Technical Field This invention relates to a bag filter, preferably a bag filter for filtering biological fluids such as blood or blood components.

Background of the Invention Bag filters can be used in variety of filtering applications. Typically, a bag filter is formed from one or more sheets of fibrous nonwoven webs that are folded into a tubular form, and then the adjoining portions and one end of the tube are sewn together.

The resulting bag is turned inside-out, and then the seams are heat-sealed with thermoplastic tape. The bag filter thus produced has two seams, namely a side seam and an end seam.

Bag filters produced by sewing and heat-sealing have certain deficiencies. Since the filter medium and/or the seams have been punctured by the sewing needle and are held together by the thread, the structural integrity of the seam and/or the medium, and hence that of the bag filter itself, is weakened. Moreover, sewn seams can provide fluid leakage pathways during use, thereby allowing unfiltered fluid to bypass the filter medium. In addition, the method of producing such bag filters is time-consuming and costly because of the number of steps involved when the seams are sewn and heat-sealed with thermoplastic tape.

Some bag filters are formed by merely gluing or thermally sealing the seams, i.e., bonding the fibrous web to itself without any sewing. Although such sealing techniques avoid the need to puncture the fibrous nonwoven web with a sewing needle, the gluing and thermal sealing techniques also result in two seams, and suffer from other drawbacks. For example, the thermal sealing technique requires the partial melting of the fibrous nonwoven web, thereby adversely affecting the structural integrity and

filtering characteristics of the bag filter. Additionally, gluing or heat-sealing may fail to provide a strong mechanical bond, and the filter thus produced may be unsuitable for use in rugged environments.

Felt bag filters have been used in cardiotomy reservoirs during surgery to remove surgical debris such as bone chips, fat, and clots from blood before returning the blood to the patient. However, these devices, which are used in an extracorporeal circuit, have suffered from a number of deficiencies. For example, the bag filter may leak and/or lack sufficient structural integrity for the reasons set forth above. Thus, the device including the bag filter may require additional elements, e.g., for support.

Additionally or alternatively, the filter may lack sufficient dirt capacity to remove all of the surgical debris without clogging over the course of the surgical procedure. This can be a particular problem, since replacing a cardiotomy reservoir during a surgical protocol can be a labor intensive effort. For example, replacing the device requires disconnecting a number of conduits from the device, and then priming the replacement device before use.

Moreover, blood includes varying amounts of leukocytes, and the contact of the blood with the various components of the extracorporeal circuit (e.g., the conduits and the cardiotomy reservoir) may cause the leukocytes in the blood to become activated.

This is a concern since these activated leukocytes may inflict damage to internal organs.

The activated leukocytes may release agents that can disrupt and destroy normal cellular functions, and cause other injuries. For example, the most common leukocyte, the granulocytic neutrophil, has been implicated as the mediator of tissue destructive events in a variety of disorders, including reperfusion injury, respiratory distress syndromes, and pulmonary edema. However, conventional cardiotomy reservoirs are not designed to remove leukocytes from blood before the blood is returned to the patient.

Accordingly, there is a need for improved bag filters that avoids the problems with sewn and/or thermally sealed seams. There is also a need for a bag filter that can be used in a cardiotomy reservoir, particularly to remove undesirable material such as leukocytes from blood before returning the blood to a patient. 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.

Summarv of the Invention In accordance with the present invention, a bag filter is provided having an open end and a closed end, wherein the closed end is formed without an end seam.

Preferably, the bag filter comprises a filter element comprising a polymeric porous medium including a continuum of polymeric material extending from the open end through the closed end, wherein the filter is formed without a side seam or an end seam.

The filter can be used to process a variety of fluids, and is especially useful for filtering a biological fluid such as blood or a blood component. In an embodiment, the bag filter is placed in a device such as a cardiotomy reservoir or a drip chamber, and can be used to deplete leukocytes from a biological fluid.

Brief Description of the Drawings Figure 1 is a cross-sectional view of embodiment of the present invention, illustrating a cardiotomy reservoir including a bag filter.

Figure 2 is a schematic illustration of an embodiment of a system according to the present invention, including a cardiotomy reservoir including a bag filter.

Figure 3 is a side view of a melt-blowing apparatus showing the translation of a collector having a cap at one end.

Figure 4 is an end view of a melt-blowing apparatus with two rows of angled and offset fiberizing nozzles.

Figure 5 is a top view of the apparatus illustrated in Figure 4 as seen along line A-A of Figure 4.

Figure 6 is a cross-sectional view of another embodiment of the present invention, illustrating a drip chamber including a bag filter.

Figure 7 illustrates a collector and a variety of different collector caps that can be used to produce bag filters in accordance with the invention. Figure 7A illustrates a collector and one cap. Figures 7B - 7F illustrate other collector caps.

Figure 8 is a cross-sectional view of another embodiment of the present invention, illustrating a cardiotomy reservoir including a bag filter, and further comprising a vent including a porous medium for passing gas therethrough.

Specific Description of the Invention In accordance with an embodiment of the invention, a filter is provided comprising a filter medium formed into a bag configuration with an opening, an inside surface, and an outside surface, said filter being free of an end seam on at least one end.

An embodiment of the present invention also provides a filter comprising a cylindrical filter element comprising a porous medium, the element having a first end, a second end, and a hollow interior, wherein the second end is closed without an end seam.

