Patent Publication Number: US-2007119780-A1

Title: Prechargable fluid filtration method and apparatus

Description:
BACKGROUND OF THE INVENTION  
      1. Field of the Invention  
      The present invention relates to a method and apparatus for processing fluids. More particularly, the present invention relates to a method and apparatus for processing biological fluids, such as donated blood, into 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 an improved ventless system to substantially increase the recovery of all the blood products from the donated blood or prepared blood component.  
      2. Discussion of the Related Art  
      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.  
      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.  
      U.S. Pat. No. 5,451,321 to Matkovich shows a blood processing system for the processing of blood or a blood component into valuable blood products having a first container, a second container downstream of the first container, a transfer line communicating between the first container and the second container, a leukocyte depletion filter carried in the transfer line between the first container and the second container, and having a gas outlet carried in the transfer line downstream of the leukocyte depletion filter and upstream of the second container.  
      U.S. Pat. No. 5,472,621 to Matkovich shows a method and apparatus for treating transition zone material having a first container, a second container downstream of the first container, and a red cell barrier medium, which may be interposed between the first container and the second container. The red cell barrier medium may also be interposed between the second container and a third container. A gas collection and displacement loop is connected between the upstream side and the downstream side of the red cell barrier medium.  
      U.S. Pat. No. 5,527,472 to Bellotti, et al. shows systems and methods for processing blood which direct blood through the inlet of a separation device for removing undesired matter while directing the blood substantially free of undesired matter from the outlet of the separation device and into a collection container through the first port.  
      U.S. Pat. No. 5,863,436 to Matkovich shows a sterile blood processing system for the post donation processing of donated blood into valuable blood products having a first container, a second container downstream of the first container, and a leukocyte depletion filter in fluid communication with, and interposed between, the first container and the second container and having a gas inlet for allowing gas to reach the leukocyte depletion filter and displace the blood from the leukocyte depletion device, wherein the inlet is disposed between the leukocyte depletion device and the first container.  
      U.S. Pat. No. 6,802,425 B2 to Zia, et al. shows open and closed loop biological fluid processing systems which all share the concept that the gases transferred into, or 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/or downstream gas inlet or outlet housings or vents, or bypassing the fluid filtration device.  
      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, and they all requires gas venting devices or bypass lines of one sort or another, which makes them more complicated, and thus more expensive.  
      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.  
     SUMMARY OF THE INVENTION  
      The problems of the prior art are solved by the present invention by utilizing a novel ventless and prechargable fluid processing system. The prior art systems are vented systems because it is known for a fluid to drain out of non-collapsible components in a biological fluid processing system such as a blood bag, gas must be transferred behind a column of fluid to allow it to drain from the system. Therefore, various venting arrangements have been devised in the prior art to address this issue. However, some of the prior art devices leave a large amount of biological fluid trapped in the various elements of the fluid processing system, and they are relatively complicated and expensive to manufacture. The present invention has solved the problem in the prior art by providing a ventless system which provides for increased recovery of biological fluid by providing drainage of substantially all collapsible and non-collapsible components. By utilizing the novel idea of precharging the system with a quantity of gas, predetermined components of the system may be drained.  
      In one embodiment of the present invention, a fluid filtration apparatus is provided which includes a fluid filtration device having and inlet and an outlet, a first biological fluid container upstream from the fluid filtration device and having an outlet, a first conduit in fluid communication with the outlet of the first biological fluid container and the inlet of the fluid filtration device, a biological fluid receiving container downstream of the fluid filtration device and having an inlet, and a second conduit in fluid communication with the inlet of said receiving container and the outlet of said fluid filtration device. To filter a fluid using the apparatus, a precharge or excess of gas is introduced into the first biological fluid, or upstream, fluid container. The fluid in the first biological fluid container is passed through the fluid filtration device into the receiving container (by methods known in the art, such as gravitational draining) to remove undesired impurities or contaminant. Since the first biological fluid container contains a precharge or excess gas, excess gas may enter the upstream tubing and drain the fluid from desired components. It is preferred that the excess or precharge of gas be introduced or injected into the upstream fluid container shortly before the fluid is to be filtered because of the undesirability of having a gas, such as air, in contact with some types of fluid.  
      In another embodiment of the present invention, a fluid filtration apparatus is provided which includes a fluid filtration device having and inlet and an outlet, a fluid container upstream from the fluid filtration device and having an outlet, a first conduit in fluid communication with the outlet of the fluid container and the inlet of the fluid filtration device, a receiving container downstream of the fluid filtration 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 device, and a precharge or excess of gas sufficient to drain the system in the receiving container. To filter a fluid using the apparatus, the precharge or excess of gas is passed from the receiving container, through the fluid filtration device, without wetting out the device, and into the fluid container. The fluid in the fluid container is then passed back through the fluid filtration device into the receiving container with any desired impurities removed.  
      In another embodiment of the present invention, a 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 the 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 leukocyte depletion device, and a precharge or excess of gas sufficient to drain the system in the receiving container.  
      In yet another 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 leukocyte depletion device, and a precharge or excess of gas sufficient to drain the system in the receiving container. A satellite bag may be provided, which may be connected in fluid communication with the receiving container.  
      In still another embodiment of the invention, a method for processing a biological fluid is shown using a leukocyte reduction system having a first biological fluid container, a first biological fluid receiving container downstream of said first biological fluid container, and being precharged with a quantity of gas sufficient to drain the system, and a leukocyte reduction device in fluid communication with the first biological fluid container and the first biological fluid receiving container, the method comprising; causing the precharge of gas to be transferred from the first biological fluid receiving container to the first biological fluid container; and passing the biological fluid from the first biological fluid container, through the leukocyte reduction device, and collecting the leukocyte depleted biological fluid in the second container.  
      In a still further embodiment of the invention, a method for processing a leukocyte containing biological fluid is shown utilizing a leukocyte reduction system having a first biological fluid or blood container, a first biological fluid receiving container downstream of said first biological fluid container and being precharged with a quantity of gas sufficient to drain the system, and a leukocyte reduction device in fluid communication with the first biological fluid container and the first biological fluid receiving container, the method comprising: causing the precharge of gas to be transferred from the first biological fluid receiving container to the first biological fluid container; and passing the biological fluid from the first biological fluid container, through the leukocyte reduction device, and collecting the leukocyte depleted biological fluid in the first biological fluid receiving container by first inverting, and then re-inverting the apparatus.  
