IE20090703A1

IE20090703A1 - Biological fluid recovery system

Info

Publication number: IE20090703A1
Application number: IE20090703A
Authority: IE
Inventors: Byron Selman; Gerard Delgiacco
Original assignee: Pall Corp
Priority date: 2009-09-16
Filing date: 2009-09-16
Publication date: 2011-06-22

Abstract

A biological fluid processing system including a biological fluid filter device, a biological fluid recovery loop including a biological fluid recovery pouch, and a vent device including a membrane, wherein the pouch has flexible side walls, and the system directs displaced air to a conduit upstream of the filter device, allowing held up biological fluid to be recovered, is disclosed. <Figure 1>

Description

[0001] This invention pertains to displacing gas in a biological fluid processing system including a filter, to recover biological fluid held up in the tubing upstream of the filter and/or in the upstream portion of the filter housing after initial filtration.

[0002] A variety of blood processing systems are used for filtering blood and/or blood components, e.g., to deplete the blood or blood components of undesirable material such as leukocytes and/or prions. Typically, the systems are also used for separating the blood into blood components. Blood components filtered in a closed system can be stored for over 24 hours in a container, typically, a plasticized bag, before use, e.g., as a transfusion product. [0003] However, after filtration, a volume of blood or blood components is typically held up in the tubing upstream of the filter and/or in the filter housing (e.g., in the upstream portion of the filter housing). Some leukocyte depletion systems provide for recovering some of this held up fluid by using gas (air) to displace the held up fluid, allowing held up fluid to be drained and collected in a receiving container. The gas can be introduced into the system from the outside environment by passing gas through a membrane with a bacterial blocking pore rating. Alternatively, or additionally, gas already in the system and displaced by the blood or blood component(s) passing through the elements of the system can be re-directed by squeezing a blood receiving bag contained displaced air to force the air via a bypass loop into the upstream tubing and/or a blood source bag upstream of the filter. Moreover, since the presence of a large volume of air in a container for storage of blood or of a blood component is undesirable, some leukocyte depletion systems provide for expelling air from the system into the outside environment, or allowing air to be passed to another container (via a bypass loop) in the blood processing system without venting the air to the outside environment.

[0004] While systems that allow air communication with the atmosphere have been accepted for use in many countries, including the U.S., regulations in some countries prevent the use of such systems, due to concerns of possible bacterial contamination of the blood or blood components, However, while systems including conventional bypass loops do not allow air to be vented to the atmosphere, the use of such systems can require a labor intensive bag to force the air through the bypass ί£ 090 703 loop. Some technicians processing blood in systems with conventional bypass loops do not utilize the bypass loops, in view of the effort required and fear of injury. (0005] The present invention provides for ameliorating at least some of the disadvantages of the prior art. These and other advantages of the present invention will be apparent from the description as set forth below.

BRIEF SUMMARY OF THE INVENTION [0006] In an embodiment, a biological fluid processing system is provided comprising (a) a biological fluid filter device, comprising a porous depletion medium, and a housing comprising an upstream section comprising an inlet and a downstream section comprising an outlet, the housing defining a fluid flow path between the inlet and the outlet, wherein the depletion medium is disposed in the housing between the inlet and the outlet and across the fluid flow path; (b) a first conduit, upstream of the filter device, the first conduit having a first end and a second end, wherein the second end of the first conduit is in fluid communication with the inlet of the filter device; (c) a second conduit, downstream of the filter device, the second conduit having a first end and a second end, wherein the first end of the second conduit is in fluid communication with the outlet of the filter device; (d) a vent device, comprising a vent housing comprising a first inlet, a first outlet, and a second outlet, the vent device defining a first fluid flow path between the first inlet and the first outlet, and defining a second fluid flow path between the first inlet and the second outlet, the vent housing containing a vent element comprising at least a hydrophobic porous membrane disposed between the first inlet and the second outlet across the second fluid flow path, the vent device being arranged downstream of the filter device, and in fluid communication with the second conduit; and, (e) a biological fluid recovery loop having a first end and a second end, wherein the first end of the recovery loop is in fluid communication with the second end of the second conduit and the vent device, and the second end of the recovery loop is in fluid communication with the first end of the first conduit, the recovery loop comprising (i) at least one biological fluid recovery conduit having a first end and a second end; and (ii) a biological fluid recovery pouch comprising flexible side walls and at least a first port and a second port; wherein the system is arranged to allow gas to pass from the biological fluid recovery pouch through the second end of the recovery loop and into the first conduit without compressing the biological fluid recovery pouch. [0007J A biological fluid processing system provided in accordance with another embodiment of the invention comprises (a) a biological fluid filter device, comprising a porous biological fluid filter medium, and a housing comprising an upstream section IE090703 comprising an inlet and a downstream section comprising an outlet, the housing defining a fluid flow path between the inlet and the outlet, wherein the filter medium is disposed in the housing between the inlet and the outlet and across the fluid flow path; (b) a first conduit, upstream of the filter device, the first conduit having a first end and a second end, wherein the second end of the first conduit is in fluid communication with the inlet of the filter device; (c) a second conduit, downstream of the filter device, the second conduit having a first end and a second end, wherein the first end of the second conduit is in fluid communication with the outlet of the filter device; (d) a vent device, comprising a vent housing comprising a first inlet, a first outlet, and a second outlet, the vent device defining a first fluid flow path between the first inlet and the first outlet, and defining a second fluid flow path between the first inlet and the second outlet, the vent housing containing a vent element comprising at least a hydrophobic porous membrane disposed between the first inlet and the second outlet across the second fluid flow path, the vent device being arranged downstream of the filter device, and in fluid communication with the second conduit; and, (e) a biological fluid recovery loop having a first end and a second end, wherein the first end of the recovery loop is in fluid communication with the second end of the second conduit and the vent device, and the second end of the recovery loop is in fluid communication with the first end of the first conduit, the recovery loop comprising; (i) at least one biological fluid recovery conduit having a first end and a second end; (ii) a biological fluid recovery pouch comprising flexible side walls and at least a first port and a second port, and, (iii) a normally closed one-way valve interposed between the first end of the biological fluid recovery loop and the biological fluid recovery pouch.

[0008] Another embodiment of the invention provides a biological fluid processing system comprising (a) a biological fluid filter device, comprising a porous biological fluid filter medium, and a housing comprising an upstream section comprising an inlet and a downstream section comprising an outlet, the housing defining a fluid flow path between the inlet and the outlet, wherein the filter medium is disposed in the housing between the inlet and the outlet and across the fluid flow path; (b) a first conduit, upstream of the filter device, the first conduit having a first end and a second end, wherein the second end of the first conduit is in fluid communication with the inlet of the filter device; (c) a second conduit, downstream of the filter device, the second conduit having a first end and a second end, wherein the first end of the second conduit is in fluid communication with the outlet of the filter device; and, (d) a biological fluid recovery loop having a first end and a second end, wherein the first end of the recovery loop is in fluid communication with the second end of the second conduit, and the second end of the recovery loop is in fluid communication with IE 0 907 03 the first end of the first conduit, the recovery loop comprising: (i) at least one biological fluid recovery conduit having a first end and a second end; (ii) a biological fluid recovery pouch comprising flexible side walls and at least a first port and a second port, and, (iii) a fluid flow control device, arranged to prevent or allow flow between the second port of the fluid recovery pouch and the second end of the recovery loop; wherein the biological fluid recovery loop is arranged such that, while the fluid flow control device is closed, the biological fluid recovery pouch is pressurizable by air displaced by biological fluid passing through the second conduit, the air passing into the pouch through the first port, and, when the fluid control device is opened, the system directs air through the second port and through the second end of the biological fluid recovery loop to the first conduit upstream of the filter device, displacing biological fluid in the first conduit from the conduit, and displacing biological fluid into a receiving container.

[0009] A biological fluid processing system provided in accordance with yet another embodiment of the invention comprises (a) a biological fluid filter device, comprising a porous biological fluid filter medium, and a housing comprising an upstream section comprising an inlet and a downstream section comprising an outlet, the housing defining a fluid flow path between the inlet and the outlet, wherein the filter medium is disposed in the housing between the inlet and the outlet and across the fluid flow path; (b) a first conduit, upstream of the filter device, the first conduit having a first end and a second end, wherein the second end of the first conduit is in fluid communication with the inlet of the filter device; (c) a second conduit, downstream of the filter device, the second conduit having a first end and a second end, wherein the first end of the second conduit is in fluid communication with the outlet of the filter device; and, (d) a biological fluid recovery loop having a first end and a second end, wherein the first end of the recovery loop is in fluid communication with the second end of the second conduit, and the second end of the recovery loop is in fluid communication with the first end ofthe first conduit, the recovery loop comprising: (i) at least one biological fluid recovery conduit having a first end and a second end; (ii) a biological fluid recovery pouch comprising flexible side walls and at least a first port and a second port, and, (iii) a normally closed one-way valve interposed between the first end of the biological fluid recovery loop and the biological fluid recovery pouch.

[0010] In a preferred embodiment, the system is arranged such that air also displaces biological fluid from the upstream section of the filter housing, and additional biological fluid is displaced into the receiving container.

[0011] In some embodiments of the system, the biological fluid filter device comprises a leukocyte depletion filter device and/or a prion depletion device. /£ 0 907 03 [0012] In a preferred embodiment, the system is a sterile-dockable system.

