PERFUSION FILTER ASSEMBLY FOR INCREASED CROSS FLOW

Abstract

Filter holders and membranes are provided that can be included within a bioreactor bag system. The filter holders and membranes include features that abut the bottom of the filter membrane and prevent or reduce sagging of the porous filter region during use.

Claims

1. A filter assembly comprising; a support plate; a filter membrane comprising a porous filter region, wherein the filter membrane is bonded to the support plate in a peripheral region of the filter membrane; and at least one support structure abutting the bottom of the filter membrane adapted to prevent or reduce sagging of the porous filter region during use.

2. The filter assembly of claim 1, wherein the support structure is post with a support head, and the post connects to the support plate through an opening in the filter membrane within the porous region of the filter membrane.

3. The filter assembly of claim 2, wherein the filter assembly comprises a plurality of posts.

4. The filter assembly of claim 3, wherein the posts are arranged into rows.

5. The filter assembly of claim 2, wherein a seal is provided, the seal being configured to prevent leakage of liquid around the porous filter region in the region of the support structure.

6. The filter assembly of claim 5, wherein the seal is an O-ring.

7. The filter assembly of claim 1, wherein the support structure is a frame comprising at least one cross-member under the porous region and at least one opening under the porous region.

8. The filter assembly of claim 7, wherein the frame includes two or more openings under the porous region.

9. The filter assembly of claim 7, wherein the frame includes four or more openings under the porous region, and the four or more openings are organized in a grid pattern.

10. The filter assembly of claim 2, wherein the filter membrane includes support regions surrounding the opening in the filter membrane within the porous region of the filter membrane, the support regions lacking pores.

11. A bioreactor bag comprising: a flexible bag having an inner surface and an outer surface; a filter assembly, the filter assembly comprising: a support plate; a filter membrane comprising a porous filter region, wherein the filter membrane is bonded to the support plate in a peripheral region of the filter membrane; and at least one support structure abutting the bottom of the filter membrane adapted to prevent or reduce sagging of the porous filter region during use; wherein the filter assembly is mounted in the flexible bag with an exposed surface of the porous filter region facing the bottom of the flexible bag.

12. The bioreactor bag of claim 11, wherein the support structure is post with a support head, and the post connects to the support plate through an opening in the filter membrane within the porous region of the filter membrane.

13. The bioreactor bag of claim 12, wherein the filter assembly comprises a plurality of posts.

14. The bioreactor bag of claim 13, wherein the posts are arranged into rows.

15. The bioreactor bag of claim 12, wherein a seal is provided, the seal being configured to prevent leakage of liquid around the porous filter region in the region of the support structure.

16. The bioreactor bag of claim 15, wherein the seal is an O-ring.

17. The bioreactor bag of claim 11, wherein the support structure is a frame comprising at least one cross-member under the porous region and at least one opening under the porous region.

18. The bioreactor bag of claim 17, wherein the frame includes two or more openings under the porous region.

19. The bioreactor bag of claim 17, wherein the frame includes four or more openings under the porous region, and the four or more openings are organized in a grid pattern.

20. The bioreactor bag of claim 17, wherein the filter membrane includes support regions surrounding the opening in the filter membrane within the porous region of the filter membrane, the support regions lacking pores.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0015] FIG. 1A shows a prior art perfusion filter assembly.

[0016] FIG. 1B shows a top down view of a portion of the prior art filter assembly shown in FIG. 1A.

[0017] FIG. 2 shows a filter assembly where sagging of the filter membrane is occurring.

[0018] FIG. 3A shows a perfusion filter membrane utilizing membrane support holes according to an embodiment of the invention.

[0019] FIG. 3B shows top down view of the perfusion filter membrane utilizing membrane support holes shown in FIG. 3A.

[0020] FIG. 4A shows a perfusion filter assembly utilizing a support frame according to an embodiment of the invention.

[0021] FIG. 4B shows bottom up view of the perfusion filter membrane shown in FIG. 4A.

[0022] FIG. 4C shows a bottom up view of the support plate of the perfusion filter membrane shown in FIG. 4A.

[0023] FIG. 4D shows a bottom up view of the support frame of the perfusion filter membrane shown in FIG. 4A.

[0024] FIG. 5A shows a bottom up view of a support plate and frame according to another embodiment of the invention.

[0025] FIG. 5B shows a bottom up view of the frame shown in FIG. 5A.

[0026] FIG. 6A shows a first perfusion filter membrane according to an embodiment of the invention.

[0027] FIG. 6B shows a second perfusion filter membrane according to an embodiment of the invention.

DETAILED DESCRIPTION OF THE INVENTION

[0028] The present invention involves perfusion filter assemblies and filer membranes for use in those perfusion filter assemblies. The perfusion filter assemblies and perfusion membranes disclosed herein are particularly adapted to membranes that are made with advanced processes, such as photolithography and etching. The present inventors have found that membranes made according to these processes have material characteristics that make them unsuitable for use with traditional perfusion filter assemblies. For example, polyimide membranes can be difficult to bond to the polyethylene components used in perfusion filter assemblies, including perfusion filter bags. The filter membranes and filter assemblies disclosed herein include features that overcome one or more of these obstacles.

[0029] The present inventors have observed that the filter membrane 107 may sag as shown in FIG. 2 under certain conditions. The sagging of the filter membrane 107 may result in undesirable flow blockage when the filter membrane 107 is placed near the bottom of a bioreactor bag 103 as shown in FIG. 2. This problem may be exacerbated when the bioreactor bag is used with a rocking motion.

