SYSTEMS AND METHODS FOR INCREASING CONVECTIVE CLEARANCE OF UNDESIRED PARTICLES IN A MICROFLUIDIC DEVICE

• US 20160045655A1
• Filed: 08/21/2015
• Published: 02/18/2016
• Est. Priority Date: 01/11/2013
• Status: Active Grant

• Current Assignee: Charles Stark Draper Laboratory Incorporated, Johnson & Johnson Innovation LLC (Johnson & Johnson)
• Original Assignee: Charles Stark Draper Laboratory Incorporated, Johnson & Johnson Innovation LLC (Johnson & Johnson)
• Inventors: Charest, Joseph L., Nohilly, Martin, Borenstein, Jeffrey T., Dibiasio, Christopher, Laurenzi, Mark, Wilson, Jonathan
• Granted Patent: US 10,342,909 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61M 1/16 with membranes
• CPC Class Codes: A61M 1/1601 Control or regulation
• CPC Class Codes: A61M 1/1631 having non-tubular membranes, e.g. sheets
• CPC Class Codes: A61M 1/1694 with recirculating dialysing liquid
• CPC Class Codes: A61M 1/34 Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration
• CPC Class Codes: A61M 1/3403 Regulation parameters
• CPC Class Codes: A61M 1/341 by measuring the filtrate rate or volume
• CPC Class Codes: A61M 1/3431 upstream of the filter
• CPC Class Codes: A61M 1/3434 with pre-dilution and post-dilution
• CPC Class Codes: A61M 1/3437 downstream of the filter, e.g. post-dilution with filtrate
• CPC Class Codes: A61M 2205/0244 Micromachined materials, e.g. made from silicon wafers, microelectromechanical systems [MEMS] or comprising nanotechnology
• CPC Class Codes: A61M 2205/33 Controlling, regulating or measuring
• CPC Class Codes: A61M 2205/3331 Pressure; Flow
• CPC Class Codes: A61M 2205/3334 Measuring or controlling the flow rate
• CPC Class Codes: A61M 2230/207 hematocrit
• CPC Class Codes: B01D 61/18 Apparatus therefor
• CPC Class Codes: B01D 63/088 Microfluidic devices comprising semi-permeable flat membranes
• CPC Class Codes: B81B 7/0009 Structural features, others than packages, for protecting a device against environmental influences B81C1/00777 takes precedence

Abstract

A microfluidic device for increasing convective clearance of particles from a fluid is provided. In some implementations, described herein the microfluidic device includes multiple layers that each define infusate, blood, and filtrate channels. Each of the channels have a pressure profile. The device can also include one or more pressure control features. The pressure control feature controls a difference between the pressure profiles along a length of the device. For example, the pressure control feature can control the difference between the pressure profile of the filtrate channel and the pressure profile of the blood channel. In some implementations, the pressure control feature controls the pressure difference between two channels such that the difference varies along the length of the channels by less than 50% of the pressure difference between the channels at the channels'"'"' inlets.

Claims

1. A microfluidic device comprising:

a first layer defining an infusate channel having an inlet and an outlet, the infusate channel having a first pressure profile;

a second layer defining a blood channel complementary to and in fluidic communication with the infusate channel, the blood channel having a second pressure profile;

an interchannel flow barrier separating the infusate channel and the blood channel allowing a portion of fluid flowing into the inlet of the infusate channel to flow through the interchannel flow barrier and into the blood channel;

a third layer defining a filtrate channel complementary to and in fluidic communication with the blood channel, the filtrate channel having a third pressure profile; and

a pressure control feature to control a difference between the second pressure profile and the third pressure profile along a length of the filtrate and blood channels such that the pressure difference between blood channel and the filtrate channel varies by less than 50% of the pressure difference between the blood channel and filtrate channel at an upstream end of the blood channel and the filtrate channel.

2. The device of claim 1, further comprising a second pressure control feature to control a difference between the first pressure profile and the second pressure profile along a length of the infusate and blood channels such that the pressure difference between blood channel and the infusate channel varies by less than 50% of the pressure difference between the blood channel and infusate channel at an upstream end of the blood channel and the infusate channel.

