SYSTEMS AND METHODS OF MICROFLUIDIC MEMBRANELESS EXCHANGE USING FILTRATION OF EXTRACTION OUTLET STREAMS

• US 20090139931A1
• Filed: 05/22/2007
• Published: 06/04/2009
• Est. Priority Date: 05/22/2006
• Status: Active Grant

• Current Assignee: Trustees Of Columbia University In The City Of New York (Columbia University)
• Original Assignee: Trustees Of Columbia University In The City Of New York (Columbia University)
• Inventors: Nanne, Edgar E., Aucoin, Christian P., West, Alan C., Leonard, Edward F.
• Granted Patent: US 7,727,399 B2
• Time in Patent Office: Days
• US Class Current: 210/645
• CPC Class Codes: A61M 1/14 Dialysis systems; Artificial kidneys; Blood oxygenators semi-permeable membranes characterised by the material, manufacturing processes therefor B01D71/00; Reciprocating systems for treatment of body fluids, e.g. single needle systems for hemofiltration or pheresis
• CPC Class Codes: A61M 1/1696 with dialysate regeneration
• CPC Class Codes: A61M 1/32 Oxygenators without membranes
• CPC Class Codes: A61M 2205/7563 with means preventing clogging of filters
• CPC Class Codes: A61M 2206/11 Laminar flow
• CPC Class Codes: A61P 7/08 Plasma substitutes; Perfusion solutions; Dialytics or haemodialytics; Drugs for electrolytic or acid-base disorders, e.g. hypovolemic shock artificial tears A61P27/04
• CPC Class Codes: B01D 11/0492 Applications, solvents used
• CPC Class Codes: B01D 11/0496 by extraction in microfluidic devices
• CPC Class Codes: G01N 2030/0045 normal, i.e. diffusion or thermal FFF

Abstract

A device, system and method for exchanging components between first and second fluids by direct contact in a microfluidic channel. The fluids flow as thin layers in the channel. One of the fluids is passed through a filter upon exiting the channel and is recycled through a secondary processor which changes the fluid'"'"'s properties. The recycled fluid is reused for further exchange. The filter excludes blood cells from the recycled fluid and prevents or limits clogging of the filter. The secondary processor removes metabolic waste and water by diafiltration.

Claims

1. A method for exchanging components between a first fluid and a second fluid, comprising:

forming at least one first layer and at least one second layer of first and second fluids, respectively, such that diffusion-based exchange of components between the first and second fluids occurs in the absence of mixing of the fluids; and

filtering at least a portion of the first fluid through pores sized to block first components from the second fluid while passing second components from the second fluid.

2. The method of claim 1, wherein the filtering includes passing the first fluid through pores whose size is smaller than 800 nm.

3. The method of claim 1, wherein the forming of the first and second layers includes flowing the first and second fluids through a channel, and the filtering includes providing a filter forming a portion of a wall of the channel.

4. The method of claim 1, wherein the forming of the first and second layers includes forming two first layers with a single second layer therebetween.

5. The method of claim 1, wherein the pores define non-serpentine, non-branching channels.

6. The method of claim 1, wherein the first components are erythrocytes.

7. The method of claim 1, wherein the second fluid includes blood.

8. The method of claim 1, wherein the first fluid includes a fluid obtained by increasing a concentration of a second component from the second fluid in a filtrate obtained from the filtering.

9. The method of claim 8, wherein the second component includes serum albumin.

10. The method of claim 1, wherein the at least one first layer is two first layers and the forming includes forming the two first layers with a single second layer between them within a channel such that the first fluid prevents the second fluid from directly contacting the walls of the channel.

11. The method of claim 1, wherein the forming includes flowing the first and second fluids through a channel having a cross-section cutting across a direction of flow whose aspect ratio is greater than ten.

12. The method of claim 1, wherein the forming includes flowing the first and second fluids through a channel whose depth across the direction of flow is between 75 and 300 microns.