      In a further embodiment of the invention, a method for processing a biological fluid is shown including the steps of: passing a predetermined quantity of a fluid (preferably a gas such as air) from a first biological fluid receiving container through a leukocyte reduction device into a first biological fluid container containing a leukocyte rich biological fluid without wetting the device; and passing the leukocyte rich biological fluid from the first biological fluid container, through the leukocyte reduction device, into the first biological fluid receiving container by a pressure differential (e.g. gravity head, pressure cuff, suction and the like).  
      Thus, it is an object of the present invention to provide an improved method and apparatus for processing fluids.  
      A further object of the present invention is to provide a simpler and less costly apparatus for processing biological fluids.  
      Another object of the present invention is to provide an improved method and apparatus for filtering biological fluids.  
      Another object of the present invention is to provide a ventless leukocyte reduction system.  
      Another object of the present invention is to provide a ventless leukocyte reduction system provided with a satellite bag.  
      A further object of the present invention is to provide a ventless leukocyte reduction system provided with a plasma bag.  
      Another object of the present invention is to provide a ventless leukocyte reduction system provided with a satellite bag and one or more additive bags.  
      A still further object of the present invention is to provide a ventless whole blood set having a donor bag, a donor line, and a blood sampling system connected to the donor bag.  
      Further objects and advantages of the present invention will be apparent from the following description and appended claims, reference being had to the accompanying drawings, wherein like reference characters designate corresponding parts in the several views. 
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       FIG. 1  is an elevational view showing a construction embodying the present invention.  
       FIG. 1A  is a key to the various types of section lining used in  FIGS. 1-25 .  
       FIG. 2  shows the construction of  FIG. 1  after it has been inverted in the practice of a method in accordance with the present invention.  
       FIG. 3  shows the construction of  FIG. 2  after the filter clamp has been opened and a precharge or excess of gas has been expressed from a first biological fluid receiving container to a first biological fluid container.  
       FIG. 4  shows the construction of  FIG. 3  after the filter clamp has been closed and the construction has been reinverted to place the first biological fluid receiving container back in the lower position.  
       FIG. 5  shows the construction of  FIG. 4  after the clamp has been opened and the precharge or excess of gas has driven the fluid from the first biological fluid container to the first biological fluid receiving container.  
       FIG. 6  is an enlarged view of the area in the view circle  6  of  FIG. 5 .  
       FIG. 7  shows the construction of  FIG. 5  after the filter clamp has been closed, and the satellite bag clamp has been opened.  
       FIG. 8  shows the construction of  FIG. 7  after any excess gas has been expressed to the satellite bag and the satellite bag clamp has been closed.  
       FIG. 9  is a view similar in part to  FIG. 8 , showing what occurs if, after the satellite bag clamp has been opened, any excess gas, together with a quantity of biological fluid, is expressed to the satellite bag before the satellite bag clamp is closed.  
       FIG. 10  shows the construction of  FIG. 9  with the second container and the satellite bag being disconnected from the remainder of the apparatus by a sterile disconnect.  
       FIG. 11  shows a modification of the present invention wherein the construction of  FIG. 1  is used, with the precharge or excess of gas in the first biological fluid receiving container about to be expressed to the first biological fluid container by applying pressure to the first biological fluid receiving container and opening the filter clamp  43  (and cannula  28  if not already open), in the practice of a second method in accordance with the present invention.  
       FIG. 12  shows the construction of  FIG. 11  after the precharge or excess of gas has been expressed to the first biological fluid container, and the filter clamp has been closed.  
       FIG. 13  shows the construction of  FIG. 12  after the filter clamp has been opened in preparation for expressing the fluid into the first biological fluid receiving container.  
       FIG. 14  shows the construction of  FIG. 13  after the biological fluid has been transferred into the first biological fluid receiving container.  
       FIG. 14A  is an enlarged view of the area in the view circle  14 A of  FIG. 14 .  
       FIG. 15  shows the construction of  FIG. 14  after the filter clamp has been closed and the satellite bag clamp has been opened, and just before pressure has been applied to the first biological fluid receiving container to drive any excess of gas into the satellite bag.  
       FIG. 16  shows the construction of  FIG. 15  after pressure has been applied to the first biological fluid receiving container to express excess air to the satellite bag, and the satellite bag clamp has been closed.  
       FIG. 17  is a view similar in part to  FIG. 16 , showing what would happen if the excess of gas and a quantity of biological fluid was expressed before the satellite bag clamp was closed.  
       FIG. 18  shows the construction of  FIG. 17 , with the first biological fluid receiving container and the satellite bag being disconnected from the rest of the apparatus by a sterile disconnect.  
       FIG. 19  is an elevational view showing a modification of the present invention.  
       FIG. 20  is an elevational view showing a further modification of the present invention.  
       FIG. 20A  is an elevational view showing a construction substantially the same as that illustrated in  FIG. 20 , but with a closable vent provided on the sampling line in place of the sterile disconnect.  
       FIG. 21  is an elevational view showing a still further modification of the present invention.  
       FIG. 21A  is an elevational view showing a construction substantially the same as that illustrated in  FIG. 21 , but with the cannula provided at the other end of the third conduit or tubing.  
       FIG. 21B  is an elevational view showing a construction substantially the same as that illustrated in  FIG. 21 , but with no cannula provided at either end of the third conduit or tubing.  
       FIG. 22  is an elevational view showing yet another modification of the present invention.  
       FIG. 22A  is an elevational view showing a construction substantially the same as that illustrated in  FIG. 22 , but with the cannula provided at the other end of the third conduit or tubing.  
       FIG. 22B  is an elevational view showing a construction substantially the same as that illustrated in  FIG. 22 , but with no cannula provided at either end of the third conduit or tubing.  
       FIG. 23  is an elevational view showing a still further modification of the present invention.  
       FIG. 23A  is an elevational view showing a construction substantially the same as that illustrated in  FIG. 23 , but with the cannula provided at the other end of the third conduit or tubing.  
       FIG. 23B  is an elevational view showing a construction substantially the same as that illustrated in  FIG. 21 , but with no cannula provided at either end of the third conduit or tubing.  
       FIG. 24  is an elevational view showing a modification of the present invention having a plasma bag and an additive bag.  
       FIG. 25  is an elevational view showing a further modification of the present invention having a plasma bag, a first additive bag, and a second additive bag.  
