Acoustic determination of properties of reservoirs and of fluids contained therein

• US 20050092058A1
• Filed: 09/20/2004
• Published: 05/05/2005
• Est. Priority Date: 12/04/2001
• Status: Active Grant

• Current Assignee: Labcyte, Inc. (Danaher Corporation)
• Original Assignee: Labcyte, Inc. (Danaher Corporation)
• Inventors: Ellson, Richard N., Stearns, Richard G.
• Granted Patent: US 7,454,958 B2
• Time in Patent Office: Days
• US Class Current: 73/1.82
• CPC Class Codes: B01J 2219/00362 Acoustic nozzles
• CPC Class Codes: B01J 2219/00702 Processes involving means for analysing and characterising the products
• CPC Class Codes: B01L 2200/143 Quality control, feedback systems
• CPC Class Codes: B01L 2300/0819 Microarrays; Biochips
• CPC Class Codes: B01L 2400/0436 acoustic forces, e.g. surface acoustic waves [SAW]
• CPC Class Codes: B01L 2400/0439 ultrasonic vibrations, vibrating piezo elements
• CPC Class Codes: B01L 3/0268 using pulse dispensing or spraying, eg. inkjet type, piezo actuated ejection of droplets from capillaries
• CPC Class Codes: C40B 60/14 for creating libraries
• CPC Class Codes: G01F 23/296 Acoustic waves
• CPC Class Codes: G01F 23/2968 Transducers specially adapted for acoustic level indicators
• CPC Class Codes: G01N 2035/00158 Elements containing microarrays, i.e. "biochip"
• CPC Class Codes: G01N 2291/02818 Density, viscosity
• CPC Class Codes: G01N 2291/02836 Flow rate, liquid level
• CPC Class Codes: G01N 2291/02881 Temperature
• CPC Class Codes: G01N 2291/2695 Bottles, containers
• CPC Class Codes: G01N 29/02 Analysing fluids using acoustic emission techniques G01N29/14 ; constructional or flow details for analysing fluids G01N29/222; optoacoustic fluid cells G01N29/2425
• CPC Class Codes: G01N 29/22 Details , e.g. general constructional or apparatus details
• CPC Class Codes: G01N 29/222 Constructional or flow details for analysing fluids optoacoustic fluid cells G01N29/2425
• CPC Class Codes: G01N 29/28 providing acoustic coupling , e.g. water impedance matching G10K11/02
• CPC Class Codes: G01N 35/1016 Control of the volume dispensed or introduced

Abstract

The invention provides devices and methods for acoustically determining the properties of the contents of one or more reservoirs in a plurality of reservoirs. Each reservoir is adapted to contain a fluid. An acoustic radiation generator can be positioned in acoustic coupling relationship to each of the reservoirs. Acoustic radiation generated by the acoustic radiation generator is transmitted through each reservoir to an analyzer. The analyzer is capable of analyzing a characteristic of the transmitted acoustic radiation and optionally correlating the characteristic to a property of the reservoirs'"'"' contents. Properties that may be determined include volume, temperature, and composition. The invention is particularly suited to determining the properties of the contents of a plurality of reservoirs to allow for accuracy and control over the dispensing of fluids therefrom.

Claims

1. A method for acoustically determining a temperature-dependent property of a fluid in a reservoir, the reservoir being integral with or located on a substrate, the method comprising:

(a) acoustically coupling an acoustic radiation generator and the reservoir, with the acoustic radiation generator located external to the reservoir;

(b) activating the acoustic radiation generator to generate acoustic radiation and direct the acoustic radiation generated into and through the substrate toward the reservoir, such that the acoustic radiation is transmitted into the fluid in the reservoir and thereafter reflected from an interior surface of the reservoir;

(c) measuring a temperature-dependent characteristic of the reflected acoustic radiation, said characteristic selected so as to correlate with a temperature-dependent property of the fluid; and

(d) analyzing the characteristic to determine the temperature-dependent property of the fluid.

2. The method of claim 1, wherein the interior surface of the reservoir is an interface between the fluid and an interior surface of the reservoir.

3. The method of claim 2, wherein the temperature (T_F1) of the fluid is lower than 20°

C. or greater than 25°

C.

4. The method of claim 3, wherein the temperature-dependent characteristic of the reflected acoustic radiation is the acoustic velocity V_F1 in the fluid at temperature T_F1.

5. The method of claim 4, wherein (d) comprises comparing V₁ with the acoustic velocity V_F-RT of the fluid at a temperature T_RT in the range of 20°

C. to 25°

C.

6. The method of claim 5, wherein (d) further comprises deriving from the difference between V_F1 and V_F-RT the difference between the acoustic impedance Z_F1 of the fluid at temperature T_F1 and the acoustic impedance Z_F-RT of the fluid at temperature T_RT.