[0013] An embodiment of a method of processing biological fluid according to the invention comprises passing biological fluid through an upstream conduit and a porous biological fluid filter medium disposed in a housing comprising an upstream section and a downstream section, and displacing air into a biological fluid recovery pouch in a biological fluid recovery loop, wherein air is prevented from passing out of the pouch; directing air from the pouch into the upstream conduit and displacing biological fluid from the conduit; and, collecting displaced biological fluid in a receiving container.

[0014] In some embodiments, the method includes directing air into the upstream section of the housing and collecting an additional volume of displaced biological fluid in the receiving container.

[0015] In preferred embodiments, the method includes directing air from the pouch into the upstream conduit (and, if desired, into the upstream section of the housing) without compressing the pouch to direct the air.

[0016] In a preferred embodiment of the method, the biological fluid is processed while maintaining a closed system.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWING(S) [0017] Figure 1 is an embodiment of a biological fluid processing system comprising a biological fluid recovery loop according to the present invention, the loop including a vent device comprising at least one porous membrane, wherein the system is sterile docked to a biological fluid source container. [001Figure 2 is another embodiment of a biological fluid processing system comprising a biological fluid recovery loop according to the present invention, the loop including a vent device comprising at least one porous membrane, wherein the system is sterile docked to a biological fluid source container.

[0019] Figure 3 is another embodiment of a biological fluid processing system comprising a biological fluid recovery loop according to the present invention, the loop including a vent device comprising at least one porous membrane, wherein the system is sterile docked to a biological fluid source container, [0020] Figure 4 is another embodiment of a biological fluid processing system comprising a biological fluid recovery loop according to the present invention, wherein the loop does not include a vent device comprising at least one porous membrane, and the system is sterile docked to a biological fluid source container.

IE 0 90 7 03 [0021] Figure 5 is another embodiment of a biological fluid processing system comprising a biological fluid recovery loop according to the present invention, wherein the loop does not include a vent device comprising at least one porous membrane, and the system is sterile docked to a biological fluid source container.

DETAILED DESCRIPTION OF THE INVENTION [0022] A biological fluid processing system according to an embodiments of the invention comprises (a) a biological fluid filter device, comprising a porous depletion medium, and a housing comprising an upstream section comprising an inlet and a downstream section comprising an outlet, the housing defining a fluid flow path between the inlet and the outlet, wherein the depletion medium is disposed in the housing between the inlet and the outlet and across the fluid flow path; (b) a first conduit, upstream of the filter device, the first conduit having a first end and a second end, wherein the second end of the first conduit is in fluid communication with the inlet of the filter device; (c) a second conduit, downstream of the filter device, the second conduit having a first end and a second end, wherein the first end of the second conduit is in fluid communication with the outlet of the filter device; (d) a vent device, comprising a vent housing comprising a first inlet, a first outlet, and a second outlet, the vent device defining a first fluid flow path between the first inlet and the first outlet, and defining a second fluid flow path between the first inlet and the second outlet, the vent housing containing a vent element comprising at least a hydrophobic porous membrane disposed between the first inlet and the second outlet across the second fluid flow path, the vent device being arranged downstream of the filter device, and in fluid communication with the second conduit; and, (e) a biological fluid recovery loop having a first end and a second end, wherein the first end of the recovery loop is in fluid communication with the second end of the second conduit and the vent device, and the second end of the recovery loop is in fluid communication with the first end of the first conduit, the recovery loop comprising (i) at least one biological fluid recovery conduit having a first end and a second end; and (ii) a biological fluid recovery pouch comprising flexible side wails and at least a first port and a second port; wherein the system is arranged to allow gas to pass from the biological fluid recovery pouch through the second end of the recovery loop and into the first conduit without compressing the biological fluid recovery pouch, [0023] In accordance with another embodiment of the present invention, a biological fluid processing system is provided comprising (a) a biological fluid filter device, comprising a porous biological fluid filter medium, and a housing comprising an upstream section comprising an inlet and a downstream section comprising an outlet, the housing defining a IE 0 907 03 fluid flow path between the inlet and the outlet, wherein the filter medium is disposed in the housing between the inlet and the outlet and across the fluid flow path; (b) a first conduit, upstream of the filter device, the first conduit having a first end and a second end, wherein the second end of the first conduit is in fluid communication with the inlet of the filter device; (c) a second conduit, downstream of the filter device, the second conduit having a first end and a second end, wherein the first end of the second conduit is in fluid communication with the outlet of the filter device; (d) a vent device, comprising a vent housing comprising a first inlet, a first outlet, and a second outlet, the vent device defining a first fluid flow path between the first inlet and the first outlet, and defining a second fluid flow path between the first inlet and the second outlet, the vent housing containing a vent element comprising at least a hydrophobic porous membrane disposed between the first inlet and the second outlet across the second fluid flow path, the vent device being arranged downstream of the filter device, and in fluid communication with the second conduit; and, (e) a biological fluid recovery loop having a first end and a second end, wherein the first end of the recovery loop is in fluid communication with the second end of the second conduit and the vent device, and the second end of the recovery loop is in fluid communication with the first end of the first conduit, the recovery loop comprising: (i) at least one biological fluid recovery conduit having a first end and a second end; (ii) a biological fluid recovery pouch comprising flexible side walls and at least a first port and a second port, and, (iii) a fluid flow control device, arranged to prevent or allow flow between the second port of the fluid recovery pouch and the second end of the recovery loop; wherein the biological fluid recovery loop is arranged to receive air displaced by the biological fluid passing through the second conduit and the system is arranged to direct the received air through the second port and through the second end of the biological fluid recovery loop to the first conduit upstream of the filter device, displacing biological fluid from the first conduit, and displacing biological fluid into a receiving container.

[0024] In accordance with another embodiment of the present invention, a biological fluid processing system is provided comprising (a) a biological fluid filter device, comprising a porous biological fluid filter medium, and a housing comprising an upstream section comprising an inlet and a downstream section comprising an outlet, the housing defining a fluid flow path between the inlet and the outlet, wherein the filter medium is disposed in the housing between the inlet and the outlet and across the fluid flow path; (b) a first conduit, upstream of the filter device, the first conduit having a first end and a second end, wherein the second end of the first conduit is in fluid communication with the inlet of the filter device; (c) a second conduit, downstream of the filter device, the second conduit having a first end IE 0 90 7 03 8 and a second end, wherein the first end of the second conduit is in fluid communication with the outlet of the filter device; and, (d) a biological fluid recovery loop having a first end and a second end, wherein the first end of the recovery loop is in fluid communication with the second end of the second conduit, and the second end of the recovery loop is in fluid communication with the first end of the first conduit, the recovery loop comprising: (i) at least one biological fluid recovery conduit having a first end and a second end; (ii) a biological fluid recovery pouch comprising flexible side walls and at least a first port and a second port, and, (iii) a fluid flow control device, arranged to prevent or allow flow between the second port of the fluid recovery pouch and the second end of the recovery loop; wherein the biological fluid recovery loop is arranged such that, while the fluid flow control device is closed, the biological fluid recovery pouch is pressurizable by air displaced by biological fluid passing through the second conduit, the air passing into the pouch through the first port, and, when the fluid control device is opened, the system directs air through the second port and through the second end of the biological fluid recovery loop to the first conduit upstream of the filter device, displacing biological fluid in the first conduit and displacing biological fluid into a receiving container.

[0025] In accordance with another embodiment of the present invention, a biological fluid processing system is provided comprising (a) a biological fluid filter device, comprising a porous biological fluid filter medium, and a housing comprising an upstream section comprising an inlet and a downstream section comprising an outlet, the housing defining a fluid flow path between the inlet and the outlet, wherein the filter medium is disposed in the housing between the inlet and the outlet and across the fluid flow path; (b) a first conduit, upstream of the filter device, the first conduit having a first end and a second end, wherein the second end of the first conduit is in fluid communication with the inlet of the filter device; (c) a second conduit, downstream of the filter device, the second conduit having a first end and a second end, wherein the first end of the second conduit is in fluid communication with the outlet of the filter device; and, (d) a biological fluid recovery loop having a first end and a second end, wherein the first end of the recovery loop is in fluid communication with the second end of the second conduit, and the second end of the recovery loop is in fluid communication with the first end of the first conduit, the recovery loop comprising: (i) at least one biological fluid recovery conduit having a first end and a second end; (ii) a biological fluid recovery pouch comprising flexible side walls and at least a first port and a second port, and, (iii) a fluid flow control device, arranged to prevent or allow flow between the second port of the fluid recovery pouch and the second end of the recovery loop; wherein the biological fluid recovery loop is arranged to receive air displaced by the biological fluid IE Ο 9 ο 7 Ο 3 passing through the second conduit and the system is arranged to direct the received air through the second port and through the second end of the biological fluid recovery loop to the first conduit upstream of the filter device, displacing biological fluid from the first conduit, and displacing biological fluid into a receiving container. (0026] In preferred embodiments, the air also displaces biological fluid from the upstream section of the filter housing, and additional biological fluid is displaced into the receiving container. (0027] In an embodiment, the biological fluid recovery loop further comprises a unidirectional flow valve, interposed between the first port of the biological fluid recovery pouch, and the first end of the recovery loop. (0028] A biological fluid processing system provided in accordance with another embodiment of the invention comprises (a) a biological fluid filter device, comprising a porous biological fluid filter medium, and a housing comprising an upstream section comprising an inlet and a downstream section comprising an outlet, the housing defining a fluid flow path between the inlet and the outlet, wherein the filter medium is disposed in the housing between the inlet and the outlet and across the fluid flow path; (b) a first conduit, upstream of the filter device, the first conduit having a first end and a second end, wherein the second end of the first conduit is in fluid communication with the inlet of the filter device; (c) a second conduit, downstream of the filter device, the second conduit having a first end and a second end, wherein the first end of the second conduit is in fluid communication with the outlet of the filter device; (d) a vent device, comprising a vent housing comprising a first inlet, a first outlet, and a second outlet, the vent device defining a first fluid flow path between the first inlet and the first outlet, and defining a second fluid flow path between the first inlet and the second outlet, the vent housing containing a vent element comprising at least a hydrophobic porous membrane disposed between the first inlet and the second outlet across the second fluid flow path, the vent device being arranged downstream of the filter device, and in fluid communication with the second conduit; and, (e) a biological fluid recovery loop having a first end and a second end, wherein the first end of the recovery loop is in fluid communication with the second end of the second conduit and the vent device, and the second end of the recovery loop is in fluid communication with the first end of the first conduit, the recovery loop comprising (i) at least one biological fluid recovery conduit having a first end and a second end; (ii) a biological fluid recovery pouch comprising flexible side walls and at least a first port and a second port, and, (iii) a normally closed one-way valve interposed between the first end of the biological fluid recovery loop and the biological fluid recovery pouch.