       FIG. 26  is an elevational view showing a still further modification of the present invention, wherein the precharge or excess of gas is contained in a diversion bag. 
    
    
     DESCRIPTION OF THE PREFERRED EMBODIMENT  
      In describing the present invention, the following terms are used as described below.  
      “Fluid” means any liquid or gas.  
      “Biological Fluid” refers to saline solutions, medicant solutions, nutrient solutions and blood or blood products.  
      “Porous Medium” refers to any porous structure through which a fluid passes. A porous medium may be formed from any synthetic or natural fiber, particulates, or from a porous or permeable membrane compatible with the fluid being filtered.  
      “Sterility” or “Sterile” refers to maintaining a system free from viable contaminating microorganisms.  
      “Connector” refers to penetrating connectors, such as a spike, cannula, or needle and mating connectors, such as Luer-type, screw-type, friction-type, or connectors which are bonded together to any structure used to form a joint or to join itself to another piece.  
      “Sterile Connection” refers to a joint between two tubings, or between a tubing and a device, container, or bag, which is hermetic in nature and maintains a system free from viable contaminating microorganisms.  
      “Sterile Disconnect” refers to any means of sealing off a “tubing” while maintaining the sterility of the contents of the tubing, if any. A heat seal is an example of a “sterile disconnect”.  
      “Liquiphillic” refers to a material having a critical wetting surface tension higher than the surface tension of the applied liquid and is readily or spontaneously wetted by the applied liquid.  
      “Liquiphobic” refers to a material having a critical wetting surface tension lower than the surface tension of the applied liquid and is not readily or spontaneously wetted by the applied liquid. Liquiphobic materials may be characterized, then, by a high contact angle between a drop of liquid placed on the surface, and the surface.  
      “Tubing” may be any conduit or means which provides fluid communication between the containers, and is typically made from the same flexible material as is used for the containers, preferably plasticized PVC.  
      “Precharge” refers to a quantity of a gas introduced into the system or system component(s) prior to its use in the system.  
      “Ventless” refers to lacking a vent during a filtration process.  
      “Functional Biomedical Device” may be any number of devices or assemblies in which air or gases are present and/or may collect or form, or should be displaced prior to use of the assembly. Exemplary devices include a filter, such as a leukocyte depletion filter; a separatory device, such as a platelet concentrator, preferably a non-centrifugal platelet concentrator; a debubbler, a pump and a connector. The device may also include a device for destroying biological contaminants, such as a high intensity light wave chamber, or a device for sampling a biological liquid.  
     DESCRIPTION OF THE PREFERRED EMBODIMENTS  
      Referring now to  FIG. 1 , there is shown a preferred embodiment of the present invention. A first novel, prechargeable and ventless fluid processing and/or sampling apparatus or system is shown, generally designated by the numeral  20 . There is shown a functional biomedical device in the form of a biological fluid filtration device  21  having an upstream chamber  21 A and a downstream chamber  21 B separated by a porous medium  22  for filtering a biological fluid. Biological fluid filtration device  21  has an inlet  23  in fluid communication with the upstream chamber  21 A, and an outlet  24  in fluid communication with the downstream chamber  21 B. A first tubing  27  is attached at one end to the inlet  23  of the biological fluid filtration device  21 . The other end of the first tubing  27  may be connected through a cannula type first connector  28  to a first biological fluid container  29 . First biological fluid container  29  may be connected to biological fluid filtration device  21  by a sterile connection, if desired. First biological fluid container  29  may be provided with a first spike port connector  34  and a second spike port connector  35 .  
      Connected to the outlet  24  of the biological fluid filtration device  21  is a second tubing  32 . A porous medium  22  is interposed between the inlet  23  and the outlet  24  of the biological fluid filtration device  21 .  
      Connected to the other end of the second tubing  32  is a first biological fluid receiving container  33  which may have a third spike port connector  39  and a fourth spike port connector  40 . Provided on the second tubing  32  proximate the outlet  24  of the biological fluid filtration device  21  may be a filter clamp  43 . A hemostat may be used in place of the filter clamp  43  if desired. Hemostat or filter clamp  43  may be provided during the manufacturing process, or provided later. Filter clamp  43  is shown in an initially closed position for purposes to be described below.  
      Connected in fluid communication with the first biological fluid receiving container  33  by a third tubing  44  is a satellite bag  45 . Provided on third tubing  44  in the manner described above may be a satellite bag clamp  46 , shown in an initially closed position for purposes to be described. Satellite bag  45  is preferably empty and does not contain excess gas.  
      Depending on the biological fluid being filtered, the components of the ventless and prechargeable fluid processing apparatus  20  may be made of a wide variety of materials. Any practical material may be used, as long as it is compatible with the biological fluid being filtered. When blood is being filtered, it is preferable that the bag and tubing components be made of plasticized poly (vinyl chloride) (PVC) in accordance with International Standard ISO 3826: 1993 (E).  
      In the practice of a first method in accordance with the present invention, no further apparatus is needed. Specifically there is no precharge or excess of gas  37  in the first biological fluid receiving container  33 . Instead, the excess of gas or precharge  37  is injected directly into the first biological fluid container  29 . This is preferably done immediately before filtration is to take place. The excess or precharge of gas is calculated as below.  
      With Reference to  FIG. 5 , after the precharge  37  is injected or introduced into first biological fluid container  29 , the filter clamp  43  is opened, (and cannula  28  if not already open) and the fluid being filtered, such as blood  30 , flows through the biological fluid filtration device  21 , with any desired impurities, in this case leukocytes or white blood cells removed.  
      In the practice of a second method embodying the present invention, a first biological fluid receiving container  33  is supplied with a precharge or excess of gas  37  in excess of the volume of gas contained in the container in its relaxed empty state (collapsed). The excess or precharge of gas  37  may be placed in the first biological fluid receiving container ( 33 ,  132 ) during manufacture, or injected into the first biological fluid receiving container ( 33 ,  132 ) before use. It is preferred that the gas being injected is sterile, and is transferred into the system in a sterile manner, such as, by passing a non-sterile gas, such as air, through a 0.2 micron filter, which is known in the art.  
      The volume of the precharge has to be greater than, or equal to, the volume of the residual air left during the manufacturing process in the components of the system that are intended to be drained when the first biological fluid container is emptied. The volume of gas sufficient to drain the intended portions and components of the system is hereby referred to as a volume sufficient to drain the system.  