7. The method of claim 6, wherein the temperature-dependent property is the composition of the fluid, and (d) further comprises determining the composition of the fluid in the reservoir from Z_F1 and Z_F-RT.

8. The method of claim 7, wherein the fluid in the reservoir is at least partially nonsolid.

9. The method of claim 7, wherein the fluid in the reservoir comprises at least one liquid.

10. The method of claim 9, wherein the fluid in the reservoir comprises a combination of miscible, partially miscible, or immiscible liquids.

11. The method of claim 10, wherein the fluid in the reservoir comprises a mixture of an organic solvent and an aqueous solvent.

12. The method of claim 11, wherein the fluid in the reservoir comprises a mixture of dimethylsulfoxide (DMSO) and water.

13. The method of claim 12, wherein the mixture contains more than 40 vol. % DMSO.

14. The method of claim 12, wherein the mixture contains more than 40 vol. % water.

15. The method of claim 1, wherein the reservoir is integral with a substrate.

16. The method of claim 15, wherein the reservoir is an individual container.

17. The method of claim 16, wherein the container is enclosed.

18. The method of claim 16, wherein the reservoir is a tube.

19. The method of claim 1, wherein the reservoir is one of a plurality of reservoirs, each reservoir being integral with or located on a substrate.

20. The method of claim 19, wherein the reservoirs are integral with a substrate.

21. The method of claim 20, wherein the substrate is a well plate and each reservoir is a well therein.

22. The method of claim 19, wherein steps (a) through (d) are repeated successively for additional reservoirs.

23. The method of claim 22, wherein steps (a) through (d) are repeated successively for each additional reservoir.

24. The method of claim 23, wherein steps (a) through (d) are repeated at a rate of at least 96 reservoirs per minute.

25. The method of claim 24, wherein steps (a) through (d) are repeated at a rate of at least about 384 reservoirs per minute.

26. The method of claim 25, wherein steps (a) through (d) are repeated at a rate of at least about 1536 reservoirs per minute.

27. The method of claim 26, wherein steps (a) through (d) are repeated at a rate of at least about 3456 reservoirs per minute.

28. The method of claim 27, wherein steps (a) through (d) are repeated at a rate of at least 10,000 reservoirs per minute.

29. The method of claim 1, wherein the acoustic radiation generated is directed into the reservoir through a region of the reservoir'"'"'s exterior surface having an identifier thereon.

30. The method of claim 29, wherein the identifier is a barcode.

31. A method for acoustically determining a temperature-dependent property of a reservoir material, the method comprising:

(a) acoustically coupling an acoustic radiation generator and the reservoir, with the acoustic radiation generator located external to the reservoir;

(b) activating the acoustic radiation generator to generate acoustic radiation and direct the acoustic radiation generated through an exterior surface of the reservoir toward an interior surface of the reservoir such that acoustic radiation is thereafter reflected from an interior surface of the reservoir;

(c) measuring a temperature-dependent characteristic of the reflected acoustic radiation, said characteristic selected so as to correlate with a temperature-dependent property of the reservoir material; and

(d) analyzing the characteristic to determine the temperature-dependent property of the reservoir material.

32. The method of claim 31, wherein the temperature (T_R1) of the reservoir is lower than 20°

C. or greater than 25°

C.

33. The method of claim 32, wherein the temperature-dependent characteristic of the reflected acoustic radiation is the acoustic velocity V_R1 in the reservoir material at temperature T_R1.

34. The method of claim 33, wherein (d) comprises comparing V_R1 with the acoustic velocity V_R-RT in the reservoir material at a temperature T_RT in the range of 20°

C. to 25°

C.

35. The method of claim 34, wherein (d) further comprises deriving from the difference between V_R1 and V_R-RT the difference between the acoustic impedance Z_R1 of the reservoir material at temperature T_R1 and the acoustic impedance Z_R-RT of the reservoir material at temperature T_RT.

36. The method of claim 31, wherein the reservoir is integral with a substrate.

37. The method of claim 36, wherein the reservoir is an individual container.

38. The method of claim 37, wherein the container is enclosed.

39. The method of claim 36, wherein the reservoir is a tube.

40. The method of claim 31, wherein the reservoir is one of a plurality of reservoirs, each reservoir being integral with or located on a substrate.

41. The method of claim 40, wherein the reservoirs are integral with a substrate.

42. The method of claim 41, wherein the substrate is a well plate and each reservoir is a well therein.

43. The method of claim 42, wherein steps (a) through (d) are repeated successively for additional reservoirs.

44. The method of claim 43, wherein steps (a) through (d) are repeated successively for each additional reservoir.

45. The method of claim 44, wherein steps (a) through (d) are repeated at a rate of at least 96 reservoirs per minute.

46. The method of claim 45, wherein steps (a) through (d) are repeated at a rate of at least about 384 reservoirs per minute.

