Abstract:
A biological fluid processing or fluid filtration system is provided having novel open and closed loop processing systems wherein the gases transferred into and out of the system during processing pass through a porous medium in upstream and/or downstream gas inlet or outlet housings or vents in a manner which precludes the fluid being processed or filtered from ever contacting the housings or vents. Each housing or vent is separated from the fluid by a column of gas in its respective transfer line. The upstream gas inlet housing or vent is in communication with the unfiltered biological fluid, and the downstream gas inlet housing or vent is in communication with the filtered biological fluid.

Description:
[0001]    This application is a divisional of pending application Ser. No. 09/688,999, filed Oct. 16, 2000, which is a divisional of application Ser. No. 09/272,203, filed Mar. 19, 1999, now U.S. Pat. No. 6,171,493, issued Jan. 9, 2001, which is hereby incorporated by reference in its entirety. application Ser. No. 09/688,999 is copending as of the filing date of the present application.  
       CROSS-REFERENCE TO RELATED APPLICATION  
       [0002]    application Ser. No. 09/688,999 claims the benefit, Under 35 U.S.C. •119 (e), of the provisional application filed on Mar. 20, 1998, under 35 U.S.C. •111(b), which was granted Serial No. 60/078,848, and of the provisional application filed on Apr. 29, 1998, under 35 U.S.C. •111(b), which was granted Serial No. 60/083,484. The provisional applications, Nos. 60/078,848 and 60/083,484 are hereby incorporated by reference. 
     
    
     
       BACKGROUND OF THE INVENTION  
         [0003]    1. Field of the Invention  
           [0004]    The present invention relates to a method and apparatus for processing biological fluids into their therapeutically valuable components. More particularly, the present invention relates to a method and apparatus for processing donated blood into its therapeutically valuable components. Most particularly, the present invention relates to an improved method and apparatus for processing donated blood into its therapeutically valuable components which uses improved open-loop and closed-loop systems to substantially increase the recovery of all the blood products from the donated blood.  
           [0005]    2. Discussion of the Related Art  
           [0006]    Methods and apparatus for processing blood are well known in the prior art. U.S. Pat. No. 3,892,236 to Djerassi shows an apparatus for the continuous withdrawal of blood from a human donor, forced extracorporeal circulation of blood of the donor with separation of granulocytes, and return by gravity of the leukocyte-poor whole blood to the donor.  
           [0007]    U.S. Pat. No. 5,126,054 to Matkovich shows a venting means for venting gas from the transfer line of a liquid delivery system comprising a housing, a first, liquid-wettable, microporous membrane carried in said housing so as to be in communication with the transfer line, and a second, non-liquid-wettable, gas permeable microporous membrane superimposed on said microporous membrane to the outward side of the housing. Gas in the delivery system is vented from the system so long as the first microporous membrane remains unwetted by the delivery liquid.  
           [0008]    U.S. Pat. No. 5,451,321 to Matkovich shows biological fluid processing assemblies having a gas inlet, and/or a gas outlet.  
           [0009]    While these devices are generally satisfactory, some of the methods and apparatus of the prior art leave a large amount of biological fluid trapped in various elements of the fluid processing apparatus. While the aforementioned U.S. Pat. No. 5,451,321 to Matkovich provides for liquid trapped in various elements of the blood processing system to be recovered either by causing a volume of gas behind the entrapped liquid to push the liquid through those elements and into the designated collection bag, or by pulling the entrapped liquid into the designated collection bag by a pressure differential (e.g. gravity head, pressure cuff, suction and the like), the system still has several drawbacks. One drawback is that they require one or more nonwettable, gas permeable, membranes. This requirement can lead to increased costs over wettable membranes.  
           [0010]    Therefore, those skilled in the art continue to search for a method and apparatus to provide for optimal recovery of the biological fluid from biological fluid processing systems, cost reduction and ease of use, and have developed novel open and closed loop systems and methods associated therewith to achieve this goal.  
