Patent Publication Number: US-2013233810-A1

Title: High Capacity BIological Fluid Filtration Apparatus

Description:
BACKGROUND OF THE INVENTION 
     This invention relates to the filtration field, and more particularly, to an improved low hold up biological fluid filtration system, including a low hold up double sided biological fluid filter device lacking a partition wall capable of filtering biological fluids, including the removal of components or chemicals from blood or blood products, and including the removal of leukocytes from packed red cells, and prions from blood or blood products. 
     Double sided biological fluid filtration devices that include a single inlet and a single outlet with a partition wall are disclosed in patent serial no. U.S. Pat. No. 6,660,171 B2, entitled HIGH CAPACITY GRAVITY FEED FILTER FOR FILTERING BLOOD AND BLOOD PRODUCTS, filed on Mar. 27, 2001 which is hereby incorporated by reference and made a part of the disclosure herein. Double sided biological fluid filtration devices that contain a partition wall are also disclosed in patent application Ser. No. 10/934,881, entitled A BIOLOGICAL FLUID FILTRATION APPARATUS, filed on Sep. 3, 2004 which is hereby incorporated by reference and made a part of the disclosure herein. Double sided biological fluid filtration devices that contain a partition wall are also disclosed in PCT application no. PCT/US2004/029026, entitled A BIOLOGICAL FLUID FILTRATION APPARATUS, filed on Sep. 7, 2004 which is hereby incorporated by reference and made a part of the disclosure herein. Application Ser. No. 10/934,881 and application no. PCT/US2004/029026 disclose a double sided biological fluid filtration device that includes two independent fluid flow paths separated by a partition wall with each fluid flow path containing a separate inlet and outlet, thereby allowing two units of biological fluid including blood or blood product to be independently filtered. 
     U.S. Pat. No. 6,231,770 B1 describes a double sided biological fluid filtration device that lacks a partition wall that includes a single inlet and a single outlet with two fluid flow paths between the inlet and outlet. The disadvantage of this type of device is that if two units of blood or blood product are filtered through this device and collected into two separate receiving blood bags, the first unit will be filtered by the device with the filter elements of the device in a relatively non-fouled condition, and the second unit will be filtered by the device with the filter elements in a relatively fouled condition. Therefore the flow rate through the device for the first until will be faster than the flow rate for the second unit. Hence the filtration efficiency may be different between the first and second units, and when the device is used for leukocyte reduction the leukocyte reduction rate may be different for the first and second units. 
     It is therefore an object of the present invention to provide a biological fluid filtration system including a biological fluid filtration device that lacks a partition wall, and that includes a single inlet and a double outlet, that will filter two units of biological fluid including blood or blood product, with both units being filtered simultaneously at approximately the same flow rate, and that will run automatically, and minimize hold up volume. It is also an object of the present invention to provide a single vent filtration device that can vent the two fluid flow paths of a biological fluid filtration device that includes two independent fluid flow paths. 
     DEFINITIONS 
     A Double Sided Biological Fluid Filtration Device (hereinafter referred to as BFFD) as used herein means a filtration device comprising a housing containing an inlet and two outlets, with a first fluid flow path defined between the inlet and the first outlet, with a second fluid flow path defined between the inlet and the second outlet, with a first biological fluid filtration media interposed between the inlet and the first outlet and across the first fluid flow path, with the first biological fluid filtration media sealed to the housing to prevent the flow of biological fluid between the housing and the first biological fluid filtration media, with a second biological fluid filtration media interposed between the inlet and the second outlet and across the second fluid flow path, with the second biological fluid filtration media sealed to the housing to prevent the flow of biological fluid between the housing and the second biological fluid filtration media. The biological fluid filtration device being capable of filtering biological fluids, including blood or blood products to remove leukocytes, prions, other blood components, cells, and chemical agents which may be used to treat the biological fluid, from the biological fluid. 
     Biological Fluid Filtration Media (hereinafter referred to as BFFM) as used herein means a porous filtration media capable of filtering biological fluids, including blood or blood products to remove leukocytes, prions, other blood components, cells, and chemical agents which may be used to treat the biological fluid, from the biological fluid. The biological fluid filtration media (BFFM) comprises at least one filter element, with each filter element containing one or more layers of porous filter material of the same type. The biological fluid filtration media may contain more than one filter element, with each filter element containing a different type of filter material. Any of the various types of biological fluid filtration media that contain one or more filter elements of the same or different types as disclosed in patent application Ser. No. 10/934,881 or in application no. PCT/US2004/029026 may be considered as biological fluid filtration media in this application. 
     Vent Filtration Media as used herein means the filtration media used in a vent filter device. The media may be microporous filter material made from a material such as Teflon or PVDF, preferably with a pore size of 0.2μ or smaller, or the media may be a depth media, such as cotton, spun bound polyester, or a molded depth media such as Porex. 
     Housing as used herein means the enclosure into which the filtration media is sealed. The housing of a BFFD contains an inlet and two outlets, with a first fluid flow path defined between the inlet and the first outlet, with a first BFFM interposed between the inlet and the first outlet and across the first fluid flow path, and sealed to the housing to prevent the flow of biological fluid between the housing and the first BFFM; with a second fluid flow path defined between the inlet and the second outlet, with a second BFFM interposed between the inlet and the second outlet and across the second fluid flow path, and sealed to the housing to prevent the flow of biological fluid between the housing and the second BFFM. The housing does not contain a partition wall. The housing may be made from a rigid material such as stainless steel or aluminum, or from any rigid molded plastic material such as Acrylic, Polycarbonate, Polypropylene, Polyethylene. The housing of a vent filtration device contains a vent port in fluid flow communication with atmosphere, and a system port in fluid flow communication with the biological fluid filtration system, with a fluid flow path defined between the vent port and the system port, with a vent filtration media interposed between the vent port and the system port and across the fluid flow path, and sealed to the housing to prevent the flow of biological fluid or gas between the vent filtration media and the housing. 
     Biological Fluid as used herein means any type of biological liquid, including blood or blood product, and including leukocyte containing suspensions or a prion containing suspensions. 