In an embodiment, the instant invention also provides a filter comprising a cylindrical filter element comprising a polymeric porous medium, said element having an open end, a closed end, and a hollow interior, wherein the element comprises a continuum of polymeric material at the closed end.

In a preferred embodiment, the filter comprises a continuum of polymeric material extending from the open end through the closed end.

The filter, which can be used to filter a variety of fluids, especially biological fluids such as blood and blood components, is typically placed in a housing.

An embodiment of the filter device according to the invention comprises a housing having an inlet and an outlet, and defining a fluid flow path between the inlet and the outlet; a filter disposed in the housing across the fluid flow path, the filter comprising a cylindrical filter element comprising a porous medium, the element having a first end, a second end, and a hollow interior, wherein the second end is closed without an end seam.

In an embodiment, the present invention also provides a filter device comprising a housing having an inlet and an outlet, and defining a fluid flow path between the inlet and the outlet; a filter disposed in the housing across the fluid flow path, the filter comprising a cylindrical filter element comprising a porous medium, the element having an open end, a closed end, and a hollow interior, wherein the element comprises a continuum of material at the closed end.

In accordance with an embodiment of the instant invention, a method for filtering a fluid is provided comprising passing the fluid through a bag filter comprising a cylindrical filter element comprising a porous medium, the element having a first end, a second end, and a hollow interior, wherein the second end is closed without an end

seam.

In an embodiment, the present invention also provides a method for processing a biological fluid comprising passing a biological fluid containing undesirable material through a bag filter comprising a cylindrical filter element comprising a porous medium, the element having a first end, a second end, and a hollow interior, wherein the second end is closed without an end seam, wherein passing the biological fluid through the filter depletes undesirable material from the biological fluid.

Systems for filtering fluids are also provided, wherein the systems include a filter according to the invention.

Preferably, filters, devices, methods and systems according to the present invention provide for depleting leukocytes from a biological fluid.

The following definitions are used in accordance with the invention: (A) Biological Fluid. A biological fluid includes any treated or untreated fluid (including a suspension) 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 solutions; blood components, such as platelet concentrate (PC), platelet-rich plasma (PRP), platelet-poor plasma (PPP), platelet-free plasma, plasma, serum, 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; red cells separated from plasma and resuspended in physiological fluid; and platelets separated from plasma and resuspended in physiological 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.

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.

(B) Porous Medium. The porous medium of the bag filter is a medium through which a fluid, typically a biological fluid (e.g., blood or at least one blood component) passes. The porous medium has two opposing sides (e.g., an upstream side and an opposing downstream side, in relation to a biological fluid to be treated by being passed through the porous medium), with a central portion therebetween. The pores in the porous medium generally enable fluid communication between the two opposing sides (e.g., between the upstream and downstream sides) of the porous medium.

The porous medium typically removes one or more undesirable substances from the fluid. For example, the porous medium can remove at least one complement component, protein and/or fragment (including biologically active fragments such as C3a); lipids (including lipid globules, lipid droplets, and lipid particulates); coalesced particles; clots; bone fragments; gels; aggregates; microaggregates; and/or leukocytes from a biological fluid.

The porous medium of the bag filter comprises a fibrous medium. Preferably, the porous medium comprises a fibrous nonwoven web, more preferably a melt-blown fibrous nonwoven web wherein material is fiberized by extrusion into a high velocity gas stream and collected as a mass of mechanically entangled or intertwined fibers. The porous medium can be multilayered and/or a composite of different materials and/or media. The porous medium may also include one or more structures having different characteristics and/or functions. For example, the porous medium can comprise a filter providing for leukocyte depletion, as well as prefiltration and/or microaggregate removal. In some embodiments, the porous medium can also provide for defoaming and/or venting.

The porous medium is configured as a bag filter. Preferably, the bag filter lacks an end seam at the closed end, i.e., the end is formed as a continuum of material without joining the material by sewing and/or melting the formed material. In a more preferred embodiment, the bag filter is formed without a side seam and without an end seam, i.e., the continuum of material extends from the closed end of the filter to include the sides of the filter. In an illustrative embodiment, wherein the bag filter comprises a cylindrical filter element, the continuum extends from the closed end of the filter to include the cylindrical side walls defining the body of the filter.

The filter may include portions or areas wherein fiber-to-fiber bonding is increased. For example, the filter can include self-bonded fibers, e.g., on the upstream and/or downstream surface of the filter, so that the fiber-to-fiber bonding provides support and/or drainage.

The bag filter may comprise other structures or layers in addition to the filter material, such as an inner liner and outer wrap of a non-woven material such as of polypropylene. The bag filter may include an end cap. The bag filter may also comprise a mesh, screen, and/or membrane. The additional structures can provide, for example, support, drainage, venting and/or defoaming.

A variety of materials can be used to produce the porous medium of the bag filter, which typically comprises a polymeric structure. In a preferred embodiment, the porous medium comprises a leukocyte depletion medium. Suitable materials include, but are not limited to, synthetic polymeric material, such as, for example, polybutylene terephthalate (PBT), polyethylene, polyethylene terephthalate (PET), polypropylene, polymethylpentene, polyvinylidene fluoride, nylon 6, nylon 66, nylon 612, nylon 11, and nylon 6 copolymers.