IE 0 9 0 7 03 [0029] A biological fluid processing system provided in accordance with another embodiment of the invention comprises (a) a biological fluid filter device, comprising a porous biological fluid filter medium, and a housing comprising an upstream section comprising an inlet and a downstream section comprising an outlet, the housing defining a fluid flow path between the inlet and the outlet, wherein the filter medium is disposed in the housing between the inlet and the outlet and across the fluid flow path; (b) a first conduit, upstream of the filter device, the first conduit having a first end and a second end, wherein the second end of the first conduit is in fluid communication with the inlet of the filter device; (c) a second conduit, downstream of the filter device, the second conduit having a first end and a second end, wherein the first end of the second conduit is in fluid communication with the outlet of the filter device; and, (d) a biological fluid recovery loop having a first end and a second end, wherein the first end of the recoveiy loop is in fluid communication with the second end of the second conduit, and the second end of the recovery loop is in fluid communication with the first end of the first conduit, the recovery loop comprising: (i) at least one biological fluid recovery conduit having a first end and a second end; (ii) a biological fluid recovery pouch comprising flexible side walls and at least a first port and a second port, and, (iii) a normally closed one-way valve interposed between the first end of the biological fluid recovery loop and the biological fluid recovery pouch.

[0030] In some embodiments of the system, the biological fluid filter device comprises a leukocyte depletion filter device and/or a prion depletion device.

[0031] In a preferred embodiment, the system comprises a sterile-dockable system.

[0032] In some embodiments of the system, the biological fluid recovery pouch has a volume of at least about 5 mL.

[0033] An embodiment of a method of processing biological fluid according to the invention comprises passing biological fluid through an upstream conduit and a porous biological fluid filter medium disposed in a housing comprising an upstream section and a downstream section, and displacing air through at least a hydrophobic membrane in a vent device and into a biological fluid recovery pouch in a biological fluid recovery loop, wherein air is prevented from passing out of the pouch; directing air from the pouch into the upstream conduit and displacing biological fluid from the conduit; and, collecting displaced biological fluid in a receiving container.

[0034] In some embodiments, the method includes directing air into the upstream section of the housing and collecting an additional volume of displaced biological fluid in the receiving container.

IE 090 7 03 [0035] In a preferred embodiment of the method, the biological fluid is processed while maintaining a closed system.

[0036] In accordance with an advantage of the present invention, air can be displaced within the biological fluid processing system comprising a biological fluid recovery loop comprising a flexible biological fluid recovery pouch, and the air can be easily channeled into the conduit(s) upstream of the biological fluid filter device and, if desired, into the housing of the filter device in the biological processing system to assist in draining the upstream tubing and, if desired, the upstream section of the housing, thus increasing the yield of recovered filtered biological fluid, while maintaining a closed biological fluid processing system. Additionally, air can be passed into the biological fluid recovery loop without passing biological fluid into the loop, thus reducing the loss of biological fluid. This can be carried out without interacting with atmospheric air.

[0037] Other advantages are that the volume of air in the container of processed biological fluid (e.g., in the effluent or receiving bag) ean be reduced without requiring compression of the container (and, if desired, without requiring compression of any other container containing air).

[0038] In accordance with some embodiments of the invention, the biological fluid processing system can, if desired, be assembled without requiring a vent device comprising a housing and at least one porous membrane suitable for passing gas therethrough disposed in the housing. Accordingly, systems according to some embodiments of the invention can be assembled more easily and less expensively than systems including vent devices comprising housings and porous membranes.

[0039] Embodiments of the invention are especially advantageous for processing small volumes of biological fluid, e.g., wherein a maximum yield is especially desirable. Thus, for example, an embodiment of the invention is desirable for use in processing biological fluid for pediatric use and/or processing biological fluid wherein the volume of biological fluid has been decreased due to previous processing, e.g., prior leukocyte depletion. While one application of the invention is for producing transfusion products, other applications include, for example, harvesting (e.g., for rare cells or a desired type of blood cell), and sample preparation.

[0040] The following definitions are used in accordance with the invention.

[0041] Biological Fluid. A biological fluid includes any treated or untreated fluid associated with living organisms, particularly blood, including whole blood, warm or cold blood, and stored or fresh blood; treated blood, such as blood diluted with at least one physiological solution, including but not limited to saline, nutrient, and/or anticoagulant /£ 0 90 7 03 solutions; blood components, such as platelet concentrate (PC), platelet-rich plasma (PRP), platelet-poor plasma (PPP), platelet-free plasma, plasma, fresh frozen plasma (FFP), components obtained from plasma, packed red cells (PRC), transition zone material or buffy coat (BC); blood products derived from blood or a blood component or derived from bone marrow; stem cells; red cells separated from plasma and resuspended in physiological fluid or a cryoprotective fluid; and platelets separated from plasma and resuspended in physiological fluid or a cryoprotective fluid. The biological fluid may have been treated to remove some of the leukocytes before being processed according to the invention. As used herein, blood product or biological fluid refers to the components described above, and to similar blood products or biological fluids obtained by other means and with similar properties, [0042] A unit is the quantity of biological fluid from a donor or derived from one unit of whole blood. It may also refer to the quantity drawn during a single donation. Typically, the volume of a unit varies, the amount differing from patient to patient and from donation to donation. Multiple units of some blood components, particularly platelets and buffy coat, may be pooled or combined, typically by combining four or more units.

[0043] As used herein, the term “closed” refers to a system that allows the collection and processing (and, if desired, the manipulation, e.g., separation of portions, separation into components, filtration, storage, and preservation) of biological fluid, e.g,, donor blood, blood samples, and/or blood components, without the need to compromise the sterile integrity of the system. A closed system can be as originally made, or result from the connection of system components using what are known as “sterile docking” devices. Illustrative sterile docking devices are disclosed in, for example, U.S. Patent Nos. 4,507,119,4,737,214, and 4,913,756. In a preferred embodiment of the invention, the system is a “sterile dockable” system.

[0044] Each of the components of the invention will now be described in more detail below, wherein like components have like reference numbers.

[0045] The biological fluid processing system typically comprises a biological fluid recovery loop, a biological fluid filter device interposed between first and second conduits, a vent device, at least one fluid control device, at least two connectors, and at least one container.

