Method and apparatus for determining one or more operating parameters for a microfluidic circuit

• US 20060046300A1
• Filed: 09/02/2004
• Published: 03/02/2006
• Est. Priority Date: 09/02/2004
• Status: Active Grant

• Current Assignee: Honeywell International Inc.
• Original Assignee: Honeywell International Inc.
• Inventors: Padmanabhan, Aravind, Reutiman, Peter, Cabuz, Eugen I.
• Granted Patent: US 8,329,118 B2
• Time in Patent Office: Days
• US Class Current: 436/55
• CPC Class Codes: B01L 2200/0621 Control of the sequence of chambers filled or emptied
• CPC Class Codes: B01L 2300/021 Identification, e.g. bar codes
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• 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: G05D 7/0694 by action on throttling means or flow sources of very small size, e.g. microfluidics microvalves F16K99/0001; microstructural devices per se B81B
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
• CPC Class Codes: Y10T 137/0318 Processes
• CPC Class Codes: Y10T 137/0391 Affecting flow by the addition of material or energy
• CPC Class Codes: Y10T 137/0396 Involving pressure control
• CPC Class Codes: Y10T 137/8593 Systems
• CPC Class Codes: Y10T 137/85978 With pump
• CPC Class Codes: Y10T 436/12 Condition responsive control

Abstract

Methods for determining one or more operating parameters for a timing protocol of a microfluidic circuit are provided. In some embodiments, wet out times are measured for certain flow channels, and start times, flow rates and/or other parameters are calculated so that the various fluids in the microfluidic cartridge arrive at certain locations at a desired time and/or in a desired sequence. To help compensate for process variations, one or more fluidic process monitor components/structures may be fabricated along with the functional components/structures of a microfluidic cartridge. Test may be performed on the process monitor components/structures to help identify process variations in the particular microfluidic cartridge at hand. By using the process monitor data, the timing protocol for a particular microfluidic cartridge may be made more accurate.

Claims

1. A method for determining a control sequence of flow through two or more flow channels in a microfluidic cartridge, the two or more flow channels being fluidly connected in an intersection region, which is fluidly connected to a downstream flow channel, the method comprising the steps of:

measuring a first wet out time to move a fluid through a first one of the flow channels along a first length to a first designated location;

measuring a second wet out time to move a fluid through a second one of the flow channels along a second length to a second designated location; and

using at least the first wet out time and the second wet out time to determine a first start time for the first one of the flow channels and a second start time for the second one of the flow channels such that the fluid from the first flow channel flows through the intersection region in a predetermined sequence relative to the fluid from the second flow channel.

2. The method of claim 1 wherein the fluid from the first flow channel flows through the intersection region before the fluid from the second flow channel.

3. The method of claim 1 wherein the fluid from the first flow channel flows through the intersection region after the fluid from the second flow channel.

4. The method of claim 1 wherein the fluid from the first flow channel flows through the intersection region at substantially the same time as the fluid from the second flow channel.

5. The method of claim 1 wherein the first wet out time is measured using a first flow rate and the second wet out time is measured using a second flow rate.

6. The method of claim 5 wherein first flow rate is different from the second flow rate.

7. The method of claim 5 wherein first flow rate is the same or substantially the same as the second flow rate.

8. The method of claim 5 wherein the first flow rate is higher than the second flow rate, and wherein the fluid from the first flow channel flows through the intersection region before the fluid from the second flow channel.

9. The method of claim 5 wherein the first flow rate and the second flow rate are provided by one or more pressure sources.

10. The method of claim 9 wherein at least one of the one or more pressure sources is controlled by one or more valves.

11. The method of claim 9 wherein the first flow rate and the second flow rate are provided by one or more volume driven sources.

12. The method of claim 11 wherein the at least one of the volume driven sources includes a syringe pump.

13. The method of claim 12 wherein the syringe pump is controlled by one or more electrical signals.

14. The method of claim 1 wherein the first one of the flow channels includes an inner surface, and wherein a first part of the inner surface is hydrophobic and a second part of the inner surface is hydrophilic.

15. The method of claim 14 wherein the second one of the flow channels includes an inner surface, and wherein a first part of the inner surface is hydrophobic and a second part of the inner surface is hydrophilic.

