Compact hydraulic manifold structure for shear sensitive fluids

• US 9,421,315 B2
• Filed: 09/05/2012
• Issued: 08/23/2016
• Est. Priority Date: 09/05/2012
• Status: Active Grant

• Current Assignee: Charles Stark Draper Laboratory Incorporated
• Original Assignee: Charles Stark Draper Laboratory Incorporated
• Inventors: Borenstein, Jeffrey, DiBiasio, Christopher, Charest, Joseph, Kim, Ernest, Harjes, Daniel
• Primary Examiner(s): Mellon, David C
• Assistant Examiner(s): PATEL, PRANAV N
• Application Number:
  US13/604,256
• Publication Number:
  US 20140061115A1
• Time in Patent Office: 1,448 Days
• Field of Search: 210224-231, 210/321.6, 210/321.75, 210/321.84, 422/44, 422/48, 422/502, 422/503, 422/507, 422/513, 422/534, 422/535
• US Class Current: 1/1
• CPC Class Codes: A61M 1/16 with membranes
• CPC Class Codes: A61M 1/1631 having non-tubular membranes, e.g. sheets
• CPC Class Codes: A61M 1/1698 Blood oxygenators with or without heat-exchangers intracorporal A61M1/1678; manufacturing of membranes therefor B01D67/00; semi-permeable membranes for separation processes characterised by their properties B01D69/00; semi-permeable membranes characterised by their material B01D71/00
• 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 1/36 Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
• CPC Class Codes: A61M 2202/0413 Blood
• CPC Class Codes: A61M 2205/0244 Micromachined materials, e.g. made from silicon wafers, microelectromechanical systems [MEMS] or comprising nanotechnology
• CPC Class Codes: A61M 2205/75 with filters
• CPC Class Codes: B01D 2313/08 Flow guidance means within the module or the apparatus
• CPC Class Codes: B01D 2313/105 Supply manifolds
• CPC Class Codes: B01D 2319/04 Elements in parallel
• CPC Class Codes: B01D 63/005 Microfluidic devices Microfluidic devices comprising semi-permeable hollow fibre membranes B01D63/028; Microfluidic devices comprising semi-permeable flat membranes B01D63/088
• CPC Class Codes: B01D 63/085 specially adapted for two fluids in mass exchange flow
• CPC Class Codes: B01D 63/088 Microfluidic devices comprising semi-permeable flat membranes
• CPC Class Codes: B01L 2300/0864 comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
• CPC Class Codes: B01L 2300/0874 Three dimensional network
• CPC Class Codes: B01L 3/5027 by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip B01L3/5023 takes precedence; micromixers B01F33/30; microreactors for synthesis B01J19/0093; microcapillary devices in general B81B1/00
• CPC Class Codes: F17D 1/00 Pipe-line systems conveying articles or materials through a pipe- line by means of a fluid carrier B65G51/00, B65G53/00; liquids B67D; special devices for transferring liquids from bulk storage containers into vehicles or boats or vice versa, e.g. loading or unloading vehicles or portable containers B67D7/00; conveying material which has been excavated by a dredger or soil shifter through a pipe-line E02F7/10; sewer pipe-line systems E03F3/00; thermal insulation of pipe-lines F16L59/00; central heating systems F24D
• CPC Class Codes: Y10T 137/794 With means for separating solid material from the fluid

Abstract

An compact hydraulic manifold for transporting shear sensitive fluids is provided. A channel network can include a trunk and branch architecture coupled to a bifurcation architecture. Features such as tapered channel walls, curvatures and angles of channels, and zones of low fluid pressure can be used to reduce the size while maintaining wall shear rates within a narrow range. A hydraulic manifold can be coupled to a series of microfluidic layers to construct a compact microfluidic device.