[0046] In the illustrated embodiments (Figures 1-5), a source container 100 of biological fluid is sterile docked to a biological fluid processing system 1000 according to the invention. [0047] in the embodiments illustrated in Figures 1-3, the biological fluid processing system 1000 comprises a biological fluid filter device 10 interposed between first conduit 2 and second conduit 3, a biological fluid recovery loop 70, and a vent device 60. ΙΕ ο 9 ο Ί ο 3 [0048] In the embodiments illustrated in Figures 1-3, the biological fluid recovery loop 70 comprises a first end 70a and a second end 70b, and a biological fluid recovery pouch 40 interposed between the first end of the loop and the second end of the loop, the pouch 40 comprising flexible side walls and first and second ports 41 and 42, Typically, the biological fluid recovery loop includes at least two biological fluid recovery conduits, in the embodiment illustrated in Figure 1, the loop 70 includes 4 conduits, 71,72, 73, and 74, in the embodiments illustrated in Figures 2 and 3, the loop includes 3 conduits, 71,72 and 75 (Figure 2) or 76, 73, and 74 (Figure 3). The recovery loop typically further comprises at least one, in some embodiments, at least two, fluid control devices, the embodiments illustrated in Figures 1 and 2 show a first fluid control device 50 for controlling fluid communication between first end 70a and the pouch 40, and a second fluid control device 32 (Figure 1) or 32a (Figure 2) for controlling fluid communication between the pouch 40 and the second end 70b. The embodiment illustrated in Figure 3 lacks a flow control device for controlling fluid communication between first end 70a and the pouch 40, but includes a flow control device 32 for controlling fluid communication between the pouch 40 and the second end 70b, [0049] In the embodiments illustrated in Figures 1-3, the biological fluid processing system 1000 further comprises conduits 1-3 and 17, a first container (or receiving container) 101, a biological fluid filter device 10, interposed between conduit 2 (having a first end 2a and a second end 2b) and a conduit 3 (having a first end 3a and a second end 3b), and a vent device 60 comprising a vent housing 65 comprising a first inlet 61, a first outlet 62, and a second outlet 63, the vent device defining a first fluid flow path between the first inlet and the first outlet, and defining a second fluid flow path between the first inlet and the second outlet, the vent housing containing a vent element 67 comprising at least a hydrophobic porous membrane 68 (in some embodiments, e.g., as shown in Figure 3, the vent element comprises a hydrophobic porous membrane 68 and a hydrophilic porous membrane 69) disposed between the first inlet and the second outlet across the second fluid flow path, the vent device being airanged downstream of the filter device 10, and in fluid communication with the conduit 3, with a first connector 21 allowing fluid communication between the second end 70b of the loop and the first end 2a of the first conduit, as well as allowing communication with source container 100 via conduit 1, and the vent device 60 allowing fluid communication between the first end 70a of the loop and the second end 3b of the conduit 3. Vent device 60 also allows fluid communication with first container 101 via conduit 17. Additionally, in these illustrated embodiments, the system 1000 further comprises a third fluid control device 31 for controlling fluid communication between connector 22 and first container 101, and a fourth fluid control device for controlling fluid communication between IE 0 90 7 03 source container 100 and conduit 1. While the embodiments illustrated in Figures 1-3 show a fluid control device such as a transfer leg closure in a port of the first container 101, in another embodiment (not shown), a flow control device can be placed in a conduit between connector 22 and first container 101, or a flow control device such as, for example, a clamp can be associated with conduit 17. Similarly, while a fourth fluid control device is shown associated with conduit 1, in another embodiment (not shown), source container 100 can include a fluid control device such as a transfer leg closure in the port of the container communicating with conduit 1.

[0050] The biological fluid recovery pouch 40 in accordance with embodiments of a system including a vent device comprising at least one porous membrane, for example, in accordance with the embodiments of the system illustrated in Figures 1-3, comprises a flexible film forming flexible side walls (in some embodiments, flexible resilient or flexible semi-resilient side walls), and the pouch has at least two ports 41 and 42, e.g., an inlet port and an outlet port. The flexible side walls can expand when air displaced by the biological fluid enters the bag and the walls can partially collapse when the outlet port is opened and air passes through the outlet port. A variety of materials, including commercially available materials, are suitable for producing the pouch. Suitable materials include, for example, plasticized polyvinyl chloride (PVC), ethylene vinyl acetate (EVA), ethylene and an acrylate, polyvinylidene fluoride (PVDF), polytetrafluoroethylene (PTFE), polyester, polyurethane, polycarbonate, polypropylene, polyolefin, polyethylene, and combinations of materials, [0051] Preferably, with respect to the embodiments of a system including a vent device comprising at least one porous membrane, e.g., as illustrated in Figures 1-3, the pouch has a volume at least approximating the volume of air to be displaced by the biological fluid passing from the source container, and through the biological fluid filter device and the downstream conduit. For example, using the illustrative embodiment shown in Figure 1 for reference, the air displaced includes the air in conduits 1 and 2, in biological fluid filter device 10, and conduit 3.

[0052] In accordance with the invention, the compliant pouch has flexible side walls and a volume, wherein the displaced air enters the pouch (typically expanding the side walls) and the system is arranged to initially prevent air from leaving the pouch. The system is arranged such that, when desired (i.e., upon allowing air to leave the pouch), and without the operator manually compressing the side walls, air is directed out of the pouch to the desired location, e.g., a conduit upstream of the biological fluid filter device, displacing biological fluid held up in the upstream conduit(s) and, and allowing an additional volume of biological fluid (displaced by the biological fluid displaced from the upstream conduit) to be collected in a /£ 0 907 03 downstream receiving container. If desired, the system can be arranged to also provide for air displacing biological fluid from the upstream section of the filter housing, allowing additional biological to be displaced and collected in the receiving container. [0053) In accordance with embodiments of the invention including a vent device comprising at least one porous membrane, the pouch can have any suitable volume. Illustratively, the preselected volume can be in the range of, for example, from about 5 mL to about 800 mL, or more, or from about 15 mL to about 600 mL, or more. In some embodiments, the preselected volume is in the range of from about 5 mL to about 70 mL, or in the range of from about 15 mL to about 40 mL. [0054J As noted above, in those embodiments wherein the system includes a vent device comprising at least one porous membrane, the pouch preferably has a volume at least approximating the volume of air to be displaced by the biological fluid passing from the source container, and through the biological fluid filter device and the downstream conduit. The pouch can have a volume greater that of the displaced air. By “a pouch having a volume at least approximating that of the displaced air,” it is meant that the volume ofthe pouch need not be the same as that of the displaced air, it can be greater than the volume of the displaced air.

[0055] In the embodiments illustrated in Figures 4 and 5, the biological fluid processing system 1000 comprises a biological fluid recovery loop 70, the loop comprising a first end 70a and a second end 70b, and a biological fluid recovery pouch 40 interposed between the first end of the loop and the second end of the loop, the pouch 40 comprising flexible side walls and first and second ports 41 and 42, Typically, the biological fluid recovery loop includes at least two biological fluid recoveiy conduits, in the embodiment illustrated in Figure 4, the loop 70 includes 3 conduits, 71,72, and 75, and in the embodiment illustrated in Figure 5, the loop includes 4 conduits, 71,72, 73 and 74. In those embodiments wherein the system does not include a vent device comprising at least one porous medium, the recovery loop typically further comprises at least one, in some embodiments, at least two, fluid control devices, the embodiments illustrated in Figures 4 and 5 show a first fluid control device 50 for controlling fluid communication between first end 70a and the pouch 40, and a second fluid control device 32A (Figure 4) or 32 (Figure 5) for controlling fluid communication between the pouch 40 and the second end 70b.

[0056] In the embodiments illustrated in Figures 4 and 5, the biological fluid processing system 1000 further comprises conduits 1-3 and 17, a first container (or receiving container) 101, a biological fluid filter device 10, interposed between conduit 2 (having a first end 2a and a second end 2b) and a conduit 3 (having a first end 3a and a second end 3b), with a first /£ 0 90 7 03 connector 21 allowing fluid communication between the second end 70b of the loop and the first end 2a of the first conduit, as well as allowing communication with source container 100 via conduit 1, and a second connector 22 allowing fluid communication between the first end 70a of the loop and the second end 3b of the second conduit. Connector 22 also allows fluid communication with first container 101 via conduit 17. Additionally, in these illustrated embodiments, the system 1000 further comprises a third fluid control device 31a (Figure 4) or 31 (Figure 5) for controlling fluid communication between connector 22 and first container 101, and a fourth fluid control device for controlling fluid communication between source container 100 and conduit 1. Similarly, while a fourth fluid control device is shown associated with conduit 1, in another embodiment (not shown), source container 100 can include a fluid control device such as a transfer leg closure in the port of the container communicating with conduit 1.

[0057] The biological fluid recoveiy pouch 40 in accordance with those embodiments of a system without a vent device comprising at least one porous membrane, for example, in the embodiments of the system illustrated in Figures 4 and 5, comprises a flexible film forming flexible side walls (in some embodiments, flexible resilient or flexible semi-resilient side walls), and the pouch has at least two ports 41 and 42, e.g,, an inlet port and an outlet port. The flexible side walls expand when air displaced by the biological fluid enters the bag and the bag is pressurized, and the compliant pouch directs the air out when the outlet port is opened. A variety of materials, including commercially available materials, are suitable for producing the pouch. Suitable materials include, for example, plasticized polyvinyl chloride (PVC), ethylene vinyl acetate (EVA), ethylene and an acrylate, polyvinylidene fluoride (PVDF), polytetrafluoroethylene (PTFE), polyester, polyurethane, polycarbonate, polypropylene, polyolefin, polyethylene, and combinations of materials, [0058] The pouch according to those embodiments of a system without a vent device comprising at least one porous membrane, e.g., in accordance with the embodiments of the system illustrated in Figures 4 and 5, has a preselected volume, wherein the preselected volume is determined based on the approximate volume of air to be displaced by the biological fluid passing from the source container, and through the biological fluid filter device and the downstream conduit. For example, using the illustrative embodiment shown in Figure 4 for reference, the air displaced includes the air in conduits 1 and 2, in biological fluid filter device 10, and conduit 3.

[0059] In accordance with the embodiments of the invention without a vent device comprising at least one porous membrane, e.g., in accordance with the embodiments of the system shown in Figures 4 and 5, the compliant pouch has flexible side walls and a IE 0 90 7 03 preselected volume, wherein the displaced air enters the pouch (expanding the side walls) and the system is arranged to initially prevent air from leaving the pouch. In these embodiments, the system is arranged such that, when desired (i.e,, upon allowing air to leave the pouch), and without the operator manually compressing the side walls, air is directed out of the pouch to the desired location, e.g., a conduit upstream of the biological fluid filter device, displacing biological fluid held up in the upstream conduit(s) and, and allowing an additional volume of biological fluid (displaced by the biological fluid displaced from the upstream conduit) to be collected in a downstream receiving container. If desired, the system can be arranged to also provide for air displacing biological fluid from the upstream section of the filter housing, allowing additional biological to be displaced and collected in the receiving container.