In one embodiment, the leukocyte depletion medium comprises a medium prepared from melt-blown fibers. Illustratively, U.S. Patent Nos. 4,880,548; 4,925,572; 5,152,905; 5,258,127, and 5,443,743; and International Publication No. WO 96/03194, disclose leukocyte adsorption media comprising melt-blown fibers. The leukocyte depletion medium can include a plurality of layers.

The porous medium of the bag filter is preferably treated for increased efficiency in processing a biological fluid. For example, the medium may be surface modified to affect the critical wetting surface tension (CWST) of the medium, as described in, for example, U.S. Patent Nos. 4,880,548; 4,925,572; 5,152,905; 5,258,127, and 5,443,743; and International Publication Nos. WO 93/04763 and WO 96/03194.

Preferably, the porous medium of the bag filter according to the invention, which is, more preferably, a porous synthetic polymeric medium, has a CWST of greater than about 58 dynes/cm. For example, the medium may have a CWST in the range from about 60 dynes/cm to about 115 dynes/cm, e.g., in the range of about 61 to about 100 dynes/cm. In some embodiments, the medium has a CWST of about 62 dynes/cm, or greater, e.g., in the range from about 63 to about 70 dynes/cm, or in the range from

about 85 dynes/cm to about 98 dynes/cm.

Surface characteristics of the medium can be modified by chemical reaction including wet or dry oxidation, by coating or depositing a polymer on the surface, or by a grafting reaction. Grafting reactions may be activated by exposure to an energy source such as gas plasma, 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.

Each of the components of the invention will now be described in more detail below. In the following description, like components have like reference numbers.

In accordance with the invention, a bag filter comprises a filter element comprising a porous medium formed into a bag configuration with an open end, an inside surface, an outside surface, and a closed end, wherein the filter is free of an end seam at the closed end. Typically, the bag filter is placed in a housing.

In the exemplary embodiment illustrated in Figure 1, device 100 comprises a housing 7, having a plurality of inlets 1, and at least one outlet 3, and a bag filter 4 disposed across the fluid flow path between the inlet(s) and the outlet. The bag filter 4, which is free of an end seam, has an inner surface 11, an outer surface 12, an open end 9, and a closed end 10. In this illustrated embodiment, device 100 includes a collar or sleeve 8 that engages the open end 9 of bag filter 4, and also includes a retainer 6 to further secure the bag filter in the housing. The illustrated device also includes a vent port 2, as well as a defoaming element 5 upstream of the bag filter 4.

Optionally, the device includes a delivery port 13 (in dotted lines). In the exemplary embodiment illustrated in Figure 8, the device also includes a vent 19, in fluid communication with an inlet 1, the vent 19 having a porous structure 21 that allows gas to pass therethrough. Typically, the ports are capped or covered until the device is connected to other components of a processing system such as a pump and/or another component of a biological fluid processing system.

In an embodiment, the device 100 comprises a cardiotomy reservoir for use in a biological fluid processing system, more preferably, an extracorporeal blood treatment system. For example, as illustrated in Figure 2, device 100 is interposed between a source of biological fluid such as a patient, and a container 30 for biological fluid such as a venous reservoir for blood. One or more pressure differential generators 70 such as

peristaltic pumps pass blood from the patient to the device 100 along conduits 61 (e.g., a cardiotomy sucker line) and 62 (e.g., a ventricular vent line). The bag filter 4 filters the blood, e.g., to remove surgical debris and, more preferably, to deplete the blood of leukocytes, and the filtered blood is passed along conduit 63 and collected in container 30. Typically, at least a portion of the blood is subsequently passed along through an oxygenator 50 and an arterial filter 40 and returned to the patient via conduits 64, 65, and 66, respectively. In the illustrated system, blood may also be passed from the patient to the container 30 along conduit 67 (e.g., a venous line).

In another exemplary embodiment, e.g., as illustrated in Figure 6, device 100 comprises a drip chamber, comprising a housing 7, having an inlet 1 and an outlet 3, and a bag filter 4 disposed across the fluid flow path between the inlet and the outlet.

The bag filter 4 has an inner surface 11, an outer surface 12, an open end 9, and a closed end 10. The filter is free of an end seam, and is preferably also free of a side seam. The filter may be of any suitable configuration and size. Typically, it is generally cylindrical in shape. In one embodiment, the cylindrical shape includes a taper along at least a portion of the length of the filter.

As noted above, the filter can be any suitable size. Illustratively, the filter can have a length of about 1 cm or more. In some embodiments, the length is in the range of about 2.5 cm, to about 2 meters, or more. Typically, the length of the filter is in the range of about 1.3 cm to about 75 cm. In one embodiment, the length of the filter is in the range of about 10 cm to about 36 cm.

Illustrative diameters can be about 1 cm or more, more preferably, about 3 cm or more. In some embodiments, the diameter is in the range of about 5 cm to about 200 cm. In other embodiments, the diameter is greater than about 200 cm. Typically, the diameter of the filter is in the range of about 4 cm to about 30 cm.

The diameter of the filter can be substantially uniform along its length.

Alternatively, portions of the filter may have different diameters. For example, as noted above, the filter can be tapered along at least a portion of its length.