      For the ventless fluid processing apparatus  20 , the volume of the precharge may be obtained from the following formula: 
 
 V   p   ≧V   ft   +V   uc  
 
 Where, 
 
      Vp=Volume of precharge,  
      Vft=Volume of first tubing,  
      Vuc=Volume of upstream chamber.  
      Therefore, the volume of the precharge or the volume of the excess gas  37  in the first biological fluid receiving container  33  is greater than or equal to the volume of the gas in the first tubing  27 , plus the volume of the gas in the upstream chamber  21 A. If gas is present in the first biological fluid container  29 , the volume of gas in first biological fluid container  29  may be subtracted from the right hand side of the formula stated above. Therefore, 
 
 V   p   ≧V   ft   +V   uc   −V   fc  
 
 Where, 
 
      V fc =Volume of gas in the first biological fluid container.  
      Per the above explanation and formulation, no precharge  37  would be necessary if the first biological fluid container  29  contained a volume of gas greater than, or equal to the volume of tubing and portions of the functional biomedical device that it is intended to drain once the first biological fluid container  29  is drained.  
      This is necessary, as will be explained below, so that when the biological fluid is filtered in accordance with the method of the present invention, there will be substantially no biological fluid left in the first biological fluid container  29 , the first tubing  27 , or the upstream chamber  21 A of the biological fluid filtration device  21 . This would be the condition in the preferred embodiment of the invention.  
      If gas may breakthrough the biological fluid filtration device  21 , it may be desired to drain additional components of the system. For example, the downstream chamber  21 B and the second tubing  32  may be drained if precharge or excess gas  37  breaks through the biological fluid filtration device  21 . Typically the precharge or excess gas  37  enters the system after fluid has drained from the first biological fluid container  29 , the first tubing  27 , and the upstream chamber  21 A. The volume of precharge may be calculated from the following formula: 
 
 Vp≧Vft+Vuc+Vb+Vdc+Vst  
 
 Where, 
 
      Vp=Volume of precharge,  
      Vft=Volume of first tubing,  
      Vst=Volume of second tubing,  
      Vuc=Volume of upstream chamber,  
      Vdc=Volume of downstream chamber, and  
      Vb=Volume of biological fluid filter−volume of residual biological fluid that would remained trapped in the device.  
      The volume of precharge in the above example will drain additional portions of the system, such as the filter medium  22 , the downstream chamber  21 B of the biological fluid filtration device  21  and the second tubing  32 . This is well within the scope of the present invention. In this example, after complete drainage of the biological fluid into the first biological fluid receiving container, a substantially gas free first biological fluid receiving container may be obtained by transferring excess gas from the first biological fluid receiving container into either the satellite bag or through the biological fluid filtration device into the first biological fluid container.  
      Under the aforementioned International Standard ISO 3826:1993(E), the volume of air contained in the filterless blood collection pathway and the container used for the collection of blood and for each transfer container and its associated tubing shall not exceed 15 ml. The volume of air contained in each additional transfer container and associated tubing shall not exceed 15 ml. Therefore, the amount of the precharge may be calculated for each application depending on the number of containers and associated tubing, and how the system is to be drained. This requirement is intended to prevent storage of blood or blood products including additive solutions and anticoagulants with excess gas. In blood bag sets, with functional biomedical devices such as leukoreduction filters, the hold up volume of such devices is typically greater than 15 ml. Therefore, sets with functional biomedical devices typically have components which hold over 15 ml of gas (typically air) and as fluid enters the devices the air is transported out of the device typically to a container downstream of the functional biomedical device. Therefore, the excess air in the container downstream of the functional medical device must be removed.  
      For purposes of illustration, since the amount of residual air in the blood collection pathway and the containers is relatively small, and may become mixed with the precharge or excess gas, it is not shown separately in the following illustrations.  
      Referring to  FIGS. 1-10 , there is shown the apparatus of  FIG. 1  as used in the practice of another, or second, method embodying the present invention. To practice this method, and assuming the first biological fluid container  29  is filled with a desired quantity of a fluid to be filtered, which may be a biological fluid, such as blood  30 , and first biological fluid receiving container  33  has precharge  37  therein, the first step is to invert the apparatus of  FIG. 1 , with the filter clamp  43  and the satellite bag clamp  46  in their closed position. This is shown in  FIG. 2 . In this position, the first biological fluid container  33  having the precharge of gas  37  is now above the first biological fluid biological fluid container  29 . It is not necessary that the first biological fluid container  33  be elevated above the first biological fluid container  29 , but for ease of understanding, and reducing the chances of premature liquid entry in first tubing and/or biological filtration device, the first biological fluid receiving container  33  is shown elevated vertically above the first biological fluid container  29  in this method. Also, for purposes of illustration, the biological fluid being filtered by the present invention is illustrated as blood  30 , although it is well within the scope of the present invention to use any “biological fluid” as defined above.  
      The next step in the practice of the method, as shown in  FIG. 3 , is to apply a force to the outer walls of the first biological fluid receiving container  33 , shown by the force arrows  49 , substantially simultaneously with opening the fluid pathway between first biological fluid container  29  and first biological fluid receiving container  33  (opening filter clamp  43  and cannula  28  if not already open). This forces the precharge of gas  37  from the first biological fluid receiving container  33  through the second tubing  32 , the biological fluid filtration device  21  and the first tubing  27  into the first biological fluid container  29  with the blood  30 . Since first biological fluid container  29  is flexible, it expands to accommodate the volume of the precharge  37 . Filter clamp  43  is then closed. An alternative method of transferring gas is to apply a vacuum around the first biological fluid container  29 , and open the fluid pathway between the first biological fluid container  29  and first biological fluid receiving container  33 . There are numerous methods known in the art that may be used to transfer the gas from one bag to another, and these are within the scope of the present invention.  
      With reference to  FIG. 4 , the system  20  is then re-inverted or positioned so that the first biological fluid container  29 , now having the blood  30  and precharge of gas  37 , is elevated above the first biological fluid receiving container  33 , which is now virtually empty (does not contain any significant precharge or excess of gas).  
