BIOLOGICAL FLUID FILTERS HAVING FLEXIBLE WALLS AND METHODS FOR

MAKING SUCH FILTERS

RELATED APPLICATION

This application claims the benefit of and priority to U.S. Patent Application Serial No. 14/223,51 1 , filed March 24, 2014, the contents of which are

incorporated by reference herein.

DESCRIPTION

TECHNICAL FIELD

The present disclosure is directed to filters for the filtration of fluids such as, but not limited to, biological fluids and to methods of making such filters wherein at least the walls of the housing are made of a flexible material. More particularly, the present disclosure is directed to flexible housing filters that include one or more peripheral seals or, in the alternative, include a molded frame with flexible walls that capture the filter medium with no peripheral seals.

BACKGROUND

Using various manual and automated systems and methods, whole blood is collected and separated into its clinical components (typically red blood cells, platelets, and plasma). The collected components are typically individually stored and used to treat a variety of specific conditions and diseased states.

Before transfusing the collected blood components to a recipient in need of the components, or before subjecting blood components to further treatment, it is often desirable to minimize the presence of impurities or other materials that may cause undesired side effects in the recipient. For example, because of possible reactions, it is generally considered desirable to reduce the number of leukocytes in blood components before storage, or at least before transfusion (i.e.,

"leukoreduction").

Filters are widely used to accomplish leukoreduction in blood products today (e.g., filtration of leukocytes from whole blood, red cells, and/or platelet products). Filters typically include a filter media disposed between mating and/or opposed walls of a filter housing. Inlet and outlet ports associated with the housing provide flow to and from the interior of the filter. Traditionally, the walls of the filter housing have been made of a rigid, typically polymeric, material. More recently, filters wherein at least the walls of the housing are made of a flexible material have been used in blood collection kits. Soft or flexible housing filters provide the advantage of being able to withstand handling and centrifuging without breakage of the filter. Examples of soft housing filters are disclosed in U.S. Patent No. 6,367,634; U.S. Patent No. 6,422,397; U.S. Patent No. 6,745,902; U.S. Patent No. 7,353,956; U.S. Patent No. 7,332,096; U.S. Patent No. 7,278,541 ; and U.S. Patent Application Publication No. 2003/0209479, all of which are hereby incorporated by reference herein.

While flexible housing filters are now commonly used in the field of blood processing, there exists an ongoing desire to improve the construction, performance, and manufacturability of such filters.

SUMMARY

In one aspect, the present disclosure is directed to a biological fluid filter assembly including a housing having first and second flexible walls wherein one of the walls includes an inlet port and the other wall includes an outlet port. The filter assembly includes a filter medium disposed between the flexible housing walls. The filter medium includes at least first, second and third elements wherein the first element is made of or includes a material suitable for removing a component or particulate of a biological fluid and is disposed between the inlet housing wall and the second element; the second element may be made of or include a material suitable for removing another component of said biological fluid and is disposed between the first element and the third element; and the third element is made of an organic or inorganic material and is disposed between the outlet housing wall and the said second filter element. The third filter element has a thickness of less than 0.04 cm or greater than 0.25 cm. The filter assembly includes an outer peripheral seal and at least one inner peripheral seal spaced inwardly from the outer peripheral seal.

In another aspect, the present disclosure is directed to a biological fluid filter assembly including a housing having first and second flexible walls wherein one of the walls includes an inlet port and the other wall includes an outlet port. The filter assembly includes a filter medium disposed between the flexible housing walls. The filter medium includes at least first, second and third elements wherein the first element is made of or includes a material suitable for removing a component or particulate of a biological fluid and is disposed between the inlet housing wall and the second element; the second element may be made of or include a material suitable for removing another component of said biological fluid and is disposed between the first element and the third element; and the third element is made of an organic or inorganic material and is disposed between the outlet housing wall and the second filter element. The third filter element has an air permeability per 1 cm of thickness of greater than 40 cm ² /s at a pressure difference of 125 Pa. Preferably, the normalized air permeability at a pressure difference of 125 Pa is in a range of approximately 40 cm ² /s - 800 cm ² /s or, more preferably, in a range of approximately 50 cm ² /s - 400 cm ² /s or, even more preferably, in a range of approximately 70 cm ² /s - 150 cm ² /s.