[0060] In accordance with embodiments of the invention without a vent device comprising at least one porous membrane, the pouch can have any suitable preselected volume. Illustratively, the preselected volume can be in the range of, for example, from about 5 mL to about 70 mL, or from about 15 mL to about 40 mL.

[0061] As noted above, in those embodiments of the invention without a vent device comprising at least one porous membrane, the pouch has a preselected volume determined based on the approximate volume of air to be displaced by the biological fluid passing from the source container, and through the biological fluid filter device and the downstream conduit. The pouch has a volume approximating that of the displaced air. By “a pouch having a volume approximating that of the displaced air,” it is meant that the volume of the pouch need not be the same as that of the displaced air, it can be greater than the volume of the displaced air, or, it can be less. In some embodiments, the pouch has a preselected volume in the range of from about 5% to about 10% less than the volume of the displaced air. [0062] Embodiments of the invention, with and without a vent device comprising at least one porous membrane, (e.g., for producing transfusion products, harvesting, and/or sample preparation) can be arranged to recover, for example, in the range of from about 2 mL to about 35 mL, or more, of biological fluid, typically, in the range of from about 5 mL to about 20 mL of biological fluid (e.g., with respect to transfusion products for adults) or from about 2 mL to about 10 mL (e.g., with respect to transfusion products for pediatric applications). [0063] Preferably, for a sterile dockable system, the second end of the biological fluid recovery loop is be arranged such that the system directs air into a conduit as close to the source container 100 as possible, e.g., to allow more of the conduit(s) upstream of the biological fluid filter device to be drained. However, in some embodiments, the second end of the biological fluid loop can be arranged such that the system directs air into a conduit closer to the biological fluid filter device housing, or can be arranged to direct air directly IE Ο 9 Ο 7 Ο 3 into the housing (e.g,, directed to the upstream section of the housing to drain the upstream section). In other embodiments, e.g., wherein the biological fluid system is closed as originally made, the biological fluid recovery loop can be arranged to direct air into the source container (e.g., by connection to a port of the source container).

[0064] The biological fluid processing system typically includes a plurality of flow control devices such as valves, clamps, and/or transfer leg closures (sometimes referred to as in-line frangible valves). A variety of flow control devices are suitable for use in the invention, and are known in the art, [0065] As noted above, in the embodiments illustrated in Figures 1 and 3, the system 1000 includes at least two flow control devices 31 and 32, shown as transfer leg closures, wherein closure 31 is associated with conduit 17 (e.g., in a port of the first container 101), and closure 32 is interposed between conduits 73 and 74 that are between biological fluid recovery pouch 40 and connector 21. In the embodiment illustrated in Figure 2, the system 1000 includes at least two flow control devices 31 and 32a, wherein flow control device 31 is shown as an in-line flow control device such as a transfer leg closure, and flow control device 32a is shown as a clamp, wherein closure 31 is associated with conduit 17, and closure 32a is associated with conduit 75 between biological fluid recovery pouch 40 and connector 21. [0066] In the embodiment illustrated in Figure 4, the system 1000 includes at least two flow control devices 3 la and 32a, shown as clamps, wherein clamp 31a is associated with conduit 17, and clamp 32a is associated with conduit 75 between biological fluid recovery pouch 40 and connector 21. In the embodiment illustrated in Figure 5, the system 1000 includes at least two flow control devices 31 and 32, shown as transfer leg closures, wherein closure 31 is associated with conduit 17, and closure 32 is interposed between conduits 773 and 74 between biological fluid recovery pouch 40 and connector 21.

[6067] The illustrated embodiments shown in Figures 1, 2,4, and 5 also show an optional flow control device 50, preferably, a one-way flow control device such as a check valve, in the biological fluid recovety loop conduit, wherein the valve is preferably interposed between the first end 70a of the biological fluid recovery loop 70 and the biological fluid recovery pouch 40. In an embodiment (not shown), the valve is adjacent to, or in, port 41 of pouch 40. A variety of check valves are suitable for use in the invention and are known in the art. The check valve preferably comprises a normally closed one-way valve that allows unidirectional fluid flow, i.e., allowing forward flow and preventing backflow. Typically, a normally closed one-way valve comprises an elastomeric material providing a sealing element that, upon applied stress (e.g., pressure), opens and allows forward flow, and, upon the release of the stress, returns or rebounds to the original closed position. Exemplary one-way valves IE 0 907 03 comprising elastomeric material include duckbill valves, e.g., including elastomeric lips in the shape of a duckbill; diaphragm valves, e.g., a diaphragm including slits providing two or more elastomeric flaps; and umbrella valves, e.g,, including an elastomeric diaphragm-shaped sealing disk or umbrella shape, typically wherein the sealing disk has a preloaded convex shape to create the sealing force against the port, or valve seat.

[0068] In other embodiments, a check valve is not present and/or a clamp or transfer leg closure can be utilized instead of, or in addition to, a check valve. For example, in another illustrative embodiment (not shown), a clamp is associated with conduit 71 either between check valve 50 and connector 22, or between check valve 50 and vent device 60. In the embodiment shown in Figure 3, there is no flow control device, e.g., neither a check valve nor a clamp, interposed between the pouch 40 and the outlet 63 of vent device 60.

[0069] In accordance with the illustrated embodiments, the biological fluid filter device 10, comprising a housing 15 comprising an upstream section 11 comprising an inlet 13 and a downstream section 12 comprising an outlet 14 and defining a fluid flow path between the inlet and the outlet, and a porous biological fluid filter medium (typically a biological fluid filter comprising at least one porous biological fluid filter element comprising at least one porous biological fluid filter medium) disposed in the housing between the inlet and the outlet and across the fluid flow path, can have a variety of configurations. Illustrative device and housing configurations include, but are not limited to, those disclosed in, for example, U.S. Patent Nos. 4,880,548 and 4,925,572.

[0070] A variety of biological fluid filter devices comprising porous biological fluid filter media (typically biological fluid filter devices comprising biological fluid filters comprising porous biological fluid filter elements comprising porous biological fluid filter media) are suitable for use in the invention. The porous filter elements and porous filter media can comprise fibrous media and/or membranes.

[0071] In a typical embodiment, the biological fluid filter device comprises a leukocyte filter device comprising a porous leukocyte depletion element comprising a porous leukocyte depletion medium. Alternatively, or additionally, in another embodiment, the biological fluid filter device comprises a prion filter device comprising a porous prion depletion element comprising a porous prion depletion medium.

[0072] The filter in the biological fluid filter device may also include, in addition to at least one porous biological fluid filter element, or as a component of at least one filter element, one or more structures having different characteristics and/or functions. For example, the filter can comprise a prefilter and/or additional structures sueh as a mesh or screen, e.g., on the downstream side of the filter element, e.g., for support and/or drainage.

IE Ο 9 Ο 7 Ο 3 2θ Alternatively, or additionally, for example, a filter can include a leukocyte depletion element and a prion depletion element, or an element can comprise a leukocyte and prion depletion element. Illustratively, a leukocyte depletion filter in a leukocyte depletion filter device may also include, in addition to at least one porous leukocyte depletion filter element comprising at least one porous leukocyte depletion medium, one or more of: a prefilter, a porous prion depletion element, a porous prion depletion medium, a porous microaggregate element, a mesh and a screen. In another exemplary illustration, a prion depletion filter in a prion depletion filter device may also include, in addition to at least one porous prion depletion filter element comprising at least one porous prion depletion medium, one or more of: a prefilter, a leukocyte depletion element, a microaggregate element, a mesh and a screen. [0073] A variety of leukocyte depletion filters, leukocyte depletion filter elements, leukocyte depletion media, prion depletion filters, prion depletion filter elements, prion deletion media, prefilters, microaggregate elements, and/or additional structures, e.g., meshes and/or screens, can be used in accordance with the invention. Illustrative leukocyte depletion filters, filter elements and porous media (including fibrous leukocyte depletion elements, prefilters, microaggregate elements) and additional structures include those disclosed in, for example, U.S. Patent Nos. 4,880,548,4,925,572,5,152,905,6,074,869, and 6,231,770, as well as International Publication No. WO 2004/039474.

[0074] The biological fluid processing system 1000 and/or the biological fluid recovery loop 70 can each include additional elements such as one or more conduits, containers, connectors, and/or flow control devices. For example, using the embodiments illustrated in the Figures for reference, the system can include one or more satellite containers in fluid communication with the receiving container. For example, Figures 1-3 show a satellite container and conduit in fluid communication with receiving container 101.

[0075] A variety of conduits and containers, e.g., plasticized tubing and bags, as well as connectors and flow control devices, are suitable for use in the invention, and are known in the art.