      Referring to  FIG. 5 , the filter clamp  43  is now opened, allowing the blood  30  from the first biological fluid container  29  to drain through the first tubing  27 , the biological fluid filter  21 , which for purposes of illustration is a leukocyte reduction filter, through the second tubing  32  into the first biological fluid receiving container  33 . Air within these components is displaced and transferred to the first biological fluid receiving container  33 .  
      It is preferred that the amount of excess gas or precharge  37  is chosen so that the blood  30  will drain completely from the first biological fluid container  29 , first tubing  27  and the upstream chamber  21 A of the biological fluid filtration device. Blood  30  will remain in the porous medium  22 , the downstream chamber  21 B of the biological fluid filtration device  21  and the second tubing  32  if the differential pressure across the porous medium  22  is not sufficient to allow some gas breakthrough the porous medium. As stated previously, by choosing the volume of the precharge or excess gas  37  appropriately, it would be possible to have the blood drain completely from the filter  21  and the second tubing  32  if gas is allowed to breakthrough the porous medium but this is not believed to be the preferred embodiment. Other applications may have different amounts of excess gas  37 , with different results.  
      With reference to  FIG. 6 , up to this point the contents of the first tubing  27 , the second tubing  32  and the upstream and downstream chambers ( 21 A,  21 B) of the biological fluid filtration device  21  have not been shown in detail as not being necessary to the understanding of the present invention. However, at this point in the process, it is important to understand that because of the volume of the precharge  37  which has been chosen, the upstream tubing  27  and the upstream chamber  21 A of the biological fluid filtration device  21  are now filled with precharge, while the filter medium  22 , the downstream chamber  21 B and the second tubing  32  are filled with blood. This condition will continue to exist in the discussion of  FIGS. 7-10  but again, for ease of illustration and understanding, is not shown in detail.  
      With reference to  FIG. 7 , the next step in the practice of the method is to close the filter clamp  43 , and open the satellite bag clamp  46 .  
      Referring now to  FIGS. 8 and 9 , two alternatives are available. Either, as shown in  FIG. 8 , enough force will be applied to the first biological fluid receiving container  33 , as indicated by the force arrows  49 , to just expel any excess gas or precharge  37  to the satellite bag  45 , or, as shown in  FIG. 9 , enough force will be applied to the first biological fluid receiving container  33 , as indicated by the force arrows  49  to expel any excess gas or precharge  37 , and a desired amount of blood  30 , to the satellite bag  45 . The alternative shown in  FIG. 9  is desirable, for example, when it is desired to test the blood  30  being filtered. In either case, the satellite bag clamp  46  is now closed.  
      With reference to  FIG. 10 , regardless of which alternative is used, the last step in the practice of the method is to make a sterile disconnect of the satellite bag  45  from the first biological fluid receiving container  33 , and a sterile disconnect of the first biological fluid receiving container  33  from filtration device  21 , both by means well known in the art. In the preferred embodiment, this is done by heat sealing. This is illustrated by first biological fluid sterile disconnect  50  and second sterile disconnect  51 . Alternatively, after filter clamp  43  has been closed, second tubing  32  may be sterile disconnected, and excess gas transferred from first biological fluid receiving container  33  into satellite bag  45  after opening satellite bag clamp  46 .  
      With reference to  FIGS. 1 and 11 - 18 , a third method embodying the present invention is illustrated. The apparatus of  FIG. 1  is used in the practice of this method. A quantity of blood  30  to be filtered is provided in first biological fluid container  29 . First biological fluid container  29  is attached in fluid communication with the first tubing  27 . First tubing  27  may be attached to the first biological fluid container  29  through a first cannula or connector  28 . First biological fluid container  29  may be sterile connected to the first tubing  27 , if desired.  
      It is desired that the blood  30  be filtered by biological fluid filtration device  21 . An amount of excess gas or precharge  37  is provided in the first biological fluid receiving container  33 . The amount of excess gas  37  is chosen as sufficient to drain the system  20  as described above. The first biological fluid receiving container  33  is connected in fluid communication with filtration device  21  by second tubing  32 . There is provided a satellite bag  45 , which is in fluid communication with the first biological fluid receiving container  33  through the third tubing  44 . Filter clamp  43  and satellite bag clamp  46  are provided as described above.  
      With reference to  FIG. 11 , the first step in the practice of the third method is to force the excess gas  37  into the first biological fluid container  29  by applying pressure to the first biological fluid container  33  as indicated by the second force arrows  60 , and substantially simultaneously opening the fluid pathway between the first biological fluid container  29  and first biological fluid container  33  via the filter clamp  43  and first cannula or connector  28 . The time between applying the pressure to the first biological fluid receiving container  33  and opening the filter clamp may vary somewhat. It is preferred to open the filter clamp  43  after enough pressure is applied to prevent the blood  30  from running into the first tubing  27 , and possibly into the biological fluid filtration device  21 , when the filter clamp  43  is opened.  
      This empties the first biological receiving fluid container  33  of the excess gas  37  by forcing the excess gas  37  through the second tubing  32 , the biological fluid filtration device  21  and first tubing  27 , into the first biological fluid container  29 , without the need to invert the ventless fluid processing apparatus  20 , as in the practice of the first method according to the present invention, described hereinabove.  
      Immediately after this operation occurs, the filter clamp  43  is closed, leaving the blood  30  and the excess gas  37  in the first biological fluid container  29 . The system  20  is now in the condition shown in  FIG. 12 .  
      The filter clamp  43  is now opened ( FIG. 13 ). Blood  30  will flow through the first tubing  27 , the filtration device  21 , the second tubing  32 , and into the first biological fluid receiving container  33 . Because of the excess of gas  37  being present in the first biological fluid container  29 , at a minimum, the first biological fluid container  29 , tubing  27  and the upstream chamber  21 A of the filtration device  21  will drain and be substantially empty. Once fluid flow ceases, the filter clamp  43  is closed ( FIG. 14 ).  
      With reference to  FIG. 14A , up until this point, the contents of first tubing  27  and second tubing  32 , as well as the upstream chamber  21 A and the downstream chamber  21 B, have not been illustrated in detail as not necessary to the understanding of the invention. However, it is now important to understand that because the volume of excess gas  37  has been chosen as sufficient to drain the system, as in the method illustrated in  FIG. 6 , the contents of the first tubing  27  and upstream chamber  21 A of the biological fluid filtration device  21  will have precharge therein, and the filter medium  22 , the downstream chamber  21 B and the second tubing  32  will be filled with blood. It may be assumed that this condition exists for  FIGS. 15-18 . It can be seen that in  FIGS. 14 through 18  the first biological fluid container  29  is shown as empty, as if the amount of precharge was exactly equal to the amount needed to drain the system. In cases where the precharge is in excess of this amount, the first biological fluid container  29  will include a precharge of gas, which is within the scope of the present invention. As with the previous methods, if different volumes of excess gas  37  are chosen, different conditions can exist, and this is well within the scope of the present invention.  