BRIEF DESCRIPTION OF THE DRAWINGS

Figure 1 is a plan view of a flexible housing filter assembly in accordance with the present disclosure;

Figure 2 is a side view of the flexible housing filter of Fig. 1 ;

Figure 3 is a cross-sectional end view taken along line 3-3 of the flexible housing filter of Fig. 1 ;

Figure 4 is an exploded view of a filter assembly in accordance with the present disclosure;

Figure 5 is an enlarged cross-sectional view of an inner peripheral seal region of the filter assembly shown in Figs. 1 -4;

Figure 6 is plan view of another embodiment of a flexible housing filter assembly in accordance with the present disclosure;

Figure 7 is a cross-sectional end view taken along line 7-7 of the flexible housing filter of Fig. 6;

Figure 8 is an enlarged cross-sectional view of the dual inner peripheral seal regions of the filter assembly shown in Figs. 6-7;

Figure 9 is plan view of still another embodiment of a flexible housing filter assembly in accordance with the present disclosure;

Figure 10 is a cross-sectional end view taken along line 10-1 0 of the flexible housing filter assembly of Fig. 9;

Figure 1 1 is a partial, cross-sectional view of the outer peripheral seal of the filter assembly of Figs. 9-1 0;

Figure 12 is a partial an enlarged cross-sectional view of an inner seal region of the filter assembly shown in Figs.9-1 0;

Figure 13 is a plan view of one embodiment of the third element of the filter assembly of any one of the previous embodiments;

Figure 14 is an exploded view of the housing walls and first, second and third filter elements including the third element of Fig 13;

Figure 15 is a partial, cross-sectional view of an inner peripheral seal of the embodiment of the filter assembly of Figs. 13-14;

Figure 16 is an exploded view of the housing walls, first, second and third filter elements and an alternative embodiment of the third element of Figs. 13-14;

Figure 17 is a cross-sectional end view of a filter assembly including the embodiment of the third element as shown in Fig. 16;

Figure 18 is plan view of another embodiment of a filter assembly in accordance with the present disclosure;

Figure 19 side view of the filter assembly of Fig. 1 8;

Figure 20 is a perspective view of the filter assembly of Figs. 18-1 9;

Figure 21 is a further perspective view of the filter assembly of Figs. 18-19 with a portion of a flexible housing wall and a portion of the molded frame broken away;

Figure 22 is a perspective view of the filter stack (of filter media sheets) in the filter assembly of Figs. 1 8-19;

Figure 23 is a perspective view of the filter assembly of Figs. 18-20 prior to attachment of the flexible outlet and inlet housing walls;

Figure 24 is a perspective view of still another embodiment of a filter assembly in accordance with the present disclosure;

Figure 25 is a partial view of the filter assembly of Fig. 24 with a port in the molded frame;

Figure 26 is a top, plan view of the filter assembly of Figs. 24-25; Figure 27 is an end view of the embodiment of the filter assembly of Figs.

24-26;

Figure 28 is an end view of an alternative embodiment of the filter assemblies of Figs. 18-26; and

Figure 29 (a)-(e) depicts the steps in a method of making a filter assembly in accordance with the present disclosure.

DETAILED DESCRIPTION OF THE EMBODIMENTS

The present disclosure is directed to a filter assembly 1 0 useful in the removal of selected components or compounds from a biological fluid, such as blood. As shown in Figs. 1 and 2 and in accordance with the present disclosure, filter assembly 10 includes a housing 12 defined by a pair of outer housing walls 14 and 1 6. In one embodiment, housing walls 14 and 16 of housing 12 may be separate sheets of a flexible material such as, but not limited to, polyvinyl chloride or any other suitable material through which the biological fluid will not flow. The separate sheets may be sealed together along their peripheries as will be described in greater detail below. Alternatively, walls 14 and 16 may be provided from a single sheet of suitable flexible material folded over itself and sealed along the non-folded sides and/or end(s) of the facing panels. Still further, housing 12 may be provided as a pocket, sealed along three sides and open along one side through which the filter medium may be introduced, followed by the sealing of the remaining open end.

As shown in Figs. 1 and 2, "inlet" housing wall 14 and "outlet" housing wall 16 include inlet port 18 and outlet port 20, respectively, positioned on opposite sides and near opposite ends of filter assembly. Ports 18 and 20 need not be located near opposite ends of the filter assembly 1 0 but may be positioned elsewhere, such as more centrally located and directly opposite each other. Ports 18 and 20 are adapted to receive other components of the fluid processing set such as tubing or the like. Inlet and outlet ports 18 and 20 may be secured to the associated walls 14 and 1 6 by any suitable means (e.g., being heat sealed thereto using radio frequency energy), or may be integrally molded with housing walls 14 and 16 as described in International Publication WO 00/62891 , the contents of which are incorporated herein by reference. Walls 14 and 16 of the filter housing 12 are each preferably provided with an opening/aperture and an internal flow path (not shown) through which fluid flows into and out of filter assembly 10.

As further shown in Figs. 1 and 2, housing walls 14 and 16 are joined together at least substantially around their peripheries to form housing 12, and preferably entirely around their peripheries. In one embodiment, housing walls 14 and 16 are joined at their outermost peripheries with an outer peripheral seal 22. In addition, in accordance with the present disclosure, housing 12 may also include one or more "inner peripheral seals" 24 (and 26, as shown in Figs. 6-8) spaced inwardly from outer peripheral seal 22. A gap 28 between outer peripheral seal 22 and inner seal 24 (or outer seal 22 and inner seals 24 and 26) provide(s) a cushioned periphery of the type described in U.S. Patent Publication No.