The fibers can have any suitable average fiber diameter, or a range of suitable fiber diameters. Illustrative average fiber diameters are about 1 clam, or less, to about 50 cm, or more. Typically, the average fiber diameters are about 1.5 ym to about 40 ym.

Illustrative fiber densities are about .05 g/cc to about .4 g/cc, typically about .10

g/cc to about .25 g/cc. Illustrative voids volumes are about 95% to about 50%, typically about 90% to about 75%.

The porosity of the filter medium of the bag filter may be any desired value.

Typically, the bag filter has a tapered or graded pore structure, with decreasing pore size from the inside surface of the bag filter to the outside surface of the bag filter, which will be in the usual direction of filtration flow. In an embodiment, the pore size decreases from the inside surface and approaching the outside surface, and then increases at the outside surface.

Generally, in those embodiments wherein the bag filter has a tapered or graded pore structure, the filter has a different density and/or a different fiber diameter along the fluid flow path through the medium. For example, the fiber diameter can be greater at the inside surface than at the outside surface. Alternatively, or additionally, the fiber density can be lesser at the inside surface than at the outside surface.

In some embodiments, the bag filter has two or more elements having different pore structures, or the filter comprises a single element providing the different pore structures. In some embodiments of the invention, particularly in some of the embodiments involving the processing of a biological fluid, the tapered or grade pore structure is capable of providing for the progressive removal of clots and/or bone fragments, microaggregates, and leukocytes, if these materials are present in the biological fluid. Illustratively, as the biological fluid passes from the inside surface of the filter to the outside surface, clots, gels and/or larger debris such as bone chips can be removed in the portion or the section of the filter having the larger pores, and microaggregates can be removed in the portion or section of the filter having the intermediate size pores. The majority of the leucocytes that are removed by the bag filter are typically removed in the portion or the section of the filter having the smaller pores. In an embodiment, the pore structure is initially tapered or graded as described above, and the pores increase in size at the downstream surface. Such a configuration may provide support and/or assist in coalescing bubbles, for example.

In an embodiment of the invention, the filter medium has a more "open" pore structure, e.g., a larger pore size, toward the open end of the filter than at the closed end of the filter.

In some applications, e.g., wherein the fluid to be filtered contains a greater level

of undesirable material such as surgical debris, the use of a larger pore size toward the open end of the filter provides some filtration while reducing the potential for an interruption in fluid flow. Thus, the filter provides a type of automatic bypass system, while providing some level of filtration efficiency.

Illustratively, the accumulation of surgical debris such as bone chips and clots near the closed end of the filter can prevent fluid flow through the smaller pores, and the level of fluid in the filter can rise. However, the larger pores near the open end may offer less resistance to fluid flow. Thus, the fluid can pass through the upper portions of the filter, and some undesirable material will still be removed from the fluid.

Embodiments of the bag filter can be used with or without a housing. Typically, the bag filter is disposed in a housing having an inlet and an outlet and defining a fluid flow path between the inlet and the outlet, wherein the bag filter is disposed across the fluid flow path. Preferably, the bag filter is disposed in a housing to provide "inside/out" fluid flow, i.e., fluid flow from the inside surface of the bag filter to the outside surface of the filter. However, other arrangements, e.g., "outside/in" to provide fluid flow from the outside surface of the bag filter to the inside surface, may also be suitable.

Figures 1 and 8 illustrate exemplary embodiments of a device 100 comprising a housing 7, having at least one inlet 1, and at least one outlet 3, and defining a fluid flow path between the inlets and the outlet. The device 100 also includes a bag filter 4 disposed across the fluid flow path between the inlets and the outlet. The bag filter 4 has an inner surface 11, an outer surface 12, an open end 9 and a closed end 10, and is disposed in the housing to provide "inside/out" fluid flow.

Typically, the device 100 includes a structure arranged to engage the filter.

Accordingly, using Figure 1 for reference, device 100 can include a collar or sleeve 8 that allows engagement with the open end 9 of bag filter 4. For example, the collar or sleeve can slidably or frictionally engage the open end of the filter. The illustrated device further includes a retainer or tie 6 (e.g., a retainer strip or an 0 ring) to further secure the bag filter in the housing. In another arrangement for engaging the filter with the housing (not shown), the bag filter includes a collar attached thereto, and the collar engages with the housing.

In some embodiments, particularly those embodiments wherein air (or any other

type of gas) is present, the device may also provide for separating the air or gas from the fluid to be filtered. For example, the device may also include a vent and/or a defoaming element. Alternatively, or additionally, the bag filter can provide for venting and/or defoaming. Illustratively, in one embodiment wherein the bag filter provides for defoaming, the efficiency of defoaming is further improved by treating the bag filter with an antifoaming agent, or including an antifoaming agent while forming the bag filter.

In an embodiment, particularly in an embodiment wherein device 100 comprises a cardiotomy reservoir, the device includes a vent and provides for defoaming. In some embodiments, the bag filter 4 provides for defoaming by coalescing bubbles of air, and the larger bubbles are vented. Of course, the device can include a separate structure, e.g., a defoaming element, that coalesces bubbles of air. In the embodiment illustrated in Figure 1, device 100 includes a vent port 2 and a defoaming element 5 located upstream of the bag filter 4. In the embodiment illustrated in Figure 8, device 100 includes a vent 19 including a porous structure 21 that allows gas to pass therethrough.