         SUMMARY OF THE INVENTION  
         [0011]    The problems of the prior art are solved by the present invention utilizing novel open and closed loop biological fluid processing systems which all share the concept that the gases transferred into, out of, or within the biological fluid processing system have the transfer lines arranged or configured in a manner which precludes the biological fluid from ever contacting the upstream and downstream gas inlet or outlet housings or vents, or bypassing the fluid filtration or leukocyte depletion device. Gases are transferred into and out of the biological fluid processing systems through a porous medium in the upstream and downstream gas inlet housings or vents.  
           [0012]    Each housing or vent is separated from, and in communication with the biological fluid by a column of gas in the transfer lines. The upstream gas inlet housing or vent is in communication with the unfiltered biological fluid and the downstream inlet or vent is in communication with the filtered biological fluid.  
           [0013]    In one embodiment of the present invention, a biological fluid filtration apparatus is provided which includes a fluid filtration or leukocyte depletion device having an inlet and an outlet, a fluid container upstream from and elevated above said fluid filtration or leukocyte depletion device and having an outlet, a first conduit in fluid communication with the outlet of said fluid container and the inlet of said fluid filtration or leukocyte depletion device, a receiving container downstream of said fluid filtration or leukocyte depletion device and having an inlet, a second conduit in fluid communication with the inlet of said receiving container and the outlet of said fluid filtration or leukocyte depletion device, an upstream gas inlet having one of its•ends elevated above said fluid container, and having its•other end in fluid communication with said first conduit, and a downstream gas inlet having one of its&#39; end elevated above said fluid container, and having its&#39; other end in fluid communication with said or leukocyte depletion or fluid filtration device.  
           [0014]    In another embodiment of the present invention, there is provided a closed loop fluid filtration or leukocyte depletion device including a fluid filtration or leukocyte depletion device having an inlet and an outlet, a fluid container upstream from, and elevated above, said fluid filtration or leukocyte depletion device and having an outlet, a first conduit in communication with the outlet of said fluid container and the inlet of said fluid filtration or leukocyte depletion device, a receiving container downstream of said fluid filtration or leukocyte depletion device and having an inlet, a second conduit in fluid communication with the inlet of said receiving container and the outlet of said fluid depletion device and a bypass line in fluid communication with said fluid container and said receiving container and having a loop portion elevated above said fluid container.  
           [0015]    In yet another embodiment of the present invention the upstream gas inlet is eliminated and the downstream gas inlet is connected to the receiving container instead of the fluid filtration or leukocyte depletion device.  
           [0016]    In another embodiment of the present invention, the downstream gas inlet may be eliminated.  
           [0017]    In still another modification of the present invention, the upstream gas inlet housing or vent and the downstream gas inlet housing or vent may be part of the same inlet device.  
           [0018]    Thus, it is an object of the present invention to provide an improved method and apparatus for filtering biological fluids.  
           [0019]    It is a further object of the present invention to provide an open gas vent that prevents premature gas introduction into the fluid stream in a biological fluid processing system.  
           [0020]    It is a further object of the present invention to provide an open loop biological fluid processing system with transfer lines or conduits arranged or configured in a matter which precludes the biological fluid from contacting the upstream and downstream gas inlet housings or vents, or bypassing the biological fluid depletion device.  
           [0021]    Another object of the present invention is to offer a wider choice of materials which may be used in the gas inlet housings or gas outlet housings or vents of biological fluid filtration systems. The present invention does not require wettable membranes. The choice of membranes for the present invention is not limited.  
           [0022]    Another object of the present invention is to provide a system of the foregoing nature where gas is transferred into and out of the biological fluid processor through porous medium in the upstream and downstream gas vents.  
           [0023]    A still further object of the present invention is to provide an open loop system of the foregoing nature where each gas vent is separated from, and in communication with the biological fluid by a column of gas in the transfer lines or conduits.  
           [0024]    A still further object of the present invention is to provide an open loop biological fluid filtration system of the foregoing nature wherein the upstream gas inlet housing or vent, and the downstream gas inlet housing or vent may be a portion of the same inlet device.  