2003/0209479, which is incorporated by reference herein in its entirety.

In one embodiment shown in Fig. 1 , both outer seal 22 and inner seal 24 may have an at least substantially uniform width of greater than 6 mm and more preferably a width of between approximately 6-12, 6-10, or 6-8 mm. Gap 28 between outer 22 and inner 24 seals of Fig. 1 may be approximately 1 -10, 1 -8 or 1 -6 mm. In the embodiment of Fig. 6, inner seal 24 may have a width of approximately 0.5-7, 0.7-5 or 1 .0-4 mm. Outer seal 22 may have a width of greater than approximately 6 mm and more particularly approximately 6-12, 6-1 0 and 6-8 mm. Gap 28 and 28' between each of the adjacent seals may have a width of approximately 1 -10, 1 -8 or 1 -6 mm.

With respect to the embodiment of Fig. 9 (discussed in more detail below) inner seal 24 may have a seal width of approximately 0.5-7, 0.7-5, 1 .0-4 mm and outer seal 22 may have a seal width of greater than 6 mm and more particularly 6- 12, 6-10 or 6-8 mm. Gap 28 between the inner and outer seals may have a width of approximately 1 -10, 1 -8 and 1 -6 mm.

As shown in Figs. 3-4, 7, 10, 14-16 filter assemblies of the type disclosed herein further include a filter medium 30 that is captured between housing walls 14 and 1 6. Filter medium 30 may include one or more sheets of one or more materials capable of removing selected components, compounds, or other particulates from the biological fluid. In one embodiment, filter medium 30 is specifically suited for the removal of at least leukocytes from blood. The one or more sheets of filter material may be made of any suitable biocompatible, medical grade material with pores sized to remove the selected components, compounds or other particulates. The one or more sheets of filter medium may be provided as a mesh, a woven fiber, a melt-blown, non-woven fibrous material or other suitable porous structure.

In one embodiment, filter medium 30 may include a plurality of sheets, such as, for example, a plurality of melt-blown, non-woven fibrous sheets. In a further embodiment, filter medium 30 may be provided as a pad or stack of a plurality of filter sheets, as shown in Figs. 3 and more particularly, in Fig. 4.

As shown in Fig. 4, a filter pad or stack of filter medium 30 may include a plurality of individual sheets, one or more of which define at least first, second and third elements or regions that are suited for the selective removal of components, or compounds, or particulates and/or to provide other functions to filter assembly 10. For example, as shown in Fig. 4, filter medium 30 may include at least a first element or region 32, a second element or region 34, and a third element or region 36. The stack of sheets that includes elements 32, 34, 36 is captured between housing walls 14 and 1 6 and sealed in the manner described above.

Thus, for example, as further shown in Fig. 4, first element or region 32 may preferably be adjacent to inlet housing wall 14. Although shown as a single sheet in Fig. 4, it will be understood that the first element or region 32 may include one or more sheets of a selected filtration material. The first element may be referred to as "pre-filter" and may be particularly well suited for the removal of microaggregates.

Continuing with a description of the elements or regions that make up filter medium 30 in the direction of flow from the inlet housing wall 14 toward the outlet housing wall 16, a second element or region 34 is located downstream of first element 32. As shown in Fig. 4, second element 34 may include one or more sheets of a filter material of the type described above that is capable of removing certain blood components, such as leukocytes. Typically, element 34 may include a plurality of sheets, most typically between 2 and 50 individual sheets each preferably made of a melt-blown, non-woven fibrous material. Continuing in the downstream direction from second element 34 is a third element 36 that is located between the second element and the adjacent outlet housing wall 16. The first, second and third elements 32, 34 and 36 will now be described in greater detail. As noted above, first element 32 may be considered a "pre-filter" for filtering out certain larger-sized particles and components. Element 32 is preferably made of any suitable biocompatible material with pores sufficiently sized to remove or retain certain particles, such as microaggregates, while allowing other components, such as leukocytes, to substantially pass. In one embodiment, the material(s) used for the sheet(s) that make up first element or region 32 may be polybutyleneterephthalate (PBT), polyethyleneterephthalate (PET), or polypropylene. In an embodiment, the overall thickness of first element 32 (in the unsealed areas of filter medium 30) may be approximately 0.127-1 .106 mm. More particularly, the thickness of first element 32 may be approximately 0.305-0.71 1 mm and even more particularly approximately 0.432-0.559 mm.

Second element or region 34 may provide the filtration region of filter medium 30 that is primarily responsible for the removal of blood cells. Thus, second element 34 may typically be made of a biocompatible material with pores sized to retain leukocytes, i.e., white blood cells. Materials suitable for use as the second element 34 include the PBT, PET and PP materials described above in connection with first element 32. Second element 34 may have a thickness in the unsealed areas of the medium of approximately 0.254-15.24 mm, or more particularly, approximately 5.08-12.7 mm, and even more particularly

approximately 7.1 1 -8.9 mm.

