Reactor mixing

• US 20050287673A1
• Filed: 06/07/2005
• Published: 12/29/2005
• Est. Priority Date: 06/07/2004
• Status: Abandoned Application

• Current Assignee: BioProcessors Corp.
• Original Assignee: BioProcessors Corp.
• Inventors: Benoit, Brian O., Johhson, Timothy J., Zarur, Andrey J., Rodgers, Seth T., Russo, A. Peter
• Application Number:
  US11/147,413
• Publication Number:
  US 20050287673A1
• Time in Patent Office: Days
• US Class Current: 436/34
• CPC Class Codes: B01F 29/322 of two or more containers supported for simultaneous mixing, e.g. for bottles in crates
• CPC Class Codes: B01F 29/60 rotating about a horizontal or inclined axis, e.g. drum mixers
• CPC Class Codes: B01F 33/25 Mixers with loose mixing elements, e.g. loose balls in a receptacle
• CPC Class Codes: B01F 33/251 using balls as loose mixing element
• CPC Class Codes: B01F 33/252 using bubbles as loose mixing element
• CPC Class Codes: B01F 33/30 Micromixers
• CPC Class Codes: B01L 2300/0825 Test strips
• CPC Class Codes: B01L 2300/10 Means to control humidity and/or other gases
• CPC Class Codes: B01L 2400/0409 centrifugal forces
• 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 3/50273 characterised by the means or forces applied to move the fluids micropumps F04B19/006, of the membrane type F04B43/043

Abstract

Immiscible substances, such as gases, solids or liquids may be included within a reaction site container as a mixer of a liquid sample. Movement of the mixer within the container may help suspend or re-suspend cells or other species. Movement of the mixer also may generate shear forces that can affect cellular activity. In some embodiments, movement of the container brings about movement of the mixer. Containers may be mounted to a rotating apparatus in various orientations to achieve different travel paths of the mixer. Varying the rotation rate and/or the relative densities of the mixer and the liquid sample also may affect the mixer travel path.

Claims

1. A method, comprising acts of:

(a) introducing a liquid sample into a reaction site container having a volume of less than about 2 mL and comprising a detection region;

(b) moving a mixer within the liquid sample to mix the liquid, wherein the mixer is freely movable within the container and able to move into the detection region;

(c) moving the mixer outside of the detection region; and

(d) detecting a property of the liquid present in the detection region.

2. A method as in claim 1, wherein the reaction site container is constructed and arranged to maintain at least one living cell.

3. A method as in claim 1, wherein a first gas permeable, liquid vapor impermeable membrane defines a first wall of the container.

4. A method as in claim 1, wherein the mixer is a solid.

5. A method as in claim 1, wherein the mixer is a gas.

6. A method as in claim 1, wherein the mixer is a liquid that is immiscible with the liquid sample.

7. A method as in claim 1, wherein the mixer has a density that is different from the average density of the liquid sample by at least 1%.

8. A method as in claim 1, wherein (d) comprises detecting a property of the liquid while the reaction site container is in a substantially horizontal position.

9. A method as in claim 1, wherein (d) comprises detecting a property of the liquid while the reaction site container is in a substantially vertical position.

10. A method as in claim 1, wherein (c) comprises orienting the container so that the mixer moves to a region outside of the detection region.

11. A method as in claim 10, wherein gravity moves the mixer to a region outside of the detection region.

12. A method as in claim 10, wherein buoyancy moves the mixer to a region outside of the detection region.

13. A method as in claim 10, wherein centrifugal force moves the mixer to a region outside of the detection region.

14. A method as in claim 1, wherein (c) comprises applying a force to the mixer so that the mixer moves to a region outside of the detection region.

15. A method as in claim 14, wherein (c) comprises applying a magnetic force to the mixer.

16. A method as in claim 5 wherein (c) comprises orienting the container so that the mixer moves to a region outside of the detection region.

17. A method as in claim 16, wherein the mixer moves to a gas containing region.

18. A method as in claim 5, wherein moving the gas outside of the detection region comprises moving the gas into a predetermined gas region in fluid communication with the reaction site container.

19. A method as in claim 1, wherein (c) comprises determining the location of the mixer.

20. A method as in claim 19, wherein (d) comprises detecting the property of the liquid in a region exclusive of the location of the mixer.

21. A method as in claim 1, wherein (c) further comprises determining whether the mixer is present within the detection region.