           [0025]    A still further object of the present invention is to provide a closed loop biological fluid filtration system having a bypass line bypassing the biological fluid filtration device, the bypass line is arranged such that a column of gas separates the unfiltered biological fluid upstream of the filtration device from the filtered biological fluid downstream of the biological fluid filtration device.  
           [0026]    A further object of the present invention is to provide an open loop biological fluid filtration system having an upstream gas inlet elevated above the level of the biological fluid container and having a satellite bag connected to the biological receiving fluid container.  
           [0027]    Further objects and advantages of the present invention will be apparent from the following description and appended claims, reference being made to the accompanying drawings forming a part of the specification, wherein like reference characters designate corresponding parts in the several views. 
       
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0028]    [0028]FIG. 1 is an elevational view of a prior art biological fluid filtration system.  
         [0029]    [0029]FIG. 2 is an elevational view of a construction embodying the present invention.  
         [0030]    [0030]FIG. 3 is an elevational view showing a modification of the construction shown in FIG. 2.  
         [0031]    [0031]FIG. 4 is an elevational view of a further modification of the construction shown in FIG. 2.  
         [0032]    [0032]FIG. 5 is an elevational view showing a further modification of the construction shown in FIG. 2.  
         [0033]    [0033]FIG. 6 is an elevational view of a closed loop construction embodying the present invention.  
         [0034]    [0034]FIG. 7 is an elevational view showing a modification of the construction shown in FIG. 6.  
         [0035]    [0035]FIG. 8 is an elevational view of a further modification of the construction shown in FIG. 6.  
         [0036]    [0036]FIG. 9 is an elevational view showing a further modification of the construction shown in FIG. 6.  
         [0037]    [0037]FIG. 10 is an elevational view showing a further modification of the construction shown in FIG. 6.  
         [0038]    [0038]FIG. 11 is an elevational view showing a further modification of the construction shown in FIG. 6.  
         [0039]    [0039]FIG. 12 is an elevational view of a construction embodying the present invention utilizing a satellite bag. 
     
    
     DESCRIPTION OF THE PREFERRED EMBODIMENT  
       [0040]    The aforementioned U.S. Pat. No. 5,451,321 to Matkovich shows a biological fluid processing assembly for filter biological processes such as blood. An example of the Matkovich apparatus is illustrated in FIG. 1. The apparatus has a blood collection bag  30  connected by a first conduit  31  to a leukocyte depletion device  32 . The leukocyte depletion device  32  is connected by a second conduit  33  to a blood receiving bag  34 . A gas inlet  35  having a cover or cap  36 , is provided in fluid communication with the first conduit  31  downstream of said collection bag  30 , and a gas outlet  37  is provided in second conduit  33  downstream of the leukocyte depletion device  32 .  
         [0041]    In one embodiment of the prior art, a first clamp  38  is placed on first conduit  31  downstream of the blood collection bag  30  and upstream of the gas inlet  35 , and a second clamp  39  is placed on the second conduit  33  downstream of the gas outlet  37 . In a typical operation the blood collection bag  30  is sterile and is connected to the conduit  31  as illustrated. The gas inlet  35  is comprised of a housing  41  and a porous medium barrier  42  in addition to cover or cap  36 . Additional details of the barrier  42  may be obtained by reference to U.S. Pat. No. 5,451,321.  
         [0042]    Prior to the start of blood processing, the inlet clamp  38 , the outlet clamp  39 , and the gas inlet  35  are all closed. The blood processing is initiated by opening the inlet clamp  38 , and allowing the blood to drain from the blood collection bag  30 . A column of blood flows through the first conduit  31  into the leukocyte depletion device  32  displacing any gas within the blood processing system. No blood enters the gas inlet device  35  since the gas inlet is closed. The displaced gas is expelled from the system through the gas outlet  37  since the second clamp  39  is closed. As substantially all the gas is expelled from the first conduit  31  and the portion of the second conduit  33  leading to the gas outlet  37 , the porous medium is wetted by the blood, and the blood flow seizes or stops at the liquiphobic bearer in the gas outlet  37 .  