In other embodiments (not shown), the device can include, for example, a vent including a porous structure, and a defoaming element downstream of the bag filter. In other illustrative embodiments, the device can include a vent including a porous medium, wherein the device either lacks a defoaming element, or has defoaming elements upstream and downstream of the bag filter.

A variety of defoaming elements 5 are suitable for carrying out the invention, and the element can be disposed upstream and/or downstream of the bag filter.

Additionally, the defoaming element can be treated with antifoaming agents as is known in the art. Moreover, as noted earlier, the bag filter can be treated with, or formed while including at least one defoaming agent. Suitable defoaming elements include, but are not limited to, those disclosed in U.S. Patent Nos. 4,572,724 and 5,362,406, and open cell foams, e.g., polyurethane foams.

The embodiment illustrated in Figure 1 includes a plurality of ports, i.e., three inlets 1, an outlet 3, a vent 2, as well as an optional delivery port 13 (dotted lines).

Typically, delivery port 13 and/or one or more inlets 1 are sealed (e.g., with a cap and/or needleless connector) when not in use and/or when the device is not attached to another element of a fluid processing system.

Of course, the device can have fewer ports, or additional ports, or other combinations of port types. In some embodiments, ports can have a plurality of functions. For example, one of the inlet ports can be used as a delivery port, particularly if it is desirable for the material to be delivered, e.g., a therapeutic agent, to be filtered by the bag filter. Alternatively, a delivery port can be utilized as a vent. In another embodiment, an inlet port can be used as a vent port. For example, as illustrated in Figure 8, an inlet port 1 can be in fluid communication with vent 19.

In yet another embodiment, the device has an additional outlet port, e.g., to provide for collecting filtered blood in a container other than a venous reservoir. Of course, the system including the device can have additional ports upstream and/or downstream of the device as desired. For example, using Figure 2 for reference, the system can include an additional port downstream of the device 100 to allow filtered blood to be collected in a container other than the venous reservoir 30. The system (and/or the device) can include one or more additional vent ports. In one embodiment, e.g., as illustrated in Figure 8, the device includes a vent 19 including a porous structure 21 for passing gas therethrough. In some embodiments a vent port also includes a pressure relief valve for relieving pressure upstream of the bag filter.

In other illustrative embodiments, the device can have two ports. For example, using the exemplary embodiment illustrated in Figure 6 for reference, device 100 can comprise a drip chamber, the housing 7 including an inlet port 1 and an outlet port 3, with bag filter 4 disposed across the fluid flow path from the inlet to the outlet.

The device 100 (e.g., a cardiotomy reservoir or a drip chamber) can be any suitable configuration and size. In some embodiments involving a cardiotomy reservoir, the device has a total capacity of several liters or less, typically about 3 liters or less. In some embodiments involving a drip chamber, particularly for those embodiments wherein the fluid to be processed comprises a biological fluid, the drip chamber has a total capacity of, for example, about 50 cc or less, more preferably about 20 cc or less.

Typically, when using a drip chamber to process a biological fluid, about two-thirds of the total capacity of the drip chamber is used for containing the biological fluid, and the rest of the capacity is used to contain air or gas.

The housing 7, that can comprise a plurality of portions or sections, can be fabricated from any suitable impervious material, including any impervious thermoplastic

material, which is compatible with the fluid being processed. For example, the housing can be fabricated from a metal, or from a polymer. In some embodiments, particularly in those embodiments involving the processing of a biological fluid, the housing is a transparent or translucent polymer, such as an acrylic, polypropylene, polystyrene, or a polycarbonate resin. Such a housing is easily and economically fabricated, and allows observation of the passage of the biological fluid through the housing.

If desired, the device can include additional structures such as a screen, core and/or cage, e.g., for support and/or drainage. In an embodiment, the device includes an end cap for the open end of the bag filter.

In an embodiment, the device includes a porous structure such as a membrane that allows gas to pass therethrough, e.g., from the interior of the housing through the membrane and the vent. For example, the porous structure can comprise a hydrophobic membrane that allows gas, but not biological fluid, to pass therethrough. If desired, the bag filter can include the membrane (e.g., as part of a composite).

In the embodiment illustrated in Figure 8, the device includes a vent 19 including a porous structure 21 that allows gas to pass therethrough. In some of the embodiments wherein the porous structure 21 comprises at least one membrane, more preferably a liquophobic membrane, the porous structure 21 prevents the passage of bacteria therethrough. For example, the porous structure can have a pore rating of about 2 ym or less. In an embodiment, the pore rating can be about .02 ym. Suitable vents and porous structures include, but are not limited to, those disclosed in U.S. Patent Nos.

5,126,054, 5,451,321, and 5,362,406.

Alternatively, or additionally, at least a portion of the bag filter 4 itself (e.g., without an additional structure or element) passes gas without passing biological fluid therethrough. For example, at least a portion of the bag filter 4 (e.g., a band nearer the open end of the filter than the closed end, or any desired area of the filter) can have a lower Critical Wetting Surface Tension (CWST) than the other portions of the bag filter.

In these embodiments, gas, but little or no biological fluid, passes through the portions that have the lower CWST. If desired, the bag filter can be treated to provide portions having different CWSTs. For example, portions of the bag filter can be surface modified to change the CWST of one or more desired portions, without modifying (or providing less modification to) the CWST of other desired portions.