Third element or region 36 (sometimes referred to as the "post-filter") may likewise be made of a suitable biocompatible porous material that allows for the filtrate to pass and exit through outlet port 20 in outlet housing wall 16. Third element 36 may further serve as a manifold or support and spacing structure between housing wall 16 and filter medium 30. Third element 36 may be made of any organic or inorganic material and may be a mesh, a woven fibrous structure, or a melt-blown, non-woven fibrous structure. The thickness of third element 36 in the unsealed areas of filter medium 30 is preferably less than 0.04 cm or greater than 0.25 cm. In one embodiment, third element 36 may be a sheet that includes a mesh interior and, optionally, a non-mesh frame, as shown in Fig. 13 and described in greater detail below.

As discussed above and shown in Figs. 1 -12, filter assembly 10 and more specifically housing 12 of filter assembly 10 includes an outer peripheral seal 22 and one or more inner seals 24 (and, optionally, 26) inwardly spaced from outer peripheral seal 22. Both inner and outer seals 24 and 26 may be formed by any suitable means, such as pressure application, heat sealing and, preferably, radio frequency (RF) sealing.

In one embodiment, outer seal 22 may be formed strictly between the opposing housing walls 14 and 1 6. Inner seal 24, on the other hand, captures both housing walls 14 and 16 and the intervening elements or regions 32, 34 and 36 of filter medium 30 and the sheets thereof, as shown in Figs. 5, 8 and 12. Thus, for example, inner seal 24 may include the housing material of housing walls 14, 1 6 and some or all of first, second and third elements described above. Where more than three elements are included in filter medium 30, inner seal 24 may likewise include material of some or all of such additional elements. Seals 22 and 24 (and 26) may be formed in a sequential process or in a simultaneous process. In addition, the elements of filter medium 30 may be sealed together first, followed by the sealing of housing walls 14 and 16 to the filter medium in a two-step process. Alternatively, the housing walls and filter medium 30 may be sealed altogether in a one-step process.

In accordance with the present disclosure, as a result of the applied pressure and RF energy, inner and outer seals 24, 26 and 22 define compressed areas that may include one or more differentiated or undifferentiated layers or bands within the seal. It will be understood that the inner seals 24 and/or 26 may themselves include a central section 38 of substantially uniform thickness between flared and less compressed peripheral sections 41 , as shown in Figs. 5, 8, 12 and 15. The thickness of the inner seals 24 and/or 26 and of the layers or bands within such seals described below are preferably an average of anywhere between 4-10 measurements taken within the central section 38 of the seal, as shown in Figs. 5, 8 and 12, for example. Thus, in one embodiment, inner seals 24 and/or 26 may have a thickness of approximately 0.762-2.286 mm, more preferably approximately 1 .02-2.032 mm and even more preferably approximately 1 .27-1 .778 mm.

In one embodiment, where housing walls 14 and 16 are sealed directly to each other at the outermost periphery, i.e., such outer seal 22 includes a single region 35 made up entirely of the material (for example, PVC) of housing walls 14 and 16. Inasmuch as inner seals 24 and/or 26 may include filter elements 32, 34 and 36, such inner seals 24 and 26 may include several layers or bands made up of the outer housing materials, materials of the filter medium 30 including the material of first, second and/or third filter elements, and composites or

commingled layers thereof. Thus, in an embodiment where inner seal 24 and/or 26 includes the material(s) of the inner and outer housing wall 14 and 16 and the three filter elements 32, 34 and 36 (described above and shown in Figs. 5, 8 and 12), seal 24 and/or 26 may include, in the direction of flow, a first layer 37 that includes entirely or at least substantially entirely the material of inlet housing wall 14. Using a scanning electron microscope, the post-seal thickness of such band 37 of the housing wall 14 may be approximately 0.076-0.381 mm or more particularly approximately 0.127-0.304 mm, or even more particularly 0.178-0.250 mm.

Adjacent to the first layer or band 37 and downstream therefrom is a second layer 44 that may be a composite of the housing material and the first and second elements or regions 32 and 34, described above and shown in Fig. 4. Composite layer 44 may have a post-seal thickness of approximately 0.1 -0.5 mm, more particularly approximately 0.1 -0.35 mm and even more particularly approximately 0.1 -0.2 mm.

Downstream of layer 44 is preferably layer or band 46, which at least substantially includes the material of element 34 (i.e., the material(s) of the filter medium 30 for removing leukocytes). In accordance with the present disclosure, layer 46 may have a post-seal thickness of approximately 0.508-1 .27 mm or more particularly approximately 0.635-1 .143 mm, or even more particularly

approximately 0.762-0.9 mm.

