Fluid filtration devices and related methods

Abstract

The present disclosure relates to a fluid filtration device, and methods of making and using the fluid filtration device of the present disclosure. The fluid filtration device includes a frame having a porous member fixed thereto, and the frame is rotatably supported within a housing. The fluid and particles therein are introduced via a non-tangential inlet, and components of the fluid may be filtered through the porous member, producing filtrate (and particles passing through the porous member) and retentate (and particles not passing through the porous member). Some embodiments include a baffle at the entrance. Methods of manufacture (and assembly) and methods of using the fluid filtration devices of the present disclosure are also described.

Description

[0001] Cross - Reference to Related Applications This application claims the benefit of U.S. Provisional Patent Application No. 63 / 384,395, filed on November 18, 2022, the content of which is incorporated herein by reference in its entirety. Technical Field

[0002] The present disclosure relates to a fluid filtration device, such as for blood or plasma processing systems and methods. More particularly, the present disclosure relates to fluid filtration devices and systems, and methods for manufacturing or using fluid filtration devices. The fluid filtration devices of the present disclosure may be included in automated closed systems for separating or enriching target cells, such as for cell therapy applications. Background Art

[0003] Automated processes for cell manufacturing and / or separation are crucial for the widespread application of cell therapy technologies. It is highly desirable that automated cell processing platforms limit the number of operations and / or exposures of cell populations to the external environment, thereby limiting contamination and other issues.

[0004] Currently, rotary filtration separators are used to separate specific cellular blood components (e.g., red blood cells, white blood cells, and platelets) from specific particulates in whole blood and then for downstream applications. The target cell product (e.g., red blood cells, white blood cells, or platelets) may be in a suspension including plasma and / or other supernatants. Thus, it is sometimes necessary to "wash" the cell suspension (usually with a physiological buffer) before reinfusion to remove the plasma / supernatants and any non - target cell material.

[0005] For example, during the manufacture of CAR T - based cell therapies, cell processing may be required, where CD4+ and CD8+ T cells are separated from a leukopak sample before T - cell activation and gene modification, CAR T - cell expansion, and CAR T - cell reinfusion into a patient. Since currently available CAR T - cell therapies are typically tailored to each individual patient, there is an increasing need for efficient automated systems.

[0006] Accordingly, there is a great need for improved fluid filtration devices and related processes for automated and / or closed systems; rapid and simple processing protocols (e.g., concentration or washing) suitable for various applications, such as CAR T - cell therapies. Summary of the Invention

[0007] The present disclosure relates to a fluid filtration device and system for automated processing of blood products for cell therapy applications. In one aspect, the present disclosure relates to a method for manufacturing the fluid filtration device.

[0008] One aspect of the present disclosure provides a fluid filtration device that can be used in a system for processing blood or apheresis samples.

[0009] In one embodiment, the fluid filtration device of the present disclosure includes: (i) a housing defining a cavity bounded by at least one sidewall, the housing having an upper end and an opposite lower end; (ii) an inlet and a first outlet passing through the housing, each of the inlet and the first outlet being in fluid communication with the cavity; (iii) a second outlet passing through the housing; (iv) a frame rotatably supported within the cavity and capable of rotating relative to the housing; (v) at least one hole passing through the frame, the at least one hole being in fluid communication with the second outlet; (vi) a first porous member fixed to or fixed around the frame.

[0010] In one embodiment, the frame and / or the housing is cylindrical or substantially cylindrical.

[0011] In one embodiment, the surface of the at least one sidewall facing the cavity tapers by about 5 degrees or less, about 3 degrees or less, or about 1 degree ± 0.5 degrees from the upper end of the housing to the lower end of the housing.

[0012] The fluid filtration device may further include an upper assembly and a lower assembly that respectively cooperate with the upper end of the housing and the lower end of the housing to rotatably support the frame within the cavity. In one embodiment, the upper assembly and the lower assembly define a longitudinal axis passing through the cavity, and the frame rotates about the longitudinal axis.

[0013] The fluid filtration device may further include baffles disposed at least in the non-tangential inlet, and preferably disposed at the opening where the inlet leads into the cavity.

[0014] The fluid filtration device may further include a magnetically responsive member fixedly disposed within the frame, preferably in the upper end of the frame. In one embodiment, the magnetically responsive member and the frame are matched via a pair of complementary features including at least one straight edge.

[0015] In one embodiment, the first porous member is fixed to the frame by a pressure-sensitive adhesive. In one embodiment, the first porous member is a track-etched membrane. In one embodiment, the porous membrane has a pore density between about 1 x 10 5 pores / cm 2 and 1 x 10 6 pores / cm 2 .

[0016] The fluid filtration device may further include a second porous member fixed to or around the frame. In one embodiment, the second porous member is fixed to or around the frame by a pressure-sensitive adhesive. In one embodiment, the second porous member is a track-etched membrane.

[0017] The fluid filtration device may further include a plurality of spaced-apart transverse grooves in the surface of the frame facing the porous member. In one embodiment, the fluid filtration device may further include a plurality of spaced-apart longitudinal grooves in the surface of the frame facing the porous member, wherein the plurality of spaced-apart longitudinal grooves are interconnected with the plurality of spaced-apart transverse grooves. In one embodiment, the plurality of spaced-apart longitudinal grooves and the plurality of spaced-apart transverse grooves cooperate to receive the filtrate that has passed through the porous member and send the filtrate to the second outlet via the at least one hole in the frame.

[0018] In one embodiment, the widths of the plurality of spaced-apart transverse and / or longitudinal grooves are equal. In one embodiment, the widths of the plurality of spaced-apart transverse and / or longitudinal grooves are not equal. In one embodiment, the dimensions of the plurality of spaced-apart transverse grooves and / or the plurality of spaced-apart longitudinal grooves at the top of the frame are greater than the dimensions at the bottom.

[0019] In one embodiment, the fluid filtration device of the present disclosure includes: (i) a housing defining a cavity bounded by at least one sidewall; (ii) an inlet and an outlet passing through the housing, each of the inlet and the outlet being in fluid communication with the cavity; (iii) a waste liquid port passing through the housing; (iv) a frame supported in the cavity in a relatively rotating relationship with the housing, the frame having at least one hole therethrough, the at least one hole being in fluid communication with the waste liquid port; (v) a first porous membrane fixed to or around the frame; (vi) an upper bearing assembly rotatably connecting the frame and the upper end of the housing at the upper end of the frame; and (vii) a lower assembly rotatably connecting the frame and the lower end of the housing at the lower end of the frame.

[0020] In one embodiment, the inlet and the first outlet are located midway between the upper assembly and the lower end of the housing.

[0021] In one embodiment, the hole passing through the inlet is non-tangential to the at least one sidewall. In one embodiment, a baffle may be configured in the hole.

[0022] In one embodiment, the upper (bearing-carrying) assembly and the lower assembly define a longitudinal axis passing through the cavity, and the frame rotates about its longitudinal axis.

[0023] In one embodiment, the magnetoresponsive member is located within the upper (bearing) assembly. In one embodiment, the fluid filtration device of the present disclosure may further include an orifice having at least two substantially straight edges that pass through the magnetoresponsive member. In one embodiment, the fluid filtration device of the present disclosure may further include a torque transmission member within the upper (bearing) assembly and connected to the orifice.

[0024] Another aspect of the present disclosure provides a method of manufacturing a fluid filtration device that can be used in an automated system for processing blood or apheresis samples.

[0025] In one embodiment, a method of manufacturing a fluid filtration device (which may be as described herein) may include (a) molding a housing having i) a cavity defined by at least one sidewall and defining a longitudinal axis, ii) an inlet, iii) a first outlet, and iv) a second outlet, each of the inlet, first outlet, and second outlet being in fluid communication with the cavity, (b) molding a frame, (c) attaching a porous membrane to the frame or around the frame by a pressure-sensitive adhesive, and (d) fixing the frame within the cavity, the frame being capable of rotating within the cavity about a rotational axis (which may coincide with the longitudinal axis).

[0026] In one embodiment, the method of manufacturing the fluid filtration device of the present disclosure may further include disposing at least one baffle within the housing, and preferably disposing at least one baffle in one or both of the inlet and the outlet. In one embodiment, the baffle is disposed at the opening where the inlet (and optionally the first inlet) leads to the cavity.

[0027] In one embodiment, the method of manufacturing the fluid filtration device of the present disclosure may further include applying a pressure-sensitive adhesive to one or more frame contact surfaces of the porous member.