Claims

1. A microfluidic device for processing blood comprising:

a first network of channels having a plurality of First Channels, each First Channel having a height in the range of about 50 microns to about 500 microns and a width in the range of about 50 microns to about 1.5 millimeters;

a second network of channels having at least one Second Channel complementary to one or more of the First Channels;

a filtration membrane separating the one or more First Channels from the at least one Second Channel;

wherein the plurality of First Channels further comprises;

an input channel forming a primary channel, a plurality of secondary channels, and an outlet channel wherein;

a diameter of the primary channel varies smoothly along the length of the primary channel such that an angle formed by a centerline of the primary channel and a wall of the primary channel is greater than zero degrees and less than or equal to about 45 degrees;

a first secondary channel connects to the primary channel at a first junction located at a first distance from a first end of the primary channel;

a second secondary channel connects to the primary channel at a second junction located at a second distance, greater than the first distance, from the first end of the primary channel;

at least one of the first and second secondary channels includes a curved portion directing flow away from the primary channel, the curved portion having a radius of curvature that is not less than its hydraulic diameter;

the primary channel and the first and second secondary channels are configured such that flow of fluid through the primary channel beyond the first junction is substantially greater than flow of fluid into the first secondary channel; and

at least one of the first and second secondary channels bifurcates into first and second tertiary channels at a third junction, such that a fluid flow rate through the first tertiary channel is substantially the same as a fluid flow rate through the second tertiary channel, and the total fluid flow rate between the first and second tertiary channels is substantially the same as the fluid flow rate through the portion of the at least one secondary channel between the primary channel and the third junction.

2. The microfluidic device of claim 1, wherein the plurality of First Channels is located within a first substrate.

3. The microfluidic device of claim 2, wherein the first substrate has a thickness of no less than 10 microns and no greater than 10 millimeters.

4. The microfluidic device of claim 1, wherein the filtration membrane separates only a subset of the plurality of First Channels from the at least one Second Channel.

5. The microfluidic device of claim 1, further comprising a flow divider for dividing fluid flow between the first and second tertiary channels, wherein the flow divider has a curved surface connecting to the walls of the first and second tertiary channel, and the radius of curvature of the flow divider is not greater than the hydraulic diameter of the at least one secondary channel.

6. The microfluidic device of claim 1, further comprising third and fourth tertiary channels that converge at a point where they have opposing curvatures to form a third secondary channel, such that all of the fluid flowing through the third and fourth tertiary channels is subsequently transported into the third secondary channel.

7. The microfluidic device of claim 1, wherein the diameter of at least one secondary channel at a portion adjacent to its junction with the primary channel is significantly greater than the diameter of the downstream portion of the at least one secondary channel, such that a zone of low fluid pressure is created at the junction.

8. The microfluidic device of claim 1, wherein an angle formed by a centerline of the secondary channel and a downstream portion of the centerline of the primary channel measures between one and sixty degrees.

9. The microfluidic device of claim 1, wherein the plurality of First Channels is further configured to maintain a shear rate of no less than two hundred inverse seconds and no more than two thousand inverse seconds when blood is transported through the channels.

10. The microfluidic device of claim 1, wherein the walls of the primary channel are disposed at an angle of no greater than thirty degrees with respect to the direction of fluid flow through the primary channel.

11. The microfluidic device of claim 1, wherein at least one of the plurality of First Channels or the at least one Secondary Channel has a substantially semicircular cross section.

19. The microfluidic device of claim 1, wherein each of the First Channels has a length in the range of about 3 centimeters to about 20 centimeters.

21. The microfluidic device of claim 1, wherein the angle formed by the centerline of the primary channel and the wall of the primary channel and a wall of the primary channel is greater than zero degrees and less than or equal to about 30 degrees.

22. The microfluidic device of claim 1, wherein the angle formed by the centerline of the primary channel and the wall of the primary inlet channel and a wall of the primary channel is greater than zero degrees and less than or equal to about 20 degrees.