Continuing with a description of the layers or bands within inner seals 24 and/or 26 (as measured within central section 38) and proceeding in the direction of flow and downstream of region 46 is region 48, which may be a composite of the material of housing wall and third filter element 36. The post seal thickness of layer 48 is less than 0.15 mm and more particularly approximately 0.001 -0.12 mm and 0.01 -0.08 mm. Finally, as further shown in Figs. 5 and 8, layer 39 may include entirely or at least substantially entirely the material of outlet housing wall 16. The post-seal thickness of layer 39 may be approximately 0.254-0.406 mm, more particularly approximately 0.304-0.381 mm or approximately 0.330-0.3556 mm.

As described above, outer seal 22 may simply consist of the housing material of inlet and outlet walls 14, 16. In another embodiment, shown in Figs. 9- 12, outer seal 22 may also capture at least the first and second elements 32 and 34, respectively, as shown in Fig. 1 1 . Thus, outer seal 22 includes, in the direction of flow, layers made up of the essentially housing material only having a thickness of approximately 0.076-0.381 mm, more particularly 0.127-0.304 mm, and even more particularly 0.1 78-0.25 mm. Following this region, there is a composite layer 22' that includes the housing material and the first and second regions, wherein the post-seal thickness of this composite layer is between approximately 0.076-0.762 mm, more particularly between 0.127-0.508 mm, and even more particularly between 0.1 78-0.381 mm. An RF die that includes a tear seal feature that also cuts and separates the now sealed filter assembly from the flexible housing sheets and filter media may be used. A smart generator may be particularly well-suited for such outer seal operation. (The thicknesses of the bands or layers within central section of inner seals 24 and/or 26 may be substantially as previously described above.)

In another embodiment, as shown in Figs. 13-17, the third element 36' may be a sheet with a central porous region 40, such as a mesh and an outer peripheral frame 42 integral with central porous region 40. As shown in Fig. 15, frame 42 or at least a portion of frame 42 may be captured within inner seal 24 and/or 26. In a further alternative, the mesh may be provided without a frame, wherein the peripheral portions of the all-mesh sheet may be captured within inner seal 24 and/or 26. In a further alternative, as depicted in Fig. 16, where the third element 36" is an all-mesh sheet without a frame, no part of the this third element is captured by inner seal 24 and/or 26. In this embodiment, third element or region 36" may be "free-floating" within filter assembly 10.

The material of the third element 36', 36" defines openings or voids through which filtered fluid passes before exiting the filter assembly 10 via the outlet port 20. The third element 36' (or 36") of Fig. 13 is shown with generally diamond- shaped openings or voids, but it is within the scope of the present disclosure for the openings or voids to be differently shaped (e.g., a regular shape, such as generally square or rectangular or circular or triangular or pentagonal or hexagonal, or an irregular shape). A primary purpose of the third element 36', 36" may be to act as a manifold which separates the filtration medium 34', 34" from the outlet side 16 of the filter housing, while allowing filtered fluid to freely flow from the filtration medium 34', 34" to outlet port 20. Accordingly, the voids in porous region 40 may be relatively large to provide third element 36', 36" with a porosity that is greater than the porosity of the filtration medium 34', 34".

However, if the voids are too large, it is possible for the outlet side 14 of the filter housing to press against the filtration medium 34', 34" during use, thereby making it more difficult for filtered fluid to flow out of the filter assembly 10. Thus, it may be preferred for the third element 36', 36" to have an intermediate porosity, with voids that are large enough to allow substantially free flow of filtered fluid out of the filter assembly 10, but not so large as to negate the desired manifold effect. In one exemplary embodiment, the voids are generally rectangular or square or diamond-shaped, each having a height and width in the range of approximately 0.5-20 mm, with the third element 36', 36" having a thickness in the range of approximately 0.5-4 mm.

Alternatively, rather than characterizing the porosity of the third element 36 (and more particularly porous region 40) in terms of the size and shape of its voids, it is also possible to characterize its porosity in terms of its permeability properties. For example, at a pressure difference of 125 Pa (1250 dyne/cm ² ), an approximately 1 .6 mm thick porous region 40 of third element 36', 36" according to the present disclosure was measured as having an air permeability of approximately 510 cm ³ /s-cm ² using an air permeability test of Frazier Precision Instrument Company of Hagerstown, Maryland (although other air permeability testers and test methods may be employed without departing from the scope of the present disclosure). This raw value for the porous region of the third element 36', 36" having a thickness of approximately 1 .6 mm may be normalized to approximately 81 .5 cm ² /s, which is the air permeability at a pressure difference of 125 Pa (1250 dynes/cm ² ) for a third element 36', 36" having a thickness of 1 cm. It may be advantageous for an approximately 1 .6 mm thick porous region of the type described herein to have an air permeability in the range of approximately 250 cm ³ /s-cm ² - 5000 cm ³ /s-cm ² at a pressure difference of 125 Pa (1250 dynes/cm ² ) or a normalized (i.e., for a 1 cm thickness) air permeability at the same pressure difference in a range of approximately 40 cm ² /s-800 cm ² /s. More preferably, the normalized air permeability at a pressure difference of 125 Pa (1250 dyne/cm ² ) is in a range of approximately 50 cm ² /s - 400 cm ² /s or, even more preferably, in a range of approximately 70 cm ² /s - 150 cm ² /s. While such normalized air permeabilities may be preferred for a porous region according to the present disclosure, but it is also within the scope of the present disclosure for the third element 36', 36" to have an air permeability that lies outside of

(preferably above) these ranges.