         [0043]    Once the gas outlet  37  is wetted, the second or outlet clamp  39  is opened, and filtered blood flows into the blood receiving bag  34 . The gas outlet  37  need not be closed prior to opening of the outlet clamp since the gas outlet is sealed by the wetted porous medium. Blood flows from the collapsible blood container or bag  30  through the leukocyte depletion device  32  and into the blood receiving bag  34  until equilibrium is reached within the system and blood ceases to flow. At this point, all of the blood has not been processed through the leukocyte depletion device  32 . The first conduit  31 , the filter device  32 , and the second conduit  33  are filled with blood.  
         [0044]    Removing the cover or cap  36  from the gas inlet  35  allows gas to enter the processing system and drive the blood through the leukocyte depletion device  32 . However, since the filter medium  32 A within the leukocyte depletion device  32  is wetted, the flow of blood seizes when gas fills the upstream chamber of the filter. When the blood flow seizes, the second or outlet clamp  39  is closed.  
         [0045]    It can be seen that, at this point, the downstream side of the leukocyte depletion device  32 , and the entire second conduit  33  are filled with blood. With ever increasing need for blood and blood products, those skilled in the prior art have strived to increase the recovery of blood, and such a relatively large quantity of blood being left in the device of the prior art is no longer satisfactory.  
         [0046]    In order to solve the recovery problems present in the prior art devices, the open-loop construction shown in FIG. 2 has been developed. There is shown a biological fluid filtration system  44  having a leukocyte depletion device  45  with a filter medium  46 , an inlet  47 , and an outlet  48 . The leukocyte depletion device may be such as the biological fluid filter shown in provisional application Serial No. 60/083,484, which has been incorporated herein by reference, or any other suitable fluid filtration or leukocyte depletion device.  
         [0047]    A blood container  49  is provided upstream from, and elevated above said leukocyte depletion device  45 . Blood container  49  is connected to, or in fluid communication with, said leukocyte depletion device  45  through first conduit  50 .  
         [0048]    There is also provided a blood receiving container  52  downstream of said leukocyte depletion device  45 . Leukocyte depletion device  45  is connected to blood receiving container  52  through second conduit  54 . An upstream gas inlet  56  is provided in fluid communication with said first conduit  50 , and a downstream gas inlet  58  is provided in fluid communication with said leukocyte depletion device  45 , downstream of said filter medium  46 .  
         [0049]    An inlet clamp  60  and an outlet clamp  61  may be provided. It should be understood that one or more of inlet clamp  60  and/or outlet clamp  61  may be provided, and be well within the scope of the present invention.  
         [0050]    Upstream gas inlet  56  may take the form of a vent line  62  being connected to an upstream gas inlet housing  64 . Vent line  62  may have a U-shaped portion  62 A to prevent drawing of gas into biological fluid filtration system  44  until substantially all of the biological fluid has drained from the biological fluid container  49 . The other end of vent line  62  should be at a sufficient height such that it is always positioned above the level of the fluid in the biological fluid container  49 .  
         [0051]    Upstream gas inlet housing or vent  64  has an inlet  65  and an outlet  66 . Interposed between the inlet  65  and the outlet  66  in a sealing relationship is at least one layer of a porous medium  67 . The porous medium may be such as a bacterial retention medium, a viral retention medium, or other suitable medium.  
         [0052]    In a similar manner, the downstream gas inlet  58  may comprise a second vent line  70  connected to a downstream gas inlet housing or vent  71  having an inlet  72  and an outlet  73 . A cap or other closure  74  may be used in connection with the opening and the closing of inlet  72 . Interposed in the housing  71 , between the inlet  72  and the outlet  73  is a second porous medium  76 . The second porous medium  76  may also be such as a bacterial retention medium, a viral retention medium, or other suitable medium.  
         [0053]    As illustrated, upstream gas inlet housing  64  and downstream gas inlet housing  71  may be provided in a single novel inlet device  80  having a barrier or wall  81  which prevents fluid communication between the upstream gas inlet porous medium  67  and the downstream gas inlet porous medium  76 . The upstream medium  67  and the downstream medium  76  may then be formed of a single sheet.  
