Capillary network devices and methods of use

• US 9,977,037 B2
• Filed: 05/22/2013
• Issued: 05/22/2018
• Est. Priority Date: 05/22/2012
• Status: Active Grant

• Current Assignee: Administrators Of The Tulane Educational Fund (ADMINISTRATORS|DAVID H. COY), Hemanext Inc.
• Original Assignee: Administrators Of The Tulane Educational Fund (ADMINISTRATORS|DAVID H. COY), New Health Sciences, Inc.
• Inventors: Yoshida, Tatsuro, Shevkoplyas, Sergey S., Burns, Jennie M.
• Primary Examiner(s): Warden, Jill A
• Assistant Examiner(s): Brazin, Jacqueline
• Application Number:
  US14/403,365
• Publication Number:
  US 20150153367A1
• Time in Patent Office: 1,826 Days
• Field of Search: 422502
• CPC Class Codes: B01L 2300/0838 Capillaries
• CPC Class Codes: B01L 2300/0861 Configuration of multiple channels and/or chambers in a single devices
• CPC Class Codes: B01L 2300/0867 Multiple inlets and one sample wells, e.g. mixing, dilution
• CPC Class Codes: B01L 2400/086 using baffles or other fixed flow obstructions
• 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: B01L 3/502715 characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: B01L 3/502746 characterised by the means for controlling flow resistance, e.g. flow controllers, baffles B01L3/502738 takes precedence
• CPC Class Codes: B01L 3/502761 specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads, for physically stretching molecules investigating characteristics of particles G01N15/00
• CPC Class Codes: G01N 33/80 involving blood groups or blood types or red blood cells white blood cells G01N33/56972

Abstract

Artificial microvascular network (AMVN) devices are provided and related methods of making and methods of using such devices are provided. The present disclosure generally relates to an AMVN device comprising a substrate including a capillary network configured so as to simulate those actually encountered in the circulation of various humans and animal model systems. In certain aspects, the AMVN devices may be used, e.g., to investigate the effect of storing RBCs under aerobic and anaerobic conditions. However, the use of such AMVN devices is not so limited.

Claims

1. An artificial microvascular network device for a biological sample comprising:

a substrate having a capillary network formed thereon;

wherein said capillary network comprises at least one unbranched microchannel of a variable cross-sectional width along its length;

at least one inlet port in communication with said capillary network microchannel for sample entry; and

at least one outlet port in communication with said capillary network microchannel for sample exit;

wherein the at least one unbranched microchannel ranges in a cross-sectional width from 3 μ

m to 70 μ

m; and

wherein said variable cross-sectional width is oriented along the longitudinal axis of said unbranched microchannel and comprises two or more expanded regions separated by a spacer, or two or more expanded regions separated by a spacer and a gradual taper having an initial width greater than a final width and a taper length ranging from 5 to 100 μ

m.

2. The device of claim 1, wherein said gradual taper comprises said initial width of about 30 μ

m and said final width of about 3 μ

m.

26. The device of claim 1, wherein said at least one unbranched microchannel further comprises a constant depth ranging from 1 μ

m to 25 μ

m.

27. The device of claim 1, wherein said at least one unbranched microchannel further comprises said two or more expanded regions comprising a length ranging from 5 μ

m to 20 μ

m.

28. The device of claim 1, wherein said spacer has a width of 5 μ

m and a length of 16 μ

m.

30. The device of claim 1, wherein said gradual taper comprises said initial width of about 8 μ

m and said final width of about 3 μ

m.

3. A capillary network device (CND) for a biological sample comprising:

a substrate;

one or more inlet ports for sample entry formed on said substrate;

one or more inlet microchannels formed on said substrate in communication with said one or more inlet ports for sample entry;

one or more outlet microchannels formed on said substrate in communication with said one or more inlet microchannels; and

one or more outlet ports formed on said substrate in communication with said one or more outlet microchannels;

wherein at least one of said one or more inlet microchannels or said one or more outlet microchannels is an unbranched microchannel having one or more cross-sectional widths ranging in size from 3 μ

m to 70 μ

m along its length; and

wherein said one or more cross-sectional widths is oriented along the longitudinal axis of said unbranched microchannel and comprises two or more expanded regions separated by a spacer, or two or more expanded regions separated by a spacer and a gradual taper having an initial width greater than a final width and a taper length ranging from 5 to 100 μ

m.

4. The device of claim 3, further comprising

an inlet channel in communication with said one or more inlet ports and said one or more inlet microchannels;

and

an outlet channel in communication with said one or more outlet ports and said one or more inlet microchannels.

5. The device of claim 3, wherein said one or more inlet microchannels is a primary inlet microchannel in communication with one or more microchannel junctions to bifurcate said primary inlet microchannel into two or more secondary inlet microchannels.

6. The device of claim 4, wherein the cross-sectional width of said primary inlet microchannel is greater than at least one of said two or more secondary inlet microchannels.

7. The device of claim 4, wherein said secondary inlet microchannel is in communication with one or more microchannel junctions to bifurcate said secondary inlet microchannel into two or more tertiary inlet microchannels.

8. The device of claim 7, wherein the cross-sectional width of said secondary microchannel is greater than at least one of said two or more tertiary inlet microchannels.

9. The device of claim 7, wherein one or more of said tertiary inlet microchannels is in communication with one or more microchannel junctions to bifurcate said tertiary inlet microchannel into two or more quaternary inlet microchannels.