      Referring to  FIG. 15 , the satellite bag clamp  46  is now opened to provide fluid communication between the first biological fluid receiving container  33  and the satellite bag  45 .  
      Referring to  FIGS. 16 and 17 , as shown in connection with the previously described method, force may be applied to the first biological fluid receiving container  33  to fill the satellite bag  45  with any excess gas  37  ( FIG. 16 ), or enough force can be applied to the first biological fluid receiving container  33  to force any excess gas  37 , plus a quantity of blood  30 , into the satellite bag  45  ( FIG. 17 ). Regardless of which alternative is used, the satellite bag clamp  46  is now closed.  
      With reference to  FIG. 18 , regardless of which alternative is used, the last step in the practice of the third method is to make a sterile disconnect of the satellite bag  45  from the first biological fluid receiving container  33 , and a sterile disconnect of the first biological fluid receiving container  33  from filtration device  21  by means well known in the art. In the preferred embodiment, this is done by heat sealing. A first heat seal and disconnect is made downstream of the filter clamp, as indicated by the numeral  50 . A second heat seal and disconnect  51  is made upstream of the satellite bag clamp  46 . Alternatively, after filter clamp  43  has been closed, second tubing  32  may be sterile disconnected, and excess gas transferred from first biological fluid receiving container  33  into satellite bag  45  after opening satellite bag clamp  46 .  
      Now that the present invention and its principle of operation have been explained, the simple fashion and great variety of ways that apparatus for its practice may be supplied to blood banks, hospitals and other organizations concerned with the gathering and/or storage and/or administration of biological fluids may be seen.  
      Referring first to  FIG. 19 , there is shown a first apparatus  105  comprising a biological fluid filtration device  21  having an upstream chamber  21 A and a downstream chamber  21 B, separated by a porous medium  22 , for filtering a biological fluid. Filtration device  21  has an inlet  23  in fluid communication with the upstream chamber  21 A, and an outlet  24  in fluid communication with the downstream chamber  21 B. A first tubing  27 , having at least a first end  27 A, and a second end  27 B, is attached at its&#39; second end  27 B in fluid communication with the inlet  23  of the biological fluid filtration device  21 . The first end  27 A of the first tubing  27  is closed or terminated by any practical means, such as a third heat seal  52 .  
      Connected in fluid communication with the outlet  24  of the biological fluid filtration device  21  is second tubing  32 . Second tubing  32  has a first end  32 A, and a second end  32 B. First end  32 A of tubing  32  is connected to outlet  24  by a sterile connection. The porous medium  22  is interposed between the inlet  23  and the outlet  24  of the biological fluid filtration device  21 .  
      Connected in fluid communication with the second end  32 B of the second tubing  32  by a sterile connection is first biological fluid receiving container  33  having an excess of gas  37 . First biological fluid receiving container  33  may have a third spike port connector  39  and a fourth spike port connector  40 .  
      There is shown in  FIG. 20  the construction shown in  FIG. 19  with the addition of a sampling tubing  106 , having a first end  106 A and a second end  106 B, to the first apparatus  105 . The second apparatus  105 A, therefore comprises the filtration device  21 , the first tubing  27 , the second tubing  32 , and a first biological fluid receiving container  33 , which may have a third spike port connector  39  and a fourth spike port connector  40 . First tubing  27  is again terminated at its first end  27 A by a third heat seal and disconnect  52 , while sampling tubing  106  is terminated at its second end  106 B by a fourth heat seal and disconnect  53 .  
       FIG. 20A  shows a third apparatus  105 B substantially similar to second apparatus  105 A shown in  FIG. 20 , and having the fourth heat seal and disconnect  53  replaced by a closable vent  54 , which may be such as a 0.2 micron vent filter (preferably with a hydrophobic porous medium) with removable cap, or a hydrophilic and hydrophobic vent filter as described by Matkovich in U.S. Pat. No. 5,126,054. When the fluid receiving container  33  is equipped with a closable vent  54 , it is within the scope of the present invention that the apparatus may be supplied without a precharge or excess of gas  37 . In this case, the precharge or excess of gas  37  may be added, in an amount calculated as described above, to the first biological fluid receiving container  33  to drain the system upon use as described in this application.  
      A first biological fluid container  29  is attached to the first tubing  27 , preferably by a sterile connection. Precharge or excess gas  37  is transferred from the first biological fluid receiving container  33  into the first biological fluid container  29 . Subsequently, fluid is transferred from the first biological fluid container  29  through the filter  21  into the first biological fluid receiving container  33 . Following the liquid transfer, precharge or excess gas  37  enters through the first tubing  27  and substantially drains the system. The initial gas volume (excess gas) transferred by the displacement of liquid from the first biological fluid container  29  into the first biological fluid receiving container  33  may be expelled from the container  33  through closeable vent  54 . It is well within the skill of those in the art to determine exactly when the precharge of gas  37  should be added when using the closable vent  54 .  
      With reference to  FIG. 21 , there is shown fourth apparatus  105 C comprising first tubing  27 , biological fluid filtration device  21 , second tubing  32 , first biological fluid receiving container  33  having excess or precharge of gas  37 , third spike port  39 , and fourth spike port  40 . A satellite bag  45  is provided connected to first biological fluid receiving container  33  by third or satellite bag tubing  44 , having a first end  44 A, and a second end  44 B. First end  44 A of satellite bag tubing  44  is connected in fluid communication with the first biological fluid receiving container  33  through receiving bag cannula  107 . Second end  44 B of satellite bag tubing  44  is connected in fluid communication with satellite bag  45 .  
       FIG. 21A  shows a fifth apparatus  105 D substantially similar to fourth apparatus  105 C shown in  FIG. 21 , and having receiving bag cannula  107  provided at the second end  44 B of third tubing  44 .  
