.  
           [0013]    Viewed from a third vantage point, it is an object of the present invention to provide a method for separating blood cells, the steps including: centrifuging a mixture of blood cells to cause stratification, the stratification producing a first cell layer and a second cell layer; opening a conduit leading to a first cell bag; centrifuging the first cell layer into the first cell bag; closing the conduit to the first cell bag; opening a conduit leading to a second cell bag; and centrifuging the second cell layer to the second cell bag.  
           [0014]    These and other objects will be made manifest when considering the following detailed specification when taken in conjunction with the appended drawing figures.  
       
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0015]    [0015]FIG. 1 depicts the bag set of the present invention.  
         [0016]    [0016]FIGS. 2A and 2B depict the clamshell container before insertion of the bag set.  
         [0017]    FIGS.  3 A- 3 C depict the clamshell bag holder after insertion of the bag set.  
         [0018]    [0018]FIGS. 4A and 4B depict the bag set in the chamber before centrifugation.  
         [0019]    [0019]FIGS. 5A and 5B depict the bag set in the chamber after centrifugation.  
         [0020]    [0020]FIGS. 6A and 6B depict the harvesting of the greater-density component.  
         [0021]    [0021]FIGS. 7A and 7B depict the harvesting of the lesser-density component.  
         [0022]    [0022]FIGS. 8A and 8B depict the separate collection lines of the bag set after disconnection from the collection bag.  
         [0023]    FIGS.  9 A- 9 C depict the operating positions of the metering valve.  
         [0024]    [0024]FIG. 10 is a flowchart of the preferred process.  
         [0025]    [0025]FIG. 11 illustrates the separation of whole blood components in graphical form.  
     
    
     DESCRIPTION OF PREFERRED EMBODIMENTS  
       [0026]    Considering the drawings, wherein like reference numerals denote like parts throughout the various drawing figures, reference numeral  10  as shown in FIG. 1 is directed to the bag set according to the present invention.  
         [0027]    Referring to FIG. 1, the bag set  10  includes a whole blood collection bag  2 , a red blood cell (RBC) bag  4 , and a freezing bag  6  for the collection and storage of white blood cells. The collection bag  2  is supplied through an inlet line  12 , preferably through a phlebotomy needle  8 . The collection bag  2  has an outlet  26 , which directs output into a three-way metering valve  20  through a spike  30  (which is inserted into outlet  26 ) which is connected to an outlet line  32 . The operation positions of the metering valve  20  are shown in FIGS.  9 A- 9 C. Two supply lines  24   a,   24   b  lead from the metering valve  20  to the RBC bag  4  and the freezing bag  6 , respectively. RBC supply line  24   a  has an optional HES inlet  14  for the introduction of a sedimenting agent, such as hydroxyethyl starch (HES) into the system. The freezing bag supply line  24   b  has an optional cryoprotectant inlet  16  for the introduction of cryoprotectant into the system. The HES inlet  14  and the cryoprotectant inlet  16  are each equipped with a filter  18 , preferably a 0.2μ filter, to, inter alia, prevent contamination from pathogens in the outside air and to allow venting of air from the freezing bag and tubing. The supply lines  24   a,   24   b  and the inlet line  12  may each be heat sealed and separated from the bag set  10 . All lines are equipped with line clamps  22  that may be closed to prevent fluid passage when desired. If other components are to be separated, the bag set  10  may include additional bags  200 , and the metering valve  20  may be modified to accommodate the additional bags  200 .  
         [0028]    Initially, the collection bag  2  is filled with an anticoagulant, such as CPD (citrate, phosphate, and dextrose). The metering valve  20  begins in the closed position (FIG. 9A). All clamps  22  are closed, with the exception of the clamp  22  on the inlet line  12 . Blood, preferably whole, placental, or umbilical cord blood, is obtained from a source through the phlebotomy needle  8  or other appropriate inlet, which feeds into the collection bag  2  through the inlet line  12 . The inlet line  12  is then clamped, heat sealed, and separated from the bag set  10 . The clamps  22  on the HES inlet line  14  are opened, and HES is introduced through the HES inlet  14  into bag  2 . The line leading to the HES inlet  14  is then clamped, heat sealed, and removed. Alternatively, the HES can be introduced into the bag  2  earlier, as, for example, during manufacture.  
