System for assessing the efficacy of stored red blood cells using microvascular networks

• US 8,828,226 B2
• Filed: 04/14/2009
• Issued: 09/09/2014
• Est. Priority Date: 03/01/2003
• Status: Active Grant

• Current Assignee: Trustees of Boston University
• Original Assignee: Trustees of Boston University
• Inventors: Bitensky, Mark, Shevkoplyas, Sergey, Yoshida, Tatsuro
• Primary Examiner(s): Menon, Krishnan S
• Application Number:
  US12/386,108
• Publication Number:
  US 20090269837A1
• Time in Patent Office: 1,974 Days
• Field of Search: None
• US Class Current: 210/321.6
• CPC Class Codes: B01D 63/088 Microfluidic devices comprising semi-permeable flat membranes
• CPC Class Codes: B01L 2200/0647 Handling flowable solids, e.g. microscopic beads, cells, particles
• CPC Class Codes: B01L 2300/0861 Configuration of multiple channels and/or chambers in a single devices
• CPC Class Codes: B01L 2300/123 Flexible; Elastomeric
• CPC Class Codes: B01L 2400/0439 ultrasonic vibrations, vibrating piezo elements
• 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: G01N 11/08 by measuring pressure required to produce a known flow
• CPC Class Codes: G01N 33/80 involving blood groups or blood types or red blood cells white blood cells G01N33/56972
• CPC Class Codes: Y10S 707/99945 Object-oriented database structure processing
• CPC Class Codes: Y10S 707/99948 Application of database or data structure, e.g. distributed, multimedia, or image

Abstract

A system for assessing the microvascular fitness of a sample of stored red blood cells. The system has a network device having at least one network unit. The network unit has a single inlet and a single outlet for the sample and a plurality of microchannels. The plurality of microchannels receive the sample from the single inlet and drain the sample into the single outlet. The network unit includes an aspiration pressure means for providing movement of liquid sample through the at least one network unit. The system further includes an analysis unit that receives the network device therein. The analysis unit includes a sensor for capturing measurements related to the sample and a processor capable of comparing the captured measurements to measurements stored in a database of healthy red blood cells to determine the microvascular fitness of the stored red blood cells.

Claims

1. A system comprising:

a network device comprising;

an inlet;

an outlet;

at least one network unit in fluid communication with said inlet and said outlet comprising a plurality of microchannels,

wherein said plurality of microchannels comprises

i) at least one parent microchannel branching into two daughter microchannels of unequal diameter or width, at least one of said two daughter microchannels branching at an angle from approximately 20°

to approximately 80°

, measured relative to the axis of said at least one parent channel, and

ii) at least one converged microchannel converging from two microchannels at an angle from approximately 20°

to approximately 80°

, measured relative to the axis of said at least one converged microchannel;

and

an analysis device comprising;

one or more sensors configured to capture measurements related to a sample of blood cells flowing from said inlet to said outlet when said system is in use; and

a processor comprising a memory device for determining the microvascular fitness of said sample of blood cells based on said measurements.

2. The system of claim 1, wherein each of said two daughter channels bifuricates from said at least one parent microchannel at an angle from approximately 20°

to approximately 80°

.

3. The system of claim 1, wherein each of said two microchannels converges at an angle from approximately 20°

to approximately 80°

to said converged channel.

4. The system of claim 1, wherein said measurements are selected from the group consisting of overall flow rate, microchannel flow rate, tube hematocrit, and any combinations thereof.

5. The system of claim 4, wherein said overall flow rate is determined by measuring flow rate of said sample of blood cells at said inlet and at said outlet of said at least one network device.

6. The system of claim 4, wherein said microchannel flow rate is measured in one or more of said plurality of microchannels.

7. The system of claim 4, wherein said hematocrit is measured in one or more of said plurality of microchannels.

8. The system of claim 1, wherein said network device is formed of at least one material selected from the group consisting of:

glass, plastic, polymer, metal, ceramic, organic material, inorganic material, and any combinations thereof.

9. The system of claim 1, wherein each of said plurality of microchannels has a diameter or width in the range between about 6 μ

m to about 63 μ

m.

10. The system of claim 1, wherein said sample of blood cells is selected from the group consisting of fresh whole blood, fresh leukoreduced blood, fresh leukoreduced and platelet reduced blood, fresh platelet reduced blood, fresh white blood cells, fresh packed white blood cells, fresh red blood cells, fresh packed red blood cells, stored whole blood, stored leukoreduced blood, stored leukoreduced and platelet reduced blood, stored platelet reduced blood, stored white blood cells, stored packed white blood cells, stored red blood cells, and stored packed red blood cells.

11. The system of claim 10, wherein said sample of blood cells is selected from the group consisting of fresh whole blood, fresh red blood cells, fresh packed red blood cells, stored whole blood, stored red blood cells, and stored packed red blood cells.

12. The system of claim 1, wherein said memory device is further configured to store measurement data of overall flow rate, microchannel flow rate, and tube hematocrit for comparison to said sample of blood cells.