         [0054]    The upstream gas inlet  56  and the downstream gas inlet  58  may be placed in any practicable location as long as they are located such that the blood product being filtered never contacts the porous medium  67 . In the preferred embodiment illustrated the porous medium  67  contained within the housing  64  is elevated above the blood container  49 , but other locations are well within the scope of the present invention.  
         [0055]    In the method of blood processing embodying the present invention, the inlet clamp  60  and the outlet clamp  61  are initially closed. The cap or closure  74  covering the inlet  72  of downstream gas inlet device, housing, or housing portion  71  is also in place.  
         [0056]    The blood processing is initiated by opening the inlet clamp  60  and allowing the biological fluid to flow through the first conduit  50 . As the fluid flows past the junction  50 A, some of the fluid will flow into the upstream gas inlet  56  through vent line  62 . A column of liquid of a predetermined, desired, length (shown as dimension A in FIG. 2), between the junction  50 A and the bottom of the loop portion of  62 A, prevents gas entry into the system until substantially all of the biological fluid has been drained from the biological fluid container  49 .  
         [0057]    The upstream gas vent may be thought of as a manometer measuring the pressure at the junction  50 A. As the level of fluid within the biological fluid container  49  decreases, the pressure at the junction  50 A decreases and, therefore, the height of the fluid in the vent line  62  decreases. When substantially all of the biological fluid has drained from the biological fluid container  49 , the atmospheric pressure acting on the column of fluid within the vent line  62  will cause all of the fluid within the upstream gas inlet  56  to drain into the conduit  50 . The remaining fluid contained with the upstream gas inlet line  62  is drained into the conduit  50  because the upstream gas inlet is open to atmosphere. Thus, dimension A in FIG. 2 must be of sufficient distance such that the above described sequence of events occur. At this point, the leukocyte depletion device  45  downstream of the filter medium  46  and the second conduit  54  between the leukocyte depletion device  45  and the blood receiving container  52 , are all filled with filtered biological fluid.  
         [0058]    The filtered biological fluid or blood downstream of the filter medium  46  in the leukocyte depletion device  45  may now be recovered by opening the cap or closure  74  covering the inlet  72  of downstream gas inlet device, housing, or housing portion  71 . In place of cap  74 , a clamp (not shown) could be used on second vent  70 .  
         [0059]    After this step substantially all of the blood previously unrecovered by the prior art devices is in the blood receiving container  52 . Any gas in the receiving container  52  and/or second conduit  54  downstream of the disconnecting point of the blood receiving container  52  may be pushed back up into the second conduit  54  by gently squeezing the blood receiving container  52 , and then the outlet clamp  61  can be closed.  
         [0060]    As is now evident, the construction shown in FIG. 2 provides an easy method of drainage of substantially all of the biological fluid from the receiving bag  52  through the leukocyte depletion device  45 . In addition, the biological fluid filtration system  44  in its preferred embodiment utilizes only a single housing in the inlet device  80 , and a single layer of porous medium and substantially all of the filtered biological fluid is recovered. The system has a lower number of parts, is easier to manufacture, and recovers more biological fluid at a lower per unit biological fluid processing cost.  
         [0061]    Alternate embodiments of the construction shown in FIG. 2 are illustrated in FIGS.  3 - 5 , with like numerals designating corresponding parts in the several views. Their operation can easily be understood by those skilled in the art in view of the foregoing description.  
         [0062]    A modification of the present invention utilizing only the upstream gas inlet  56  and a satellite bag  83  is shown in FIG. 12. Satellite bag  83  is connected in fluid communication with blood receiving container  52  by satellite conduit  84 . Satellite clamp  85  opens and closes satellite conduit  84 . In this embodiment of the present invention, the satellite bag is used to vent the gas displaced from the receiving container  52 . The volume of the satellite bag  83  should be sufficient to accept all of the gas displaced. After all the blood has flowed into the receiving container  52 , the container is gently squeezed until all of the gas is vented past the satellite clamp  85 , at which time the satellite clamp  85  is closed.  