     Leukocyte Containing Suspension as used herein means a liquid in which leukocytes are suspended. Examples of leukocyte-containing suspensions include whole blood; red cell products, such as concentrated red cells, washed red cells, leukocyte-removed cells, thawed red cell concentrate and thawed red cell suspension; plasma products, such as platelet-poor plasma, platelet-enriched plasma, fresh lyophilized plasma, fresh liquid plasma and cryoprecipitate; and other leukocyte-containing blood products, such as concentrated platelet cells, buffy coat and buffy coat-removed blood. The leukocyte-containing suspension to be filtered by the devices and systems described in the present invention is not limited to the above examples. 
     Prion Containing Suspension as used herein means a liquid in which prions are suspended. 
     Diaphragm Draining Device (hereinafter referred to as DDD) as used herein means a device having a housing with an inlet in fluid flow communication with atmosphere, with an outlet in fluid flow communication with a second device to be drained, and with a diaphragm interposed between the inlet and the outlet, with the housing containing a volume of gas between the diaphragm and the outlet in its normal state. 
     SUMMARY OF THE INVENTION 
     The foregoing problems of the prior art are solved, and the objects of the present invention are achieved, by use of a biological fluid filtration device (BFFD) and system constructed in accordance with the principles of the present invention. The biological fluid filtration system of the present invention is capable of filtering biological fluids, including blood or blood products to remove leukocytes, prions, other blood components, cells, and chemical agents which may be used to treat the biological fluid, from the biological fluid. 
     The biological fluid filtration system includes a feed container, normally a collapsible blood bag and a receiving container, normally a collapsible blood bag with a BFFD interposed between the two blood bags. The BFFD includes a housing lacking a partition wall having an inlet and two outlets, with a first fluid flow path defined between the inlet and the first outlet, with a first biological fluid filtration media (BFFM) is interposed between the inlet and the first outlet, and across the first fluid flow path; and with a second fluid flow path defined between the inlet and the second outlet, with a second biological fluid filtration media (BFFM) interposed between the inlet and the second outlet, and across the second fluid flow path. The BFFM&#39;s may contain one filter element or multiple filter elements of different types. The housing also includes a chamber located between the inlet and the upstream surface of the two BFFM&#39;s. A first flow restriction may be located downstream of the first BFFM, and a second flow restriction may be located downstream of the second BFFM. The biological fluid filtration system also includes a means to automatically drain the upstream chamber of the BFFD when the filtration cycle is complete. The draining means may include a diaphragm draining device (DDD) that includes a built in flow restriction. Any of the various types of in line automatic draining means that are disclosed in patent application Ser. No. 10/934,881 or in application no. PCT/US2004/029026 may be used as automatic draining means in this application. 
     In any of the embodiments the BFFM may include a first filter element composed of one or more layers of porous filter material of a first pore size, followed by a second filter element composed of one or more layers of porous filter material of a second pore size smaller than that of the first pore size, followed by a third filter element composed of one or more layers of porous filter material of a third pore size larger than that of the second pore size, followed by a fourth filter element composed of one or more layers of porous filter material of a fourth pore size smaller than the pore size of the second filter element. The first filter element may include means to remove gels from blood or blood product, the second filter element may include means to remove microaggregates from blood or blood products, the fourth filter element may include means to remove leukocytes from blood or blood products, while the third filter element acts as a flow distribution layer. However, the BFFM is not restricted to the type just described, any suitable type of BFFM for a particular application may be used. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The invention may be best understood by reference to the detailed description of the preferred embodiments herein when read in conjunction with the drawings in which; 
         FIG. 1  is an isometric view of a first embodiment of a biological fluid filtration system constructed in accordance with the principles of the present invention, usable for the filtration of biological fluids, containing a feed blood bag, a first receiving blood bag, a second receiving blood bag, with the first embodiment of a BFFD interposed between the feed blood bag and the receiving blood bag, and with a diaphragm draining device (DDD) that includes a built in flow restriction interposed between the feed blood bag and the BFFD; 
         FIG. 2  is a cross-sectional view of the first embodiment of a BFFD constructed in accordance with the principles of the present invention, usable for the filtration of biological fluids; 
         FIG. 3  is an isometric view of portions thereof removed of the DDD shown in  FIG. 1 ; 
         FIG. 4  is an isometric view of portions thereof removed of the housing inlet half of the BFFD shown in  FIG. 2 ; 
         FIG. 5  is an isometric view with portions thereof removed of the first housing outlet half of the BFFD shown in  FIG. 2 , the second housing outlet half is identical to the first housing outlet half; 
         FIG. 6  is a isometric view with portions thereof removed of a housing inlet half including a baffle, that can be used to replace the housing inlet half shown in  FIG. 4 ; and 
         FIG. 7  is a side view of a second embodiment of a biological fluid filtration system constructed in accordance with the principles of the present invention, usable for the filtration of biological fluids, containing a feed blood bag, a first receiving blood bag, a second receiving blood bag, with a second embodiment of a BFFD interposed between the feed blood bag and the receiving blood bags, with a diaphragm draining device (DDD) that includes a built in flow restriction interposed between the feed blood bag and the BFFD. 
     
    
    
     DETAILED DESCRIPTION OF THE FIRST EMBODIMENT 
     One embodiment of the biological fluid filtration system constructed in accordance with the principles of the present invention, is shown in  FIG. 1  through  FIG. 5 . Biological fluid filtration system  1000  shown in  FIG. 1  contains feed blood  98 , first receiving blood bag  99  and second receiving blood bag  99   a.  Interposed between feed blood bag  98  and the two receiving blood bags is a biological fluid filtration device (BFFD)  1000 . Diaphragm draining device (DDD  50 ) is interposed between feed blood bag  98  and BFFD  100 . First length of tubing  81  connects the outlet of feed blood bag  98  to the inlet tube socket  51  of DDD  50 . Second length of tubing  81   a  connects outlet tube socket tube socket  52  of DDD  50  to the inlet tube socket  6  of BFFD  100 . A third length of tubing  82  connects first outlet tube socket  28  of BFFD  100  to the inlet of first receiving blood bag  99 . A fourth length of tubing  82   a  connects second outlet tube socket  28   a  of BFFD  100  to the inlet of second receiving blood bag  99   a.  Tubing  81  may contain tube clamp  95 , tubing  82  may contain tube clamp  96 , tubing  82   a  may contain tube clamp  96   a.    