The porous region 40 of third element 36', 36" may have a generally uniform porosity or permeability, with generally uniform voids arranged in a uniform pattern, or may have a non-uniform porosity or permeability, with differently sized and/or shaped voids in a uniform or non-uniform pattern or generally uniform voids arranged in a non-uniform pattern.

As in the embodiments described above, inner seal 24 of the embodiment of Fig. 15 may include layers or bands made up of the outer housing materials, materials of the filter medium 30 including the materials of the first, second and third filter elements and/or composites thereof. Thus, as shown in Fig. 15, inner seal 24 may include, in the direction of flow, a first layer 37' made up at least substantially entirely of the inlet housing material, such as polyvinyl chloride.

Downstream of layer 37' is a second layer 44' that may be a composite of the housing material and the first and possibly also the second elements or regions 32' and 34' (see Fig. 14). Downstream of layer 44' is preferably a layer or band 46' which at least substantially includes the material of filter element 34', i.e., the material(s) of the filter medium for removing leukocytes.

Next, the seal region may include a band or layer 48' which may be a composite of the material of the third filter element 36', 36" (and/or frame 42 thereof) the material of the outer housing wall 16, if the material of the third element is different from the material of the housing wall. Composite layer 48' may be followed by and adjacent to a layer 39' that includes primary or at least substantially the material of outer housing wall 16.

In an embodiment, such as for example, where the third filter element is a mesh (with or without a frame region) as described in connection with Figs. 13-17, the material of the third element may be identical to the material of the outer housing wall (e.g., polyvinyl chloride). In this embodiment, the seal may be devoid of composite layer made up of the third filter element and outer housing wall 1 6. In this embodiment, the downstream most layer or band may be present as an undifferentiated layer, band or region or aggregate of the common material. In one embodiment, a (molten) layer 46' of the second filter element 34' may be at least substantially excluded from central region 38' of inner seal 24 (and 26) such that a more downstream layer (e.g., the third element/outlet housing commingled layer), band or region may be adjacent to the upstream composite layer 44' described above in at least central section 38'. In one embodiment, this may be achieved by a sealing process in which the commingled and typically

undifferentiated layer or region at least substantially displaces the layer of molten main filter material 46' toward and into peripheral sections 41 . A more detailed discussion of a seal utilizing a mesh element of the type described above, the characteristics of the bands or layers within the inner seal, and methods for forming such a seal are set forth in simultaneously filed U.S. Patent Application No. 14/222,961 , filed March 24, 2014, the contents of which are incorporated by reference herein.

Fig. 18 shows an alternative embodiment of a filter assembly 50 in accordance with the present disclosure. As shown in Figs. 18-21 , filter assembly 50 includes a frame 52 that houses filter medium 60, described in greater detail below. Frame 52 includes a rim 53 that defines central opening 55 with walls 54 and 56 located at the inlet side and the outlet side of filter assembly (as defined by the placement of the inlet and outlet ports described below). Frame 42 and, for that matter, rim 53 and central opening 55, may be rectangularly-shaped, but may also have other shapes such as a square, circle, oval, triangle, diamond, etc. Walls 54 and 56 may be made of any flexible medical grade polymeric material that is impermeable to liquid including, but not limited to, plasticized polyvinyl chloride (PVC).

As in the previous embodiments described above, walls 54 and 56 may carry inlet and outlet ports 57 and 58, respectively. Ports 57 and 58 define flow paths 59 that allow liquid introduction into and liquid withdrawal from filter assembly 50. Filtration medium 60 (Figs. 21 -22) may be provided as a stack or pad of selectively porous sheets substantially as described above in connection with the earlier embodiments of Fig. 1 -17. Thus, filter medium 60 may include at least first and second regions such as a first (pre-filter) element and a second (main filter) element. A third filter element 36 may optionally be included, but more preferably is not included. In an alternative embodiment, frame 52 may be molded with ribs to space filter medium 60 from outlet housing wall 56. Materials suitable for the different elements include, but are not limited to PBT, PET and PP and the thicknesses of the sheets or plurality of sheets may be as previously described.

Unlike the embodiments of Figs. 1 -1 7, the filter assembly of Fig. 18 does not require and typically does not include internal seals (24 and/or 26), although some joining of the filter elements by welding or adhesion may be employed. Accordingly, filter assembly 50 does not have layers or bands within a seal that includes composites of two or more materials, or a cushioned periphery. With a molded frame, filter assembly would likewise not include an outer peripheral seal of flexible housing walls 54 and 56.