22. A method as in claim 1, wherein (b) comprises revolving the container around an axis that does not pass through the container.

23. A method as in claim 22, wherein revolving the container comprises rotating an apparatus to which the container is attached.

27. A method as in claim 1, wherein the liquid sample comprises dissolved species.

28. A method as in claim 1, wherein the liquid sample comprises suspended species.

29. A method as in claim 28, wherein the suspended species comprises cells.

30. A method as in claim 1, further comprising performing (a) through (d) for a plurality of reactors contained on a chemical, biological, or biochemical reactor chip.

31. A method as in claim 1, further comprising impeding the movement of a substance toward the detection region in the presence of a different, immiscible substance.

32. A method as in claim 5, further comprising:

(e) impeding movement of the gas into the detection region.

33. A method as in claim 32, wherein (e) comprises positioning a physical barrier within the container.

34. A method as in claim 1, wherein (b) comprises rotating the container around an axis that passes through the container.

35. A method as in claim 1, wherein introducing a liquid into the chip comprises accessing the inlet port via penetrating a self-sealing elastomeric material defining a portion of the inlet port.

36. A method as in claim 1, further comprising an inlet port and an outlet port, each in fluid communication with the reaction site container.

24. A method as in clam 23, wherein the container is attached to the apparatus in a substantially radial orientation.

25. A method as in clam 23, wherein the container is attached to the apparatus in a substantially vertical orientation.

26. A method as in clam 23, wherein the container is attached to the apparatus in a substantially horizontal orientation.

37. An apparatus comprising:

a chemical, biological, or biochemical reactor chip comprising a reaction site container having a volume of less than about 2 mL, the container comprising a detection region;

a volume of a liquid sample within the container;

a mixer for mixing the liquid sample, the mixer freely movable within the container in at least one container orientation; and

an impediment within the reaction site container constructed and arranged to limit the presence of the mixer within the detection region.

38. An apparatus as in claim 37, wherein the chip is able to maintain at least one living cell.

39. An apparatus as in claim 38, wherein the at least one living cell is mammalian.

40. An apparatus as in claim 37, further comprising a first gas permeable, liquid vapor impermeable membrane that defines a first wall of the container.

41. An apparatus as in claim 37, wherein the container has a volume of less than about 1 mL.

42. An apparatus as in claim 37, wherein the mixer is a gas bubble.

43. An apparatus as in claim 37, wherein the chip further comprises a predetermined gas region in fluid communication with the container.

44. An apparatus as in claim 43, wherein the mixer is positionable in the predetermined gas region when the mixer is not positioned in the detection region.

45. An apparatus as in claim 37, further comprising a self-sealing elastomeric material defining portions of the inlet and outlet ports.

46. An apparatus as in claim 37, wherein the container is defined by a void in a substrate layer.

47. An apparatus as in claim 46, wherein an adhesive layer binds the gas permeable, liquid vapor impermeable membrane to the substrate layer.

48. An apparatus as in claim 47, wherein the impediment is formed in the adhesive layer.

49. A method, comprising acts of:

(a) introducing a liquid sample into a reaction site container having a volume of less than about 2 mL, the reaction site container comprising a detection region and an impediment within the reaction site container;

(b) orienting the container in a first orientation that causes the mixer to move within the detection region to mix the liquid;

(c) orienting the container in a second orientation that causes the mixer to move outside of the detection region;

(d) orienting the container into a detection orientation in which the mixer is impeded from moving into the detection region by the impediment; and

(e) detecting a property of the liquid present in the detection region.

50. A method as in claim 49, wherein the reaction site container is constructed and arranged to maintain at least one living cell.

51. A method as in claim 49, wherein a first gas permeable, liquid vapor impermeable membrane defines a first wall of the reaction site container.

52. A method as in claim 51, where the reaction container further comprises a second gas permeable, liquid vapor impermeable membrane defining a second wall of the reaction site container.

53. A method as in claim 49, wherein the second orientation is a substantially vertical orientation.

54. A method as in claim 49, further comprising (f) orienting the reaction site container such that the mixer returns to the detection region.

55. A method as in claim 49, wherein the mixer is a gas bubble.

56. An apparatus as in claim 49, wherein the reaction site container is defined by a void in a substrate layer.

57. An apparatus as in claim 56, wherein an adhesive layer binds a gas permeable, liquid vapor impermeable membrane to the substrate layer.

58. An apparatus as in claim 50, wherein the impediment is formed in the adhesive layer.