[0028] In one embodiment, the method of manufacturing the fluid filtration device of the present disclosure may further include applying a pressure-sensitive adhesive to the frame corresponding to the dimensions of the frame-facing side of the porous member.

[0029] In one embodiment, the method of manufacturing the fluid filtration device of the present disclosure may further include applying the porous member to the frame by rotating the frame about the rotational axis to place the porous member on the frame before inserting the frame into the cavity.

[0030] In one embodiment, the method of manufacturing the fluid filtration device of the present disclosure may further include applying pressure to the porous member and the frame to fix the porous member to the frame.

[0031] In one embodiment, one or both of the housing and the frame are injection molded. In one embodiment, one or both of the frame and the housing are molded from a polymer.

[0032] In one embodiment, the frame is rotatably supported in the cavity between the upper end portion and the lower end portion of the housing by an upper assembly and a lower assembly that respectively cooperate with the upper end portion and the lower end portion of the housing.

[0033] In one embodiment, the surface of the at least one sidewall facing the cavity tapers by about 5 degrees or less, about 3 degrees or less, or about 1 degree ± 0.5 degrees from the upper end portion to the lower end portion of the housing. BRIEF DESCRIPTION OF THE DRAWINGS

[0034] To better understand the various embodiments described herein and to more clearly show how these various embodiments may be implemented, reference will be made, by way of example, to the accompanying drawings, in which at least one example embodiment is shown and described. The drawings are not intended to limit the scope of the teachings described herein.

[0035] Figure 1 A exploded perspective view of a fluid filtration device according to an exemplary embodiment is shown.

[0036] Figure 2 A perspective view of an assembled fluid filtration device according to an exemplary embodiment is shown.

[0037] Figure 3 A cross-sectional bottom view of the fluid filtration device is shown, showing the structural configuration of the inlet and outlet passing through the housing when viewed in the direction of arrow A in Figure 2 The structural configuration of the inlet and outlet passing through the housing when viewed in the direction of arrow A in

[0038] Figure 4 A longitudinal cross-section of the upper portion of the fluid filtration device according to an exemplary embodiment is shown, showing the structural interaction between the upper (bearing) assembly, the frame, and the housing.

[0039] Figure 5 A cross-section of the upper (bearing) assembly is shown when viewed in the direction of arrow B in Figure 2 The cross-section of the upper (bearing) assembly when viewed in the direction of arrow B in

[0040] Figure 6 A longitudinal cross-section of the lower portion of the fluid filtration device according to an exemplary embodiment is shown. The grey arrows indicate the flow of fluid (and any particulate matter that may be suspended therein) towards the porous membrane, and the black arrows indicate the flow of filtrate (and any particulate matter that may be suspended therein) towards and through the second outlet.

[0041] Figure 7Shows a longitudinal section of the lower part of a fluid-filled fluid filtration device according to an exemplary embodiment. As the frame rotates, the fluid moves away from the axis of rotation of the frame under the action of centrifugal force, forming bubbles or cavitation at the lower assembly. Detailed Description

[0042] The present disclosure relates to a rotary filtration device that can be used for a method of separating particulate matter from a fluid or classifying particulate matter in a fluid based on size. The fluid processed by the device of the present disclosure is not particularly limited as long as it contains or includes particulate matter. In one embodiment, the fluid is a biological sample, such as blood, plasma, urine, etc.

[0043] Device In one aspect, the present disclosure relates to a rotary membrane / filtration device (e.g., a fluid filtration device).

[0044] Reference Figures 1 to 7 , shows an embodiment of a fluid filtration device 1. The fluid filtration device 1 includes a housing 5 that defines a cavity 7 bounded by at least one sidewall 10. In one embodiment, the housing 5 includes an upper end portion and an opposite lower end portion connected by at least one sidewall 10, and the direction (or length) of at least one sidewall between the upper end portion and the lower end portion defines the longitudinal axis of the fluid filtration device 1 l .

[0045] The housing 5 can be of any shape. In one embodiment, the shape of the housing 5 is suitable for injection molding. The housing 5, more particularly, is the cross-section of the cavity 7 taken in a plane orthogonal to the longitudinal axis of the housing 5, and its shape receivingly accommodates a frame 30 (described further below), which is rotatably supported within the cavity 7 and is capable of rotating relative to the housing 5 (about a rotation axis that can coincide with the longitudinal axis l ). l coincide).

[0046] In one embodiment, the housing 5 is cylindrical or substantially cylindrical. In one embodiment, the cavity 7 of the housing 5 is cylindrical or substantially cylindrical.

[0047] In one embodiment, the housing 5 (or at least on its sidewalls) includes an outer surface and an inner surface (e.g., the surface facing the cavity). In one embodiment, the outer surface of at least one sidewall 10 of the housing 5 tapers from the upper end portion of the housing 5 towards the lower end portion of the housing 5. In one embodiment, the surface of at least one sidewall 10 facing the cavity tapers from the upper end portion of the housing 5 towards the lower end portion of the housing 5. In one embodiment, both the outer surface and the surface facing the cavity taper. In one embodiment, both the outer surface and the surface facing the cavity taper from the upper end portion of the housing 5 towards the lower end portion of the housing 5.

[0048] If present, the taper (or draft angle) of at least one outer surface and / or the cavity-facing surface of the sidewall 10 is less than 10 degrees, or less than 9 degrees, or less than 8 degrees, or less than 7 degrees, or less than 6 degrees, or less than 5 degrees, or less than 4 degrees, or less than 3 degrees, or less than 2 degrees, or approximately 1 degree (±0.5 degrees) or less.

[0049] The housing 5 can be made of or formed from any material. In one embodiment, the material is biocompatible. In one embodiment, the housing 5 is made of a polymer or plastic, such as any type of polymer or plastic used to form conventional cell culture containers or devices. In one embodiment, the housing 5 is sterilizable, such as by contact with alcohol, irradiation, or autoclaving.

[0050] The fluid filtration device 1 further includes a plurality of ports ( Figure 1 and Figure 2 ). In one embodiment, the fluid filtration device 1 includes an inlet 12 and an outlet 16 passing through the housing 5. In one embodiment, one or both of the inlet 12 and the outlet 16 are configured in at least one sidewall 10 (or passing through at least one sidewall). Each of the inlet 12 and the outlet 16 is in fluid communication with the cavity 7.

[0051] In one embodiment, the inlet 12 and the outlet 16 are integrally formed with the housing 5 and include holes therethrough. In one embodiment, the inlet 12 and the outlet 16 are connected to or continuous with corresponding holes passing through at least one sidewall 10.

[0052] In one embodiment, the inlet 12 (or the hole therethrough) is tangent to at least one sidewall 10. In one embodiment, the inlet 12 (or the hole therethrough) is non-tangent to at least one sidewall 10. In one embodiment, the outlet 16 (or the hole therethrough) is tangent to at least one sidewall 10. In one embodiment, the outlet 16 (or the hole therethrough) is non-tangent to at least one sidewall 10. In one embodiment, both the inlet 12 and the outlet 16 (or the holes therethrough) are tangent to at least one sidewall 10. In one embodiment, both the inlet 12 and the outlet 16 (or the holes therethrough) are non-tangent to at least one sidewall 10.

[0053] The fluid filtration device 1 may further include a second outlet 18 (e.g., a waste liquid port) passing through the housing 5 ( Figure 1 , Figure 2 and Figure 7 ). In one embodiment, the second outlet 18 is configured on the bottom wall 20 of the housing 5. In one embodiment, the second outlet 18 is integrally formed with the housing 5. In one embodiment, the second outlet 18 is connected to or continuous with a hole passing through the housing 5 (such as through the bottom wall 20).

[0054] The positions of the inlet 12, the first outlet 16, and the second outlet 18 (if present) within / through the housing 5 are flexible. In one embodiment, at least the inlet 12 and the first outlet 16 are spaced apart, such as along the longitudinal axis of the housing 5 l , and more particularly along the longitudinal axis of the sidewall 10. In one embodiment, each of the inlet 12, the first outlet 16, and the second outlet 18 is spaced apart, such as along the longitudinal axis of the housing 5 l , and more particularly along the longitudinal axis of the sidewall 10.