[0030] In one aspect, the present invention involves the use of a support structure comprising a support pin having a portion abutting the bottom of the filter membrane adapted to prevent or reduce sagging of the porous filter region during use.

[0031] As shown in FIGS. 3A-B, a bioreactor bag 303 includes a filter holding device 301 placed at the bottom of the bioreactor bag 303 where the filter membrane 307 faces the bottom of the bioreactor bag 303. A port 311 allows filtered fluid to exit the bioreactor bag through opening 313 and out of the tube 315. The filter holding device includes openings 319a-d which are used for attaching to standoffs 321a-d (only 321a and 321b are shown). The filter holding device 301 includes deflector areas 323 that improve the flow under the filter holding device 301 within the bioreactor bag 305. The bioreactor bag 305 may be placed on a rocker tray 317. The filter holding device 301 may be attached to the bottom of the bioreactor bag 303 using standoffs 321a-d (only 321a and 321b are shown) which correspond to holes 319a-d as seen in FIG. 3B.

[0032] The filter membrane 307 may be attached to the filter holding device 301 using a bond 309. The bond 309 can be a heat weld in the case that the filter membrane is made of a material that can be heat bonded to the filter holding device 301. For example, where both filter membrane 307 and filter holding device 301 are made from polyethylene, the bond 309 may be a heat weld. The bond 309 must be sufficient to prevent liquid from leaking from the bioreactor bag past the filter membrane 307.

[0033] The support structure may include support pins 330 that attach directly to the middle part 305 of the support structure. The support pins 330 include several configurations but so long as a portion of the support pin, such as a head abuts a portion of the filter membrane 307 and reduces sagging in particular areas. The support pins 330 may be threaded such that they may be screwed into the middle part 305 of the filter membrane support. The support pins are provided with seals 331, which may be O-rings. The O-ring is typically made from a resilient material such as rubber, which provides compression and sealing around the support post 330 and prevent leakage around the filter membrane 309.

[0034] In another aspect, the present invention involves the use of a support structure comprising a frame having a portion abutting the bottom of the filter membrane adapted to prevent or reduce sagging of the porous filter region during use.

[0035] As shown in FIGS. 4A-D, a bioreactor bag 403 includes a filter holding device 401 placed at the bottom of the bioreactor bag 403 where the filter membrane 407 faces the bottom of the bioreactor bag 403. A port 411 allows filtered fluid to exit the bioreactor bag through opening 413 and out of the tube 415. The filter holding device includes openings 419a-d which are used for attaching to standoffs 421a-d (only 421a and 421b are shown). The filter holding device 401 includes deflector areas 423 that improve the flow under the filter holding device 401 within the bioreactor bag 405. The bioreactor bag 405 may be placed on a rocker tray 417. The filter holding device 401 may be attached to the bottom of the bioreactor bag 403 using standoffs 421a-d (only 421a and 421b are shown) which correspond to holes 419a-d as seen in FIG. 4B.

[0036] The filter membrane 407 may be attached to the filter holding device 401 using a bond 409. The bond 409 can be a heat weld in the case that the filter membrane is made of a material that can be heat bonded to the filter holding device 401. For example, where both filter membrane 407 and filter holding device 401 are made from polyethylene, the bond 409 may be a heat weld. The bond 409 must be sufficient to prevent liquid from leaking from the bioreactor bag past the filter membrane 407.

[0037] The support structure may include a frame 432 that attach directly to the middle part 405 of the support structure. In the case where a frame 342 is used, the bond 409 may be an O-ring that is placed between the frame 342 and the filter support 405. The support pins 430 may be threaded such that they may be screwed into the middle part 405 of the filter membrane support. The support pins are provided with seals 431, which may be O-rings. The O-ring is typically made from a resilient material such as rubber, which provides compression and sealing around the support post 430 and prevent leakage around the filter membrane 409. Where a frame 432 is used, the support pin 330 head abuts the support frame 432 which abuts the filter membrane 407 and prevents sagging. FIGS. 4C-D show the deconstructed filter holding device and frame 432.

[0038] FIGS. 5A-B show an alternative embodiment of a frame 532 that can be used without support pins. In this case, the support frame 532 does not include support pins and eliminates the need for seals since the filter membrane is a unitary part. The frame includes holes 519a-c adapted to interface with standoffs for supporting the filter membrane holder. The filter holder includes ribs 531 that abut portions of the filter membrane. The frame may be used with a filter membrane that can be attached to the filter membrane support using a bond 509 or alternatively an O-ring placed between the filter membrane and either the frame 532 and membrane or the filter holder and the membrane.

[0039] FIGS. 6A-6B show filter membranes that can be used with certain embodiments of this invention. The filter membrane 600 includes three holes 603 that are adapted to allow a support pin to be placed in the membrane 600. Each of the support holes is surrounded by a support region 602 that lacks pores. The support region 602 is useful for interfacing with an O-ring 604 indicated by dashed lines since they are not part of the filter membrane. The dashed line 605 may represent a heat bond region or the placement of an O-ring in the case that a frame is used. FIG. 6B shows an alternative embodiment where a support region 621 surrounds several holes 622, which each can use their own O-ring 623.

[0040] Other embodiments and uses of the invention will be apparent to those skilled in the art from consideration of the specification and practice of the invention disclosed herein. All references cited herein, including all U.S. and foreign patents and patent applications, are specifically and entirely hereby incorporated herein by reference. It is intended that the specification and examples be considered exemplary only, with the true scope and spirit of the invention indicated by the following claims