Continuous purification device

Abstract

This specification provides apparatus, systems, and methods for purifying biological products. The purification apparatus may comprise a mixing module, a washing module, a separation module, an elution module, and an additional separation module.

Claims

1. i) A first network comprising a first plurality of gyroids arranged in layers to provide a first plurality of microchannels, wherein the first plurality of microchannels are fluidly interconnected. A mixed module including, ii) A first port configured to receive a first liquid, wherein the first port comprises a first plurality of subports, each subport being in fluid communication with the inlet of a first layer of the first plurality of gyroids, iii) A second port configured to receive a second liquid, wherein the second port comprises a second plurality of subports, each subport being in fluid communication with the inlet of a microchannel in the first layer of the first plurality of gyroids, iv) A second network comprising a second plurality of gyroids configured to be in fluid communication with the mixing module and to provide a second plurality of microchannels, wherein the second plurality of microchannels are fluidly interconnected. A washing module located downstream of the mixing module, v) A third port configured to receive a third liquid, wherein the third port is located upstream of the cleaning module, vi) At least one channel that communicates with the cleaning module via fluid, A fourth port configured to receive a fourth liquid containing the elution solution, A first transport component configured to interact with a plurality of particles and thereby guide the plurality of particles into the fourth liquid in the at least one channel, and A first outlet and a second outlet, each in fluid communication with at least one channel, wherein the first outlet is configured to receive the fourth liquid and the plurality of particles exiting the cleaning module, and the second outlet is configured to receive the remaining liquid. A first separation module located downstream of the cleaning module, comprising: vii) A third network of a third plurality of gyroids configured to provide a third plurality of microchannels, wherein the third plurality of microchannels are fluidly interconnected and in fluid communication with the first outlet. An elution module located downstream of the first separation module, including, viiii) At least one channel that is in fluid communication with the elution module, A fifth port configured to receive a fifth liquid containing a re-equilibrium solution, A third outlet and a fourth outlet, each in fluid communication with at least one channel, wherein the fourth outlet is configured to receive the reequilibrium solution and the plurality of particles exiting the elution module, and the third outlet is configured to receive the remaining liquid, and A second transport component configured to interact with the plurality of particles and thereby guide the plurality of particles to the re-equilibrium solution. A second separation module located downstream of the elution module, comprising: A device equipped with the following features.

2. The apparatus according to claim 1, wherein the elution module further comprises a sixth port configured to receive a sixth liquid containing an elution solution.

3. The cleaning module and the mixing module are connected by at least one channel that communicates fluidly with them. A third transport component configured to interact with the plurality of particles and thereby guide the plurality of particles into the washing solution in the at least one channel, A fifth outlet configured to receive the waste flow and The apparatus according to claim 1, further comprising a third separation module located upstream of the cleaning module and downstream of the third port, wherein the cleaning module is provided for.

4. The cleaning module and the mixing module are connected by at least one channel that communicates fluidly with them. A third transport component configured to interact with the plurality of particles and thereby guide the plurality of particles into the washing solution in the at least one channel, A fifth outlet configured to receive the waste flow and The apparatus according to claim 2, further comprising a third separation module located upstream of the cleaning module and downstream of the third port, the apparatus comprising the cleaning module.

5. The mixing module has at least one channel that is in fluid communication with it, A third transport component configured to interact with the plurality of particles and thereby separate the plurality of particles from the liquid in at least one channel, A fifth outlet configured to receive the waste flow and The apparatus according to claim 1, further comprising a third separation module located downstream of the mixing module and upstream of the third port, the apparatus comprising the mixing module.

6. The mixing module has at least one channel that is in fluid communication with it, A third transport component configured to interact with the plurality of particles and thereby separate the plurality of particles from the liquid in at least one channel, A fifth outlet configured to receive the waste flow and The apparatus according to claim 2, further comprising a third separation module located downstream of the mixing module and upstream of the third port, the apparatus comprising the mixing module.

7. The apparatus according to any one of claims 1 to 6, wherein the first liquid contains the substance of interest.

8. The apparatus according to claim 7, wherein the target substance is selected from the group consisting of cells, proteins, peptides, antibodies, antigen-binding fragments, nutrient requirements, amino acid nutrient requirements, base nutrient requirements, natural drugs, semi-synthetic drugs, and synthetic drugs.