     Referring to  FIG. 2  through  FIG. 5 , BFFD  100  contains a rigid housing that includes housing inlet half  1 , first housing outlet half  20 , and second housing outlet half  20   a.  Housing seal surface  19  of housing inlet half  1  is bonded to housing seal surface  29  of first housing outlet half  20 . Housing seal surface  19   a  of housing inlet half  1  is bonded to housing seal surface  29   a  of second housing outlet half  20   a.  The bonds are preferably ultrasonic welds but could be a heat bonds, glue bonds, solvent bonds, or any other type of leak tight bonds. 
     Referring to  FIG. 2 ,  FIG. 4 , and  FIG. 5  housing inlet half  1  contains first filter well  11  bounded by inner side wall  8  and by a plane that goes through filter seal surface  7 . Housing inlet half  1  also contains second filter well  11   a  bounded by inner side wall  8   a  and by a plane that goes through filter seal surface  7   a.  Upstream chamber  13  is bounded by inner surface  10   a  of inner wall  10  of housing inlet half  1 , and by upstream surface  16   b  of filter element  16 , and by upstream surface  16   ab  of filter element  16   a.  Hence upstream chamber contains a space between the upstream surface of the first BFFM and the upstream surface of the second BFFM, with the upstream surface of the first BFFM opposing the upstream surface of the second BFFM. The first and second BFFM&#39;s are further defined below. Inlet  5  is in fluid flow communication with upstream chamber  13 . The outlet end of tubing  81   a  is inserted into and bonded to inlet tube socket  6 . Inlet  5  is shown located at the top of upstream chamber  13  and on the vertical center line of housing inlet half  1 , it could however, be located anywhere between the top and the bottom of upstream chamber  13 , and could also be located to the right or to the left of the vertical center line. 
     Referring to  FIG. 2  and  FIG. 5 , BFFD  100  contains first housing outlet half  20  and second housing outlet half  20   a.  Housing outlet half  20   a  is identical to housing outlet half  20 . Housing outlet half  20  contains circular outlet channel  25  and outlet  27 . Outlet  27  may contain a flow restriction as shown in  FIG. 2  and  FIG. 5 . Circular outlet channel  25  is in direct fluid flow communication with outlet  27 , and the portion of circular outlet channel  25  that adjoins outlet  27  has a cross-sectional flow area that is greater than the cross-sectional flow area of outlet  27 . Housing outlet half  20  also contains a plurality of open top closed bottom vertical channels  22  and  22   a.  One end of each of the vertical channels  22  and  22   a  is in fluid flow communication with circular outlet channel  25 . The upper part of circular outlet channel  25  increases in width to accommodate the flow of biological fluid from vertical channels  22  and  22   a.  The width of the remainder of circular outlet  25  (i.e. the lower part of circular outlet channel  25 ) is preferably equal to the width of the vertical channels. The two outermost vertical channels designated as vertical channels  22   a  adjoin circular outlet channel  25  where the width of circular outlet channel  25  is equal to the width of the vertical channels. The outlet channel and the vertical channels combined, create a filter under drain structure that is cut into wall  37  of housing outlet half  20  so that the inner surface of all of the channels lies below inner wall  21  of housing outlet half  20  as shown in  FIG. 5 . The cross sectional area of the outlet channel and of the vertical channels is defined by the inner surface of each channel and by the downstream surface of the BFFM. As shown in  FIG. 5 , the distance between vertical channels  22  and  22   a  is much greater than the width of vertical channels  22  and  22   a,  and the distance between vertical channels  22  and  22   a  is also much greater than the depth of vertical channels  22  and  22   a.  For example, the center line distance between the vertical channels may be equal to 0.150 in., with the width of the vertical channels equal to 0.032 in., and with the depth of the vertical channels equal to 0.025 in. Housing outlet half  20  also contains filter seal surface  24 . Because housing outlet half  20  does not contain an open chamber or plenum downstream of the BFFM, hold up volume of biological fluid will be minimized. Housing outlet half  20  of this application is identical to housing outlet half  220  that is disclosed in patent application Ser. No. 10/934,881 and in application no. PCT/US2004/029026, with the exception that housing outlet half  220  does not contain a flow restriction in the outlet. 
     Referring to  FIG. 2 , a first biological fluid filtration media (BFFM) that contains at least one filter element is interposed between inlet  5  and first outlet  27 , and is sealed to the housing to prevent the flow of unfiltered biological fluid from flowing between the housing and the first BFFM to prevent bypass of unfiltered biological fluid around the first BFFM. A second biological fluid filtration media (BFFM) that contains at least one filter element is interposed between inlet  5  and second outlet  27   a,  and is sealed to the housing to prevent the flow of unfiltered biological fluid from flowing between the housing and the second BFFM to prevent bypass of unfiltered biological fluid around the second BFFM. The first BFFM shown in  FIG. 2  contains filter elements  16  and  18 . The filter elements may all be of the same type or may be different types filter elements. For example filter element  16  may be a microaggregate filter element and filter elements  18  may be leukocyte removing filter elements. Each filter element contains an upstream surface designated as upstream surface  16   b  for filter element  16 , a downstream surface designated as downstream surface  16   c  for filter element  16 , and a perimeter surface designated as perimeter surface  16   d  for filter element  16 . The downstream surface of the BFFM shown as downstream surface  18   c  of filter element  18  is in contact with inner wall  21  of housing outlet half  20 . Because the downstream surface of the BFFM contacts inner wall  21  of housing outlet half  20 , BFFD  100  does not contain an open chamber or plenum downstream of the BFFM. The air or liquid that is forced through the BFFM must pass through the vertical channels and the circular outlet channel before flowing into outlet  27  of BFFD  100 . The at least one filter element may be sealed to the housing with an interference fit between the perimeter surface of the at least one filter element and inner side wall  8  of housing inlet half  1  as shown for filter elements  18 , or the at least one filter element may be sealed to the housing with a compression seal by compressing the outer periphery of the at least one filter element with filter seal surface  7  of housing inlet half  1  as shown for filter element  16 , or the at least one filter element may be sealed to the housing using a heat seal, an ultrasonic weld, a glue seal, a solvent seal, a radio frequency weld, or any other type of leak tight seal. A combination of sealing methods may also be used to seal the at least one filter element to the housing. The second BFFM is preferably the same as the first BFFM and is preferably sealed to the housing the same way that the first BFFM is sealed to the housing. Any of the filter element combinations that are disclosed in patent application Ser. No. 10/934,881 and in application no. PCT/US2004/029026, can also be used in the present invention. For example a gel filter element followed by a microaggregate filter element, followed by a flow distribution filter element, followed by a leukocyte removing filter element could be used in the present invention. 