In accordance with the present disclosure, frame 52 may be molded such as by injection molding. More particularly, frame 52 may be insert molded such that the outer edges of the filter medium 60 pad or stack (and in the embodiment described in the preceding paragraph, the flexible housing walls) are contained and captured within the frame, as shown for example in Figs. 21 . Frame 52 may be molded from any suitable polymeric material. In one embodiment, frame 52 may be molded from polyvinyl chloride (PVC). Other suitable materials include polyester, hytrel and other material suitable for RF or thermal induced welding. Flexible walls 54 and 56 may be attached to frame 52 by, for example, welding or adhesion preferably along the entirety of rim 53 of both the front and rear of frame 52, i.e., at the inlet side and the outlet side of frame 52. As shown in Fig. 23, ports may be pre-attached to flexible walls 54 and 56.

In another alternative, rather than sealing flexible housing walls 54 and 56 to frame 52 and over central opening 55, flexible housing walls 54 and 56 may be "stacked" and joined with the sheets of the filter medium 60 around which frame 52 is molded. Thus, flexible housing 52 and 54 with or without ports 57 and 58 are captured with filter medium 60 by the molded frame 52. Also, in an alternative embodiment of filter assembly 50', shown in Figs. 24- 28, ports 57' and 58' may be integral with frame 52' and not pre-attached to walls 54 and 56. More particularly, ports 57' and 58' may be integrally formed (i.e., molded) with frame 52'. Thus ports 57' and 58' shown in Figs. 24-28 define flow paths 59' through frame 52. Ports 57' and 58' define apertures at opposing ends 62 and 64 of frame 52' for connection or attachment with tubing of a blood collection set. Flexible walls 52 and 54 are attached to the outer surface of frame 52' along rim 53' or, alternatively may be pre-assembled with filter medium and captured by frame 52 during the insert molding process, as described above.

As shown in Fig. 29, filter assembly 50 (or 50') may be assembled as follows. A sheet 66 of multi-layered filter media 60 is provided and segmented into individual, smaller-sized pads 60. Pads 60 may be segmented by cutting, as seen in Fig. 29(b). Individual pads 60 may then be inserted into a mold 61 for molding with an injected molten polymer (See Fig. 29(c)). Once the molded frame has cooled, filter subassembly 50 is removed from the mold. Flexible housing sheets 54 and 56 (with or without pre-attached inlet and outlet ports 57 and 58) may then be attached to frame 52'. Alternatively, flexible housing sheets 54 and 56 may be joined to the filter stack prior to molding of the frame. It will be appreciated that frame 52 may include integrally molded ports as shown in Figs. 25-28, in which case flexible housing sheets would not include pre-attached ports.

Examples

Without limiting any of the foregoing, the subject matter described herein may be found in one or more apparatus. For example, in a first aspect of the present subject matter, a biological fluid filter assembly is set forth. The assembly includes a housing having first and second flexible walls wherein one of the walls includes an inlet port and the other wall includes an outlet port. The filter assembly includes a filter medium disposed between said flexible housing walls. The filter medium includes at least first, second and third elements wherein the first element is made of or includes a material suitable for removing a component of a biological fluid and is disposed between said housing wall that includes inlet port and the second element; the second element may be made of or include a material suitable for removing another component of said biological fluid and is disposed between the first element and the third element; and the third element is made of an organic or inorganic material and is disposed between a housing wall that includes outlet port and said second filter element. The third filter element has a thickness of less than 0.04 cm or greater than 0.25 cm. The filter assembly includes an outer peripheral seal and at least one inner peripheral seal spaced from the outer peripheral seal.

A second aspect of the present subject matter includes the above- described assembly wherein the third element has an air permeability per 1 cm of thickness of greater than 40 cm ² /s at a pressure difference of 125 Pa.

A third aspect of the present subject matter includes a filter assembly in accordance with any one of the first or second aspects described above wherein the outer peripheral seal comprises a seal joining only said housing walls.

A fourth aspect of the present subject matter includes a filter assembly in accordance with any one of the first or second aspects described above wherein the outer peripheral seal comprises a seal joining said first and second housing walls and at least one of the first, second and third elements.

A fifth aspect of the present subject matter includes a filter assembly in accordance with any one of the first through fourth aspects described above including a first inner peripheral seal and a second inner peripheral seal spaced from said first inner peripheral seal.

A sixth aspect of the present subject matter includes a filter assembly in accordance with the fifth aspect described above wherein the space between the first inner peripheral seal and outer peripheral seal or the space between first and second inner peripheral seal is 1 -10 mm.

A seventh aspect of the present subject matter includes a filter assembly in accordance with any one of the first through sixth aspects wherein the inner seal includes a central section between peripheral sections.