[0076] A biological fluid filter element (e.g., a porous leukocyte depletion filter element and/or a porous prion depletion element) and/or a biological fluid filter medium (e.g., a porous leukocyte depletion filter medium and/or a porous prion depletion medium) can have any suitable pore structure, e.g., a pore size (for example, as evidenced by bubble point, or by Kl as described in, for example, U.S. Patent No. 4,340,479), a pore rating, a pore diameter (e.g,, when characterized using the modified OSU F2 test as described in, for example, U.S. Patent No. 4,925,572), that reduces or allows the passage therethrough of one or more materials of interest as the fluid is passed through the element. While it is believed IE 09 07 03 leukocytes are primarily removed by adsorption, they can also be removed by Filtration. The pore structure can be selected to remove at least some level of leukocytes, while allowing desired components to pass therethrough, e.g., at least one of plasma, platelets, and red blood cells. The pore size or removal rating used depends on the composition of the fluid to be treated, and the desired effluent level of the treated fluid. (0077] A filter element and/or a porous medium can have any desired critical wetting surface tension (CWST, as defined in, for example, U.S. Patent No, 4,925,572). Typically, the filter element has a CWST of greater than about 53 dynes/cm (about 53 χ IO5 N/cm), more typically greater than about 58 dynes/cm (about 58 χ 10'5 N/cm), and can have a CWST of about 66 dynes/cm (about 66 χ 105 N/cm) or more. In some embodiments, the element has a CWST of 75 dynes/cm (about 75 χ IO5 N/cm) or more. In some embodiments, the element may have a CWST in the range from about 62 dynes/cm to about 115 dynes/cm (about 62 to about 162 χ 10'5 N/cm), e.g., in the range of about 80 to about 100 dynes/cm (about 80 to about 100 χ 105 N/cm). In some embodiments, the element has a CWST of about 85 dynes/cm (85 χ 10'5 N/cm), or greater, e.g., in the range from about 90 to about 105 dynes/cm (about 90 to about 105 χ 10'5 N/cm), or in the range from about 85 dynes/cm to about 98 dynes/cm (about 85 to 98 χ 10‘5 N/cm).

[0078] The surface characteristics of the element and/or porous medium can be modified (e.g., to affect the CWST, to include a surface charge, e.g., a positive or negative charge, and/or to alter the polarity or hydrophilicity of the surface) by wet or dry oxidation, by coating or depositing a polymer on the surface, or by a grafting reaction. Modifications include, e.g., irradiation, a polar or charged monomer, coating and/or curing the surface with a charged polymer, and carrying out chemical modification to attach functional groups on the surface. Grafting reactions may be activated by exposure to an energy source such as gas plasma, vapor plasma, corona discharge, heat, a Van der Graff generator, ultraviolet light, electron beam, or to various other forms of radiation, or by surface etching or deposition using a plasma treatment.

[0079] A variety of materials are suitable for use as vent elements. Suitable elements, including hydrophilic porous and microporous membranes and hydrophobic porous and microporous membranes are disclosed in, for example, U.S. Patent Nos. 5,126,054 and 5,451,321. The hydrophilic and hydrophobic membranes can have any suitable pore size. Typically, the hydrophilic and/or the hydrophobic membrane has a pore size (preferably, a pore rating) of about 3 micrometers or less, preferably, about 1 micrometers or less, and more preferably, about 0.65 micrometers or less. While a portion of liquid could pass through a porous membrane, e.g., a hydrophilic porous membrane, the operating conditions for using IE Ο 9 Ο 7 Ο 3 the apparatus and the pore size or pore rating (and, in some embodiments, the biological fluid processed, e.g., a cell-containing fluid) are such that, as is known by one of skill in the art, biological fluid does not pass through the vent into the first container.

[0080] The filter and/or vent housing can be fabricated from any suitable rigid impervious material, including any impervious thermoplastic material, which is compatible with the biological fluid being processed. For example, the housing can be fabricated from a metal, such as stainless steel, or from a polymer. In a preferred embodiment, the housing is a polymer, more preferably a transparent or translucent polymer, such as an acrylic, polypropylene, polystyrene, or a polycarbonated resin. Such a housing is easily and economically fabricated, and allows observation of the passage of the biological fluid through the housing.

[0081] The filter and/or vent housing can be sealed utilizing, for example, an adhesive, a solvent, laser welding, radio frequency sealing, ultrasonic sealing and/or heat sealing. Additionally, or alternatively, the housing can be sealed via injection molding.

[0082] A variety of biological fluid filter devices (including leukocyte depletion filter devices and prion depletion devices), biological fluid filter elements and biological fluid filter media (including leukocyte depletion filter elements, leukocyte depletion media, prion depletion filter elements, and prion depletion media), vent devices, conduits, containers, and flow control devices, including those that are commercially available, are suitable for use in accordance with the invention.

[0083] In accordance with embodiments of a method according to the invention, biological fluid is passed from a source container and through a biological fluid filter device, displacing air into the biological fluid recovery pouch of the biological fluid recovery loop. Air is prevented from exiting the pouch, and typically, the walls of the pouch expand. Processed biological fluid, typically filtered biological fluid (e.g., leukocyte depleted biological fluid and/or prion depleted biological fluid), is passed into a receiving container until the source container is empty or essentially empty. Air is then allowed to exit the pouch and the air is directed into the conduit(s) upstream of the filter device and/or into the filter housing, thus displacing previously held-up biological fluid. Displaced biological fluid is collected in a receiving container.

[0084] In one illustrative embodiment of a method wherein the system includes a vent device comprising at least one porous membrane according to the invention, and using the embodiment of the biological fluid processing system illustrated in Figure 1 (wherein biological processing system 1000 has been sterile-docked to a source container 100 containing biological fluid) for reference, flow control devices 31 and 32 are initially closed, ΙΕ ο 9 Ο 7 Ο 3 and check valve 50 is a normally closed valve, A closed flow control device is associated with conduit 1 (alternatively or additionally, for example, source container 100 can includes a transfer leg closure (not shown) in the port communicating with conduit 1), and the transfer leg closure and/or flow control device is/are opened, allowing biological fluid to flow through from the container 100, through conduit 1, connector 21, conduit 2, biological fluid filter device 10, and into conduit 3. Air is displaced by the biological fluid, and passes ahead of the biological fluid and through the conduits and device and through at least the hydrophobic porous membrane 68 in vent device 60, and into biological fluid recovery loop 70. In those embodiments wherein the vent element 67 comprises a hydrophobic porous membrane 68 and a hydrophilic porous membrane, air passes through the hydrophilic membrane and the hydrophobic membrane until the hydrophilic membrane is wetted with biological fluid, and flow stops. Air passes through the first end 70a of the loop, conduit 71, check valve 50, conduit 72, and inlet port 41 into the biological fluid recovery pouch. Since flow control device 32 remains closed, the walls of the pouch typically expand. (0085] Flow control device 31 is opened, and filtered biological fluid passes through conduit 17 into receiving container 101. Once the source container 100 is essentially empty, flow control device 32 is opened. Since a negative pressure is created, e.g., due to gravity and the column of biological fluid downstream of the filter device, air is directed from pouch 40, through outlet port 42, through the second end 70b of the biological fluid recovery loop 70 via conduits 73 and 74, and through connector 21, and upstream conduit 2. The air passing through conduit 2 displaces biological fluid from the conduit, and the displaced biological fluid displaces biological fluid into receiving container 101. Preferably, air passes from conduit 2 into the upstream section 11 of the biological fluid device housing 15, displacing biological fluid from the upstream section of the housing, and additional displaced biological fluid is passed into receiving container 101.

[0086] Using the illustrative embodiment of the system shown in Figure 2 for reference, another embodiment of a method wherein the system includes a vent device comprising at least one porous membrane can be carried out similarly to that described above with respect to Figure 1, wherein flow control devices 31 and 32a (Figure 2) are operated as described with respect to flow control devices 31 and 32 (Figure 1). Thus, flow control devices 31 and 32a are initially closed, and biological fluid flows from the container 100, through conduit 1, connector 21, conduit 2, biological fluid filter device 10, and into conduit 3. Air is displaced by the biological fluid, and passes ahead of the biological fluid and through at least the porous hydrophobic membrane in vent device 60, and into biological fluid recovery loop 70. In those embodiments wherein the vent element comprises a hydrophobic porous membrane IE 0 9 07 03 and a hydrophilic porous membrane, air passes through the hydrophilic membrane and the hydrophobic membrane until the hydrophilic membrane is wetted with biological fluid, and flow stops. Air passes through the first end 70a of the loop, conduit 71, check valve 50, conduit 72, and inlet port 41 into the biological fluid recovery pouch. Since flow control device 32a remains closed, the walls of the pouch typically expand.

[0087] Flow control device 31 is opened, and filtered biological fluid passes through conduit 17 into receiving container 101, Once the source container 100 is essentially empty, flow control device 32a is opened. Since a negative pressure is created, e.g., due to gravity and the column of biological fluid downstream of the filter device, air is directed from pouch 40, through outlet port 42, through the second end 70b of the biological fluid recovery loop 70 via conduit 75, and through connector 21, and upstream conduit 2. The air passing through conduit 2 displaces biological fluid from the conduit, and the displaced biological fluid displaces biological fluid into receiving container 101. Preferably, air passes from conduit 2 into the upstream section 11 of the biological fluid device housing 15, displacing biological fluid from the upstream section of the housing, and additional displaced biological fluid is passed into receiving container 101, [0088] In a variation of the embodiments of the method described above, e.g., to further reduce the chance that biological fluid will enter the first end 70a of the biological fluid recovery loop, a clamp (not shown) is associated with conduit 71 between vent device 60 and check valve 50, and the clamp remains open while air enters the biological fluid recovery pouch 40. Before flow control device 32 (Figure 1) or 32a (Figure 2) is opened, the clamp is closed. Flow control device 32 or 32a is opened and air is directed into conduit 2, displacing biological fluid, as described above.