     Referring to  FIG. 2  and  FIG. 5 , a first fluid flow path is defined between inlet  5  of BFFD  100  and first outlet  27  of BFFD  100  with the at least one filter element of the first BFFM interposed between inlet  5  and first outlet  27 , and across the fluid flow path. The first fluid flow path flows from inlet  5 , into upstream chamber  13 , through the at least one filter element of the first BFFM, into vertical channels  22  and  22   a,  into circular outlet channel  25 , and then into outlet  27  which may contain a flow restriction, all of first housing outlet half  20 . A second fluid flow path is defined between inlet  5  of BFFD  100  and second outlet  27   a  of BFFD  100  with the at least one filter element of the second BFFM interposed between inlet  5  and second outlet  27   a,  and across the second flow path. The second fluid flow path flows from inlet  5 , into upstream chamber  13 , through the at least one filter element of the second BFFM, into vertical channels  22  and  22   a,  into circular outlet channel  25 , and then into outlet  27   a  which may contain a flow restriction, all of second housing outlet half  20   a.    
       FIGS. 1  and  FIG. 3  show diaphragm draining device  50  (hereinafter referred to as DDD  50 ). DDD  50  contains rigid housing inlet half  58 , rigid housing outlet half  59  and flexible diaphragm  53 . Housing outlet half  59  contains inlet tube socket  51 , outlet tube socket  52 , first channel  54 , second channel  55 , third channel  56 , and common node  60 . Common node  60  (shown as a dot) places each one of the three channels in fluid flow communication with the other two channels. Second channel  55  contains a flow restriction shown as a channel that is longer and smaller in diameter than the first and third channels. The first channel may be referred to as inlet  54 , the second channel may be referred to as outlet  55 , and the third channel may be referred to as side port  56 . Housing outlet half  59  combines three tube connector  1650  and housing outlet half  1820  that are disclosed in patent application Ser. No. 10/934,881 and in application no. PCT/US2004/029026 into a single component. The shape of the three tube connector made up of first channel  54 , second channel  55 , and third channel  56 , is shown as a tee, but is not restricted to this shape, it could be in the form of a Y, for example.  FIG. 3  shows DDD  50  in its normal state with housing inlet half  58  sealed to housing outlet half  59 . The seal is preferably an ultrasonic seal, but could be a heat seal, a solvent seal, a glue seal, or a compression seal between housing inlet half  58  and housing outlet half  59 , or any other type of leak tight seal. Flexible diaphragm  53  may be molded from a flexible rubber material such as silicone rubber, or it may be molded or thermo formed from a material such as PVC, polyethylene, or polypropylene, but is not limited to these materials. Flexible diaphragm  53  is preferably shaped so that in its normal state outer surface  66  conforms to inner surface  67  of housing inlet half  58 . Flexible diaphragm  53  contains flange  58  which may be bonded to housing inlet half  58  or to housing outlet half  59 . The bond may be a heat bond, an ultrasonic bond, a glue bond, a solvent bond, or any other type of leak tight bond. Alternatively, flange  68  may be compression sealed between housing inlet half  68  and housing outlet half  59 .  FIG. 3  shows DDD  50  in its normal state with outer surface  66  of diaphragm  53  in contact with inner surface  67  of housing inlet half  58 . In its normal state, DDD  50  contains chamber  63  that is in fluid flow communication with third channel  56 . In the normal state chamber  63  is filled with a gas (normally sterile air) at atmospheric pressure. When diaphragm  53  is completely collapsed inner surface  69  of diaphragm  53  will contact inner surface  70  of housing outlet half  59 . 
     Referring to  FIG. 1  through  FIG. 3 , a third fluid flow path is defined between feed blood bag  98  and common node  60  of housing outlet half  59  of DDD  50 , with the flow in the third fluid flow path flowing from feed blood bag  98  through tubing  81 , into inlet  54  of DDD  50 , to common node  60 . A fourth fluid flow path is defined between common node  60  of DDD  50  and inlet  5  of BFFD  100 , with the flow in the fourth fluid flow path flowing from common node  60 , through outlet  55  of DDD  50  (including the flow restriction), through tubing  81   a,  to inlet  5  of BFFD  100 . A fifth fluid flow path is defined between the common node and chamber  63  of DDD  50 , with the flow of the fifth fluid flow path flowing from chamber  63 , through third channel  56 , to the common node  60 . 
     Referring to  FIG. 1  through  FIG. 5 , biological fluid filtration system  1000  functions as follows. The user will purchase the system with all components as shown in  FIG. 1 , less feed blood bag  98 . The user will connect tubing  81  to outlet  92  of feed blood bag  98  in a manner known in the art. Feed blood bag  98  may be hung from a hook on a blood bag pole, and first receiving blood bag  99  and second receiving blood bag  99   a  may be placed on a table top or the like, so that the various components of the system will be positioned as shown in  FIG. 1 . Alternatively feed blood bag  98  may be part of a set that includes all of the components shown in  FIG. 1 , in which case the blood or blood product that is collected from a donor will be collected in feed blood bag  98 . Tube clamp  95  should be closed before connecting tubing  81  to feed blood bag  98 . Before opening tube clamp  95  to start the flow of biological fluid (i.e. liquid) through the system, tube clamps  96  and  96   a  should be open. 
     When tube clamp  95  is opened biological fluid (i.e. liquid) will flow from feed blood bag  98 , through tubing  81 , into inlet  54  of DDD  50 , through outlet  55  of DDD  50 , through tubing  81   a,  into inlet  5  of BFFD  100 , into upstream chamber  13  of BFFD  1000 . Because outlet  55  of DDD  50  contains a flow restriction, the flow downstream of the inlet and downstream of the side port of the DDD will be automatically restricted, and a positive pressure will be created at common node  60  of DDD  50 . Also because flexible diaphragm  53  is sealed to DDD  50  with a liquid/air tight seal, air can not escape through inlet  57  of DDD  50 . Therefore the air in chamber  63  of DDD  50  will be pressurized so that only a very small quantity of biological fluid if any will enter side port  56  of DDD  50 . 