13. The method of claim 12, wherein the depth is about 120 microns.

14. The method of claim 11, wherein the filtering includes providing a filter forming a portion of a wall of the channel.

15. A method for clearing first components from a first fluid, comprising:

flowing a layer of the first fluid surrounded by at least one co-flowing layer of solvent to isolate the layer from the wall of a conveying channel while permitting diffusion of the first component from the first fluid into the solvent without mixing of the first fluid and solvent;

removing the first component from the solvent; and

replenishing the co-flowing layer of solvent with the first component-depleted solvent resulting from the removing.

16. The method of claim 15, wherein the fluid is blood.

17. The method of claim 16, wherein the solvent is an aqueous solution.

18. The method of claim 17, wherein the removing includes filtering solvent by passing it through a filter and passing the resulting filtrate across another filter and recovering the filtrand therefrom, the fitrand being the result of the removing.

19. The method of claim 15, wherein the removing includes filtering solvent by passing it through a filter and passing the resulting filtrate across another filter and recovering the filtrand therefrom, the fitrand being the result of the removing.

20. The method of claim 15, wherein the removing includes passing the solvent through a first filter and recovering the filtrate then passing the filtrate through a second filter and recovering the filtrand, the first filter having a pore size of less than 800 nm.

21. The method of claim 15, wherein the first fluid is blood and the removing includes filtering the solvent to block blood cells.

22. The method of claim 15, wherein the first fluid is blood and the removing includes dialyzing the solvent at a location remote from blood cells and returning the dialyzed solvent to the co-flowing layer to permit the diffusion of the first component back into the blood.

23. The method of claim 22, wherein the first component includes a blood protein.

24. A method of processing blood, comprising:

co-currently flowing blood and an aqueous solvent in respective laminar layers through a channel having a greater all and a wall portion of the greater wall, the wall portion having a regular pattern of pores, the pores having a maximum size less than 1 micron and the solvent respective laminar layer being adjacent the wall portion;

circulating the solvent through the pores and into a flow circuit that returns the solvent back to the channel at a point upstream of the wall portion.

25. The method of claim 24, wherein the flow circuit includes a fluid processor that removes water from the solvent.

26. The method of claim 24, wherein the flow circuit includes a fluid processor that removes uremic toxins from the solvent.

27. The method of claim 24, wherein the pores have a maximum size of less than 600 microns.

28. The method of claim 24, wherein the co-currently flowing creates a flow that keeps blood cells from contacting substantially all of the greater wall.

29. The method of claim 24, wherein the pores have a maximum size of about 100 nm or less.

30. The method of claim 24, wherein the co-currently flowing includes flowing blood and aqueous solvent at approximately equal volume rates in the channel.

31. A fluid processing device, comprising:

a channel having an input end and an output end separated by a length and defining a direction of flow through the channel, a ratio of a channel width to a channel depth of more than 10, the channel depth being no more than 300 microns, both the channel width and the channel depth being perpendicular to the direction of flow;

two extraction fluid inlet ports and one sample fluid inlet port between the two extraction fluid inlet ports located proximate to the input end and two extraction fluid outlet ports and one sample fluid outlet port between the two extraction fluid outlet ports located proximate to the output end, the extraction fluid outlet ports each having first filters;

at least one of the extraction fluid outlet ports being coupled by another channel to at least one of the extraction fluid inlet ports.

32. The device of claim 31, wherein the channel has a wall surface with dimensions that are equal to the width and the length, the first filters forming a portion of the wall.

33. The device of claim 31, wherein the first filters have a pore size no greater than 1000 nm.

34. The device of claim 31, wherein the first filters have a pore size no greater than 800 nm.

35. The device of claim 31, wherein the first filters have a pore size no greater than 300 nm.

36. The device of claim 31, wherein channel has a depth of no more than 120 microns.

37. The device of claim 36, wherein ratio of width to depth is more than 50.

38. The device of claim 31, further comprising at least one pump configured to pump at least 1 liter of blood and at least one liter of solvent through the channel during a treatment cycle lasting no more than one day.