[0089] Alternatively, using the embodiment of the biological fluid processing system lacking a flow control device such as a clamp or check valve between the vent device and pouch, e,g„ the embodiment illustrated in Figure 3 for reference, flow control devices 31 and 32 are initially closed. A closed flow control device is associated with conduit 1 (alternatively or additionally, for example, source container 100 can includes a transfer leg closure (not shown) in the port communicating with conduit 1), and the transfer leg closure and/or flow control device is/are opened, allowing biological fluid to flow through from the container 100, through conduit 1, connector 21, conduit 2, biological fluid filter device 10, and into conduit 3. Air is displaced by the biological fluid, and passes ahead of the biological fluid and through the conduits and device and through the hydrophilic porous membrane 69 and the hydrophobic porous membrane 68 in vent device 60, and into biological fluid recovety loop 70. Air passes through the hydrophilic membrane and the hydrophobic IE Ο 9 Ο 7 Ο 3 25 membrane until the hydrophilic membrane is wetted with biological fluid, and flow stops (and the wetted hydrophilic membrane does not allow further air passage in either direction through the membrane). Air passes through the first end 70a of the loop, conduit 76, and inlet port 41 into the biological fluid recovery pouch. Since flow control device 32 remains closed, the walls of the pouch typically expand.

[0090] Flow control device 31 is opened, and filtered biological fluid passes through conduit 17 into receiving container 101. Once the source container 100 is essentially empty, flow control device 32 is opened. Since a negative pressure is created, e.g., due to gravity and the column of biological fluid downstream of the filter device, air is directed from pouch 40, through outlet port 42, through the second end 70b of the biological fluid recovery loop 70 via conduits 73 and 74, and through connector 21, and upstream conduit 2. The air passing through conduit 2 displaces biological fluid from the conduit, and the displaced biological fluid displaces biological fluid into receiving container 101. Preferably, air passes from conduit 2 into the upstream section 11 of the biological fluid device housing 15, displacing biological fluid from the upstream section of the housing, and additional displaced biological fluid is passed into receiving container 101.

[0091] In another illustrative embodiment of a method according to the invention, wherein the system does not include a vent device comprising at least one porous membrane, and using the embodiment of the biological fluid processing system illustrated in Figure 4 (wherein biological processing system 1000 has been sterile-docked to a source container 100 containing biological fluid) for reference, flow control devices 31a and 32a are initially closed, and check valve 50 is a normally closed valve. A closed flow control device is associated with conduit 1 (alternatively or additionally, for example, source container 100 can includes a transfer leg closure (not shown) in the port communicating with conduit 1), and the transfer leg closure and/or flow control device is/are opened, allowing biological fluid to flow through from the container 100, through conduit 1, connector 21, conduit 2, biological fluid filter device 10, and into conduit 3. Air is displaced by the biological fluid, and passes ahead of the biological fluid and through the conduits and device and through connector 22, into biological fluid recovery loop 70. Air passes through the first end 70a of the loop, conduit 71, check valve 50, conduit 72, and inlet port 41 into the biological fluid recovery pouch. Since flow control device 32a remains closed, the compliant pouch 40 becomes pressurized with air, and the walls of the pouch expand.

[0092] Flow control device 31 a is opened, and filtered biological fluid passes through conduit 17 into receiving container 101, Once the source container 100 is essentially empty, flow control device 32a is opened. Since a negative pressure is created, e.g., due to gravity IE 0 9 0 7 03 and the column of biological fluid downstream of the filter device, air is directed from pouch 40, through outlet port 42, through the second end 70b of the biological fluid recovery loop 70 via conduit 75, and through connector 21, and upstream conduit 2. The air passing through conduit 2 displaces biological fluid from the conduit, and the displaced biological fluid displaces biological fluid into receiving container 101. Preferably, air passes from conduit 2 into the upstream section 11 of the biological fluid device housing 15, displacing biological fluid from the upstream section of the housing, and additional displaced biological fluid is passed into receiving container 101.

[0093] Using the illustrative embodiment of the system shown in Figure 5 for reference, another embodiment of a method wherein the system does not include a vent device comprising at least one porous membrane can be carried out similarly to that described above with respect to Figure 4, wherein flow control devices 31 and 32 (Figure 5) are operated as described with respect to flow control devices 31a and 32a (Figure 4). Thus, flow control devices 31 and 32 are initially closed, and biological fluid flows from the container 100, through conduit 1, connector 21, conduit 2, biological fluid filter device 10, and into conduit 3. Air is displaced by the biological fluid, and passes ahead of the biological fluid and through connector 22, into biological fluid recovery loop 70, Air passes through the first end 70a of the loop, conduit 71, check valve 50, conduit 72, and inlet port 41 into the biological fluid recovery pouch. Since flow control device 32a remains closed, the compliant pouch 40 becomes pressurized with air, and the walls of the pouch expand.

[0094] Flow control device 31 is opened, and filtered biological fluid passes through conduit 17 into receiving container 101. Once the source container 100 is essentially empty, flow control device 32 is opened. Since a negative pressure is created, e.g., due to gravity and the column of biological fluid downstream of the filter device, air is directed from pouch 40, through outlet port 42, through the second end 70b of the biological fluid recovery loop 70 via conduits 73 and 74, and through connector 21, and upstream conduit 2, The air passing through conduit 2 displaces biological fluid from the conduit, and the displaced biological fluid displaces biological fluid into receiving container 101. Preferably, air passes from conduit 2 into the upstream section 11 of the biological fluid device housing 15, displacing biological fluid from the upstream section of the housing, and additional displaced biological fluid is passed into receiving container 101.

[0095] In a variation of the embodiments of the method for processing biological fluid in a system without a vent device comprising at least one porous medium described above, e.g., to further reduce the chance that biological fluid will enter the first end 70a of the biological fluid recovery loop, a clamp (not shown) is associated with conduit 71 between connector 22 IE 09 07 03 27 and check valve 50, and the clamp remains open while biological fluid recovery pouch 50 is pressurized. Before flow control device 32a (Figure 4) or 32 (Figure 5) is opened, the clamp is closed. Flow control device 32 or 32a is opened and air is directed into conduit 2, displacing biological fluid, as described above, [0096] The following examples further illustrate the invention but, of course, should not be construed as in any way limiting its scope.

EXAMPLE 1 [0097] This example shows a sterile dockable system can be provided and blood can be filtered while maintaining a closed biological fluid processing system, to provide filtered blood product in an effluent bag, while, without a labor intensive effort, displacing air in the system and re-directing it into upstream tubing and into the upstream portion of the biological fluid filter housing to allow blood that would typically be held up in the tubing and filter to be drained and recovered in the effluent bag.

[0098] A biological fluid processing system comprising a biological fluid recovery loop as generally shown in Figure 1 is assembled. For ease of reference, the system is described below using the reference numbers in Figure 1.

[0099] The check valve 50 is a Vemay® 1300-243 (Vemay Laboratories, Inc., Yellow Springs, OH), having a breakaway pressure of at least 30 inches water column.

[0100] The clamp 32 is an in-line breakaway valve (transfer leg closure).

[0101] Upstream conduit 2 and downstream conduit 3 are 5,5 inches and 4.5 inches in length, respectively. Conduit 71 is 4 inches in length, and conduits 72,73 and 74 are each 1 inch in length. The conduits are commercially available PVC tubing.

[0102] The biological fluid filter device is a commercially available prion depletion device (Pall Affinity Prion Reduction Filter) from Pall Corporation, East Hills, NY, The upstream section 11 of the filter device housing has a volume of about 14 mL.

[0103] The vent element 67 in the vent device 60 is a hydrophobic microporous membrane 68 superimposed on a hydrophilic microporous membrane (not shown in drawing).

[0104] The biological fluid recovery pouch is a pouch formed from plasticized PVC film, and has an internal volume of about 600 mL.

[0105] The system is connected, via sterile docking, to a source bag containing 300 mL leukoreduced S AG-M-added red cells. Clamps 31 and 32 are initially closed, and the check IE 0 9 0 7 03 valve 50 is a normally closed valve. The red cells are filtered from about a 45 inch head height with the filter device located about 7 inches above the receiving container 101.

[0106] Red cells are passed from the source bag and through the filter device, thus priming the device. Air is displaced through the hydrophilic membrane, the hydrophobic membrane, and the check valve, into the recovery pouch. Once the filter device is fully primed, e.g., the filtered red cells pass through the conduit downstream of the filter device and contact the hydrophilic membrane in the vent device, clamp 31 is opened, and the filtered red cells pass into the receiving container.

[0107] Once source container 100 is essentially empty, clamp 32 is opened, and air is directed into conduit 2, upstream of the filter device, displacing red cells into the receiving container. As air passes toward the filter device housing 15, additional filtered red cells are displaced into the receiving container. Once the upstream section of the housing is essentially drained of red cells, liquid flow stops, as the air does not pass through the wetted filter medium.