         [0063]    Referring now to FIG. 6, there is shown a closed loop biological fluid filtration system  90 . As in previous embodiments of the present invention, there is a leukocyte depletion device  45  having a filter medium  46 , an inlet  47 , and an outlet  48 . The filter medium  46  is interposed in a sealing relationship between the inlet  47  and the outlet  48 . The system  90  also includes a blood container  49  connected by first conduit  50  to the inlet  47  of leukocyte depletion device  45 . Inlet clamp  60  is provided as before.  
         [0064]    Provided downstream of the leukocyte depletion device  45  is a blood receiving container  52 . A second conduit  54  is connected between the outlet  48  of the leukocyte depletion device  45  and the inlet of the blood receiving container  52 . Used in place of the upstream gas inlet  56  and a downstream gas inlet  58  is a by-pass line  91 , which may be opened and closed by by-pass clamp  92 . A first end of the by-pass line  91  is connected in fluid communication with the blood container  49  proximate the outlet thereof, and the other end of the by-pass line  91  is connected in fluid communication with the blood receiving container  52  proximate the inlet thereof. The loop portion  93  of the by-pass line  91  is positioned such that when the blood container  49  is full of blood, the blood will not reach the loop portion  93  and thus, there can be no flow of blood through the by-pass line. One such position is illustrated in FIG. 6 with the loop portion  93  elevated above the blood container  49 .  
         [0065]    In place of loop portion  93 , a one way check valve or other device may be used such that a column of gas will always separate the unfiltered biological fluid upstream of the filtration device from the filtered biological fluid downstream of the leukocyte depletion device  45 . The positioning of the loop portion  93 , and the bypass line  91  may also be varied to accomplish this.  
         [0066]    The method of operating the the closed loop embodiment of the invention differs in several respects from the method used with the open loop embodiment. As illustrated in FIG. 6, the additional by-pass clamp  92  is needed because no gas inlet or gas outlet devices are provided, as were necessary in the prior art. Prior to the start of blood processing, the inlet clamp  60  is closed and the bypass clamp  92  is open. The blood processing is initiated by opening the inlet clamp  60  and allowing blood to drain from the blood container  49  through first conduit  50  into the leukocyte depletion device  45  and therethrough to the blood receiving container  52 . The blood does not by-pass the leukocyte depletion device  45  because of the loop portion  93  of the by-pass line  91  being elevated to a sufficient height. The gas within the closed loop biological fluid filtration system  90  is displaced by the blood flow into the blood receiving container  52 . As the blood container  49  approaches its nearly empty condition, the gas stored within the receiving container  52  automatically flows through the by-pass line  91  into the blood container  49  and allows substantially all of the blood to be processed through the leukocyte filtration device  45 . It is important to note that the chamber of the leukocyte depletion device  45  downstream of the filter media  46  at this point will be filled with blood, as will the second conduit  54  between the leukocyte depletion device and the blood receiving container  52 . If there is any gas left in the receiving container  52  it may be displaced into the by-pass line  91  by closing the outlet clamp  61 , gently squeezing the blood receiving container  52  and closing the by-pass clamp  92 . In this embodiment of the invention comprising the closed loop biological fluid filtration system, the chamber downstream of the filter medium  46  in the leukocyte depletion device  45  is not drained of blood, nor is second conduct  54 . However, the inlet device and the outlet devices of the prior art are eliminated, and a simplified system is provided.  
         [0067]    Additional modifications of the closed loop biological fluid filtration system  90  are shown in FIGS.  7 - 11 . Their operation can be understood by those skilled in the art from the foregoing description.  
         [0068]    Therefore, by carefully studying the problems present in prior art biological filtration fluid systems, I have developed a novel method and apparatus for biological fluid filtration.  
         [0069]    In accordance with the provisions of the patent statutes, the present invention has been described in what is considered to represent its preferred embodiment. However, it should be noted that the invention can be practiced otherwise than as specifically illustrated and described without departing from its spirit or scope.