[0055] In one embodiment, the inlet 12 is configured to pass through the housing 5 at a relatively higher position along the longitudinal axis l than the first outlet 16. In this embodiment, the inlet 12 may be configured to pass through the housing 5 (e.g., the sidewall 10) at or near the upper end of the housing 5, while the first outlet 16 may be configured to pass through the housing 5 (e.g., the sidewall 10) at or near the lower end of the housing 5.

[0056] In one embodiment, the inlet 12 is configured to pass through the housing 5 at a relatively lower position along the longitudinal axis l than the first outlet 16. In this embodiment, the inlet 12 may be configured to pass through the housing 5 (e.g., the sidewall 10) at or near the lower end of the housing 5, while the first outlet 16 may be configured to pass through the housing 5 (e.g., the sidewall 10) at or near the upper end of the housing 5.

[0057] Regardless of which of the inlet 12 or the first outlet 16 is lower in position relative to the other (along the longitudinal axis l ), the lower of the two may be configured to be at the lower end of the housing 5 and substantially flush with the cavity-facing surface of the bottom wall 20.

[0058] In an embodiment of the fluid filtration device 1 including the second outlet 18, the second outlet 18 may be configured to pass through the housing 5, and more particularly, may be configured to pass through the bottom wall 20 of the housing 5. Thus, one of the inlet 12 and the first outlet 16 may be located between the other and the second outlet 18.

[0059] In an embodiment where one or both of the inlet 12 and the first outlet 16 are located at or near the upper end of the housing 5 (through at least one sidewall 10), it may be important to maintain a sufficient amount of clearance between the position of the inlet 12 and / or the first outlet 16 and the top of the housing 5. For example, as further described below, mechanical components for the rotating frame 30 and / or for rotatably connecting the housing 5 and the frame 30 that can rotate within the cavity 7.

[0060] Since the inlet 12, the first outlet 16, and the second outlet 18 are all configured to transmit the fluid flowing therethrough, they can be adapted to match the corresponding ends of the tubes or other conduits through which the fluid flows. In one embodiment, one or more of the inlet 12, the first outlet 16, and the second outlet 18 include an adapter or connector that mediates the matching or connection with the corresponding ends of the pipes or conduits.

[0061] In one embodiment, one or more of the inlet 12, the first outlet 16, and the second outlet 18 can be adapted to match the corresponding ends of the pipes or conduits, such as by inserting or sliding the ends of the pipes or conduits around the corresponding mouths of the inlet 12, the first outlet 16, and the second outlet 18. In one embodiment, one or more of the inlet 12, the first outlet 16, and the second outlet 18 can be adapted to match the corresponding ends of the pipes or conduits, such as by means of an adhesive or other type of fastener (e.g., Luer lock, threads, etc.).

[0062] In one embodiment, the inlet 12 can include a pressure sensor to measure the fluid pressure at the inlet 12. In one embodiment, the first outlet 16 can include a pressure sensor to measure the fluid pressure at the first outlet 16. In one embodiment, the second outlet 18 can include a pressure sensor to measure the fluid pressure at the second outlet 18.

[0063] The fluid filtration device 1 can further include a baffle 13a disposed at least in the inlet 12 ( Figure 3 ). Preferably, the baffle 13a can be disposed at the opening of the inlet 12 leading to the chamber 7. The baffle 13a can be provided in and / or integrally formed with at least one side wall 10 of the housing 5, and more particularly, can be provided in a hole extending through at least one side wall 10.

[0064] In one embodiment, the fluid filtration device 1 can further include a baffle 13b disposed in the first outlet 16. Preferably, the baffle 13b can be disposed at the opening of the first outlet 16 leading to the chamber 7. The baffle 13b can be provided in and / or integrally formed with at least one side wall 10 of the housing 5, and more particularly, can be provided in a hole extending through at least one side wall 10. In one embodiment, both the inlet 12 and the first outlet 16 include the baffles 13a and 13b.

[0065] In one embodiment, the tangential inlet 12 introduces the fluid into the housing 5, more particularly into its chamber 7. In one embodiment, the non-tangential inlet 12 introduces the fluid into the housing 5, more particularly into its chamber 7. In this embodiment, the baffle 13a can promote the dispersion of the fluid (and the particles suspended therein) in the chamber 7 and / or promote the dispersion of the fluid mixture to be processed by the fluid filtration device 1.

[0066] The fluid filtration device 1 further includes a frame 30 that is supported within a cavity 7 of the housing 5 ( Figure 1 and Figure 2 ). The frame 30 may also be referred to herein as a rotor, spinner, or rotator, and these terms may be used interchangeably with the term "frame". Thus, in one embodiment, the frame 30 is rotatably supported within the cavity 7 and is capable of rotating relative to the housing 5. In one embodiment, the frame 30 is capable of rotating in a clockwise and / or counterclockwise direction.

[0067] The frame 30 can be made or formed of any material. In one embodiment, the material is biocompatible. In one embodiment, the frame 30 is made of a polymer or plastic, such as any type of polymer or plastic used to form conventional cell culture containers or devices. In one embodiment, the frame 30 is sterilizable, such as by contact with alcohol, irradiation, or autoclaving.

[0068] The frame 30 can be any shape. In one embodiment, the shape of the frame 30 is suitable for injection molding or other types of molding. The cross-section of the frame 30, taken in a plane orthogonal to the longitudinal axis of the housing 5 and the frame 30 l is shaped such that it can be received and accommodated within the housing 5 (e.g., within the cavity 7) and is capable of rotating about the longitudinal axis.

[0069] In some embodiments, the housing 5 is cylindrical or substantially cylindrical, and the frame 30 is cylindrical or substantially cylindrical. Thus, the cavity 7 and the frame 30 have diameters (or major axes) that are measured in a plane orthogonal to the longitudinal axis l In this embodiment, the diameter (or major axis) of the frame 30 is less than the diameter of the cavity 7. In one embodiment, the diameter of the frame 30 is concentric with the diameter of at least one sidewall 10.

[0070] In one embodiment, the frame 30 includes at least one hole 32 passing through it ( Figure 6 ). In one embodiment, the frame 30 includes more than one hole 32 passing through it. One or more holes 32 may converge and be in fluid communication with the second outlet 18. After fluid and / or filtrate is introduced into the fluid filtration device 1 via the inlet 12 and passes through the first porous member, one or more holes 32 and the second outlet 18 together convey the fluid and / or filtrate out of the fluid filtration device 1, as further described below.

[0071] At least one hole 32 can be located at any point along the length of the frame 30 (by the longitudinal axis lDefinition). Preferably, at least one hole 32 is located at or near the base or lower end of the frame 30 where the filtrate can precipitate after passing through the first porous member supported on the frame 30. In one embodiment, at least one hole 32 is located near the lower end of the frame 30 but is spaced from the base of the frame 30 by a bearing surface surrounding the perimeter of the frame 30. This bearing surface (between the lower end of the frame 30 and at least one hole 32) surrounding the perimeter of the frame 30 may be important for securing the first porous member 40 to the frame 30, as further described below.

[0072] In one embodiment, the frame 30 may include two holes 32 that are opposite each other (e.g., diametrically), and these holes converge within the frame 30 to create a passage that is in fluid communication with the second outlet 18, or a passage that is in fluid communication with a conduit leading to the second outlet 18.

[0073] The frame 30 may further include a plurality of spaced-apart transverse grooves 34 in the surface of the frame 30 facing the porous member (e.g., the surface of the frame 30 facing the chamber) Figure 1 , Figure 2 and Figure 6 ). In one embodiment, the plurality of spaced-apart transverse grooves 34 are parallel or substantially parallel to each other. Each of the plurality of spaced-apart transverse grooves 34 forms a groove in the surface of the frame 30 facing the chamber. Thus, the plurality of spaced-apart transverse grooves 34 may interpose a plurality of spaced-apart transverse ridges 35. In one embodiment, the plurality of spaced-apart transverse ridges 35 are parallel or substantially parallel to each other (and parallel to the plurality of spaced-apart transverse grooves 34).

[0074] In one embodiment, some or all of the plurality of spaced-apart transverse grooves 34 (and the plurality of spaced-apart transverse ridges 35) are disposed entirely around the surface of the frame 30 facing the chamber. In one embodiment, some or all of the plurality of spaced-apart transverse grooves 34 (and the plurality of spaced-apart transverse ridges 35) are not disposed entirely around the surface of the frame 30 facing the chamber.