10. The device of claim 9, wherein the cross-sectional width of said tertiary microchannel is greater than at least one of said two or more quaternary inlet microchannels.

11. The device of claim 9, wherein two or more microchannels selected from the group consisting of a primary inlet microchannel, a secondary inlet microchannel, a tertiary inlet microchannel, and a quaternary inlet microchannel are in communication with a junction that converges to form at least one primary outlet microchannel.

12. The device of claim 11, wherein the cross-sectional width of said primary outlet microchannel is greater than the cross-sectional width of at least one converged microchannel selected from the group consisting of a primary inlet microchannel, a secondary inlet microchannel, a tertiary inlet microchannel, and a quaternary inlet microchannel.

13. The device of claim 11, wherein two or more microchannels selected from the group consisting of a primary inlet microchannel, a secondary inlet microchannel, a tertiary inlet microchannel, a quaternary inlet microchannel, and a primary outlet microchannel in communication with a junction that converges to form at least one secondary outlet microchannel.

14. The device of claim 13, wherein the cross-sectional width of said secondary outlet channel is greater than the cross-sectional width of at least one converged microchannel selected from the group consisting of a primary inlet microchannel, a secondary inlet microchannel, a tertiary inlet microchannel, a quaternary inlet microchannel, and a primary outlet microchannel.

15. The device of claim 13, wherein two or more microchannels selected from the group consisting of a primary inlet microchannel, a secondary inlet microchannel, a tertiary inlet microchannel, a quaternary inlet microchannel, a primary outlet microchannel, and a secondary outlet microchannel in communication with a junction that converges to form at least one tertiary outlet microchannel.

16. The device of claim 15, wherein the cross-sectional width of said tertiary outlet microchannel is greater than the cross-sectional width of at least one converged microchannel selected from the group consisting of a primary inlet microchannel, a secondary inlet microchannel, a tertiary inlet microchannel, a quaternary inlet microchannel, a primary outlet microchannel, and a secondary outlet microchannel.

17. The device of claim 15, wherein two or more microchannels selected from the group consisting of primary inlet microchannel, secondary inlet microchannel, tertiary inlet microchannel, quaternary inlet microchannel, primary outlet microchannel, secondary outlet microchannel, and tertiary outlet microchannel in communication with a junction that converges to form at least one quaternary outlet microchannel.

18. The device of claim 17, wherein the cross-sectional width of said quaternary outlet microchannel is greater than the cross-sectional width of at least one converged microchannel selected from the group consisting of a primary inlet microchannel, a secondary inlet microchannel, a tertiary inlet microchannel, a quaternary inlet microchannel, a primary outlet microchannel, a secondary outlet microchannel, and a tertiary outlet microchannel.

19. The device of claim 3, wherein said inlet microchannel is in communication with one or more junctions that bifurcate said inlet microchannel into two or more division microchannels having a smaller cross-sectional width than said inlet microchannel.

20. The device of claim 19, wherein said division microchannels are in communication with one or more junctions that converge said division microchannels into an outlet microchannel having a greater cross-sectional width than said division microchannel.

21. The device of claim 3, wherein said substrate is selected from the group consisting of glasses, crystals, silicon wafers, plastics, thermoplastics, waxes, gels, hydrogels, polymers, metals, ceramics, organic materials, inorganic materials, and any combinations thereof.

22. The device of claim 3, wherein said microchannels are in communication with one or more junctions that converge on a common outlet microchannel.

23. A method of measuring red blood cell (RBC) deformability comprising:

a. obtaining a blood sample from a unit of blood or a unit of stored blood;

b. applying said blood sample to a capillary network device (CND), wherein said capillary network comprises at least one unbranched microchannel of a variable cross-sectional width ranging in size from 3 μ

m to 70 μ

m along its length;

at least one inlet port in communication with said capillary network microchannel for sample entry; and

at least one outlet port in communication with said capillary network microchannel for sample exit; and

wherein said variable cross-sectional width is oriented along the longitudinal axis of said unbranched microchannel and comprises two or more expanded regions separated by a spacer, or two or more expanded regions separated by a spacer and a gradual taper having an initial width greater than a final width;

wherein said gradual taper has a taper length ranging from 5 to 100 μ

m; and

c. measuring RBC deformability in said blood sample and comparing said RBC deformability to a predetermined value; and

d. selecting said unit of blood for extended storage or selecting said unit of stored blood for transfusion into a patient in need of a unit of blood.

24. The method of claim 23, wherein said measure of RBC deformability is selected from the group consisting of the flow rate through a CND measured at an inlet port or an outlet port, the number of plugging events of individual microchannels in a CND, the plugging frequency of individual microchannels in a CND, the overall flow rate through the CND and the flow rates in individual microchannels of CND, an aggregate perfusion index comprising the overall flow rate through the CND and the flow rates in individual microchannels of CND, the overall RBC flux through a CND, the RBC flux through individual microchannels of a CND, and the aggregate index comprising the RBC flux measured in various channels of a CND.

25. The method of claim 23, wherein said CND comprises at least one unbranched microchannel of a variable size along its length;

at least one inlet to the capillary network microchannel for sample entry; and

at least one outlet port from the capillary network microchannel for sample exit.

29. The method of claim 23, wherein said capillary network comprises a constant depth ranging from 1 μ

m to 25 μ

m.