Systems and methods for control of pH and other reactor environment conditions

• US 20050026134A1
• Filed: 09/16/2003
• Published: 02/03/2005
• Est. Priority Date: 04/10/2002
• Status: Abandoned Application

• Current Assignee: BioProcessors Corp.
• Original Assignee: BioProcessors Corp.
• Inventors: Malin, Gennady, Zarur, Andrey J., Miller, Scott E., Rodgers, Seth T., Schreyer, Howard B.
• Application Number:
  US10/664,068
• Publication Number:
  US 20050026134A1
• Time in Patent Office: Days
• US Class Current: 506/14
• CPC Class Codes: B01L 2200/0668 Trapping microscopic beads
• CPC Class Codes: B01L 2200/12 Specific details about manufacturing devices
• CPC Class Codes: B01L 2300/0654 Lenses; Optical fibres
• CPC Class Codes: B01L 2300/0819 Microarrays; Biochips
• CPC Class Codes: B01L 2300/0822 Slides
• CPC Class Codes: B01L 2300/0867 Multiple inlets and one sample wells, e.g. mixing, dilution
• CPC Class Codes: B01L 2300/0874 Three dimensional network
• CPC Class Codes: B01L 2300/0883 Serpentine channels
• CPC Class Codes: B01L 2300/0887 Laminated structure
• CPC Class Codes: B01L 2300/1838 using fluid heat transfer medium
• CPC Class Codes: B01L 2400/046 Chemical or electrochemical formation of bubbles
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 2400/086 using baffles or other fixed flow obstructions
• CPC Class Codes: B01L 3/5025 for parallel transport of multiple samples
• 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: C12M 23/16 Microfluidic devices; Capillary tubes integrated microfluidic structures B01L3/5027; microreactors B01J19/0093
• CPC Class Codes: C12M 29/04 Filters; Permeable or porous membranes or plates, e.g. dialysis
• CPC Class Codes: C12M 41/26 of pH

Abstract

The present invention generally relates to chemical, biological, and/or biochemical reactor chips and other reaction systems such as microreactor systems, as well as systems and methods for constructing and using such devices. In one aspect, a chip or other reaction system may be constructed so as to promote cell growth within it. In certain embodiments, the chips or other reaction systems of the invention include one or more reaction sites. The reaction sites can be very small, for example, with a volume of less than about 1 ml. In one aspect of the invention, a chip is able to detect, measure and/or control an environmental factor such as the temperature, pressure, CO₂ concentration, O₂ concentration, relative humidity, pH, etc. associated with one or more reaction sites, by using one or more sensors, actuators, processors, and/or control systems. In another aspect, the present invention is directed to materials and systems having humidity and/or gas control, for example, for use with a chip. Such materials may have high oxygen permeability and/or low water vapor permeability. The present invention, in still another aspect, generally relates to light-interacting components suitable for use in chips and other reactor systems. These components may include waveguides, optical fibers, light sources, photodetectors, optical elements, and the like.

Claims

1. A method, comprising:

permeating a pH-altering agent into a predetermined reaction site having a volume of less than about 1 ml.

2. A method as in claim 1, wherein the predetermined reaction site is able to maintain at least one living cell.

3. A method as in claim 1, wherein the pH-altering agent comprises ammonia.

4. A method as in claim 1, wherein the pH-altering agent comprises acetic acid.

5. A method as in claim 1, wherein the pH-altering agent is a gas.

6. A method as in claim 1, wherein the pH-altering agent comprises CO₂.

7. A method as in claim 1, wherein the pH-altering agent, when contacted with water, reacts to produce an acid.

8. A method as in claim 7, wherein the pH-altering agent, when contacted with water, reacts to produce carbonic acid.

9. A method as in claim 1, wherein the pH-altering agent, when contacted with water, reacts to produce a base.

10. A method as in claim 1, wherein the pH-altering agent is a liquid.

11. A method as in claim 1, wherein the permeating step comprises permeating the pH-altering agent across a surface defining a portion of a boundary of the predetermined reaction site.

12. A method as in claim 11, wherein the diffusing step comprises permeating at least some of the pH-altering agent across the surface in a time of less than about 10 minutes.

13. A method as in claim 11, wherein the diffusing step comprises permeating at least some of the pH-altering agent across the surface in a time of less than about 5 minutes.

14. A method as in claim 11, wherein the diffusing step comprises permeating at least some of the pH-altering agent across the surface in a time of less than about 3 minutes.