[0075] The frame 30 may further include a plurality of spaced-apart longitudinal grooves 37 in the surface of the frame 30 facing the porous member (e.g., the surface of the frame 30 facing the chamber) Figure 1 , Figure 2 and Figure 6 ). In one embodiment, the plurality of spaced-apart longitudinal grooves 37 are parallel or substantially parallel to each other. Each of the plurality of spaced-apart longitudinal grooves 37 forms a groove in the surface of the frame 30 facing the chamber. Thus, the plurality of spaced-apart longitudinal grooves 37 may be interposed by a plurality of spaced-apart longitudinal ridges 38. In one embodiment, the plurality of spaced-apart longitudinal ridges 38 are parallel or substantially parallel to each other (and parallel to the plurality of spaced-apart longitudinal grooves 37).

[0076] In one embodiment, some or all of the plurality of spaced longitudinal grooves 37 are parallel to the longitudinal axis of the frame 30 (and the housing 5). l In one embodiment, the plurality of spaced longitudinal grooves 37 are formed substantially along the entire frame 30. In one embodiment, the porous membrane support surface of the frame 30 may be defined by the longitudinal extent of a plurality of spaced transverse grooves 34 (and a plurality of spaced transverse ridges 35). In one embodiment, the porous membrane support surface of the frame 30 may be defined by a plurality of transverse ridges 35 and / or a plurality of longitudinal ridges 38.

[0077] In one embodiment, the plurality of spaced longitudinal grooves 37 are interconnected with the plurality of spaced transverse grooves 34, thereby generating a network of grooves / channels in the cavity-facing surface (and the membrane support surface) of the frame 30.

[0078] The plurality of spaced transverse grooves 34 can be of any width as long as their width (and depth) is sufficient to accommodate cells or any particulate matter in the filtrate that has passed through the first porous membrane 40. For example, the width (and depth) of the plurality of spaced transverse grooves 34 can be between about 2 µm and 5 mm, or between about 3 µm and 4 mm, or between about 5 µm and 3 mm.

[0079] Similarly, the plurality of spaced longitudinal grooves 37 can be of any width as long as their width (and depth) is sufficient to accommodate cells or any particulate matter in the filtrate that has passed through the first porous membrane 40. For example, the width (and depth) of the plurality of spaced longitudinal grooves 37 can be between about 2 µm and 5 mm, or between about 3 µm and 4 mm, or between about 5 µm and 3 mm.

[0080] In one embodiment, each of the plurality of spaced transverse grooves 34 has an equal width. In one embodiment, each of the plurality of spaced transverse grooves 34 has an unequal width. In a non-limiting example, the width of each of the plurality of transverse grooves 34 can increase from the lower end portion to the upper end portion of the frame 30. In a different non-limiting example, the width of each of the plurality of transverse grooves 34 can decrease from the lower end portion to the upper end portion of the frame 30.

[0081] The fluid filtration device 1 further includes a first porous member 40 fixed to or surrounding the frame 30 ( Figure 1)。In one embodiment, the fluid filtration device 1 includes only one porous member. In one embodiment, the fluid filtration device 1 includes a plurality of porous members, such as two stackable porous members. In embodiments including a plurality of porous members, the inner porous member may be sandwiched between the frame 30 and the outer porous member (in an overlapping manner).

[0082] The first porous member 40 (and additional porous members) is not particularly limited as long as it does not tear or otherwise get damaged (e.g., become weak, stretched, or have reduced performance) under the conditions under which the fluid filtration device 1 operates (e.g., pressure and pressure change forces).

[0083] One or more porous members may be one or more types of fiber mesh membranes, cast films, track-etched membranes, or other types of membranes known to those skilled in the art. In one embodiment, the first porous member 40 is a track-etched membrane. In one embodiment, the first porous member 40 is made of a polymer, such as polyester or polycarbonate.

[0084] Since a pressure difference may occur on either side of the first porous membrane 40 during the operation of the fluid filtration device 1, the first porous member can withstand this pressure drop. In one embodiment, the attachment means for fixing the first porous member 40 to the frame 30 can withstand the pressure difference on either side of the first porous membrane 40.

[0085] The first porous member 40 (and additional porous members) may also be restricted by the pore size. Generally, the pore size depends on the specific application of the fluid filtration device 1 and the nature of the fluid to be processed. Therefore, the pore size can be carefully selected according to the nature of the particles in the fluid intended to pass through the first porous member 40. For example, by selecting the pore size of the first porous member 40, at least two populations of particles (based on average diameter) included in the fluid can be fractionated, and the pore size only allows the relatively smaller one or more populations of particles to pass through. As a more specific but non-limiting example, the size of the pores can be such that small filtrates (e.g., platelets, microparticles, etc.) are allowed to pass through the first porous member 40 (and additional porous members), while the required retentate residues (e.g., cells, such as white blood cells) do not pass through. In this way, different-sized particles or cells in the fluid can be fractionated by selecting a pore size that excludes at least part of the particles or cells.

[0086] In terms of pore diameter, the first porous member may include a plurality of pores having a nominal pore diameter below 10 μm. In one embodiment, the first porous member includes a plurality of pores having a nominal pore diameter of about 9 μm. In one embodiment, the first porous member includes a plurality of pores having a nominal pore diameter of about 8 μm. In one embodiment, the first porous member includes a plurality of pores having a nominal pore diameter of about 7 μm. In one embodiment, the first porous member includes a plurality of pores having a nominal pore diameter of about 6 μm. In one embodiment, the first porous member includes a plurality of pores having a nominal pore diameter of about 5 μm. In one embodiment, the first porous member includes a plurality of pores having a nominal pore diameter of about 4 μm. In one embodiment, the first porous member includes a plurality of pores having a nominal pore diameter of about 3 μm. In one embodiment, the first porous member includes a plurality of pores having a nominal pore diameter of about 2 μm. In one embodiment, the first porous member includes a plurality of pores having a nominal pore diameter in the range of 2 μm to 6 μm.

[0087] In one embodiment, the first porous member 40 (and additional porous members) is also constrained by pore density. In one embodiment, the pore density can be in the range of 1 x 10 5 pores / cm 2 to 1 x 10 6 pores / cm 2 . In one embodiment, the pore density can be in the range of 2 x 10 5 pores / cm 2 to 8 x 10 5 pores / cm 2 . In one embodiment, the pore density can be in the range of 3 x 10 5 pores / cm 2 to 6 x 10 5 pores / cm 2 . In one embodiment, the pore density can be about 4 x 10 5 pores / cm 2 ± 1 x 10 5 .

[0088] In one embodiment, the first porous member 40 is fixed to the frame 30 using a biocompatible adhesive 42. In one embodiment, the adhesive 42 is a pressure-sensitive adhesive. In one embodiment, the adhesive 42, such as a pressure-sensitive adhesive, can be applied around the perimeter of the first porous member 40. In one embodiment, the adhesive 42, such as a pressure-sensitive adhesive, can be applied to some or all of the plurality of spaced-apart transverse ridges 35 and / or the plurality of spaced-apart longitudinal ridges 38 of the frame 30.

[0089] In one embodiment, the first porous member 40 may be supported on the membrane bearing surface of the frame 30, such as against a plurality of spaced-apart transverse ridges 35 and / or a plurality of spaced-apart longitudinal ridges 38. In one embodiment, the first porous member 40 adheres to a plurality of spaced-apart transverse ridges 35 and / or a plurality of spaced-apart longitudinal ridges 38. In one embodiment, the first porous member 40 is not adhered to a plurality of spaced-apart transverse ridges 35 and / or a plurality of spaced-apart longitudinal ridges 38, but is in close contact with a plurality of spaced-apart transverse ridges 35 and / or a plurality of spaced-apart longitudinal ridges 38, and its outermost edge is fixed to the frame 30 by an adhesive 42. As described above, the bearing surface on the frame 30, such as the perimeter around the opposite ends of the frame 30 and / or the length of the frame 30 extending in the direction of the longitudinal axis l can facilitate attaching the first porous member 40 to the frame 30.

[0090] In one embodiment, the ends of the first porous member 40 do not overlap when fixed to the frame 30 or around the frame. In one embodiment, the ends of the first porous member 40 overlap when fixed to the frame 30 or around the frame.