9. The apparatus according to claim 7 or 8, wherein the target substance is a therapeutic protein or antibody.

10. The apparatus according to any one of claims 1 to 9, wherein the second liquid contains a plurality of particles.

11. The apparatus according to claim 10, wherein the plurality of particles include one or more nanoparticles.

12. The apparatus according to claim 11, wherein one or more of the nanoparticles include magnetic nanoparticles.

13. The apparatus according to any one of claims 10 to 12, wherein the plurality of particles include a binder.

14. The apparatus according to claim 13, wherein the binder can interact with the target substance.

15. The apparatus according to claim 13 or 14, wherein the binder is selected from the group consisting of proteins, antibodies, antigen-binding fragments, and nucleic acids.

16. The apparatus according to any one of claims 13 to 15, wherein the binder is protein A, protein G, protein M, protein L, recombinant fusion proteins thereof, variants thereof, or combinations thereof.

17. The apparatus according to any one of claims 1 to 16, wherein the plurality of microchannels of the mixing module, the washing module, and / or the elution module are configured to mix two liquids, or a liquid and a plurality of particles.

18. The apparatus according to any one of claims 1 to 17, wherein the gyroid contained in the mixing module, the washing module, and / or the elution module has a certain cross-section.

19. The distance the fluid travels through the mixing module, the washing module, and / or the dissolution module is, [Math 1] Determined by, During the ceremony, D is the distance the fluid travels. Q ｉ is the flow rate of liquid i, Q ｉｉ This is the flow rate of liquid ii, d is the diameter of the microchannel, T ｒｅｓ This is the dwell time, f ｃｏｒ This is the correlation coefficient, The apparatus according to any one of claims 1 to 18, wherein n is the number of gyroids.

20. The apparatus according to any one of claims 1 to 19, wherein the plurality of microchannels in the mixing module, the washing module, and / or the dissolution module have different diameters and / or distances over which the fluid travels.

21. The apparatus according to any one of claims 1 to 20, wherein the plurality of microchannels in the mixing module, the washing module, and / or the elution module are configured to ensure laminar flow inside the microchannels.

22. The apparatus according to any one of claims 1 to 21, wherein the flow rate ratio of the first liquid to the second liquid is 1:2 to 1:

8.

23. The apparatus according to any one of claims 1 to 22, wherein the flow rate ratio of the first liquid to the second liquid is 2:1 to 8:

1.

24. The apparatus according to any one of claims 1 to 23, wherein the first transport component and the second transport component each include an electromagnetic field.

25. The apparatus according to claim 24, wherein the electromagnetic field of the first transport component is positioned laterally with respect to at least one channel of the first separation module.

26. The apparatus according to claim 24, wherein the electromagnetic field of the second transport component is positioned laterally with respect to at least one channel of the second separation module.

27. The apparatus according to any one of claims 3 to 26, wherein the third transport component includes an electromagnetic field.

28. The apparatus according to claim 27, wherein the electromagnetic field of the third transport component is positioned laterally with respect to at least one channel of the third separation module.

29. The apparatus according to any one of claims 1 to 28, further comprising a recirculation line configured to guide the particles back into the mixing module from the fourth outlet of the second separation module.

30. The apparatus according to any one of claims 1 to 29, wherein the at least one channel of the first separation module is configured not to allow mixing of two incoming liquid flows.

31. The apparatus according to claim 30, wherein the two incoming liquid streams include the elution solution and the solution from the washing module.

32. The apparatus according to any one of claims 1 to 31, wherein the at least one channel of the second separation module is configured not to allow mixing of two incoming liquid flows.

33. The apparatus according to claim 32, wherein the two incoming liquid streams include the reequilibrium solution and the solution from the elution module.

34. The apparatus according to any one of claims 1 to 33, wherein the at least one channel of the third separation module is configured not to allow mixing of two incoming liquid flows.

35. The apparatus according to claim 34, wherein the two incoming liquid streams include the cleaning solution and the solution from the mixing module.

36. The apparatus according to any one of claims 1 to 35, wherein the washing solution is configured to dissolve a substance nonspecifically bound to the plurality of particles.

37. The apparatus according to any one of claims 1 to 36, wherein the elution solution is configured to elute the target substance from the plurality of particles.

38. The apparatus according to any one of claims 1 to 37, wherein one of the first plurality of gyroids, the second plurality of gyroids, and / or the third plurality of gyroids is a single gyroid or a modified single gyroid.

39. The apparatus according to any one of claims 1 to 38, wherein one of the first plurality of gyroids, the second plurality of gyroids, and / or the third plurality of gyroids is a double gyroid or a modified double gyroid.