       FIG. 21B  shows a sixth apparatus  105 E substantially similar to fifth apparatus  105 D shown in  FIG. 21A , and having no receiving bag cannula  107  provided at either end of third tubing  44 . Therefore, an excess or precharge of gas  37  is also present in satellite bag  45 .  
      With reference to  FIG. 22 , the seventh apparatus  105 F shown therein is substantially similar to the fourth apparatus  105 C shown in  FIG. 21 . The only substantial difference is the addition of the second receiving bag cannula  108  interposed between the first biological fluid receiving container  33  and second end  32 B of second tubing  32 .  
       FIG. 22A  shows an eighth apparatus  105 G substantially similar to the seventh apparatus  105 F shown in  FIG. 22 , and having the receiving bag cannula  107  at the second end  44 B of third tubing  44 , interposed between satellite bag  45  and third tubing  44 .  
       FIG. 22B  shows ninth apparatus  105 H substantially similar to eighth apparatus  105 G shown in  FIG. 22A , and having no receiving bag cannula  107  at either end of third tubing  44 . In other words, there is no cannula interposed between satellite bag  45  and third tubing  44 , or between biological fluid receiving container  33  and third tubing  44 .  
      With reference to  FIG. 23 , tenth apparatus  105 I comprises a spike  109  having spike cover  109 A being connected to the upstream or first end  27 A of first tubing  27 . The downstream or second end  27 B of first tubing  27  is connected in fluid communication with inlet  23  of biological fluid filtration device  21 . The apparatus  105 I further comprises a second tubing  32  connected between the downstream side of biological fluid filtration device  21  through second receiving bag cannula  108  to be in fluid communication with the interior of the biological fluid receiving container  33 , which contains a precharge or excess of gas  37 , which cannot be released until second receiving bag cannula  108  is opened. In tenth apparatus  105 I the receiving bag cannula  107  is connected to the biological fluid receiving container  33  and, in turn is connected by third tubing  44  to satellite bag  45 .  
       FIG. 23A  shows an eleventh apparatus  105 J substantially similar to tenth apparatus  105 I shown in  FIG. 23 , and having the receiving bag cannula  107  at the second end  44 B of third tubing  44 , interposed between satellite bag  45  and third tubing  44 .  
       FIG. 23B  shows twelfth apparatus  105 K substantially similar to eleventh apparatus  105 J shown in  FIG. 23A , and having no receiving bag cannula  107  at either end of third tubing  44 . In other words, there is no receiving bag cannula  107  interposed between satellite bag  45  and third tubing  44 , or between biological fluid receiving container  33  and third tubing  44 . Therefore, an excess or precharge of gas  37  is also present in satellite bag  45 .  
      Referring to  FIG. 24 , there is shown a second ventless, and prechargeable, fluid processing and/or sampling apparatus, generally indicated by the numeral  120 , which has proved particularly useful for the collection of biological fluids which must be later processed and/or sampled. Such apparatus may also be referred to as a “whole blood set” (WBS)  120 .  
      The whole blood set (WBS)  120  comprises a first biological fluid container  29 , which may be used to collect blood or blood product, provided upstream from biological fluid filtration device  21 , which may be such as the LeukoSep™ Model No. HWB-600-W, manufactured by Hemerus Medical, LLC of St Paul, Minn. A quantity of anticoagulant  126  is usually provided in first biological fluid container  29 .  
      The biological fluid filtration device  21  has an inlet  23  and an outlet  24 , separated by porous medium  22 . First biological fluid container is connected in fluid communication with the biological fluid filtration device  21  through first cannula or connector  28  and first tubing  27  having a first end  27 A and a second end  27 B.  
      There is also provided a first biological fluid receiving container  33  downstream of the biological fluid filtration device  21 , which may be used to receive blood or blood products after they have been filtered or leukocyte reduced by the biological fluid filtration device  21 . Biological fluid filtration device  21  is connected in fluid communication with first biological fluid receiving container  33  through second tubing  32 , having a first end  32 A and a second end  32 B.  
      If the fluid or fluids, such as blood or blood products, in the first biological fluid receiving container  33  are to be separated into component parts, a plasma bag  135  may be provided in fluid communication with first biological fluid receiving container  33  through red blood cell (RBC) cannula  141  (when opened). Plasma bag  135  is connected to the first biological fluid receiving container  33  by red blood cell (RBC) tubing  136  (and Y-connector  138  and plasma line  136 B, if needed).  
      In some applications, one or more additives may be added to the fluid in the first biological fluid receiving container  33  during processing. This may be accomplished by providing a first additive bag  137 . First additive bag  137  is connected in fluid communication with RBC tubing  136  by primary additive tubing  139  and Y-connector  138  (when first additive bag cannula  142  is opened).  
      It may be desirable for one or more of the containers described above ( 29 ,  33 ,  135 ,  137 ) to have a cannula provided between the bag or container and its&#39; associated conduit or tubing. For example, first biological fluid container  29  may have a first cannula or connector  28  interposed between first biological fluid container  29  and the first end  27 A of first tubing  27 . Blood could not pass from first biological fluid container  29  to first tubing  27  (or vice versa) until first cannula  28  was broken or otherwise compromised. It is well within the scope of the present invention to have first cannula  28  replaced by any other practical device for controlling blood flow.  
      Likewise, an RBC cannula  141  may be interposed between first biological fluid receiving container  33  and first end  136 A of RBC tubing  136 . A first additive bag cannula  142  may be interposed between first additive bag  137  and second end  139 B of primary additive tubing  139 . Additional cannulas or connectors may be added, depending on the particular application, and this is within the scope of the present invention. In all cases, the system may be assembled by connecting (with sterile connections, if desired) various containers and sets together.  
      It may be desirable to have one or more whole blood set spike ports or connectors provided on the containers ( 135  and/or  137 ) described above.  
      The biological fluid processing system or whole blood set  120  described above preferably includes donor apparatus  146  in connection therewith. Such an apparatus would include a donor line  147  in fluid communication with the first biological fluid container  29  at its first end  147 A, and with a needle set  148  at its second end  147 B. Needle set  148  includes a needle  149  in fluid communication with the donor line  147 , and a needle protector  150 . Donor apparatus  146  is illustrated by way of example only. It is well within the scope of the present invention to use other donor apparatus or sets known in the art.  