[0091] As described above, the frame 30 is capable of rotating within the housing 5, and more particularly, within the cavity 7 of the housing 5, about a rotational axis (which may coincide with the longitudinal axis l coincide). Therefore, there should be sufficient clearance between the extremities of the frame 30 and the inner sidewall 10 of the housing 5, which can be referred to as the shear clearance. A typical shear clearance can be approximately between 0.1 mm and 10 mm, or between about 0.25 mm and 5 mm, or between about 0.5 mm and 3 mm. In one embodiment, the shear clearance may be uniform or substantially uniform along its length (i.e., parallel to the longitudinal axis). In one embodiment, the shear clearance may vary along its length (i.e., parallel to the longitudinal axis), for example, the shear clearance may increase or decrease (continuously) in the direction from the upper end of the frame 30 to the lower end of the frame 30.

[0092] In one embodiment, the diameter of the cavity 7 is larger at the upper end of the housing 5 relative to the lower end of the housing 5. In this embodiment, the diameter of the cavity 7 may gradually / continuously decrease from the upper end of the housing 5 to the lower end of the housing 5. In the same or different embodiments, the diameter of the frame 30 may be larger at its upper end relative to its lower end, and in this embodiment, the diameter of the frame 30 may gradually / continuously decrease from its upper end to its lower end.

[0093] In one embodiment, the diameter of the cavity 7 is smaller at the upper end portion of the housing 5 relative to the lower end portion of the housing 5. In this embodiment, the diameter of the cavity 7 can increase gradually / continuously from the upper end portion of the housing 5 to the lower end portion of the housing 5. In the same or different embodiments, the diameter of the frame 30 can be smaller at its upper end portion relative to its lower end portion, and in this embodiment, the diameter of the frame 30 can increase gradually / continuously from its upper end portion to its lower end portion.

[0094] At least one side wall 10, and more particularly, the cavity-facing surface of at least one side wall 10, having a tapered configuration from the upper end portion to the lower end portion of the housing 5 can improve the filtration efficiency. In one embodiment, the tapered configuration of at least one side wall 10 can affect the fluid flow pattern within the cavity 7. For example, the tapered configuration and the resulting shear gap width (continuous) variation in the direction of the longitudinal axis l may cause the axial wavelength of the annular vortices and / or Taylor vortices to gradually increase (or decrease).

[0095] Reference Figures 4 to 7 , the fluid filtration device 1 may further include an upper assembly 50 and a lower assembly 70 (described further below), which cooperate with the upper end portion of the housing and the lower end portion of the housing, respectively, to rotatably support the frame 30 within the cavity 7. In one embodiment, the upper assembly 50 includes a bearing. In one embodiment, the lower assembly 70 includes a bearing. In one embodiment, only one of the upper assembly 50 and the lower assembly 70 includes a bearing. In one embodiment, both the upper assembly 50 and the lower assembly 70 include bearings. In an embodiment where the upper assembly 50 includes a bearing, it may be referred to as the upper bearing assembly 50. In an embodiment where the lower assembly 70 includes a bearing, it may be referred to as the lower bearing assembly 70.

[0096] The upper assembly 50 may include a number of components that cooperate with each other to seal the upper end portion of the housing 5. The upper (bearing-containing) assembly 50 and its components may also cooperate to rotatably support the upper end portion of the frame 30 in a rotational relationship relative to the upper end portion of the housing 5. Thus, in one embodiment, the upper (bearing-containing) assembly 50 rotatably connects the frame and the upper end portion of the housing 5 at the upper end portion of the frame 30.

[0097] In one embodiment, the upper (bearing-containing) assembly 50 includes a housing cover 51. The housing cover 51 is mounted or otherwise attached to the housing 5. In one embodiment, the housing cover 51 is mounted to the housing 5 by means of an adhesive or other type of fastening device (such as threads or screws). In one embodiment, the housing cover 51 is mounted or attached to the housing 5 by an interference fit or a press fit.

[0098] In one embodiment, the housing cover 51 seals the upper end of the housing 5, such as by being slidably received or screwed into the cavity 7. In one embodiment, the housing cover 51 includes a collar descending from its bottom surface, and the collar is sized to be received within the cavity 7 of the housing 5. In one embodiment, a flange on the housing cover 51 limits the distance by which it can be received within the cavity 7.

[0099] In one embodiment, the upper (bearing-containing) assembly 50 includes an upper bearing 53. The upper bearing 53 can be connected to the bottom surface of the housing cover to the housing cover 51. The upper bearing 53 can be adhered to the housing cover 51, connected to the housing cover by an interference fit, or attached by any other means. In one embodiment, the upper bearing 53 mediates the rotatable coupling of the frame 30, or more directly, its frame cover 55, to the stationary or fixed housing cover 51. In addition to mediating the rotation of the frame 30 (and the frame cover or rotor cover 55) within the housing 5, the upper bearing 53 can further align the frame 30 (and the frame cover or rotor cover 55) located within the housing 5 for controlled rotation of the frame 30 (and the frame cover or rotor 55) relative to the housing cover 51 about its axis of rotation.

[0100] In one embodiment, the housing cover 51 and / or the frame cover 55 are made of or formed from any material. In one embodiment, the material is biocompatible. In one embodiment, the housing cover 51 and / or the frame cover 55 are made of a polymer or plastic, such as any type of polymer or plastic used to form conventional cell culture containers or devices. In one embodiment, the housing cover 51 and / or the frame cover 55 are sterilizable, such as by contact with alcohol, irradiation, or autoclaving.

[0101] In one embodiment, the frame cover 55 is mounted or connected to the frame 30 by means of an adhesive. In one embodiment, the frame cover 55 is screwed into the frame 30. In one embodiment, the frame 30 is mounted to the frame cover 55 by means of screws and nuts, rivets, or any other fastening means. Thus, the frame cover 55 (and the frame 30) can be rotatably supported within the upper (bearing-containing) assembly 50, and more particularly, fixed to the upper bearing 53 in a manner that allows the frame 30 to rotate relative to the housing 5.

[0102] In one embodiment, the frame cover 55 seals the upper end of the frame 30, such as by being slidably received or screwed into the upper end of the frame 30. In one embodiment, the frame cover 55 includes a collar descending from its bottom surface, and the collar is sized to be received within the upper end of the frame 30. In one embodiment, a flange on the frame cover 55 limits the distance by which it can be received within the upper end of the frame 30.

[0103] The upper (bearing-carrying) assembly 50 may further include a drive device for rotating the frame (or rotor) 30 within the housing 5, or a device for cooperating with a drive device external to the housing 5 to rotate the frame (or rotor) 30 within the housing 5.

[0104] In one embodiment, the upper (bearing-carrying) assembly 50 further includes a magneto-responsive member 57, which is arranged within the frame 30, preferably within its upper end portion ( Figure 4 and Figure 5 ). The magneto-responsive member 57 may be embedded within the frame or rotor cover 55, or it may be a separate part of the upper (bearing-carrying) assembly 50, but in a fixed relationship therewith (e.g., not capable of rotating relative to the frame 30 or the frame cover 55). In one embodiment, the magneto-responsive member 57 is mounted or adhered to the bottom surface of the frame cover 55. In one embodiment, the magneto-responsive member 57 is received within the frame 30 before the frame cover 55 is fixed to the frame 30.

[0105] The magneto-responsive member 57 may comprise or be made of a permanent magnet. Thus, the magneto-responsive member 57 may indirectly facilitate the rotation of the frame 30 under the influence of a suitable magnetic field (such as an oscillating magnetic field, an intermittent magnetic field, or a rotating magnetic field). In one embodiment, the magneto-responsive member includes points or protrusions with voids or non-magneto-responsive segments interspersed therebetween (when viewed in a plane orthogonal to the longitudinal axis l ).

[0106] The magneto-responsive member 57 includes one or more magnetic or magneto-responsive segments, with non-magneto-responsive or non-magneto-sensitive segments interspersed therebetween, and can be manufactured into a desired shape by stamping, machining, or other means. In one embodiment, the magneto-responsive member 57 is star-shaped or gear-shaped.

[0107] In one embodiment, the rotation of the frame or rotor 30 within the housing 5 is achieved by the response of the magneto-responsive member 57 to an externally applied magnetic field. Thus, manipulating the externally applied magnetic field will cause the magneto-responsive member 57 (and the frame 30) to rotate about the axis of rotation.

[0108] The magneto-responsive member 57 may further include features that mediate its coupling to the frame 30 or the frame cover 55. Thus, the magneto-responsive member 57 and the frame 30 or the frame cover 55 can be magnetically matched via a pair of complementary features.