15. A method, comprising:

providing a chip comprising a predetermined reaction site having a volume of less than about 1 ml;

generating an acid or a base proximate the predetermined reaction site; and

contacting the acid or base with a substance within the predetermined reaction site to substantially alter the pH of the substance.

16. A method as in claim 15, wherein the chip is constructed and arranged to maintain at least one living cell at the predetermined reaction site.

17. A method as in claim 15, wherein the contacting step comprises altering the pH by at least 0.3 pH units.

18. A method as in claim 15, wherein the contacting step comprises altering the pH by at least 0.5 pH units.

19. A method as in claim 15, wherein the contacting step comprises altering the pH by at least 1 pH unit.

20. A method as in claim 15, wherein the acid or base comprises ammonia.

21. A method as in claim 15, wherein the acid or base comprises acetic acid.

22. A method as in claim 15, wherein the acid or base comprises carbonic acid.

23. A method as in claim 15, wherein the generating step comprises chemically reacting a precursor to produce the acid or base.

24. A method as in claim 23, wherein the precursor comprises a salt.

25. A method as in claim 23, wherein the generating step comprises thermally decomposing the precursor.

26. A method as in claim 23, wherein the generating step comprises exposing the precursor to energy.

27. A method as in claim 26, wherein the energy comprises electromagnetic energy.

28. A method as in claim 26, wherein the energy comprises electrical energy.

29. A method, comprising:

providing a chip defining at least one compartment, the chip further comprising a predetermined reaction site having a volume of less than about 1 ml; and

permeabilizing a component positioned between the predetermined reaction site and the at least one compartment.

30. A method as in claim 29, wherein the chip is constructed and arranged to maintain at least one living cell at the predetermined reaction site.

31. A method as in claim 29, wherein the permeabilizing step comprises exposing the surface to an agent that increases the permeability of the component.

32. A method as in claim 29, wherein the permeabilizing step comprises increasing the temperature of the component.

33. A method as in claim 29, further comprising allowing an agent to move across the component.

34. A method as in claim 29, further comprising allowing an agent to permeate across the component.

35. A method as in claim 29, further comprising allowing an agent to move from the at least one compartment to the predetermined reaction site.

36. A method as in claim 29, wherein the permeabilizing step comprises increasing the permeability of the component to an agent by at least about 2 orders of magnitude.

37. A method as in claim 29, wherein the permeabilizing step comprises increasing the permeability of the component to an agent by at least about 3 orders of magnitude.

38. A method as in claim 29, wherein the permeabilizing step comprises increasing the permeability of the component to an agent by at least about 4 orders of magnitude.

39. A method as in claim 29, wherein the permeabilizing step comprises decomposing at least a portion of the component.

40. A method as in claim 39, wherein the decomposing step comprises exposing the surface to an agent that decomposes at least a portion of the component.

41. An apparatus, comprising:

a chip comprising a predetermined reaction site having a volume of less than about 1 ml; and

a component separating the predetermined reaction site from a source of a non-pH-neutral composition.

42. An apparatus as in claim 41, wherein the chip is constructed and arranged to maintain at least one living cell at the predetermined reaction site.

43. An apparatus as in claim 41, wherein the component is permeable to a gas.

44. An apparatus as in claim 41, wherein the component is permeable to CO₂.

45. An apparatus as in claim 41, wherein the component is permeable to a liquid.

46. An apparatus as in claim 41, wherein the predetermined reaction site has a volume of less than about 500 microliters.

47. An apparatus as in claim 41, wherein the predetermined reaction site has a volume of less than about 100 microliters.

48. An apparatus as in claim 41, wherein the predetermined reaction site has a volume of less than about 10 microliters.

49. An apparatus as in claim 41, wherein the predetermined reaction site has a volume of less than about 1 microliter.

50. An apparatus as in claim 41, wherein the predetermined reaction site has a maximum dimension of less than about 1 cm.

51. An apparatus as in claim 41, wherein the predetermined reaction site has a maximum dimension of less than about 1 mm.

52. An apparatus as in claim 41, wherein the predetermined reaction site has a maximum dimension of less than about 100 micrometers.

53. An apparatus as in claim 41, wherein the predetermined reaction site has a maximum dimension of less than about 10 micrometers.