In accordance with a preferred embodiment of the invention, a filter medium having a closed end is produced by forming the medium in a tubular configuration onto a rotating mandrel or collector. For example, as illustrated in Figures 3 and 4, fibers can be melt-blown onto a collector 200 (which is preferably generally cylindrical in shape) while the collector is rotating and translating, with the fibers being deposited on the surface of the collector and on one end of the collector. Figure 3 illustrates the translation of the collector 200 with respect to a fiberizer assembly 302.

One method of preparing a melt-blown fibrous nonwoven web comprises extruding molten resin from two parallel rows of linearly arranged, substantially equally spaced nozzles to form fibers onto the surface of a collector having a longitudinal axis arranged parallel to the rows of nozzles, wherein the rows of nozzles are offset from each other and are angled toward each other. Figures 4 and 5 illustrate one exemplary arrangement of nozzles 300 on a manifold 301.

The rows of nozzles can be offset from each other by, for example, about one-half the spacing between the nozzles within each row and the rows of nozzles are preferably angled toward each other by substantially equal but opposite angles, e.g., each of the rows of nozzles is angled by about 40° or less, more preferably, about 25° or less, from a vertical plumb line originating at the center of the collector.

Other suitable methods for preparing a melt-blown fibrous nonwoven web include using a single row of nozzles, and/or asymmetrically arranged nozzles. The nozzles may be arranged to provide crossed stream fibers or non-crossed stream fibers.

Exemplary methods for preparing melt-blown nonwoven webs include but are not limited to those disclosed in U.S. Patent Nos. 4,726,901 and 4,594,202, and International Publication WO 96/03194.

The collector 200 can have any suitable diameter, and the diameter can be substantially constant along the length of the collector. Typically, the diameter is about 2 cm or more, more preferably about 4 cm or more. In some embodiments, the diameter is about 5 cm to about 200 cm, e.g., about 10 cm to 150 cm. In other embodiments, the diameter may be greater than about 200 cm, or about 1 cm, for example.

In accordance with the invention, the collector can have, for example, a changing diameter along at least a portion of its length. Illustratively, the collector can include a

diameter that generally decreases along a portion of the length, or generally decreases from one end of the collector to the other. Figure 7A illustrates an embodiment of a collector that can be used in accordance with the invention, having a tapered diameter over a portion of its length.

One end of the collector 200 can be configured to produce a desired characteristic or feature for a closed end of the bag filter. For example, the end of the collector can be tapered to produce a less rounded end for the filter. Alternatively, the end of the collector can be inverted to produce, for example, a filter end having a desired density.

In some embodiments, the collector 200 has a cap 201 to provide the desired filter end characteristic or feature.

Of course, the collector can be used with a variety of different caps having different characteristics (e.g., shapes and/or angles) for a desired result. Figures 7A - 7F illustrate a few of the exemplary shapes of caps 201 that can be used in accordance with the invention. Figures 7A - 7D illustrate caps having angles of 90°, 60°, 60°, and 30°, respectively. Figure 7B illustrates a cap having a stepped shape, Figure 7E illustrates a cap having a dimpled shape, and Figure 7F illustrates a cap having a compound angle, i.e., 60° and 30".

While a cap 201 having any angle (including any compound angle) and/or shape can be used in accordance with the invention, one preferred angle is in the range of from about 45" to about 90". In some embodiments, using a lesser angle than about 90" (e.g., about 65" or less) provides a medium having a more uniform weight along the cross-section of the medium.

Additionally, the collector 200 can be hollow, with one or more holes in the end and/or sides. The cap 201 can also have one or more holes therethrough. Such configurations may be useful during various stages of producing and handling the filter medium. Illustratively, in some embodiments wherein the collector has one or more holes in the end and/or sides, a positive pressure can be created within the interior of the collector for ease in removing the formed bag filter from the collector. In other embodiments, a negative pressure can be created within the interior of the collector while forming the bag filter to more efficiently control the density of the bag medium.

The collector (which can be hollow or solid) may be surfaced with a suitable release coating.

The collector can be rotated at any suitable surface velocity, generally at least about 20 m/min, and preferably not exceeding about 1000 m/min. In an embodiment, the surface velocity is in the range from about 150 m/min to about 250 m/min.

The collector 200 is preferably translated at a rate not exceeding about 2 cm/revolution. In one illustrative embodiment, the translation rate does not exceed about 1 cm/revolution.

In accordance with the invention, bag filters can be produced having a desired fiber density. The fiber density can be substantially uniform over the entire bag.

Alternatively, different portions, sections or areas of the bag can have different densities. For example, the fiber density at the closed end of the bag can be higher or lower than that of the more cylindrical portion of the bag.

The nozzles can be spaced any suitable distance from the collector, preferably about 2 cm to about 50 cm, more preferably about 2 cm to about 25 cm. In general, the die-to-collector distance (DCD), which is the distance from the nozzle tip to the surface of the collector, is smaller when a filter medium of higher density with lower voids volume and higher tensile strength is desired.