[0109] In one embodiment, the magneto-responsive member 57 further includes an aperture or recess that mates with a protrusion of the frame 30 (or the frame cover 55). The aperture or recess can be any shape as long as it is complementary to the frame 30 or the frame cover 55 and / or capable of mating or connecting. In one embodiment, the aperture or recess includes at least one straight or substantially straight edge. In one embodiment, the aperture or recess includes at least two straight or substantially straight edges.

[0110] In one embodiment, the magneto-responsive member 57 further includes a protrusion that mates with an aperture or recess of the frame 30 (or the frame cover 55). The aperture or recess can be any shape as long as it is complementary to the magneto-responsive member 57 and / or capable of mating or connecting. In one embodiment, the aperture or recess includes at least one straight or substantially straight edge. In one embodiment, the aperture or recess includes at least two straight or substantially straight edges.

[0111] At least one or at least two straight or substantially straight edges of the aperture or recess (and complementary protrusions capable of mating with the aperture or recess) may allow a higher degree of torque to be applied to the frame 30 through the magneto-responsive member 57, as opposed to circular or rounded apertures or recesses that may experience slippage under a high degree of torque and / or repeated use.

[0112] In one embodiment, the magneto-responsive member 57 is fixed within the upper (bearing) assembly 50, such as by adhesive bonding or by interference or press fitting. In one embodiment, the magneto-responsive member 57 is embedded or fixed within a component of the upper (bearing) assembly 50, such as the frame cover 55.

[0113] Reference Figure 6 and Figure 7 and, the fluid filtration device 1 may further include a lower assembly 70 that connects the lower ends of the frame and the housing 5 at the lower end of the frame 30. In one embodiment, the lower assembly 70 rotatably connects the lower ends of the frame and the housing 5 at the lower end of the frame 30. In one embodiment, sub-components of the lower assembly 70 are received within apertures of the bottom wall 20, such as may be coupled to the second outlet 18. Thus, if the sub-component is configured as a conduit, it can thereby mediate the flow of fluid and particulates suspended therein through at least one aperture 32 of the frame 30 and out of the fluid filtration device 1 through the second outlet 18.

[0114] In one embodiment, the lower assembly 70 includes a plurality of sub-components, including a seal 71. The seal 71 can be made of any material as long as the material prevents fluid (and particulates suspended therein) from leaking from the fluid filtration device 1 except via the second outlet 18. More particularly, the seal 71 desirably prevents fluid (and particulates suspended therein) - fluid that has flowed through the first porous member 40 and into at least one aperture 32 - from leaking from the fluid filtration device 1 except via the second outlet 18. In one embodiment, the seal 71 is a gasket, a retaining ring, etc. In one embodiment, the seal 71 is beads or a layer of an inert material such as silicone-based grease.

[0115] The lower assembly 70 may further include a lower bearing 73. In one embodiment, the lower bearing 73 includes a conduit capable of receiving within the lower end portion of the frame 30 and being in fluid communication with at least one aperture 32. In one embodiment, the lower bearing 73 may be adhered to the lower end portion of the frame 30. In one embodiment, the lower bearing 73 may be connected to the lower end portion of the frame 30, such as by an interference fit, or attached by any other means. In one embodiment, the lower bearing 73 is a conduit in fluid communication with at least one aperture 32 of the frame 30.

[0116] In one embodiment, one side or end of the lower bearing 73 may be connected or adhered to the housing 5, such as at an aperture in the bottom wall 20 that is coupled to the second outlet 18. In one embodiment, the lower bearing 73 may be connected to it by an interference fit, or attached by any other means.

[0117] In one embodiment, the lower bearing 73 mediates the rotational alignment of the frame 30 within the housing 5, such as at the second outlet 18. In addition to mediating the rotation of the frame 30 within the housing 5, the lower bearing 73 may cooperate with the upper bearing 53 to align the frame 30 (and the upper assembly 50) relative to the second outlet 18 for controlled rotation of the frame 30 about its axis of rotation (which axis of rotation may coincide with the longitudinal axis l coincide) within the housing 5.

[0118] In one embodiment, the lower assembly 70 includes a bearing support 75. The bearing support 75 can be received within the housing 5, such as on or within a hole in the bottom wall 20 that is coupled to the second outlet 18. In one embodiment, the bearing support 75 can be adhered to the second outlet 18 or within the second outlet. In one embodiment, the bearing support 75 can be connected to the second outlet 18 or within the second outlet, such as by an interference fit, an adhesive, or attached by any other means. In one embodiment, the bearing support 75 includes a conduit that communicates with the lower bearing 73 (more particularly, a conduit passing through the lower bearing) and with at least one hole 32 of the frame 30. In one embodiment, the bearing support 75 provides a seat or interface for the lower bearing 73 such that it can be supported within the housing 5, such as on or within the second outlet 18.

[0119] In one embodiment, the seal 71 can cooperate with other features, such as features of the housing 5 and / or the frame 30 and / or the lower assembly 70, to prevent or limit leakage of fluid (and particulates suspended therein) from the fluid filtration device 1 except via the second outlet 18.

[0120] In one embodiment, the bottom side of the frame 30 includes an annular recess that is concentric with the lower bearing 73 and / or the bearing support 73 ( Figure 6 and Figure 7 ).

[0121] In operation, magnetic field oscillations or magnetic field rotation external to the fluid filtration device 1 can cause the frame 30 to rotate about its axis of rotation (which can coincide with the longitudinal axis l , which can be defined by the direction between the upper assembly 50 and the lower assembly 70, or more particularly, by the upper bearing 53 and the lower bearing 73) by affecting the movement of the magnetically responsive member 57. Thus, rotation of the frame 30 in a clockwise or counterclockwise direction can be achieved by the magnetic field. When fluid (and any particulates suspended therein) is introduced into the housing 5 via the inlet 12 and the frame 30 rotates within the housing 5, toroidal or Taylor vortices may appear in the shear gap between the frame 30 and the inner sidewall 10. A portion of the fluid and some of the particulates suspended therein (e.g., filtrate) can flow through the first porous member 40, while the remaining portion of the fluid and the remaining filtrate (e.g., residue or retentate) flows out of the fluid filtration device 1 via the first outlet 16. See Figure 6 , the plurality of spaced-apart transverse 34 and longitudinal grooves 37 cooperate to receive the filtrate that has flowed through at least the first porous member 40 and deliver the filtrate to the second outlet 18 via at least one hole 32 in the frame 30.

[0122] Accordingly, the fluid filtration device 1 described herein can be used in a method of filtering or treating a fluid that includes particulates. In various embodiments, the method can include one or more of the following: introducing a fluid stream into the fluid filtration device 1 via the inlet 12, more particularly into the chamber 7, and even more particularly into the shear gap between at least one sidewall 10 and the first porous member 40; rotating the frame 30, such as by an oscillating or rotating (external) magnetic field to affect the movement of the magneto-responsive member 57; passing the filtrate (and size-limited particulates) through the first porous member 40; sending the filtrate to the second outlet 18 via at least one hole 32 in the frame 30; and removing the retentate or residue (not passing through the first porous member) from the chamber 7 (or more particularly from the shear gap) via the first outlet 16. In one embodiment, the rotating frame generates Taylor and / or toroidal vortices in the shear gap between the frame 30 and the housing 5 (more particularly at least one inner sidewall thereof) at a desired rate, and the axial wavelength of the Taylor and / or toroidal vortices can be widened or narrowed according to factors including the taper of the inner sidewall of the housing and / or the size / width of the plurality of longitudinal grooves, in the direction of the longitudinal axis l as described above.

[0123] In one embodiment, when the fluid is introduced via the inlet 12, bubbles or cavitations may form within the annular recess 79 of the fluid filtration device 1 or its method of use. In one embodiment, when the frame 30 is rotated and the fluid is centrifugally pushed / pulled away from the axis of rotation of the frame 30 (e.g., the longitudinal axis l ), the bubbles or cavitations within the annular recess 79 may assume a generally funnel-shaped or hemispherical shape. Accordingly, the bubbles or cavitations can cooperate with other features of the frame 30 and the housing 5 (such as the lower assembly) to prevent or limit leakage of the fluid (and particulates suspended therein) from the fluid filtration device 1 except via the second outlet 18.