A eighth aspect of the present subject matter includes a filter assembly in accordance with any one of the first through seventh aspects described above wherein inner peripheral seal has a thickness of approximately 0.762-2.286 mm.

A ninth aspect of the present subject matter includes a filter assembly in accordance with any one of the first through eighth aspects wherein the third element is a sheet including a mesh. A tenth aspect of the present subject matter includes a filter assembly in accordance with any one of the first through ninth aspects wherein the third filter element is a sheet including a non-porous frame defining a central mesh portion.

An eleventh aspect of the present subject matter includes a filter assembly of any one of the ninth or tenth aspects wherein the sheet is made at least substantially of polyvinyl chloride.

A twelfth aspect of the present subject matter includes a filter assembly in accordance with any one of the first through eleventh aspects described above wherein said inner peripheral seal includes a plurality of filter layers comprising (a) a layer at least substantially comprised of the material of the inlet housing wall (b) a layer adjacent to region (a) and comprising a material that is a composite of the material of the inlet housing wall and the first and second filter element materials (c) a layer adjacent to said regions (b) and (d) comprised of the material of the second filter element (d) a layer adjacent to layer (c) and layer (e) comprising a material that is a composite of said material of said outlet housing wall and the third filter element material and (e) a layer at least substantially comprised of the material of the outlet housing wall.

A thirteenth aspect of the present subject matter includes a filter assembly in accordance with the twelfth aspect described above wherein the layer (d) has a thickness of less than 0.15 mm.

A fourteenth aspect of the present subject matter includes a filter assembly in accordance with any one of the first through thirteenth aspects described above wherein the filter medium including the first, second and third filter elements comprises a plurality of stacked sheets.

A fifteenth aspect of the present subject matter includes a filter assembly in accordance with the fourth aspect wherein said outer peripheral seal includes a plurality of layers comprising (a) a layer at least substantially comprised of the material of housing wall including said inlet port (b) a layer adjacent to said region (a) and comprising a material that is a composite of said material of said inlet housing wall and the first and second filter element materials and (c) a layer at least substantially comprised of the material of the outlet housing wall.

A sixteenth aspect of the present subject matter includes a filter assembly in accordance with any one of the first through fifteenth aspects described above wherein the first and second filter elements are made of a material selected from the group consisting of polybutylene terephthalate, polyethylene terephthalate and polypropylene.

A seventeenth aspect of the present subject matter includes a filter assembly in accordance with any one of the first through eleventh and fourteenth through sixteenth aspects wherein the inner peripheral seal includes a plurality of the filter layers including (a) a layer at least substantially made of the inlet housing wall material, (b) a layer adjacent to the layer (a) that includes a composite of the inlet housing wall material and the first filter element and (c) a layer downstream of layer (b) consisting essentially of a material of the outlet housing wall and the third filter element.

An eighteenth aspect of the present subject matter includes a filter assembly in accordance with the seventeenth aspect wherein the layer (c) material is polyvinyl chloride.

In a nineteenth aspect of the present subject matter, a biological fluid filter assembly is set forth. The assembly includes a housing having first and second flexible walls wherein one of the walls includes an inlet port and the other wall includes an outlet port. The filter assembly includes a filter medium disposed between said flexible housing walls. The filter medium includes at least first, second and third elements wherein the first element is made of or includes a material suitable for removing a component of a biological fluid and is disposed between said housing wall that includes inlet port and the second element; the second element may be made of or include a material suitable for removing another component of said biological fluid and is disposed between the first element and the third element; and the third element is made of an organic or inorganic material and is disposed between a housing wall that includes outlet port and said second filter element. The third filter element having an air permeability per 1 cm of thickness of greater than 40 cm ² /s at a pressure difference of 125 Pa.

A twentieth aspect of the present subject matter includes the biological fluid filter assembly of the nineteenth aspect wherein said third filter element has an air permeability per 1 cm of thickness of approximately 40 cm ² /s-800 cm ² /s at a pressure difference of 125 Pa.

A twenty-first aspect of the present subject matter includes the biological fluid filter assembly of any one of the nineteenth or twentieth aspects wherein the third filter element has a thickness of approximately 0.5-4 mm.

A twenty-second aspect of the present subject matter includes the biological fluid filter assembly of any one of the nineteenth through twenty-first aspects wherein said the filter element includes a porous region comprising a mesh of polyvinyl chloride.

A twenty-third aspect of the present subject matter includes the twenty- second aspect wherein the third filter element further includes a substantially non- porous frame surrounding said porous region.

It will be understood that the embodiments and examples described above are illustrative of some of the applications of the principles of the present subject matter. Numerous modifications may be made by those skilled in the art without departing from the spirit and scope of the claimed subject matter, including those combinations of features that are individually disclosed or claimed herein. For these reasons, the scope of the invention(s) is not limited to the above description but is as set forth in the following claims, and it is understood that claims may be directed to the features hereof, including as combinations of features that are individually disclosed or claimed herein.