      A blood sampling system  152  may also be provided to, for example, provide a donor blood sample for testing, or to divert an initial blood sample before it is allowed to pass into first biological fluid container  29 . Sampling system  152  may include such as a sampling Y-connector  154  interposed in donor line  147 . Sampling tubing  155  would be connected at a first end  155 A to Y-connector  154 , and at its second end  155 B to a vacuum tube holder  156  or other desired way to collect blood for testing, such as a pouch, or combinations of the two. Other sampling systems known in the art may also be used.  
      Referring now to  FIG. 25 , there is shown a third ventless, and prechargeable, fluid processing and/or sampling apparatus, which may also be referred to as second whole blood set  157 , which is nearly identical to second ventless, and prechargeable fluid processing and/or sampling apparatus or whole blood set  120 . The only substantial difference between the two is the addition of a second additive bag  158  for those applications where the processing of a biological fluid requires two or more additives. It is well within the scope of the present invention, given the teachings of the present invention, to add as many additive bags as are necessary.  
      Second additive bag  158  is provided, and is in fluid communication with first additive bag  137  through second additive bag cannula or connector  159  (when open) and secondary additive tubing  160 .  
      All three methods described above may be practiced with the apparatus illustrated in  FIGS. 24 and 25 . In the practice of the first method, a precharge or excess of gas  37 , the amount of which was calculated as described above, would be injected or introduced into first biological fluid container  29  by means well known in the art before or after it is filled with blood by the donor. This would permit the blood and anti-coagulant  126  to flow through first tubing  27 , and through biological fluid filtration device  21 , into first biological fluid receiving container  33 .  
      If first biological fluid receiving container  33  is provided with an excess of gas or precharge  37  as described above, blood has been introduced into first biological fluid container  29 , donor cannula  129  is operated as described for cannula  28 , filter clamp  43  is operated as previously described, and RBC bag cannula  141  is operated as described for the satellite clamp  46  above, the second method embodying the present invention may be practiced in connection with the apparatus as shown and described in  FIGS. 24 and 25 . The first biological fluid receiving container  33 , the plasma bag  135 , the first additive bag  137 , and the second additive bag  158  (if used) and subsequent additive bags, would be placed or held one next to each other, by means well known in the art, while the biological fluid processing system  157  was inverted or raised in the practice of the second method described above, with all other steps remaining the same. No change in the position of the components shown is necessary to practice the third method described above.  
      Referring now to  FIG. 26 , there is shown a fourth ventless, and prechargeable fluid processing and/or sampling apparatus  170 . The use of fourth ventless, and prechargeable fluid processing and/or sampling apparatus  170  enables the practice of a fourth method embodying the present invention. The apparatus of  FIG. 26  is similar in large part to the apparatus of  FIG. 24  except for the donor apparatus  146  and the blood sampling system  152 .  
      In this modification of the invention, second donor apparatus  172  is used in connection therewith. Such an apparatus would include, as before, a donor line  147  in fluid communication with the first biological fluid container  29  at its first end  147 A, and with a needle set  148  at its second end  147 B. Needle set  148  includes a needle  149  in fluid communication with the donor line  147 , and a needle protector  150 . to cover the needle  150  after use. A donor line clamp  176  is provided on the donor line between the needle  149  and the first biological fluid container  29 . Second donor apparatus  172  is illustrated by way of example only. It is well within the scope of the present invention to use other donor apparatus or sets known in the art.  
      A second blood sampling system  174  is provided. Second sampling system  174  may include such as a sampling Y-connector  154  interposed in donor line  147 . However, in this modification of the invention, instead of the sampling tubing  155  being connected at a first end  155 A to Y-Connector  154 , and at its second end  155 B to a vacuum tube holder  156  or other desired way to collect blood for testing, a second sampling tubing  175  is connected at its&#39; first end  175 A to sampling cannula  177  which, in turn, is connected to the Y-connector  154 . Second sampling tubing  175  is connected at its second end  175 B to a second Y-connector  180 . Second Y-connector  180  is connected in a manner known in the art to provide fluid communication between diversion bag  182 , the second end  175 B of second sampling tubing  175 , and one end of third sampling tubing  184 . Third sampling tubing is connected at its other end to vacuum tube holder  156 . A sampling system clamp  178  is provided on the second sampling tubing  175  between the Y-Connector  154  and the second Y-Connector  180 .  
      While anti-coagulant  126  may be contained in first biological fluid container  29 , if desired, in this modification of the invention, no precharge  37  is contained in first biological fluid receiving container  33 . Instead, the precharge  37 , in an amount calculated as set forth above, in other words, in an amount sufficient to drain the system, is contained in diversion bag  182 .  
      With the above description of the fourth whole blood set  170 , the fourth method according to the present invention may be understood by those skilled in the art. With donor line clamp  176  and second sampling system clamp  178  initially open, the precharge  37  in the diversion bag  182  is expressed into the first biological fluid container  29 , after sampling cannula  177  is compromised. This is preferably done before, but may be done after, blood is collected in first biological fluid container  29 . Because of the design of the donor needle  149  and the vacuum tube holder  156 , none of the precharge can pass out of these devices until they are prepared for use. Therefore, the precharge travels through the second sampling tubing  175 , sampling cannula  177 , sampling Y-connector  154 , and through the donor line  147 , into the first biological fluid container  29 . The donor line clamp  176  is then closed.  
      The donor needle  149  is inserted into the donor and the sampling system clamp  178  is left open. An initial amount of blood is drawn into the diversion bag  182  (and/or into the vacuum tube that may be connected to vacuum tube holder  156  if desired) for purposes known in the art, and the sampling system clamp  178  is closed. In this condition, no more blood is flowing from the donor into the fourth whole blood set  170 .  
      Donation is continued by opening the donor line clamp  176 . Blood then resumes flow into the first biological fluid container  29 , where it displaces the precharge, and mixes with the anti-coagulant, if any. Once sufficient blood is collected, donor line clamp  176  is closed, and the needle  149  is removed from the donor and pulled into needle protector  150  to prevent accidental needle stick. The donor line  176  may then be sterile disconnected (and sterile segmented, if desired) from first biological fluid container  29 .  
      To process the blood, the filter clamp  43  is then opened, permitting the blood to flow through the biological fluid filtration device  21 , with the rest of the processing taking place as described above.  
      Therefore, by carefully studying the problems present in previous biological fluid filtration systems, I have developed a novel, method and apparatus for processing biological fluid.  
      In accordance with the provisions of the patent statutes, the present invention has been described in what is considered to be 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.