13. The system of claim 1, wherein said one or more sensors is selected from the group consisting of a camera, a pair of photodiodes, an ultrasonic transducer, and combinations thereof, for obtaining images of said sample of blood cells flowing from said inlet to said outlet in said plurality of microchannels when said system is in use.

14. The system of claim 1, wherein said plurality of microchannels comprises dimensionally homogenous cross-sections along any one of said microchannels.

15. The system of claim 1, wherein said plurality of microchannels comprises dimensionally heterogeneous cross-sections along any one of said microchannels.

16. The system of claim 1, wherein said network device further comprises a substrate.

35. The system of claim 1, further comprising a narrow band pass filter for measuring the hematocrit of said sample of red blood cells.

36. The system of claim 1, wherein said one or more sensors is selected from the group consisting of a photodiode, an ultrasonic transducer, and combinations thereof, for measuring the average velocity of said sample of red blood cells in said plurality of microchannels.

37. The system of claim 1, wherein said angle is 45°

.

17. A method for assessing the microvascular fitness of a sample of blood cells comprising:

obtaining and storing measurements from a plurality of samples of healthy blood cells;

flowing a sample of blood cells through a network device and sensing measurements related to said sample of blood cells with an analysis device; and

comparing measurements obtained from said plurality of samples of healthy blood cells to measurements derived from said sample of blood cells with said analysis device to determine the microvascular fitness of said sample of blood cells,

wherein said network device comprises;

an inlet;

an outlet;

at least one network unit in fluid communication with said inlet and said outlet comprising a plurality of microchannels,

wherein said plurality of microchannels comprises

i) at least one parent microchannel branching into two daughter microchannels of unequal diameter or width, at least one of said two daughter microchannels branching at an angle from approximately 20°

to approximately 80°

, measured relative to the axis of said at least one parent channel, and

ii) at least one converged microchannel converging from two microchannels at an angle from approximately 20°

to approximately 80°

, measured relative to the axis of said at least one converged microchannel, and

wherein said analysis device comprises;

one or more sensors configured to capture measurements related to said sample of blood cells flowing from said inlet to said outlet; and

a processor comprising a memory device for determining the microvascular fitness of said sample of blood cells based on said measurements.

18. The method of claim 17, wherein said obtaining is flowing said plurality of samples of healthy blood cells through said network device and sensing said measurements from a plurality of samples of healthy blood cells with said analysis device.

19. The method of claim 18,

wherein said one or more sensors comprises a sensor that captures images of said sample of blood cells flowing in said network devices;

said analysis device stores said images; and

said processor accesses said images from said storage device and calculates measurement derived from said images of said healthy blood cells and said stored blood cells.

20. The method of claim 19, wherein each of said two daughter channels bifuricates from said at least one parent microchannel at an angle from approximately 20°

to approximately 80°

.

21. The method of claim 19, wherein each of said two microchannels converges at an angle from approximately 20°

to approximately 80°

to a convergent channel.

22. The method of claim 17, wherein said measurements from said plurality of samples of healthy blood cells and said sample comprise overall flow rate, microchannel flow rate and tube hematocrit.

23. The method of claim 22, wherein said overall flow rate is determined by measuring flow rate of said sample at said inlet and at said outlet of said network device.

24. The method of claim 22, wherein said microchannel flow rate is measured in one or more of said plurality of microchannels.

25. The method of claim 22, wherein said hematocrit is measured in one or more of said plurality of microchannels.

26. The method of claim 19, wherein said one or more sensors is selected from the group consisting of a camera, a pair of photodiodes, an ultrasonic transducer, and combinations thereof, for obtaining images of said flowing sample in said plurality of microchannels.

27. A device comprising:

at least one network unit comprising

a single inlet;

a single outlet; and

a plurality of microchannels receiving a sample from said single inlet and drains said sample into said single outlet;

and

a substrate disposed beneath said at least one network unit,

wherein said plurality of microchannels comprises i) at least one parent microchannel that branching into two daughter microchannels of unequal diameter or width, at least one of said two daughter microchannels branching at an angle from approximately 20°

to approximately 80°

, measured relative to the axis of said at least one parent microchannel, and ii) at least one converged microchannel converging from of two daughter microchannels at an angle from approximately 20°

to approximately 80°

, measured relative to the axis of said at least one converged microchannel.

28. The device of claim 27, wherein said plurality of microchannels has a diameter or width in the range between about 6 μ

m to about 63 μ

m.

29. The device of claim 27, wherein said sample is selected from the group consisting of fresh blood and stored red blood cells.

30. The device of claim 27, wherein said sample is whole blood.

31. The device of claim 27, wherein said sample comprises red blood cells.

32. The method of claim 27, wherein said plurality of microchannels are selected from the group consisting of:

one or more microchannels comprising dimensionally homogeneous cross-sections along said one or more microchannels, one or more microchannels comprising dimensionally heterogeneous cross-sections along said one or more microchannels, and combinations thereof.

33. The device of claim 27, wherein said at least one network unit is a molded network unit.

34. The device of claim 27 being molded from a material selected from the group consisting of:

glass, plastic, polymer, metal, ceramic, organic material, inorganic material, and any combinations thereof.

38. The device of claim 27, wherein said angle is 45°

.