[0124] In one embodiment, the fluid filtration device 1 can be used to filter or treat whole blood to separate or substantially separate red blood cells and / or platelets and / or other similarly sized (or smaller) particulates from lymphocytes and / or other similarly sized (or larger) cells or particulates. In one embodiment, the fluid filtration device 1 can be used to filter or treat apheresis blood samples to separate or substantially separate platelets and / or other similarly sized (or smaller) particulates in the plasma from lymphocytes and / or other similarly sized (or larger) cells or particulates.

[0125] In one embodiment, the fluid filtration device 1 can be included in a cell separation system, which can be further classified: in a separate cell separation vessel or container, the filtrate has passed through the first porous member and flowed out via the second outlet 18, or the retentate or residue has been discharged from the first outlet 16 into the chamber 7. In one embodiment, the separate cell separation vessel or container is a flask or a bag. In one embodiment, the system can further include a pipe connecting the cell separation vessel or container to a reservoir that includes cell separation reagents, such as (paramagnetic or magnetosensitive particles) and an antibody composition that mediates the attachment of target cells to the particles. In one embodiment, the cell separation system can further include a magnet, such as a planar magnet array, to achieve immunomagnetic separation of target cells. In one embodiment, the pipe can further connect the cell separation vessel or container to a collector for accommodating target cells (in the case of positive cell selection) or non-target cells (in the case of negative cell selection).

[0126] Method In one aspect, the present disclosure relates to a method of manufacturing a rotary filtration device (e.g., a fluid filtration device) as described above.

[0127] A method of manufacturing a fluid filtration device (as described above) includes molding various components incorporating one or more of the advantageous features described above and assembling these components into the fluid filtration device of the present disclosure. Thus, any feature or embodiment of the fluid filtration device described above can also be introduced or formed during the manufacturing and / or assembly of the fluid filtration device, as further described below.

[0128] The method can include molding a housing and molding a frame. The frame and the housing can be molded from any material suitable for placement in a mold, such as in liquid or semi-solid form and subsequently cured in the mold into the desired shape or structure. In one embodiment, the frame and the housing are made of a polymer. In one embodiment, the frame and the housing are made of plastic. In one embodiment, the frame and the housing are made of the same polymer or plastic. In one embodiment, the frame and the housing are made of different polymers or plastics.

[0129] In one embodiment, the frame and the housing are made by the same molding method. In one embodiment, the frame and the housing are made by different molding methods. In one embodiment, the frame and / or the housing are made by injection molding.

[0130] The molded housing may include a cavity defined by at least one sidewall. The molded housing (and cavity) may include an upper end portion and a lower end portion connected by at least one sidewall. Thus, the upper end portion and the lower end portion may define a longitudinal axis of the molded housing. In one embodiment, the longitudinal axis passes through the cavity. In one embodiment, the longitudinal axis passes through the center point of the cavity and may thus coincide with the rotational axis of the frame 30 within the cavity 7.

[0131] The molded housing (and cavity) and / or the frame 30 may be cylindrical or substantially cylindrical. In embodiments of a substantially cylindrical housing, the surface of at least one sidewall facing the cavity tapers along its longitudinal axis. In one embodiment, at least one sidewall tapers from the upper end portion of the housing towards the lower end portion of the housing. In one embodiment, at least one sidewall tapers from the lower end portion of the housing towards the upper end portion of the housing. In any case, the taper may be 10 degrees or less, 9 degrees or less, 8 degrees or less, 7 degrees or less, 6 degrees or less, 5 degrees or less, 4 degrees or less, 3 degrees or less, 2 degrees or less, or about 1 degree (±0.5 degrees) or less.

[0132] The tapered or conical sidewall may optimize the manufacturing process (e.g., the molding process such as injection molding). When the frame rotates within the housing, the tapered or conical sidewall may affect the annular and / or Taylor vortices generated within the fluid filtration device. The tapered or conical sidewall may improve the performance of the fluid filtration process, such as by changing the wavelength of the annular and / or Taylor vortices.

[0133] In one embodiment, one of the upper end portion or the lower end portion of the housing is open and sized to receive the molded frame that enters the cavity of the housing through the opening. In one embodiment, the upper end portion is open and the bottom end portion includes a closed or substantially closed bottom wall. In one embodiment, the bottom end portion is open and the upper end portion includes a closed or substantially closed top wall. In a preferred embodiment, the bottom end portion includes a closed or substantially closed bottom wall.

[0134] In embodiments of the molded housing including a closed or substantially closed top wall or bottom wall, an outlet (e.g., the second outlet as described above) may be molded therein (e.g., integrally formed with the bottom wall) and / or holes may be molded therethrough.

[0135] The outlet and / or hole passing through the closed or substantially closed top wall or bottom wall may include a shoulder or seat that helps to rotatably secure the frame within the cavity, such as by receiving one or more components of the upper assembly or the lower assembly, as described above. In one embodiment, the second outlet is sized to define the longitudinal axis passing through the cavity and the rotational axis of the frame within the housing. Thus, in certain embodiments described herein, the rotational axis and the longitudinal axis may be the same axis.

[0136] The molded housing may further include one or both of an inlet and a first outlet. The inlet and / or the first outlet will be in fluid communication with the cavity. Thus, the inlet and / or the first outlet may minimally include a hole through at least one sidewall of the housing. In one embodiment, although including a hole therethrough, the inlet and / or the first outlet is integrally formed with at least one sidewall and includes features for mediating connection to a pipe or conduit, such as a plug or threads.

[0137] As described above, the inlet may be tangent to at least one sidewall, and more particularly, tangent to the inner sidewall of the housing (i.e., the surface facing the cavity). In another embodiment, the inlet may be non - tangent to at least one sidewall, and more particularly, non - tangent to the inner sidewall of the housing (i.e., the surface facing the cavity). Similarly, in certain embodiments, the first outlet may be tangent or non - tangent to at least one sidewall, and more particularly, non - tangent to the inner sidewall of the housing (i.e., the surface facing the cavity).

[0138] In one embodiment, each of the inlet, the first outlet, and the second outlet is in fluid communication with the housing cavity. In one embodiment, each of the inlet, the first outlet, and the second outlet is integrally formed with the housing.

[0139] The molded housing may further include at least one baffle disposed in the housing. In one embodiment, the baffle is disposed in the inlet. In one embodiment, the baffle is disposed in the first outlet. In one embodiment, the baffle is disposed in both the inlet and the first outlet. The baffle (in one or both of the inlet and the outlet) may be disposed within and / or integrally formed with at least one sidewall of the housing. In one embodiment, the baffle (in one or both of the inlet and the outlet) may be disposed at the opening where the inlet and / or the first outlet leads to the cavity.

[0140] The baffle in the inlet may facilitate the mixing of the fluid sample introduced through the inlet into the fluid filtration device, particularly into its cavity. The baffle in the inlet may improve the performance of the fluid filtration process, such as by enhancing the mixing of the fluid sample introduced through the inlet into the fluid filtration device. The baffle in the inlet may facilitate the molding process, such as injection molding. The baffle in the first outlet may facilitate the molding process, such as injection molding.

[0141] In one embodiment, the molded frame includes at least one hole formed therethrough. In one embodiment, the molded frame includes at least two holes formed therethrough. In one embodiment, one or more holes through the frame are formed at its lower end. In one embodiment, one or more holes in the frame are opposite and form a channel therethrough.

[0142] In one embodiment, the molded frame may include a plurality of spaced-apart transverse grooves defined therein, as described above. Additionally or alternatively, the molded frame may include a plurality of spaced-apart longitudinal grooves defined therein, as described above. Also as described above, in certain embodiments, the plurality of spaced-apart transverse grooves and the plurality of spaced-apart longitudinal grooves intersect, as described above. In one embodiment, the plurality of spaced-apart transverse grooves and the plurality of spaced-apart longitudinal grooves form an intersecting groove network that mates with, leads to, and / or flows into at least one hole through the frame.

[0143] A method of manufacturing a fluid filtration device (as described above) may further include attaching a porous member to or around the frame. The porous member may be attached to the frame using any means, such as using an adhesive, by ultrasonic welding, etc. In one embodiment, the porous member may be attached to the frame by a pressure-sensitive adhesive.

[0144] In one embodiment, a method of manufacturing a fluid filtration device (as described above) includes applying an adhesive (such as a pressure-sensitive adhesive) to one or more frame-contact surfaces of the porous member. For example, the adhesive (e.g., a pressure-sensitive adhesive) may be applied around or near the perimeter of the porous member on the side facing the frame. In one embodiment, a method of manufacturing a fluid filtration device (as described above) includes applying an adhesive strip, such as a pressure-sensitive adhesive, around or near the perimeter of the porous member on the side facing the frame. In one embodiment, the adhesive strip corresponds to the dimensions of the perimeter of the porous member on the side facing the frame and / or the dimensions of one or more frame-contact surfaces of the porous member.