3. The device of claim 2, wherein the second pressure control feature is complementary to the first pressure control feature.

4. The device of claim 1, wherein the interchannel flow barrier comprises a non-porous material and the pressure control feature comprises a plurality of apertures through the non-porous material distributed across a face of the interchannel flow barrier.

5. The device of claim 4, wherein the plurality of apertures has a diameter between about 50 μ

m and about 300 μ

m.

6. The device of claim 4, wherein the plurality of apertures has a pitch between about 2 cm and about 10 cm.

7. The device of claim 1, wherein the pressure control feature comprises a fluid flow restriction material substantially filling the filtrate channel, wherein the restrictiveness of the fluid flow restriction material varies along a length of the filtrate channel.

8. The device of claim 1, wherein the pressure control feature comprises a tapering of the cross-sectional area of the filtrate channel along a length of the filtrate channel.

9. The device of claim 1, wherein the first pressure profile, the second pressure profile, and the third pressure profile are substantially linear.

10. The device of claim 1, wherein the first pressure profile and the third pressure profile comprise a step function.

11. The device of claim 1, wherein the interchannel flow barrier comprises a permeable membrane comprising a plurality of sealed, non-porous portions.

12. The device of claim 11, wherein the pressure control feature comprises an intrachannel flow barrier coupled to each of the plurality of sealed, non-porous portions of the interchannel flow barrier.

13. The device of claim 12, wherein the intrachannel flow barrier defines an end of a respective zone within the infusate channel, and each of the respective zones of the infusate channel comprises a respective inlet.

14. The device of claim 12, further comprising a plurality of infusate pumps, each infusate pump coupled to a respective zone inlet.

15. The device of claim 1, further comprising a plurality of infusate channels across the first layer, a plurality of blood channels across the second layer, and a plurality of filtrate channels across the third layer.

16. The device of claim 1, wherein interchannel flow barrier is a filtration membrane.

17. The device of claim 16, further comprising a second filtration membrane separating the blood channel and the filtrate channel.

18. The device of claim 17, wherein the blood channel has a height in the range of about 50 μ

m to about 500 μ

m, a width in the range of about 50 μ

m to about 900 μ

m, and a length in the range of about 3 cm to about 20 cm.

19. The device of claim 1, wherein the blood channel, infusate channel, and filtrate channel are parallel.

20. The device of claim 1, wherein the blood channel has a length in the range of about 20 cm to about 30 cm.

21. The device of claim 1, wherein the pressure control feature comprises a recirculation pump coupling an inlet and an outlet of the filtrate channel, thereby forming a filtrate fluid circuit, wherein the recirculation pump is configured to control a filtrate flow rate through the filtrate channel.

22. The device of claim 21, wherein the pressure control feature further comprises a pump configured to draw filtrate out of the filtrate fluid circuit.

23. The device of claim 21, further comprising a second recirculation pump coupling the inlet and the outlet of the infusate channel, thereby forming an infusate fluid circuit, the second recirculation pump configured to control an infusate flow rate through the infusate channel and serving as a second pressure control feature.

24. The device of claim 1, wherein the pressure difference between blood channel and the infusate channel varies by less than 30% of the pressure difference between the blood channel and infusate channel at the upstream end of the blood channel and the infusate channel.

25. The device of claim 1, wherein the pressure difference between blood channel and the infusate channel varies by less than 5% of the pressure difference between the blood channel and infusate channel at the upstream end of the blood channel and the infusate channel.

26. A method comprising:

introducing a first fluid into a first inlet of an infusate channel defined in a first layer and having a first pressure profile and an outlet;

introducing blood into a second inlet of a blood channel complementary to and in fluidic communication with the infusate channel, the blood channel having a second pressure profile and defined in a second layer;

introducing a filtrate into a third inlet of a filtrate channel complementary to and in fluidic communication with the blood channel, defined in a third layer, and having a third pressure profile; and

maintaining, with a pressure control feature, a difference between the second pressure profile and the third pressure profile along a length of the filtrate and blood channels such that the pressure difference between blood channel and the filtrate channel varies by less than 50% of the pressure difference between the blood channel and filtrate channel at an upstream end of the blood channel and the filtrate channel.