     Once tube clamp  95  is opened, one of four conditions can occur. The first condition is: If the volume of upstream chamber  13  is small enough, and if the initial combined flow rate of the first and second BFFM&#39;s does not exceed the flow rate of the biological fluid entering inlet  5 , upstream chamber  13  of BFFD  100  will rapidly fill with biological fluid from the bottom up. As upstream chamber  13  fills from the bottom up, the initial air in upstream chamber  13  will be displaced by the biological fluid filling upstream chamber  13 . A portion of the displaced air will be forced through the first BFFM, into vertical channels  22  and  22   a,  into circular outlet channel  25 , and then into outlet first  27 , all of first housing outlet half  20 . The remainder of the displaced air will be forced through the second BFFM, into vertical channels  22  and  22   a,  into circular outlet channel  25 , and then into second outlet  27   a,  all of second housing outlet half  20   a.  The biological fluid in upstream chamber  13  will be pressurized, with the pressure at the bottom of upstream chamber  13  being proportional to the distance from the top of the biological fluid in feed blood bag  98  to the bottom of upstream chamber  13 , and with the pressure at the top of upstream chamber  13  being proportional to the distance from the top of the biological fluid in feed blood bag  98  to the top of upstream chamber  13 . Hence the pressure at the top of upstream chamber  13  will be less than the pressure at the bottom of upstream chamber  13 . The positive pressure in upstream chamber  13  will cause the biological fluid to flow through the first and second BFFM&#39;s over the entire surface area of the first and second BFFM&#39;s and to displace the air within the pores of the first and second BFFM&#39;s with biological fluid, thereby wetting the first and second BFFM&#39;s from the upstream side of the first and second BFFM&#39;s to the downstream side of the first and second BFFM&#39;s. As the BFFM&#39;s wet the air that was initially in the pores of BFFM&#39;s will be displaced by biological fluid and flow into the vertical channels  22  and  22   a,  and into circular outlet channel  25 , of the respective housing outlet half&#39;s, and then into outlet  27  of housing outlet half  20  and outlet  27   a  of housing outlet half  20   a,  into tubing  82 , and then into first receiving blood bag  99 , and into tubing  82   a,  and then into second receiving blood bag  99   a.  Because the pressure at the bottom of upstream chamber  13  is greater than the pressure at the top of upstream chamber  13 , the initial flow rate of biological fluid through the BFFM&#39;s will be greater at the bottom of the BFFM&#39;s than at the top of the BFFM&#39;s. Therefore, the BFFM&#39;s will first become completely wetted from the upstream surface of the BFFM&#39;s to downstream surface of the BFFM&#39;s at the bottom of the BFFM&#39;s. If the width of vertical channels  22  and  22   a  of the respective housing outlet half&#39;s is sufficiently small, and the depth of vertical channels  22  and  22   a  is sufficiently shallow, so that the cross-sectional flow area of vertical channels  22  and  22   a  is sufficiently small, and if the distance between vertical channels  22  is sufficiently large, the path of least resistance for continued biological fluid flow through the BFFM&#39;s will be through the capillaries of the BFFM&#39;s in both the horizontal and vertical directions and not through the vertical channels; because if the cross-sectional flow area of the vertical channels is sufficiently small, the displaced air flowing into and through the vertical channels will create a sufficiently high positive pressure in the vertical channels to prevent biological fluid from entering the vertical channels. The downstream surface of the BFFM&#39;s will therefore wet from the bottom up and the displaced air that was within the BFFM&#39;s will continue to flow into the vertical channels, and into the circular outlet channel, and then into the outlets. When the downstream surface of the respective BFFM&#39;s has become wetted to the level of the top of vertical channels  22   a,  air flow through the two outermost vertical channels  22   a  will stop because the downstream surface of the BFFM&#39;s below the top of the two outermost vertical channels will be wetted. Therefore the pressure in the two outermost vertical channels will decrease allowing biological fluid to enter the two outermost vertical channels from the bottom up, thereby displacing the air that was in the two outermost vertical channels. At the same time the wetted level of the downstream surface of the BFFM&#39;s will continue to wet in the vertical direction, wetting the downstream surface of the BFFM&#39;s adjoining the respective circular outlet channel&#39;s  25 . Because the cross-sectional flow area of the top of circular outlet channel&#39;s  25  is not sufficiently small to create a positive pressure in them due to the air flow through them, biological fluid will begin to flow into vertical channels  22  and into the top of circular outlet channel&#39;s  25  of BFFM&#39;s continue to wet in the vertical direction. The biological fluid flowing into vertical channels  22  and  22   a,  and into circular outlet channel&#39;s  25  will flow into the respective outlets  27  and  27   a  of BFFD  100  and then into tubing  82  toward receiving blood bag  99 , and into tubing  82   a  toward receiving blood bag  99   a.  As biological fluid starts to flow into outlets  27  and  27   a,  the first and second BFFM&#39;s will continue to wet vertically. Hence the initial flow through circular outlet channel&#39;s  25 , and through outlet  27  and  27   a,  will first be air, and then be a mixture of air and biological fluid, and finally biological fluid only, so that the initial flow into tubing  82  and  82   a  will be first air and then consist of alternate segments of biological fluid and air, and finally consist of biological fluid only. Once the BFFM&#39;s have been wetted, the flow of biological fluid through them will be uniform over their entire surface area so that the entire surface area of the BFFM&#39;s will be used to filter the biological fluid, thereby utilizing the BFFM&#39;s most efficiently. The present invention is not limited to the filter underdrain shown in  FIG. 5 . For example any of the filter underdrains disclosed in patent application Ser. No. 10/934,881, or in application no. PCT/US2004/029026, or in U.S. Pat. No. 6,660,171 could also be used in the present invention. 