[0145] A method of manufacturing a fluid filtration device (as described above) may further include applying the porous member to the frame before inserting the frame into a cavity. In one embodiment, applying the porous member to the frame includes rotating the frame about its axis of rotation to place the porous member on the frame. In one embodiment, the molded frame is fixed to a lathe or lathe-like instrument and rotated about its axis of rotation to place the porous member on the frame.

[0146] When placing the porous member on the frame, the rotational speed of the frame is not particularly limited. In one embodiment, the rotational rate of the frame is about 0.1 rpm to 60 rpm, between about 0.25 rpm to 45 rpm, between about 0.5 rpm to 30 rpm, or between about 0.75 rpm to 15 rpm. In one embodiment, the rotational rate of the frame is between about 0.1 rpm to 10 rpm. In one embodiment, the rotational rate of the frame is higher than 5 rpm.

[0147] A method of manufacturing a fluid filtration device (as described above) may further include applying pressure to the porous member and the frame to secure the porous member to the frame. The amount of pressure should be sufficient to bring the two components into contact but not so much as to crush or potentially crush the molded frame. However, the degree of pressure that the porous member and / or the frame can withstand will depend on the materials used to manufacture each component. In one embodiment, a pressure of about 0 to 100 psi may be applied to the porous member and the frame to secure the porous member to the frame.

[0148] In one embodiment, a method of manufacturing a fluid filtration device (as described above) may further include inserting the molded frame into a cavity of the housing and rotatably supporting the frame within the cavity (about its axis of rotation).

[0149] In one embodiment, the frame is secured between an upper end portion of the housing and a lower end portion of the housing, such as by an upper (bearing - equipped) assembly and a lower assembly (both as described above) that respectively mate with the upper end portion and the lower end portion of the housing.

[0150] Glossary of Terms Although processes, steps, or modules are presented in a given order, alternative instances may execute routines with steps in a different order, or employ systems with modules or steps, and some processes, steps, or modules may be deleted, moved, added, subdivided, combined, and / or modified to provide alternative or sub - combinations. Each of these processes or steps or modules may be implemented in many different ways. Additionally, although processes or steps or modules are sometimes shown as being executed serially, these processes or steps or modules may also be executed in parallel or at different times.

[0151] Furthermore, although the elements are sometimes shown as being executed in sequence, they may also be executed simultaneously or in a different order. Accordingly, the following claims are intended to be construed to include all such variations within their intended scope.

[0152] When a component is referred to above, unless otherwise specified, a reference to that component (including a reference to a "device") shall be construed to include any component that performs the function of the described component (i.e., a functional equivalent) as an equivalent of that component, including components that are not structurally equivalent to the disclosed structure that performs the function in the exemplary embodiments shown in the present invention.

[0153] The present text describes various features as being present in "one embodiment" or in "some embodiments". Such features are not mandatory and may not be present in all embodiments. Embodiments of the present invention may include any combination of zero, any one, or two or more of such features, provided only that there are no cases where some of such features are incompatible with some others of such features, i.e., where a person skilled in the art could not construct a practical embodiment combining such incompatible features. Thus, the description that "some embodiments" have feature A and "some embodiments" have feature B should be interpreted as clearly indicating that the inventors have also contemplated embodiments combining features A and B (unless the specification states otherwise or features A and B are incompatible at all).

[0154] Accordingly, the appended claims and the claims introduced hereafter are intended to be interpreted to include all such reasonably inferable modifications, permutations, additions, omissions, and sub-combinations. The scope of the claims should not be limited by the preferred embodiments stated in the examples, but should be given the broadest interpretation consistent with the entire specification.

Claims

1. A fluid filtration device, comprising: a housing that defines a chamber bounded by at least one sidewall, the housing having an upper end and an opposite lower end; a non-tangential inlet and a first outlet through the housing, each of the inlet and the first outlet being in fluid communication with the chamber; a second outlet through the housing; a frame rotatably supported within the chamber and capable of rotating relative to the housing; at least one hole through the frame, the at least one hole being in fluid communication with the second outlet; and a first porous member fixed to or fixed around the frame.

2. The device according to claim 1 or any other claim herein, further comprising an upper assembly and a lower assembly that respectively cooperate with the upper end of the housing and the lower end of the housing to rotatably support the frame within the chamber.

3. The apparatus according to claim 1 or any other claim herein, wherein, The surface of the at least one sidewall facing the chamber tapers by about 5 degrees or less, about 3 degrees or less, or about 1 degree ± 0.5 degrees from the upper end of the housing to the lower end of the housing.

4. The device according to any one of claims 1 to 3 or any other claim herein, further comprising a baffle disposed at least in the non-tangential inlet, and preferably disposed at the opening where the inlet leads into the chamber.

5. The device according to any one of claims 1 to 4 or any other claim herein, further comprising a plurality of spaced-apart transverse grooves in the surface of the frame facing the porous member.

6. The apparatus according to claim 5 or any other claim herein, further comprising a plurality of spaced longitudinal grooves in the surface of the frame facing the porous member, wherein, The plurality of spaced-apart longitudinal grooves are interconnected with the plurality of spaced-apart transverse grooves.

7. The apparatus according to claim 6 or any other claim herein, wherein, The plurality of spaced-apart longitudinal grooves and the plurality of spaced-apart transverse grooves cooperate to receive the filtrate that has passed through the porous member and send the filtrate to the second outlet via the at least one hole in the frame.

8. The apparatus according to claim 1 or any other claim herein, wherein, The frame and / or the housing is cylindrical or substantially cylindrical.

9. The device according to claim 2 or any other claim herein, wherein, The upper assembly and the lower assembly define a longitudinal axis passing through the chamber, and the frame rotates about the longitudinal axis.

10. The device according to any one of claims 1 to 9 or any other claim herein, further comprising a magnetically responsive member fixedly disposed in the frame, preferably in the upper end of the frame.

11. The apparatus according to claim 10 or any other claim herein, wherein, The magnetically responsive member and the frame match via a pair of complementary features including at least one straight edge.

12. The apparatus according to any one of claims 1 to 11 or any other claim herein, wherein, The first porous member is fixed to the frame by a pressure-sensitive adhesive.

13. The device according to any one of claims 1 to 12 or any other claim herein, wherein, The first porous member is a track-etched membrane.

14. The device according to any one of claims 1 to 13 or any other claim herein, further comprising a second porous member fixed to or fixed around the frame, preferably by a pressure-sensitive adhesive.

15. A method of manufacturing a fluid filtration device as claimed in any one of claims 1 to 14, the method comprising: A molded housing having i) a cavity defined by at least one sidewall and defining a longitudinal axis, ii) an inlet, iii) a first outlet, and iv) a second outlet, each of the inlet, the first outlet, and the second outlet being in fluid communication with the cavity; A molded frame; Attaching the porous member to or around the frame by a pressure-sensitive adhesive; And Fixing the frame within the cavity, the frame being capable of rotating about a rotational axis within the cavity.

16. The method according to claim 15 or any other claim herein, further comprising disposing at least one baffle within the housing, and preferably disposing at least one baffle in one or both of the inlet and the outlet.

17. The method according to claim 15 or 16 or any other claim herein, further comprising applying the pressure-sensitive adhesive to one or more frame contact surfaces of the porous member.

18. The method according to any one of claims 15 to 17 or any other claim herein, further comprising applying the porous member to the frame by rotating the frame about the rotational axis to place the porous member on the frame before inserting the frame into the cavity.

19. The method according to claim 18 or any other claim herein, further comprising applying pressure to the porous member and the frame to secure the porous member thereto.

20. The method according to any one of claims 15 to 19 or any other claim herein, wherein The frame is rotatably supported within the cavity between an upper end portion and a lower end portion of the housing by an upper assembly and a lower assembly that respectively cooperate with the upper end portion and the lower end portion of the housing.

21. The method according to claim 15 or any other claim herein, wherein, The cavity-facing surface of the at least one sidewall tapers by about 5 degrees or less, about 3 degrees or less, or about 1 degree from an upper end portion of the housing to a lower end portion of the housing.

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