27. The method of claim 26, further comprising flowing at least a portion of a filtrate through the pressure control feature.

28. The method of claim 26, further comprising flowing at least a portion of the first fluid through a second pressure control feature to control a difference between the first pressure profile and the second pressure profile along a length of the infusate and blood channels such that the pressure difference between the first pressure profile and the second pressure profile varies by less than 50% of the pressure difference between the blood channel and the infusate channel at an upstream end of the blood channel and the infusate channel.

29. The method of claim 28, further comprises flowing at least the portion of the first fluid through a plurality of apertures distributed across a face of an interchannel flow barrier.

30. The method of claim 29, wherein the plurality of apertures have a diameter between about 50 μ

m and about 300 μ

m.

31. The method of claim 29, wherein the plurality of apertures have a pitch between about 2 cm and about 10 cm.

32. The method of claim 26, further comprising:

collecting the filtrate from an outlet of the filtrate channel; and

recirculating the filtrate to the third inlet of the filtrate channel.

33. The method of claim 26, wherein maintaining, with the pressure control feature, the difference between the second pressure profile and the third pressure profile along the length of the filtrate and blood channels further comprises flowing at least the portion of the filtrate through a fluid flow restriction material substantially filling the filtrate channel, wherein the restrictiveness of the fluid flow restriction material varies along the length of the filtrate channel.

34. The method of claim 26, wherein maintaining, with the pressure control feature, the difference between the second pressure profile and the third pressure profile along the length of the filtrate and blood channels further comprises flowing at least the portion of the filtrate through a tapering of the cross sectional area of the filtrate channel along the length of the filtrate channel.

35. The method of claim 26, wherein the first pressure profile, the second pressure profile, and the third pressure profile are substantially linear.

36. The method of claim 26, wherein the first pressure profile and the third pressure profile comprise a step function.

37. The method of claim 26, further comprises driving at least a portion of the first fluid through a first interchannel flow barrier and driving at least a portion of the blood through a second interchannel flow barrier.

38. The method of claim 37, wherein the first and second interchannel flow barriers each comprises a permeable membrane comprising a plurality of sealed, non-porous portions.

39. The method of claim 38, wherein the pressure control feature comprises an intrachannel flow barrier coupled to each of the plurality of sealed, non-porous portions of the interchannel flow barrier.

40. The method of claim 39, wherein the intrachannel flow barrier defines an end of a respective zone within the infusate channel, and each of the respective zones of the infusate channel comprises an inlet.

41. The method of claim 37, wherein the first and second interchannel flow barriers are filtration membranes.

42. The method of claim 26, wherein the blood channel has a height in the range of about 50 μ

m to about 500 μ

m, a width in the range of about 50 μ

m to about 900 μ

m, and a length in the range of about 3 cm to about 20 cm.

43. The method of claim 26, wherein the blood channel, infusate channel, and filtrate channel are parallel.

44. A microfluidic device comprising:

a first layer defining an infusate channel having an inlet and an outlet, the infusate channel having a first pressure profile;

a second layer defining a blood channel complementary to and in fluidic communication with the infusate channel, the blood channel having a second pressure profile;

an interchannel flow barrier separating the infusate channel and the blood channel allowing a portion of fluid flowing into the inlet of the infusate channel to flow through the interchannel flow barrier and into the blood channel;

a third layer defining a filtrate channel complementary to and in fluidic communication with the blood channel, the filtrate channel having a third pressure profile; and

a pressure control feature to control a pressure difference between at least two of the first pressure profile, the second pressure profile, and the third pressure profile along a length of the device such that the pressure difference varies by less than 50% of the pressure difference between the at least two of the first pressure profile, the second pressure profile, and the third pressure profile at an upstream end of the infusate, blood, and filtrate channels.