12. A microfluidic device for processing blood comprising:

a first manifold having a primary inlet channel and a plurality of secondary inlet channels, coupled to a first plurality of substrates each having a network of First substrate channels;

a plurality of second substrates, each second substrate corresponding to one of the first substrates and including at least one Second channel complementary to one or more of the First substrate channels; and

a plurality of filtration membranes, each filtration membrane separating the First substrate channels of one of the plurality of first substrates from the at least one Second channel included in a corresponding second substrate, wherein;

each of the First substrate channels has a height in the range of about 50 microns to about 500 microns and a width in the range of about 50 microns to about 1.5 millimeters;

a diameter of the primary inlet channel varies smoothly along the length of the primary inlet channel such that an angle formed by a centerline of the primary channel and a wall of the primary channel is greater than zero degrees and less than or equal to about 45 degrees;

a first secondary inlet channel connects to the primary inlet channel at a first junction located at a first distance from a first end of the primary inlet channel;

a second secondary inlet channel connects to the primary inlet channel at a second junction located at a second distance, greater than the first distance, from the first end of the primary inlet channel;

at least one of the first and second secondary inlet channels includes a curved portion directing flow away from the primary inlet channel, the curved portion having a radius of curvature that is not less than its hydraulic diameter;

the inlet channels are configured such that flow of fluid through the primary inlet channel beyond the first junction is substantially greater than flow of fluid into the first secondary inlet channel; and

at least one of the first and second secondary channels bifurcates into first and second tertiary channels at a third junction, such that a fluid flow rate through the first tertiary channel is substantially the same as a fluid flow rate through the second tertiary channel, and the total fluid flow rate between the first and second tertiary channels is substantially the same as the fluid flow rate through the portion of the at least one secondary channel between the primary inlet channel and the third junction.

13. The microfluidic device of claim 12, wherein:

the network of First substrate channels in at least one of the first plurality of substrates comprises a primary substrate channel and a plurality of secondary substrate channels, wherein;

a first secondary substrate channel connects to the primary substrate channel at a first junction located at a first distance along the primary substrate channel;

a second secondary substrate channel connects to the primary substrate channel at a second junction located at a second distance, greater than the first distance, along the primary substrate channel; and

the substrate channels are configured such that flow of fluid through the primary substrate channel beyond the first junction is substantially greater than flow of fluid into the first secondary substrate channel.

14. The microfluidic device of claim 12, wherein at least one of the plurality of filtration membranes separates only a subset of the plurality of First substrate channels from the at least one corresponding Second substrate channel.

15. The microfluidic device of claim 12, further comprising:

a second manifold having a primary inlet channel and a plurality of secondary inlet channels, coupled to a second plurality of substrates each having a network of Second substrate channels, wherein;

a first secondary inlet channel connects to the primary inlet channel at a first junction located at a first distance along the primary inlet channel;

a second secondary inlet channel connects to the primary inlet channel at a second junction located at a second distance, greater than the first distance, along the primary inlet channel; and

the secondary channels of each of the second plurality of substrates connects to a secondary inlet channel at a junction such that fluid can be transported from the second manifold to the network of Second substrate channels of each of the second plurality of substrates.

16. The microfluidic device of claim 15, wherein each of the second plurality of substrates is coupled to a respective one of the first plurality of substrates to form a bilayer.

17. The microfluidic device of claim 12, wherein an angle formed by a surface of at least one of the first plurality of substrates and a downstream portion of the primary inlet channel of the first manifold measures between one and sixty degrees.

18. The microfluidic device of claim 12, wherein at least one of the primary inlet channel, the secondary inlet channel, the First substrate channels, or the at least one Second substrate channel has a substantially semicircular cross section.

20. The microfluidic device of claim 12, wherein each of the First substrate channels has a length in the range of about 3 centimeters to about 20 centimeters.

23. The microfluidic device of claim 12, wherein the angle formed by the centerline of the primary inlet channel and the wall of the primary inlet channel and a wall of the primary inlet channel is greater than zero degrees and less than or equal to about 30 degrees.

24. The microfluidic device of claim 12, wherein the angle formed by the centerline of the primary inlet channel and the wall of the primary inlet channel and a wall of the primary inlet channel is greater than zero degrees and less than or equal to about 20 degrees.