     The second condition that can occur after tube clamp  95  is opened is: BFFD  100  will wet as described in the first condition above, with the initial flow rates (i.e. the flow rates before the BFFM&#39;s have been wetted) being as described in the first condition. However, once the BFFM&#39;s have been wetted with biological fluid the flow rate through the BFFM&#39;s may increase so that the combined flow rate through the first and second BFFM will exceed the flow rate of biological fluid entering chamber  13  through inlet  5 . In this case biological fluid will initially fill chamber  13  from the bottom to the top, and then after BFFM&#39;s have been wetted, the liquid level in chamber  13  will drop to a level below the top of chamber  13 . Hence, once the BFFM&#39;s have been wetted the flow rate of biological fluid through the portion of the BFFM&#39;s below the top of the liquid level in chamber  13  will be much greater than the flow rate of biological fluid through the portion of the BFFM&#39;s above the top of the liquid level in chamber  13 , so that the portions of the BFFM&#39;s above the liquid level will not be properly utilized. If BFFD  100  is used to remove leukocytes from blood or blood product, the leukocyte removing capability of the BFFM&#39;s may be reduced in the second condition when measured against the first condition above. Hence in the second condition the filtered blood or blood product in the receiving blood bag&#39;s may contain more leukocytes than the filtered blood or blood product in the receiving blood bag&#39;s under the first condition. The second condition can be rectified by adding flow restrictions to first outlet  27  and second outlet  27   a  as shown in  FIG. 2 . The flow restrictions should be sized so that the combined flow rate of biological fluid through the first and second BFFM&#39;s, and therefore through outlets  27  and  27   a,  is less than or equal to the flow rate of biological fluid entering chamber  13  through inlet  5 . The flow restrictions could be located anywhere downstream of the BFFM&#39;s. For example a first flow restriction could be located in tubing  82  between outlet  27  and first receiving blood bag  99 , and a second flow restriction could be located in tubing  82   a  between outlet  27   a  and second receiving blood bag  99   a.  Alternately all or part of tubing  82  and tubing  82   a  could have a smaller inside diameter than tubing  81  and tubing  81   a  to create the restrictions downstream of the first and second BFFM&#39;s respectively. Flow restrictions could also be used downstream of the BFFM in a single sided BFFD. A flow restriction could be added downstream of the BFFM in any of the single sided devices disclosed in patent application Ser. No. 10/934,881 or in application no. PCT/US2004/029026. 
     The third condition that can occur after tube clamp  95  is opens, is: If the volume of upstream chamber  13  is large enough, the BFFM&#39;s will be wetted before the liquid level in upstream chamber reaches the top of upstream chamber  13 , by a combination of liquid flow through the BFFM&#39;s below the liquid level in upstream chamber  13 , and capillary wetting above the liquid level, thereby allowing the air to be purged from the BFFM&#39;s. Once the BFFM&#39;s have been wetted, the air in upstream chamber  13  above the liquid level will be trapped in upstream chamber  13 , because the wetted BFFM&#39;s will not allow this air to be purged from upstream chamber  13 . Once the BFFM&#39;s have been wetted the flow rate of biological fluid through the portion of the BFFM&#39;s below the top of the liquid level in chamber  13  will be much greater than the flow rate of biological fluid through the portion of the BFFM&#39;s above the top of the liquid level in chamber  13 , so that the portions of the BFFM&#39;s above the liquid level will not be properly utilized. If BFFD  100  is used to remove leukocytes from blood or blood product, the leukocyte removing capability of the BFFM&#39;s may be reduced in the third condition when measured against the first condition above. Hence in the third condition the filtered blood or blood product in the receiving blood bag&#39;s may contain more leukocytes than the filtered blood or blood product in the receiving blood bag&#39;s under the first condition. The third condition can be rectified by reducing the volume of upstream chamber  13 . Referring to  FIG. 4 , the width of inner surface  10   a  of housing inlet half  1  (i.e. the distance between filter seal surface  7  and filter seal surface  7   a ) must be made sufficiently wide if the cross-sectional area of inlet  5  is to be made large enough so as not to restrict the flow of biological fluid through inlet  5 . In this case the volume of upstream chamber  13  may be minimized by adding baffle  12  to inner wall  10  of housing inlet half  1   a,  as shown in  FIG. 6 . Baffle  12  extends from one side of inner wall  10  to the other side of inner wall  10 . Baffle  12  may contain filter support ribs  15  located on its first surface  9 , and filter support ribs  15   a  located on its second surface  9   a  as shown in  FIG. 6 . Housing inlet half  1   a  is identical to housing inlet half  1  with the exceptions that baffle  12  has been added to housing inlet half  1   a,  and the cross-sectional area of inlet  5   a  has been increased so that its cross-sectional area of inlet  5   a  will be greater than or equal to the cross-sectional area of the interior of tubing  81   a  shown in  FIG. 1 , and the width of inner wall  10   a  has been increased. However, the volume of upstream chamber  13  of housing inlet half  1   a,  will be less than the volume of upstream chamber  13  of housing inlet half  1 , because of the volume taken up by baffle  12  and filter support ribs  15  and  15   a.  Baffle  12  does not act as a partition wall to divide upstream chamber  13  into two distinct and separate chambers, because of the gaps  14  and  14   a  above and below the top and bottom respectively, of baffle  12 . The combined cross-sectional area of the two gaps should be large enough to prevent upstream chamber  13  from being divided into two separate distinct chambers. The cross-sectional area of each gap is defined as the cross-sectional area of the gap measured in a plane that passes through the center of the baffle and that is parallel to filter seal surface  7  and filter seal surface  7   a.  The only purpose for adding baffle  12  to the housing inlet half is to reduce the volume of upstream chamber  13 , and to add filter support ribs  15  and  15   a  which provide a means to keep the two BFFM&#39;s properly separated. The filter support ribs could be replaced with an array of filter support pins, or by other means. Although the baffle shown in  FIG. 6  has a first gap at the top and a second gap at the bottom, a single gap at the top or bottom or anywhere in between that prevents the baffle from acting as a partition wall to divide upstream chamber  13  into two distinct and separate chambers will suffice. The gap may also be referred to as an aperture. 