40. A mixing module configured to mix a liquid containing a target substance with a liquid containing a plurality of particles, wherein the plurality of particles include a binder configured to capture the target substance, A separation module configured to separate the plurality of particles from the liquid, An elution module configured to elute the target substance from the plurality of particles, An additional separation module configured to separate the particles from the eluted target substance, A device equipped with the following features.

41. The apparatus according to claim 40, wherein the separation module further comprises a transport component.

42. The apparatus according to claim 41, wherein the transport component includes an electromagnetic field or magnetic field configured to interact with the plurality of particles.

43. The apparatus according to any one of claims 40 to 42, wherein the additional separation module further comprises additional transport components.

44. The apparatus according to claim 43, wherein the additional transport component includes an electromagnetic field or magnetic field configured to interact with the plurality of particles.

45. The apparatus according to any one of claims 40 to 44, wherein the mixing module includes a certain double gyroid structure.

46. The apparatus according to any one of claims 40 to 45, wherein the elution module includes a certain double gyroid structure.

47. The apparatus according to any one of claims 40 to 46, wherein the separation module is located downstream of the mixing module.

48. The apparatus according to any one of claims 40 to 47, wherein the second separation module is located downstream of the elution module.

49. The apparatus according to any one of claims 40 to 48, further comprising a washing module located downstream of the mixing module, configured to remove substances nonspecifically bound to the plurality of particles.

50. Introducing a first liquid containing the target substance into a first module of the apparatus according to any one of claims 1 to 49, Introducing a second liquid containing multiple particles into the first module of the apparatus, The first liquid and the second liquid are flowed into the apparatus. A method for purifying a target substance, including [specific substance].

51. The method according to claim 50, wherein the first liquid comprises a culture medium from a reactor, processor, bioreactor, or bioprocessor.

52. The method according to claim 50 or 51, wherein the target substance is selected from the group consisting of cells, proteins, peptides, antibodies, antigen-binding fragments, nutrient requirements, amino acid nutrient requirements, base nutrient requirements, natural drugs, semi-synthetic drugs, and synthetic drugs.

53. The method according to claim 52, wherein the substance in question is an antibody.

54. The method according to any one of claims 50 to 53, wherein the plurality of particles comprises one or more nanoparticles.

55. The method according to claim 54, wherein one or more of the nanoparticles include magnetic nanoparticles.

56. The method according to claim 55, wherein one or more nanoparticles are coated with a binder.

57. The method according to claim 56, wherein the binder can interact with the target substance.

58. The method according to claim 57, wherein the binder is selected from the group consisting of proteins, antibodies, antigen-binding fragments, and nucleic acids.

59. The method according to claim 58, wherein the binder is protein A, protein G, protein M, protein L, recombinant fusion proteins thereof, variants thereof, or combinations thereof.

60. The method according to any one of claims 50 to 59, wherein the flow rate ratio of the first liquid to the second liquid is 1:4 to 4:

1.

61. The method according to any one of claims 50 to 60, further comprising introducing a cleaning solution into the apparatus.

62. The method according to any one of claims 50 to 61, further comprising introducing the elution solution into the first separation module.

63. The method according to any one of claims 50 to 62, further comprising introducing the re-equilibrium solution into the second separation module.

64. To provide 3D model design for purification devices including multiple microchannels, Converting the aforementioned 3D model design into a slice file, The slice file is transmitted to a vat polymerization or stereolithography 3D printing device. The process involves preparing a resin and supplying the resin to the stereolithography 3D printing device. The process involves printing each layer to produce the aforementioned purification device. A method for manufacturing a purification device, including [the specified element].

65. The method according to claim 64, further comprising creating a constructive solid geometry (CSG) tree for the 3D model design.

66. The method according to claim 64, further comprising representing the 3D model design as a signed distance function.

67. The method according to claim 64, further comprising rendering the 3D model design by utilizing ray marching.

68. The method according to any one of claims 64 to 67, wherein the plurality of microchannels have a gyroid structure or a modified gyroid structure.

69. The method according to any one of claims 64 to 68, wherein the plurality of microchannels are arranged in a plurality of layers.

70. The method according to any one of claims 64 to 69, wherein the resin comprises at least one photoinitiator and at least one photosensitive resin.

71. Printing layer by layer is Printing the first layer, The process involves using an optical assembly to project one or more beams to solidify the resin, Printing the second layer and The method according to any one of claims 64 to 70, including the method described in that claim.

72. The method according to claim 71, further comprising moving the optical assembly along the z-axis while printing layer by layer.

73. The method according to claim 71 or 72, wherein the optical assembly includes a static optical assembly.

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