39. The device of claim 31, wherein the inlet and outlet sample ports are connected to channels with connectors connectable to arterial and venous lines of a patient access.

40. A device for exchanging components between a first fluid and a second fluid, where the second fluid contains first and second components, comprising:

a channel that receives a first fluid and a second fluid to form at least one first layer and at least one second layer of the first and second fluids, respectively, such that they are in direct contact with each other and do not mix;

the at least one first layer and at least one second layer flowing in a same flow direction;

the channel having outlets with at least one filter that receive only the first fluid, the at least one filter having pores sized to block the first components from the second fluid while passing the second components from the second fluid.

41. The device of claim 40, wherein the at least one filter has pores whose size is smaller than 800 nm.

42. The device of claim 40, wherein the channel has walls and the at least one filter defines a portion of the channel walls.

43. The device of claim 40, wherein the at least one first layer is two first layers and the at least one second layer is one second layer, the second layer being positioned between the two first layers.

44. The device of claim 40, wherein the pores define non-serpentine, non-branching channels.

45. The device of claim 40, wherein the first components are erythrocytes.

46. The device of claim 40, wherein the second fluid includes blood and the first components are erythrocytes.

47. The device of claim 40, wherein the first fluid includes a fluid obtained by increasing the concentration of the second component in a filtrate obtained from passing the first fluid through the at least one filter.

48. The device of claim 47, where in the second component includes serum albumin.

49. The device of claim 40, wherein the channel has walls and the at least one first layer is two first layers and the forming includes forming the two first layers with a single second layer between them such that the first fluid prevents the second fluid from directly contacting the walls.

50. The device of claim 40, wherein the channel has a cross-section cutting across the flow direction whose aspect ratio is greater than ten.

51. The device of claim 40, wherein the channel has a depth across the flow direction between 75 and 300 microns.

52. The device of claim 51, wherein the depth is about 120 microns.

53. The device of claim 52, wherein at least one filter forms a portion of a wall of the channel.

54. A device for exchanging components between a first fluid and a second fluid, comprising:

first and second channels each having respective inlets and outlets to permit at least two fluids flowing into the inlets to flow co-currently therethrough, the at least two fluids flowing in direct contact with each other and out of the outlets;

a fluid processor, with an inlet and an outlet, which changes a property of fluids received at the inlet and conveys a changed fluid to the outlet;

a first of the first channel outlets being connected to a first of the second channel inlets;

a second of the first channel outlets being connected to the fluid processor inlet;

a second of the second channel inlets being connected to the fluid processor outlet.

55. The device of claim 54, wherein the fluid processor includes a membrane.

56. The device of claim 54, wherein the fluid processor includes a dialyzer.

57. The device of claim 54, further comprising fluid conveyance devices to cause fluids to flow through the first and second channels in laminar fashion such that transport between the fluids in the channels is primarily by diffusion.

58. The device of claim 54, wherein the second of the first channel outlets contains a filter.

59. The device of claim 58, wherein the filter has pores whose sizes are a maximum of 600 nm.

60. A method of separating blood cells from plasma, comprising:

drawing most of the blood cells, in a layer including blood cells and plasma, away from a vessel surface having a filtered outlet;

removing the plasma through the filtered outlet to block blood cells entering the outlet.

61. The method of claim 60, wherein the layer is a flowing layer.

62. The method of claim 61, wherein the drawing includes creating a shear gradient in the flowing layer that is higher near the wall than remote from the surface.

63. The method of claim 60, wherein the layer includes an aqueous solvent.

64. The method of claim 60, wherein the filtered outlet has a filter with a surface that is coplanar with the vessel surface.

65. The method of claim 60, wherein the filtered outlet has a filter with a surface that is coplanar with the vessel surface, the layer is a flowing layer having a shear near the surface which is effective to scour the surface of the filter.