54. An apparatus as in claim 41, wherein at least one surface of the predetermined reaction site comprises a polymer.

55. An apparatus as in claim 41, wherein the component is acid-permeable.

56. An apparatus as in claim 41, wherein the component is alkaline-permeable.

57. An apparatus as in claim 41, wherein the component comprises a polymer.

58. An apparatus as in claim 41, wherein the component comprises polydimethylsiloxane.

59. An apparatus as in claim 41, wherein the component comprises a silicone.

60. An apparatus as in claim 41, wherein the component has a permeability of at least about 590 cm³_STP cm/s cm² cmHg to ammonia.

61. An apparatus as in claim 41, wherein the component has a permeability of at least about 500 cm³_STP cm/s cm² cmHg to acetic acid

62. An apparatus, comprising:

a chip comprising a predetermined reaction site having a volume of less than about 1 ml; and

a precursor able to react to form a gaseous agent able to substantially alter the pH of a substance within the predetermined reaction site,

wherein the chip is arranged to allow gaseous non-liquid transport of the agent to the predetermined reaction site.

63. An apparatus as in claim 62, wherein the chip is constructed and arranged to maintain at least one living cell at the predetermined reaction site.

64. An apparatus as in claim 62, wherein the precursor comprises a source of acid gas.

65. An apparatus as in claim 62, wherein the precursor comprises a source of alkaline gas.

66. An apparatus as in claim 62, wherein the precursor comprises CO₂.

67. An apparatus as in claim 62, wherein the precursor comprises a salt.

68. An apparatus as in claim 62, wherein the source comprises a radiation-absorbing material.

69. An apparatus as in claim 62, wherein the source is activatable upon absorption of energy.

70. An apparatus as in claim 69, wherein the source is activatable upon absorption of electromagnetic radiation.

71. An apparatus as in claim 62, wherein the source is activatable at a temperature of at least about 200°

C.

72. An apparatus as in claim 62, wherein the source is activatable at a temperature of at least about 300°

C.

73. An apparatus as in claim 62, wherein the source is activatable at a temperature of at least about 500°

C.

74. An apparatus, comprising:

a chip comprising a predetermined reaction site having a volume of less than about 1 ml; and

a pH-altering agent dispensing unit integrally connected to the chip in fluid communication with the predetermined reaction site.

75. An apparatus as in claim 74, wherein the chip is constructed and arranged to maintain at least one living cell at the predetermined reaction site.

76. An apparatus as in claim 74, wherein the acid or base dispensing unit is able to generate the acid or base.

77. An apparatus as in claim 76, wherein the acid or base dispensing unit is connectable to a source of a precursor of the acid or base.

78. An apparatus as in claim 77, wherein the source of the precursor comprises a source of CO₂.

79. An apparatus as in claim 74, wherein the acid or base dispensing unit is connectable to a source of acid or base.

80. An apparatus, comprising:

a chip comprising a predetermined reaction site having a volume of less than about 1 ml; and

a source of gas integrally connected to the chip.

81. An apparatus as in claim 80, wherein the chip is constructed and arranged to maintain at least one living cell at the predetermined reaction site.

82. An apparatus as in claim 80, wherein the source of gas comprises a precursor compound.

83. An apparatus as in claim 80, wherein the source of gas comprises a salt.

84. An apparatus as in claim 80, wherein the source of gas is able to produce gas upon application of energy thereto.

85. An apparatus as in claim 84, wherein the energy comprises electromagnetic energy.

86. An apparatus as in claim 80, wherein the source of gas comprises at least one sealed compartment.

87. An apparatus as in claim 80, wherein the source of gas is not in fluid communication with the predetermined reaction site.

88. An apparatus as in claim 80, wherein the gas is a non-pH-neutral gas.

89. An apparatus as in claim 80, wherein the gas is an acidic gas.

90. An apparatus as in claim 80, wherein the gas is an alkaline gas.

91. An apparatus as in claim 80, wherein the gas comprises CO₂.

92. An apparatus, comprising:

a chip comprising a predetermined reaction site having a volume of less than about 1 ml; and

a laser waveguide in optical communication with a surface defining the predetermined reaction site.

93. An apparatus as in claim 92, wherein the chip is constructed and arranged to maintain at least one living cell at the predetermined reaction site.

94. A method, comprising:

producing a gas in a chip comprising a predetermined reaction site having a volume of less than about 1 ml by directing a laser at at least a portion of the chip.

95. A method as in claim 94, wherein the chip is constructed and arranged to maintain at least one living cell at the predetermined reaction site.