16. The method of claim 1 wherein the intersection region is configured so that the fluid from the first flow channel flows circumferentially around the fluid from the second flow channel when fluid from both the first and second flow channels is flowing through the intersection region.

17. The method of claim 16 wherein the fluid from the first flow channel flows through the intersection region before the fluid from the second flow channel.

18. The method of claim 1 wherein the first wet out time and the second wet out time are measured when fluid is simultaneously flowing through both the first flow channel and the second flow channel.

19. The method of claim 18 further comprises the step of checking whether there is a backflow in the first flow channel and/or the second flow channel.

20. The method of claim 18 further comprises the step of checking whether there is a stop flow in the first flow channel and/or the second flow channel.

21. The method of claim 18 further comprises the step of checking whether there are bubbles in the first flow channel, the second flow channel and/or the intersection region.

22. The method of claim 18 further comprises the step of checking whether there is a backflow, a stop flow and/or bubbles in the first flow channel, the second flow channel and/or the intersection region, and if so, changing the first start time and/or second start time.

23. The method of claim 1 wherein the microfluidic cartridge is used for cytometry, hematology, blood chemistry analysis, urinalysis, and/or blood gas analysis.

24. The method of claim 1 wherein the fluid that passes through the first one of the flow channels is a first color, and the fluid that passes through the second one of the flow channels is a second color.

25. The method of claim 24 wherein the first color and/or second color is provided by a fluorescein dye.

26. A method for controlling the flow of fluid through a microfluidic cartridge, wherein the microfluidic cartridge includes two or more flow channels, wherein the two or more flow channels are fluidly connected at an intersection region, which is fluidly connected to a downstream flow channel, the method comprising the steps of:

causing flow of a fluid in a first flow channel;

slowing or stopping the flow of the fluid in the first flow channel when the fluid is at a predetermined location relative to the intersection region;

causing the fluid in the second flow channel to pass through the intersection region; and

causing the flow of the fluid in the first flow channel to flow through the intersection region.

27. The method of claim 26 wherein a first pressure source is used to cause the fluid to flow in the first flow channel.

28. The method of claim 27 wherein the pressure provided by the first pressure source is controlled by one or more valves.

29. The method of claim 27 wherein the pressure provided by the first pressure source is controlled by one or more electrical signals.

30. The method of claim 26 wherein the first pressure source is a volume driven source.

31. The method of claim 26 wherein a second pressure source is used to cause the fluid to flow in the second flow channel.

32. The method of claim 31 wherein the pressure provided by the second pressure source is controlled by one or more valves.

33. The method of claim 31 wherein the pressure provided by the second pressure source is controlled by one or more electrical signals.

34. The method of claim 31 wherein the second pressure source is a volume driven source.

35. The method of claim 26 wherein the predetermined location is before the intersection region.

36. The method of claim 26 wherein the predetermined location is at or substantially at the intersection region.

37. The method of claim 26 wherein the predetermined location past the intersection region.

38. The method of claim 26 further comprising the step of slowing or stopping the flow of the fluid in the second flow channel when the fluid is before the intersection region prior to causing the fluid in the second flow channel to pass through the intersection region.

39. A method for controlling the flow of fluid through a microfluidic cartridge, wherein the microfluidic cartridge includes two or more flow channels, wherein the two or more flow channels are fluidly connected at an intersection region, which is fluidly connected to a downstream flow channel, the method comprising the steps of:

causing flow of a fluid in a first flow channel at a first flow rate;

causing flow of a fluid in a second flow channel at a second flow rate; and

increasing the flow rate of the fluid in the first flow channel when the fluid in the first flow channel reaches or substantially reaches a first predetermined location.

40. The method of claim 39 further comprising the step of:

increasing the flow rate of the fluid in the second flow channel when the fluid in the second flow channel reaches or substantially reaches a second predetermined location.

41. The method of claim 40 wherein the first predetermined location and the second predetermined location correspond to a location before the intersection region.

42. The method of claim 40 wherein the first predetermined location and the second predetermined location correspond to a location after the intersection region.

43. The method of claim 40 wherein the first predetermined location and the second predetermined location correspond to a location that is at or substantially at the intersection region.