Within each of the rows, the nozzles can be spaced apart any suitable distance, generally about 2 cm or less. In an illustrative embodiment, the space between the nozzles is about 1 cm or less. The parallel rows can be spaced apart any suitable distance, preferably such that the nozzle tip to nozzle tip separation between rows is about 1 to 2 cm. Moreover, in a preferred embodiment, the web is prepared while a negative pressure is maintained between the rows of the nozzles. Illustratively, a negative pressure in the range from zero to about 4" of water column can be generated within the nozzle manifold 301 to produce a more uniform product.

If desired, multiple passes can be made, typically while adjusting the DCD and/or the fiber diameter, to produce a bag filter with the desired characteristics.

Alternatively, or additionally, the rotation and/or translation of the collector can be adjusted or arranged to produce a bag filter with the desired characteristics. For example, as the end of the collector remains in the melt-blown fiber stream, the translation of the collector can be briefly stopped while rotation continues. If desired, the translation of the collector can be adjusted or arranged such that the end of the collector remains in the melt-blown fiber stream for a longer period of time. In general,

these arrangements increase the fiber density at the closed end of the filter.

Of course, bag filters having a decreased fiber density at the closed end of the filter can also be produced in accordance with the invention. This can be especially suitable for some embodiments, e.g., in some embodiments wherein the bag filter is a cardiotomy filter and the closed end of the filter contacts a projection on the inner surface of the cardiotomy housing. Such a bag configuration can be easier to fit and seal in conventional cardiotomy housings.

The bag filter according to the present invention can be used in any filtering protocol, especially those involving conventional bag filters. For example, the bag filter can be used to filter paints and coatings, especially water-based paints and primers, chemicals, petrochemical products, water, and aqueous suspensions.

In some embodiments of the invention, the inventive bag filter is used to filter a biological fluid. For example, the bag filter can be used in a drip chamber to remove at least one complement protein, component and/or fragment (e.g., C3a). Alternatively or additionally, the bag filter can be used in a drip chamber to remove clots, microaggregates and leukocytes from a biological fluid. In one embodiment, the bag filter is used to deplete surgical debris and leukocytes from a biological fluid.

An illustrative method for using the bag filter to filter biological fluid can be described with reference to Figures 1, 2, and 8. Figures 1 and 8 illustrate exemplary embodiments of device 100 including a bag filter 4 according to the invention, and Figure 2 illustrates a system for filtering a biological fluid in an extracorporeal circuit using the device 100.

During surgery, a biological fluid such as blood is removed from the cavity of the patient and delivered to the device 100 (sometimes referred to below as the "cardiotomy reservoir") via the ventricular vent line and the cardiotomy sucker line(s).

In some embodiments, at least two cardiotomy sucker lines are utilized. Blood passes through inlets 1, defoaming element 5, and bag filter 4. As the fluid passes through the filter, the fluid is depleted of undesirable material such as lipids (e.g., lipid globules) and/or surgical debris (e.g., aggregates, bone chips and/or clots). In a preferred embodiment, the fluid is also depleted of leukocytes. In one illustrative embodiment, the biological fluid is depleted of about 90% of the leukocytes or more. In some embodiments, the biological fluid is depleted of about 99% of the leukocytes or more,

even about 99.9% of the leukocytes or more.

Additionally, since air is typically present in the cardiotomy reservoir 100 (e.g., due to the delivery of foamy fluid to the device), the air is vented from the reservoir through vent port 2. Generally, the defoaming element 5 acts to coalesce bubbles of air, and the coalesced bubbles are vented through vent port 2. As noted earlier, defoaming elements can be disposed upstream and/or downstream of the bag filter 4.

Alternatively, or additionally, the bag filter 4 coalesces bubbles. Thus, in some embodiments wherein cardiotomy reservoir 100 lacks at least one defoaming element 5, the bag filter 4 provides for coalescing the bubbles, which are vented through vent port 2.

In some embodiments, e.g., wherein the bag filter 4 also includes a hydrophobic membrane and/or one or more portions with lower CWSTs, the air (but little or no biological fluid) passes through the membrane and/or the lower CWST portion(s).

In some embodiments, e.g., with or without one or more defoaming elements, some of the air can be vented without passing it through the bag filter 4. For example, using the exemplary device 100 illustrated in Figure 8 for reference, some of the air entering the device 100 passes out of the device through porous structure 21 and vent 19, without passing through the bag filter 4.

In some embodiments, e.g., wherein device is utilized as a cardiotomy reservoir, the differential pressure across the device preferably is about 15 p.s.i or less. In more preferred embodiments involving a cardiotomy reservoir, the differential pressure is about 10 p.s.i. or less, even more preferably, about 6 p.s.i. or less.

In the illustrative embodiment shown in Figure 2, the filtered blood passing through cardiotomy reservoir 100 is collected in a container 30 such as a venous reservoir. Typically, at least a portion of this blood is returned to the patient via the arterial line (e.g., after passing through an oxygenator 50 and an arterial filter 40).

However, in some embodiments (not shown), at least a portion of filtered blood is passed from the cardiotomy reservoir 100 to a container other than container 30, or the fluid is passed to another container downstream of container 30. Illustratively, it may be desirable to further process the biological fluid before returning it to the patient.

For example, in some embodiments wherein the biological fluid is a red blood cell containing fluid, the red blood cells can be saline washed, and the washed cells can be

returned to the patient at the patient's bedside, e.g., after the patient has been disconnected from the extracorporeal circuit illustrated in Figure 2.