[0108] About 14 mL of held-up red cells is recovered using the biological fluid recovery loop, with most of the red cells being recovered in about 5 minutes. By the end of about 10 minutes, no additional fluid is recovered.

[0109] Recovering the held-up red cells does not significantly add to the processing time for obtaining the filtered red cells.

EXAMPLE 2 [0110] This example shows a sterile dockable system without a vent device comprising at least one porous membrane can be provided and blood can be filtered while maintaining a closed biological fluid processing system, to provide filtered blood product in an effluent bag, while, without a labor intensive effort, displacing air in the system and re-directing it into upstream tubing and into the upstream portion of the biological fluid filter housing to allow blood that would typically be held up in the tubing and filter to be drained and recovered in the effluent bag.

[0111] A biological fluid processing system comprising a biological fluid recovery loop as shown in Figure 4 is assembled. For ease of reference, the system is described below using the reference numbers in Figure 4.

[0112] The check valve is a Vemay® 1300-243 (Vemay Laboratories, Inc., Yellow Springs, OH), having a breakaway pressure of at least 30 inches water column.

[0113] Upstream conduit 2 and downstream conduit 3 are each 4 inches in length. Conduits 71,72, and 75 are, respectively, 2 inches, 1 inch, and 1.5 inches, in length. The IE 0 9 0 7 0 3 conduits are commercially available PVC tubing. The internal volume of the conduits is about .2 mL/inch of conduit.

[0114] The biological fluid filter device is a commercially available prion depletion device (Pall Affinity Prion Reduction Filter) from Pall Corporation, East Hills, NY. The upstream section 11 of the filter device housing has a volume of about 8 mL.

[0115] The volume of air to be displaced by the blood product is about 47 mL.

[0116] The biological fluid recovery pouch is a compliant pouch formed from plasticized PVC film, and has an internal volume of about 47 mL (about the volume of air displaced by the biological fluid). The film, when tested by ISO 3826, plastics collapsible containers for human blood and blood components, has a tensile (machine direction) of at least 3200 psi, a tensile (cross direction) of at least 3000 psi, an elongation (machine direction) of at least 300%, and an elongation (cross direction) of at least 325%.

[0117] The system is connected, via sterile docking, to a source bag containing 100 mL leukoreduced SAG-M-added red celts. Clamps 31a and 32 are initially closed, and the check valve 50 is a normally closed valve. The red cells are filtered from a 30 inch head height with the filter device located about 7 inches above the receiving container 101.

[0118] 10 units of 100 mL leukoreduced SAG-M-added red cells are each processed as follows:

[0119] Red cells are passed from the source bag and through the filter device, thus priming the device. Air is displaced through the check valve into the recovery pouch, and the walls ofthe pouch expand. Once the filter device is fully primed, e.g., the filtered red cells pass through the conduit downstream of the filter device toward connector 22, clamp 3 la is opened, and the filtered red cells pass into the receiving container.

[0120] Once source container 100 is essentially empty, clamp 32 is opened, and air is directed into conduit 2, upstream of the filter device, displacing red cells into the receiving container. As air passes toward the filter device housing 15, additional filtered red cells are displaced into the receiving container. Once the upstream section of the housing is essentially drained of red cells, liquid flow stops, as the air does not pass through the wetted filter medium.

[0121] On the average: about 9 mL of held-up red ceils is recovered using the biological fluid recovery loop, about 47 mL of air is contained in the pouch after priming, and about 29 mL of air remains in the pouch after recovering the held-up red cells. Recovery of the held-up cells is completed in about 5 minutes, [0122J Recovering the held-up red cells does not significantly add to the processing time for obtaining the filtered red cells.

IE ο 9 0 7 0 3 |0123| All references, including publications, patent applications, and patents, cited herein are hereby incorporated by reference to the same extent as if each reference were individually and specifically indicated to be incorporated by reference and were set forth in its entirety herein.

[0124] The use of the terms “a” and “an” and “the” and similar referents in the context of describing the invention (especially in the context of the following claims) are to be construed to cover both the singular and the plural, unless otherwise indicated herein or clearly contradicted by context. The terms “comprising,” “having,” “including,” and “containing” are to be construed as open-ended terms (i.e., meaning “including, but not limited to,”) unless otherwise noted. Recitation of ranges of values herein are merely intended to serve as a shorthand method of referring individually to each separate value falling within the range, unless otherwise indicated herein, and each separate value is incorporated into the specification as if it were individually recited herein. All methods described herein can be performed in any suitable order unless otherwise indicated herein or otherwise clearly contradicted by context. The use of any and all examples, or exemplary language (e.g., “such as”) provided herein, is intended merely to better illuminate the invention and does not pose a limitation on the scope of the invention unless otherwise claimed. No language in the specification should be construed as indicating any non-claimed element as essential to the practice of the invention.

[0125] Preferred embodiments of this invention are described herein, including the best mode known to the inventors for carrying out the invention. Variations of those preferred embodiments may become apparent to those of ordinary skill in the art upon reading the foregoing description. The inventors expect skilled artisans to employ such variations as appropriate, and the inventors intend for the invention to be practiced otherwise than as specifically described herein. Accordingly, this invention includes all modifications and equivalents of the subject matter recited in the claims appended hereto as permitted by applicable law. Moreover, any combination of the above-described elements in all possible variations thereof is encompassed by the invention unless otherwise indicated herein or otherwise clearly contradicted by context.

Claims

1. CLAIM(S):

I. A biological fluid processing system comprising: (a) a biological fluid filter device, comprising a porous depletion medium, and a housing comprising an upstream section comprising an inlet and a downstream section comprising an outlet, the housing defining a fluid flow path between the inlet and the outlet, wherein the depletion medium is disposed in the housing between the inlet and the outlet and across the fluid flow path; (b) a first conduit, upstream of the filter device, the first conduit having a first end and a second end, wherein the second end of the first conduit is in fluid communication with the inlet of the filter device; (c) a second conduit, downstream of the filter device, the second conduit having a first end and a second end, wherein the first end of the second conduit is in fluid communication with the outlet of the filter device; (d) a vent device, comprising a vent housing comprising a first inlet, a first outlet, and a second outlet, the vent device defining a first fluid flow path between the first inlet and the first outlet, and defining a second fluid flow path between the first inlet and the second outlet, the vent housing containing a vent element comprising at least a hydrophobic porous membrane disposed between the first inlet and the second outlet across the second fluid flow path, the vent device being arranged downstream of the filter device, and in fluid communication with the second conduit; and, (e) a biological fluid recovery loop having a first end and a second end, wherein the first end of the recovery loop is in fluid communication with the second end of the second conduit and the vent device, and the second end of the recovery loop is in fluid communication with the first end of the first conduit, the recovery loop comprising: (i) at least one biological fluid recovery conduit having a first end and a second end; and (ii) a biological fluid recovery pouch comprising flexible side walls and at least a first port and a second port; IE 09 0 7 03 wherein the system is arranged to allow gas to pass from the biological fluid recovery pouch through the second end of the recovery loop and into the first conduit without compressing the biological fluid recovery pouch.
2. The system of claim 1, arranged to also displace biological fluid from the upstream section of the housing, and to pass additional displaced biological fluid into the receiving container,
3. The system of claim 1 or 2, comprising a sterile-dockable system.
4. The system of any one of claims 1 -3, wherein the biological fluid recovery loop further comprises a unidirectional flow valve, interposed between the first port of the biological fluid recovery pouch, and the first end of the recovery loop.
5. The system of any one of claims 1 -4, wherein the biological fluid recovery loop further comprises a fluid control device interposed between the second port of the biological fluid recovery pouch, and the second end of the biological fluid recovery loop.
6. The system of any one of claims 1 -5, wherein the fluid control device comprises an in-line frangible valve,
7. The system of any one of claims 1-6, wherein the biological fluid recovery pouch has a volume of at least about 5 mL.
8. The system of any one of claims 1-7, wherein the biological fluid recovery pouch has a volume in the range of from about 15 mL to about 600 mL.
9. The system of any one of claims 1 -8, wherein the system is arranged to recover in the range of from about 2 mL to about 35 mL of held up biological fluid.
10. The system of any one of claims 1-9, wherein the system is arranged to recover in the range of from about 2 mL to about 20 mL of held up biological fluid.
11. The system of any one of claims 1-10, wherein the biological fluid filter device comprises a leukocyte depletion filter device and/or a prion depletion device,
12. The system of any one of claims 1-11, wherein the vent element further comprises a hydrophilic porous membrane.
13. A method of processing biological fluid comprising: IE 0 907 03 passing biological fluid through an upstream conduit and a porous biological fluid filter medium disposed in a housing comprising an upstream section and a downstream section, and displacing air through at least a hydrophobic porous membrane in a vent device and into a biological fluid recovery pouch in a biological fluid recovery loop comprising, 5 wherein air is prevented from passing out of the pouch; directing air from the pouch into the upstream conduit and displacing biological fluid from the conduit; and, collecting displaced biological fluid in a receiving container.
14. The method of claim 13, including directing air into the upstream section of 10 the housing and collecting an additional volume of displaced biological fluid in the receiving container,
15. The method of claim 13 or 14, wherein the filter medium comprises a prion depletion and/or a leukocyte depletion medium, and the method comprises depleting prions and/or leukocytes from the biological fluid.