     The fourth condition that can occur after tube clamp  95  is opens, is: If the initial combined flow rate of the first and second BFFM&#39;s exceeds the flow rate of the biological fluid entering inlet  5 , the BFFM&#39;s will be wetted before the liquid level in upstream chamber reaches the top of upstream chamber  13 , by a combination of liquid flow through the BFFM&#39;s below the liquid level in upstream chamber  13 , and capillary wetting above the liquid level, thereby allowing the air to be purged from the BFFM&#39;s. Once the BFFM&#39;s have been wetted, the air in upstream chamber  13  above the liquid level will be trapped in upstream chamber  13 , because the wetted BFFM&#39;s will not allow this air to be purged from the upstream chamber  13 . Once the BFFM&#39;s have been wetted the flow rate of biological fluid through the portion of the BFFM&#39;s below the top of the liquid level in chamber  13  will be much greater than the flow rate of biological fluid through the portion of the BFFM&#39;s above the top of the liquid level in chamber  13 , so that the portions of the BFFM&#39;s above the liquid level will not be properly utilized. If BFFD  100  is used to remove leukocytes from blood or blood product, the leukocyte removing capability of the BFFM&#39;s may be reduced in the fourth condition when measured against the first condition above. Hence in the fourth condition the filtered blood or blood product in the receiving blood bag&#39;s may contain more leukocytes than the filtered blood or blood product in the receiving blood bag&#39;s under the first condition. The fourth condition can be rectified by reducing the initial flow rate through the BFFM&#39;s, by reducing the surface area of the BFFM&#39;s, or by increasing the resistance to flow through the BFFM&#39;s, or both. 
     Referring to  FIG. 1  through  FIG. 5 , once all of the air has been purged from the first and second fluid flow paths within BFFD  100 , biological fluid will continue to flow through the first fluid flow path from inlet  5  of BFFD  100  to first outlet  27  of BFFD  100 , and then through tubing  82  into first receiving blood bag  99 , and through the second fluid flow path from inlet  5  of BFFD  100  to second outlet  27   a  of BFFD  100 , and then through tubing  82   a  into second receiving blood bag  99   a  until feed blood bag  98  is emptied of biological fluid. Adding flow restrictions to outlets  27  and  27   a,  as shown in  FIG. 2 , will assure that the flow of biological fluid through the first and second BFFM&#39;s will be balanced, and therefore both BFFM&#39;s will be properly utilized, and the filtered biological fluid in receiving blood bag  99  and in receiving blood bag  99   a  will be of the same quality. Once feed blood bag  98  has been emptied, feed blood bag  98  will be collapsed, effectively sealing the top of tubing  81 , thereby preventing the flow of biological fluid in tubing  81 . If first receiving blood bag  99  and second receiving blood bag  99   a  are positioned at a level that is sufficiently lower than BFFD  100 , the pressure downstream of the first and second BFFM&#39;s will be negative. Once feed blood bag  98  collapses and biological fluid flow through the first and second fluid flow path&#39;s stop, the differential pressure across the first BFFM and second BFFM will become zero, hence the pressure in upstream chamber  13 , and in the interior of tubing  81   a,  and in outlet  55 , side port  56  and chamber  63  of DDD  50  will become negative. Because the outer surface  66  of flexible diaphragm  53  is at atmospheric pressure via inlet  57  of DDD  50 , the suction force (i.e. negative pressure) will automatically drain the biological fluid from the side port  56 , and from outlet  55  of DDD  50 , and from tubing  81   a,  and from upstream chamber  13 , through the BFFM&#39;s, through outlet&#39;s  27  and  27   a  of BFFD  100  through tubing  82  and  82   a,  into receiving blood bag&#39;s  99  and  99   a.  The suction force will automatically cause flexible diaphragm  53  to collapse so that the air that was in chamber  63  of DDD  50  will displace the biological fluid being drained from upstream of the BFFM&#39;s. As long as the volume of chamber  63  of DDD  50  is greater than or equal to the volume of biological fluid being drained, all of the biological fluid will be automatically drained as just described. If the volume of chamber  63  of DDD  50  is greater than the volume of biological fluid being drained, then flexible diaphragm  53  will only partially collapse. When the filtration cycle is complete, biological fluid will remain within the BFFM&#39;s, and in the filter under drain structure&#39;s of the first and second housing outlet half&#39;s, and in tubing  82  and  82   a.  Although DDD  50  is used as an automatic draining means in biological fluid filtration system  1000 , any other automatic draining means could be used, including any of the automatic draining means disclosed in patent application Ser. No. 10/934,881 or in application no. PCT/US2004/029026. 
     A single sided BFFD with a single inlet and a single outlet, with a fluid flow path defined between the inlet and the outlet, with a BFFM interposed between the inlet and the outlet, and across the fluid flow path can benefit by adding a flow restriction downstream of the BFFM. If for example the single sided BFFD is used to remove leukocytes from a biological fluid, the initial flow rate of the biological fluid through the BFFM will start out high and decrease as the BFFM fouls. If the initial flow rate is too high the leukocyte removing capability of the BFFM may be reduced, so that fewer leukocytes per unit volume of filtered biological fluid will be removed from the biological fluid initially, than will be after the flow rate has been reduced due to fouling. In this case restricting the flow of biological fluid through the BFFD by using a restriction downstream of the BFFM will produce a more uniform flow rate through the BFFM throughout the entire filtration cycle, thereby increasing the leukocyte removal rate. In this case a single sided BFFD will have a single inlet and a single outlet, with a fluid flow path defined between the inlet and the outlet, with a BFFM interposed between the inlet and the outlet, and across the fluid flow path, with a flow restriction located downstream of the BFFM, with the fluid flow path flowing through the flow restriction. 
     A double sided BFFD that lacks a partition wall, that includes a single inlet and a single outlet, with a first fluid flow path defined between the inlet and the outlet, with a first BFFM interposed between the inlet and the outlet, and across the first fluid flow path, with a second fluid flow path defined between the inlet and the outlet, with a second BFFM interposed between the inlet and the outlet, and across the second fluid flow path, can benefit by adding a flow restriction downstream of the first and second BFFM&#39;s. If for example such a double sided BFFD is used to remove leukocytes from a biological fluid, the initial flow rate of the biological fluid through the BFFM&#39;s will start out high and decrease as the BFFM&#39;s foul. If the initial flow rate is too high the leukocyte removing capability of the BFFM&#39;s may be reduced, so that fewer leukocytes per unit volume of filtered biological fluid will be removed from the biological fluid initially, than will be after the flow rate through the BFFM&#39;s has been reduced due to fouling. In this case restricting the flow of biological fluid through the BFFD by using a restriction downstream of both the BFFM&#39;s will produce a more uniform flow rate through the BFFM&#39;s throughout the entire filtration cycle, thereby increasing the leukocyte removal rate. In this case a double sided BFFD that lacks a partition wall will have a single inlet and a single outlet, with a first fluid flow path defined between the inlet and the outlet, with a first BFFM interposed between the inlet and the outlet, and across the first fluid flow path, with a second fluid flow path defined between the inlet and the outlet, with a second BFFM interposed between the inlet and the outlet, and across the second fluid flow path, with a flow restriction located downstream of both the first and second BFFM&#39;s, with the first and second fluid flow paths flowing through the flow restriction. 