Other embodiments including a device including a bag filter are encompassed by the invention. For example, in one embodiment, e.g., as illustrated in Figure 6, device 100 comprises a drip chamber. In some embodiments, e.g., wherein the fluid passing into the device comprises a biological fluid, the biological fluid passing through the bag filter 4 can be depleted of undesirable material, if the material is present in the fluid.

For example, in some embodiments, the biological fluid passing through the bag filter is depleted of lipids, clots, microaggregates and/or at least one complement protein, component and/or fragment. Alternatively, or additionally, the biological fluid passing through the filter is depleted of leukocytes.

Further embodiments are encompassed by the invention. For example, in one embodiment, the bag filter produced as described above is subsequently modified, for example, by sewing and/or heat sealing. Additionally or alternatively, the open end of the bag filter can be closed, or a filter can be produced that is closed at both ends without an end seam at either end. In other embodiments, the bag filter can be produced as described above and subsequently pleated along at least a portion of its length, or the fibers can be melt-blown onto a collector shaped to provide a bag filter that is pleated along at least part of its length.

Examples Example 1.

The bag filter used in this Example is prepared as follows. Two fiberizers, each with a row of nozzles, are offset axially of each other by 0.38 cm, and are angled toward each other at an inclination of 13° from the vertical. The two sets of intersecting fiber streams deliver polybutylene terephthalate (hereinafter PBT) resin on a cylindrical collector.

The collector is 17.8 cm in length (including the cap), and has a tapered diameter over a portion of its length. The diameter ranges from 6.4 cm near the cap, to 8.4 cm at the other end of the collector. A cap with a 90" angle is used.

Release paper is placed over the length of the collector.

The collector is rotated at 880 rpm while it is simultaneously translated axially at

the rate of .5 cm per revolution for the length of each pass or stroke. The stroke, which is 114 cm, is longer than the length of the collector. Fibers are deposited on the surface of the collector, including the capped end of the collector.

The collector is operated for 6 passes, and the PBT resin throughput through the nozzles is kept essentially constant.

The resin temperature, and the air temperature are each about 650"F (about 346"C). The resin is delivered at the rate of 1.36 grams per minute per nozzle.

The air pressure through the fiberizing nozzles is changed before each of the first 5 passes to provide a different fiber diameter for each of the first 5 layers of the filter.

The air pressure is essentially the same for passes 5 and 6, and thus, the fiber diameter provided during passes 5 and 6 is essentially the same.

The air pressure for the successive passes is 15 p.s.i., 18 p.s.i., 25 p.s.i., 32 p.s.i., 39 p.s.i., and 39 p.s.i. The average fiber diameter for the successive passes is 10 ym, 5 ,um, 4 clam, 2.5 ,um, 2 m, and 2 ym.

The die-to-collector distance (DCD) is varied from 2.4 cm for the first pass to 1 cm for the last pass while maintaining an essentially uniform density of .13 g/cc for each layer.

The bag filter thus produced is removed from the collector. The filter, which is formed without an end seam and without a side seam, is gas plasma treated to provide a critical wetting surface tension (CWST) of about 67 dynes/cm. The bag filter is flexible, and the closed end of the filter is inverted slightly, e.g., by pushing against the downstream surface of the end of the filter to form a flattened end, before placing the filter in a housing.

The treated bag filter is placed in a commercially available cardiotomy reservoir housing after the commercially available cardiotomy filter (and defoamer) is removed.

The housing includes an open vent port, a vent port with a pressure relief valve, three inlet ports, and an outlet port. Upon assembly of the housing, the flattened end of the filter contacts a small projection on the inner surface of the housing.

Approximately 1 liter of blood is passed through the device at a flow rate of about 500 cc/min. The differential pressure does not exceed 6 p.s.i. A comparison of influent and effluent leukocyte counts shows that the blood is depleted of at least 99% of the leukocytes.

Example 2.

A bag filter is produced as described in Example 1. The closed end of the filter is inverted as described above.

The treated bag filter is placed in a commercially available cardiotomy reservoir housing after the commercially available cardiotomy filter (and defoamer) is removed.

The flattened end of the filter contacts a small projection on the inner surface of the housing.

The housing includes an open vent port, a vent port with a pressure relief valve, three inlet ports, and an outlet port.

A venting device comprising a housing having an inlet and an outlet and a liquophobic membrane having a diameter of 25 mm disposed across the fluid flow path between the vent housing inlet and outlet is provided. The membrane, which is produced in accordance with U.S. Patent No. 5,451,321, has a pore rating of about 2 ,um or less. The venting device is placed in fluid communication with one of the cardiotomy reservoir inlet ports as generally illustrated in Figure 8.

Approximately 1 liter of blood is passed through the device at a flow rate of about 500 cc/min. The differential pressure is less than 3 p.s.i. A comparison of influent and effluent leukocyte counts shows that the blood is depleted of at least 99% of the leukocytes.

All of the references cited herein, including publications, patents, and patent applications, are hereby incorporated in their entireties by reference.

While the invention has been described in some detail by way of illustration and example, it should be understood that the invention is susceptible to various modifications and alternative forms, and is not restricted to the specific embodiments set forth. It should be understood that these specific embodiments are not intended to limit the invention but, on the contrary, the intention is to cover all modifications, equivalents, and alternatives falling within the spirit and scope of the invention.