         [0029]    At this point, the bag set  10  is placed in a clamshell bag holder  50 , shown in FIGS.  3 A- 3 C. Referring to FIGS. 2A,2B, the bag holder  50  includes hooks  60  that engage the loops  28  on the collection bag  2 . The interior of the bag holder  50  is shaped to receive the collection bag  2 , having a bag holding wall  152 , a bag-supporting wall  154 , and straight sidewalls  156  near the top of the bag holder  50 , which intersect with angled walls  156  at the bottom of the collection bag  2 . The angled walls  156  terminate at the bottom of the bag-holding wall  152  in an outport  160  dimensioned to receive the outlet  26  of the collection bag  2 . On the bag-supporting wall  154 , the angled walls  158  terminate at an angled point  162 . The sidewalls  156 , 158  help to cradle the collection bag  2  loosely at the top (near the loops  28 ) and more tightly at the bottom (near the outlet  26 ). Closer tolerance near the bottom of bag  2  is desired to minimize disturbing the contents of the bag after sedimentation. The metering valve  20  is connected to a motor driver  56  in the bag holder  50 . The motor driver  56  is connected to a software-controlled wireless control chip module  54  powered by a rechargeable battery  52 . A port  64  is provided to utilize a battery charger. The motor driver  56  controls the operation of the metering valve  20  while the bag set  10  is mounted in the bag holder  50 . One or more optical sensors  58  (e.g., FIGS. 2A,2B) positioned near the collection bag outlet  26  and/or located on the bag holder  50  triggers the proper time for the motor driver  56  to close the metering valve  20  after each fraction is harvested. Alternatively, an optical sensor  58  (FIG. 1) may be located just upstream of the metering valve  20  to allow greater control over the harvest of each component by “reading” strata change closest to the metering valve  20 . The bag holder  50 , when closed, is adapted to fit into a centrifuge cup  66  dimensioned to reside within a conventional centrifuge  100  (FIG. 4A). The RBC bag  4  and the freezing bag  6  are cradled in the bottom of the bag holder  50  in separate recesses  62   a,   62   b  (FIGS. 2A,2B) of the bag holder  50 .  
         [0030]    The bag set  10  in the centrifuge cup  66  may be subjected to more than one G-force in order to achieve the optimum stratification of components (FIGS. 5A,5B). The motor driver  56  then operates the metering valve  20  to open and allow access to supply line  24   a  for the harvest of red blood cells, at an optimum G-force, into bag  4 . The motor driver  56  closes the metering valve  20  when the optical sensor  58  indicates that the red blood cells are harvested (FIGS. 6A,6B). The next fraction, which includes white cells and/or platelets, is then harvested from the collection bag  2 ; the motor driver  56  opens the metering valve  20  to allow access to supply line  24 b (FIG. 9C) leading to bag  6  for the next harvest. As shown in FIGS. 7A,7B, during the harvest (WBC) into the freezing bag  6 , air in the supply line adds to air already in the freezing bag  6 , producing an air bubble  70 , which is useful to assist the proper mixing of the WBC and/or platelets with the cryoprotectant. The motor driver  56  then closes the metering valve  20 , as shown in FIG. 9A, and the centrifuge  100  is allowed to stop.  
         [0031]    The bag holder  50  is removed from the centrifuge cup  66  and opened, and the bag set  10  is removed, with the motor driver disconnected from the metering valve  20 . Each supply line  24   a,   24   b  is clamped, heat sealed, and removed from the collection bag  2  (FIGS. 8A,8B). Any additional bags  200  (FIG. 1) may be similarly removed.  
         [0032]    After the supply line  24   b  connected to the freezing bag  6  is disconnected, a cryoprotectant may be introduced into the component in the freezing bag  6  through cryoprotectant inlet  16 . The air bubble  70  in the freezing bag  6  allows the cryoprotectant to be thoroughly mixed with the collected component. After mixing, the air bubble  70  is expelled through the filter  18  of the cryoprotectant inlet  16 . The component is then prepared for storage by heat-sealing the tubing and removing the bag  6  downstream of the cryoprotectant inlet  16 .  
         [0033]    Preferably, each line (the inlet line  12  and the supply lines  24   a,   24   b ) is oriented to allow access to a sampling site  34  near the collection or storage bags. Thus, a sample of the blood or fluid in the line may be taken without disturbing the bulk of the collected component.  
         [0034]    [0034]FIG. 11 depicts the separation of whole blood components as a function of time. Under centrifugation, each fraction stratifies in the collection bag  2  as a function of its density. The overlapping areas  205  indicate the area in the separation along each strata line in the collection bag  2 . As centrifugation continues, the boundary of each fraction becomes more clearly defined; thus, the area  205  decreases and each fraction is more completely harvested. Thus, the centrifugation strategy combines separation by density, the time involved for stratification, centrifuge force, and boundary layer clarity. Decisions on harvesting will vary based on these tradeoffs as a function of the constituent of greatest value and its desired purity.  
         [0035]    It is appreciated that while the instant invention is preferably used in the separation of blood components, the separation techniques and apparatus are suitable for separation of other fluids. The software programmed into the control chip module may cause the motor driver to open and close the valve many times, thereby throttling the valve during strata delivery. Also by varying time increments during a harvest procedure, precise cut-offs between the cell components can be achieved in order to reduce the mixing between cell types that may occur as a result of the “toroidal” (Coriolis) effect during removal of the blood component from bag  2  and may be modified for the separation of other fluids or to compensate for various hardware conditions, such as uneven centrifuge loading. Moreover, having thus described the invention, it should be apparent that numerous structural modifications and adaptations may be resorted to without departing from the scope and fair meaning of the instant invention as set forth hereinabove and as described hereinbelow by the claims.