     A double sided BFFD, such as the ones disclosed in U.S. Pat. No. 6,660,171, and in U.S. patent application Ser. No. 10/934,881, that include a partition wall, and that include a single inlet and a single outlet, with a first fluid flow path defined between the inlet and the outlet, with a first BFFM interposed between the inlet and the outlet, and across the first fluid flow path, with a second fluid flow path defined between the inlet and the outlet, with a second BFFM interposed between the inlet and the outlet, and across the second fluid flow path, can benefit by adding a flow restriction downstream of the first and second BFFM&#39;s. If for example such a double sided BFFD is used to remove leukocytes from a biological fluid, the initial flow rate of the biological fluid through the BFFM&#39;s will start out high and decrease as the BFFM&#39;s foul. If the initial flow rate is too high the leukocyte removing capability of the BFFM&#39;s may be reduced, so that fewer leukocytes per unit volume of filtered biological fluid will be removed from the biological fluid initially, than will be after the flow rate through the BFFM&#39;s has been reduced due to fouling. In this case restricting the flow of biological fluid through the BFFD by using a restriction downstream of both the BFFM&#39;s will produce a more uniform flow rate through the BFFM&#39;s throughout the entire filtration cycle, thereby increasing the leukocyte removal rate. In this case a double sided BFFD that includes a partition wall will have a single inlet and a singlet outlet, with a first fluid flow path defined between the inlet and the outlet, with a first BFFM interposed between the inlet and the outlet, and across the first fluid flow path, with a second fluid flow path defined between the inlet and the outlet, with a second BFFM interposed between the inlet and the outlet, and across the second fluid flow path, with a flow restriction located downstream of both the first and second BFFM&#39;s, with the first and second fluid flow paths flowing through the flow restriction. 
     A double sided BFFD, such as the ones disclosed in patent application Ser. No. 10/934,881 or in application no. PCT/US2004/029026, that include a solid partition wall, and that include two inlets and two outlets, with a first fluid flow path defined between the first inlet and the first outlet, with a first BFFM interposed between the first inlet and the first outlet, and across the first fluid flow path, with a second fluid flow path defined between the second inlet and the second outlet, with a second BFFM interposed between the second inlet and the second outlet, and across the second fluid flow path, can benefit by adding a first flow restriction downstream of the first BFFM, and a second flow restriction downstream of the second BFFM. If for example such a double sided BFFD is used to remove leukocytes from a single or two independent biological fluid sources, the initial flow rate of the biological fluid or fluids through the first and second BFFM&#39;s will start out high and decrease as the BFFM&#39;s foul. If the initial flow rate is too high through either of the BFFM&#39;s, the leukocyte removing capability of the BFFM&#39;s may be reduced, so that fewer leukocytes per unit volume of filtered biological fluid or fluids through either fluid flow path will be removed from the biological fluid or fluids initially, than will be after the flow rate through the BFFM&#39;s has been reduced due to fouling. In this case restricting the flow of biological fluid or fluids through the first and second flow paths of the BFFD by using a first flow restriction downstream of the first BFFM, and a second flow restriction downstream of the second BFFM will produce a more uniform flow rate through both of the BFFM&#39;s throughout the entire filtration cycle, thereby increasing the leukocyte removal rate through both BFFM&#39;s. In this case a double sided BFFD that includes a solid partition wall will have first inlet and a first outlet, with a first fluid flow path defined between the first inlet and the first outlet, with a first BFFM interposed between the first inlet and the first outlet, and across the first fluid flow path, with a second fluid flow path defined between the second inlet and the second outlet, with a second BFFM interposed between the second inlet and the second outlet, and across the second fluid flow path, with a first flow restriction located downstream of the first BFFM, with a second flow restriction located downstream of the second BFFM with a first fluid flow path flowing through the first flow restriction, and with the second fluid flow path flowing through the second flow restriction. 
     A double sided BFFD, with or without a partition wall that includes a single inlet and a single outlet, with a first fluid flow path defined between the inlet and the outlet, with a first BFFM interposed between the inlet and the outlet, and across the first fluid flow path, with a second fluid flow path defined between the inlet and the outlet, with a second BFFM interposed between the inlet and the outlet, and across the second fluid flow path, can benefit by adding two flow restrictions downstream of the outlet as shown in  FIG. 7 . Referring to  FIG. 7 , double sided BFFD  200  may or may not contain a partition wall. The outlet of BFFD  200  is in fluid flow communication with the inlet of tee  70  via tubing  82   b.  Side arm  70   a  of tee  70  is in fluid flow communication with the inlet of receiving blood bag  99  via tubing  82   c,  and side arm  70   b  of tee  70  is in fluid flow communication with the inlet receiving blood bag  99   a  via tubing  82   d.  A first restriction may be included in side arm  70   a  or in tubing  82   c,  while a second restriction may be included in side arm  70   b  or in tubing  82   d.  If the first and second restrictions provide equal back pressure to biological fluid flow from tubing  82   b,  then equal amounts of filtered biological fluid will flow into the two receiving blood bags. Furthermore as in the above cases, the two restrictions will restrict the flow of biological fluid through the BFFD, thereby producing a more uniform flow rate through the BFFM&#39;s throughout the entire filtration cycle, thereby increasing the leukocyte removal rate. 
     Although the filter underdrain structure shown in  FIG. 5  is used in BFFD  100  shown in  FIGS. 1 and 2 , any other type of filter underdrain structure that provides the proper support for the BFFM can be used. 
     Although the present invention has been shown and described in terms of specific preferred embodiments, it will be appreciated by those skilled in the art that changes or modifications are possible which do not depart from the inventive concepts described and taught herein. Such changes and modifications are deemed to fall within the purview of these inventive concepts. Any combination of the various features of the described embodiments are deemed to fall within the purview of these inventive concepts.