MICROSCALE MULTIPLE-FLUID-STREAM BIOREACTOR FOR CELL CULTURE

• US 20110082563A1
• Filed: 10/05/2009
• Published: 04/07/2011
• Est. Priority Date: 10/05/2009
• Status: Abandoned Application

• Current Assignee: Charles Stark Draper Laboratory Incorporated
• Original Assignee: Charles Stark Draper Laboratory Incorporated
• Inventors: Charest, Joseph, Borenstein, Jeffrey T.
• Application Number:
  US12/573,561
• Publication Number:
  US 20110082563A1
• Time in Patent Office: Days
• US Class Current: 623/23.65
• CPC Class Codes: A61F 2/022 Artificial gland structures using bioreactors hemodialysis A61M1/16; hemofiltration A61M1/34; other extracorporeal blood treatment A61M1/36
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: C12M 23/16 Microfluidic devices; Capillary tubes integrated microfluidic structures B01L3/5027; microreactors B01J19/0093
• CPC Class Codes: C12M 29/04 Filters; Permeable or porous membranes or plates, e.g. dialysis

Abstract

Microfluidic bioreactor devices may feature intercommunicating microchannels defined in two polymer layers separated by a membrane. A geometric parameter associated with the microchannels in one layer may vary along a length of those channels.

Claims

1. A microfluidic bioreactor device comprising:

at least one polymer layer defining first, second and third microchannels therein; and

a membrane separating the first and second channels from the third channel at geometrically overlapping portions therebetween, the membrane permitting communication between the overlapping portions of the microchannels,

wherein at least one geometric parameter of at least one of the microchannels varies along a length thereof within the overlapping portions.

2. The device of claim 1 wherein the first microchannel communicates with the second microchannel via the third microchannel.

3. The device of claim 1 wherein the at least one polymer layer comprises two polymer layers separated by the membrane.

4. The device of claim 1, wherein the at least one polymer layer comprises or consists essentially of a biopolymer.

5. The device of claim 1, wherein the communication between the microchannels comprises at least one of fluid communication or mechanical communication.

6. The device of claim 1, wherein at least one geometric parameter is a distance between the first and second microchannels.

7. The device of claim 1, wherein at least one geometric parameter is a depth of one of the microchannels.

8. The device of claim 1, wherein the least one geometric parameter is a width of one of the microchannels.

9. The device of claim 1, wherein at least a portion of the membrane is semi-permeable.

10. The device of claim 9, wherein the semi-permeable portion of the membrane is at least one of porous or bulk-semi-permeable.

11. The device of claim 1, wherein the membrane comprises at least one of fleece, an electrospun material, micromolded polydimetylsiloxane, polyethersulfone, or a track-etched membrane.

12. The device of claim 1, further comprising cells in at least one of the microchannels.

13. The device of claim 12, wherein the cells comprise kidney cells.

14. The device of claim 13, wherein the microchannels are configured so as to collectively mimic kidney tissue.

15. The device of claim 12, wherein at least some of the cells adhere to the membrane.

16. The device of claim 12, wherein at least some of the cells adhere to walls of the microchannels.

17. The device of claim 12, wherein at least some of the cells are suspended in fluid contained in the microchannels.

18. The device of claim 12, wherein the cells comprise multiple cell types.

19. The device of claim 18, wherein the type of cells varies along a length of the microchannel.

20. The device of claim 1, further comprising fluid in the microchannels.

21. The device of claim 20, wherein the fluid comprises at least one of cell culture medium, buffer solution, blood components, whole blood, urine, dialysate, water, or filtrate.

22. The device of claim 20, wherein the fluid comprises a solution mimicking a bodily fluid.

23. The device of claim 20, wherein a value of a fluid mechanical parameter in at least one of the first and second microchannels is substantially different from a value of the fluid mechanical parameter in the third microchannel.

24. The device of claim 23, wherein the fluid mechanical parameter is one of a pressure, a flow rate, a shear rate, or a viscosity.

25. The device of claim 20, wherein a value of a fluid mechanical parameter in the first microchannel is substantially different from a value of the fluid mechanical parameter in the second microchannel.

26. The device of claim 20, further comprising a fourth microchannel on the same side of the membrane as the third microchannel, a value of a fluid mechanical parameter in the fourth microchannel being substantially different from a value of the fluid mechanical parameter in the third microchannel.

27. The device of claim 20, wherein a concentration of a constituent in the fluid in at least one of the first and second microchannels is substantially different from a concentration of the constituent in the fluid in the third microchannel.

28. The device of claim 20, wherein a concentration gradient of a constituent in the fluid in at least one of the first and second microchannels is substantially different from a concentration gradient of the constituent in the fluid in the third microchannel.

29. The device of claim 1, wherein the at least one geometric parameter varies gradually along the length of the microchannels.

30. The device of claim 1, wherein the at least one geometric parameter varies based on a predetermined fluid-mechanical profile in at least one of the first and second microchannels.

31. The device of claim 30, wherein the fluid-mechanical profile comprises at least one of a convective transport profile, a diffusive transport profile, or a shear stress profile.

32. The device of claim 1, wherein the variation of the at least one geometric parameter along the length of one of the microchannels facilitates variance of at least one of a chemical or a mechanical stimulus along the length of that microchannel.

33. A method of culturing cells, the method comprising:

(a) providing a bioreactor comprising (i) at least one polymer layer defining first, second and third microchannels therein, and (ii) a membrane separating the first and second channels from the third channel at geometrically overlapping portions therebetween, the membrane permitting communication between the overlapping portions of the microchannels, wherein at least one geometric parameter of at least one of the microchannels varies along a length thereof within the overlapping portions;

(b) introducing cells into at least one of the microchannels; and

(c) culturing the cells.

34. The method of claim 33, further comprising introducing a fluid into at least one of the microchannels.

35. The method of claim 33, wherein step (c) comprises exposing the cells to at least one of a mechanical, a chemical, or a biological stimulus.

36. The method of claim 35, further comprising measuring a response of the cells to the stimulus.

37. The method of claim 36, wherein the response comprises a change in a cell function.

38. The method of claim 33, wherein step (b) comprises seeding cells at selected locations within the at least one microchannel.

39. The method of claim 38, wherein step (c) comprises exposing cells seeded at a first of the selected locations to a first stimulus and exposing cells seeded at a second of the selected locations to a second stimulus.

40. The method of claim 33, wherein step (b) comprises introducing different types of cells into the at least one microchannel.

41. The method of claim 40, wherein step (b) comprises introducing different types of cells into different microchannels.

42. The method of claim 40, wherein step (b) comprises seeding different types of cells at different selected locations within the at least one microchannel.

43. A method of mimicking a kidney, the method comprising:

(a) providing a bioreactor comprising (i) at least one polymer layer defining first, second and third microchannels therein, and (ii) a membrane separating the first and second channels from the third channel at geometrically overlapping portions therebetween, the membrane permitting communication between the overlapping portions of the microchannels, wherein at least one geometric parameter of at least one of the microchannels varies along a length thereof within the overlapping portions so as to mimic a kidney structure;

(b) introducing kidney cells into at least one of the microchannels; and

(c) culturing the kidney cells.

44. The method of claim 43, further comprising implanting the bioreactor into a patient.

45. The method of claim 43, further comprising using the bioreactor extracorporeally in renal therapy.