44. The method of claim 40 wherein the first predetermined location corresponds to a location that is before the intersection region and the second predetermined location corresponds to a location that is at or after the intersection region.

45. A microfluidic cartridge, comprising:

one or more functional elements that are used during normal functional operation of the microfluidic cartridge; and

at least one test element having a test interface, the at least one test element fabricated along with the one or more functional elements but not used during normal functional operation of the microfluidic cartridge.

46. The microfluidic cartridge of claim 45 wherein the at least one test element is the same or substantially the same as at least part of one of the one or more functional elements, and is used to measure at least one characteristic of the at least one test element.

47. The microfluidic cartridge of claim 45 wherein the microfluidic cartridge includes a fluidic process monitor region, and wherein the at least one test element is located in the fluidic process monitor region.

48. The microfluidic cartridge of claim 45 wherein one of the one or more functional elements includes a functional flow channel, and the at least one test element includes a test flow channel that has the same or substantially the same cross-section as the functional flow channel.

49. The microfluidic cartridge of claim 45 wherein one of the one or more functional elements includes two or more functional flow channels that are fluidly connected at a functional intersection region, and the at least one test element includes two or more test flow channels that are fluidly connected at a test intersection region.

50. The microfluidic cartridge of claim 45 wherein the microfluidic cartridge includes three or more layers, with a functional flow channel traversing between two or more of the layers, the microfluidic cartridge further having a test flow channel traversing between the same two or more of the layers.

51. The microfluidic cartridge of claim 45 wherein one of the one or more functional elements includes a functional reservoir for storing a fluid, and the at least one test element includes a test reservoir that has the same or substantially the same cross-section as the functional reservoir.

52. The microfluidic cartridge of claim 45 wherein one of the one or more functional elements includes a functional valve, and the at least one test element includes a test valve that is identical or substantially identical to the functional valve.

53. The microfluidic cartridge of claim 46 further comprising a machine readable indicia, wherein the machine readable indicia represents the at least one characteristic of the at least one test element.

54. The microfluidic cartridge of claim 53 wherein the machine readable indicia can be optically read.

55. The microfluidic cartridge of claim 53 wherein the machine readable indicia can be magnetically read.

56. The microfluidic cartridge of claim 47 wherein the fluidic process monitor region is separatable from the remainder of the microfluidic cartridge.

57. A method for characterizing a microfluidic cartridge, the method comprising:

providing one or more test elements on the microfluidic cartridge, wherein the one or more test elements are fabricated along with a functional part of the microfluidic cartridge;

performing one or more tests using the one or more test elements to generate characterization data for at least part of the functional part of the microfluidic cartridge.

58. The method of claim 57 further comprising the step of:

operating the microfluidic cartridge using a microfluidic cartridge reader, wherein one or more operating parameters of the microfluidic cartridge reader are changed in response to the characterization data.

59. The method of claim 57 further comprising the step of recording at least some of the characterization data on the microfluidic cartridge.

60. The method of claim 57 further comprising the step of recording at least some of the characterization data on a tab that is secured to the microfluidic cartridge.

61. The method of claim 60 wherein the characterization data on the tab is adapted to be machine readable.

62. A microfluidic cartridge, comprising:

a microfluidic circuit;

a machine readable indicia, the machine readable indicia including one or more performance characteristics of at least part of the microfluidic cartridge, wherein the one or more performance characteristics are determined by making one or more measurements on one or more test elements that are fabricated along with the microfluidic cartridge.

63. A method for operating a microfluidic cartridge reader, the method comprising the steps of:

receiving a microfluidic cartridge having a fluidic circuit;

reading one or more indicia from the microfluidic cartridge, wherein the one or more indicia include one or more performance characteristics of at least part of the microfluidic cartridge, wherein at least some of the one or more performance characteristics are determined by making one or more measurements on one or more test elements that are fabricated along with the microfluidic cartridge;

changing one or more operating parameters of the microfluidic cartridge reader in response to the information read; and

operating the microfluidic cartridge reader using the changed operating parameters.

64. The method of claim 63 wherein the indicia are optically read.

65. The method of claim 63 wherein the indicia are magnetically read.

66. The method of claim 63 wherein at least some of the one or more performance characteristics are unique to the particular microfluidic cartridge.