47. The method of claim 46, wherein steps (a) through (d) are repeated at a rate of at least about 1536 reservoirs per minute.

48. The method of claim 47, wherein steps (a) through (d) are repeated at a rate of at least about 3456 reservoirs per minute.

49. The method of claim 48, wherein steps (a) through (d) are repeated at a rate of at least 10,000 reservoirs per minute.

50. The method of claim 31, wherein the acoustic radiation generated is directed into the reservoir through a region of the reservoir'"'"'s exterior surface having an identifier thereon.

51. The method of claim 50, wherein the identifier is a barcode.

52. A device for acoustically determining a property of a fluid in a reservoir adapted to contain the fluid, the reservoir contained in or disposed on a solid surface of a substrate, the device including

an acoustic radiation generator for generating acoustic radiation;

means for positioning the acoustic radiation generator in an acoustically coupled relationship to the reservoir;

means to actuate the acoustic radiation generator to transmit acoustic radiation through the reservoir to be reflected from an interface between the fluid and the reservoir; and

an analyzer to receive the acoustic radiation reflected from the interface for processing, the analyzer processing the reflected acoustic radiation to determine a characteristic thereof that provides information about a property of the fluid in the reservoir.

53. A temperature-based method for converting reflection amplitude to fluid composition based on the effect of temperature on acoustic impedance for a fluid, the method comprising the steps of

(a) processing a reflected acoustic signal through the material for time-of-flight and amplitude data;

(b) extracting transit time through the material from the data obtained in step (a);

(c) retrieving reference times for material transit from a data reference source;

(d) retrieving the speed of sound as a function of temperature for the material from a data reference source;

(e) processing the data obtained in steps (a)-(d), using a temperature based model for converting reflection amplitude to fluid composition using temperature-based acoustic impedance to determine fluid composition; and

(f) using the data processed in step (e) to determine fluid composition.

54. A method for acoustically determining the properties of a fluid in a reservoir contained in or located on a substrate, the reservoir comprising a solid surface of the substrate and a holding portion adapted to contain a fluid, the method comprising the steps of:

(a) positioning an acoustic radiation generator in acoustic coupling relationship to the reservoir;

(b) actuating the acoustic radiation generator to generate acoustic radiation, then transmitting the generated acoustic radiation through the selected reservoir, to be reflected from an interface of the fluid and the reservoir;

(c) delivering the acoustic radiation reflected from the interface to an analyzer to determine the transit time of acoustic energy through the reservoir;

(d) using the transit time obtained in step (c) provided to the analyzer to determine a property of the fluid in the reservoir.

55. The method of claim 54 wherein the property to be determined for the fluid in the reservoir is temperature.

56. The method of claim 55 wherein the property to be determined for the fluid in the reservoir is fluid composition.

57. The method of claim 54 wherein there are multiple reservoirs contained in, disposed in, or contained on a substrate, and steps (a)-(d) are performed for selected reservoirs on the substrate.

58. The method of claim 57 wherein the property to be determined for the fluid in each of the reservoirs is temperature.

59. The method of claim 58 wherein the property to be determined for the fluid in each of the reservoirs is fluid composition.

60. The method of claim 54 wherein steps (a)-(d) are performed for all of the reservoirs on the substrate.

61. The method of claim 60 wherein the property to be determined for the fluid in each of the reservoirs is temperature.

62. The method of claim 61 wherein the property to be determined for the fluid in each of the reservoirs is fluid composition.

63. The method of claim 54, including the steps of:

(e) positioning an acoustic radiation generator in acoustic coupling relationship to the substrate adjacent to the reservoir;

(f) actuating the acoustic radiation generator to generate acoustic radiation, then transmitting the generated acoustic radiation through the substrate adjacent to the reservoir, to be reflected from an upper surface of the substrate

(g) delivering the generated acoustic radiation reflected from the upper surface of the substrate adjacent to the reservoir to an analyzer to determine the transit time of reflected acoustic energy through the substrate; and

(h) using the transit time obtained in steps (c) and (g), and provided to the analyzer, to determine a property of the fluid in the reservoir.

64. The method of claim 63 wherein the property to be determined for the fluid in the reservoir is temperature.

65. The method of claim 64 wherein the property to be determined for the fluid in the reservoir is fluid composition.

66. The method of claim 63 wherein there are multiple reservoirs contained in, disposed in, or contained on a substrate, and steps (a)-(h) are performed for selected reservoirs on the substrate.

67. The method of claim 66 wherein the property to be determined for the fluid in each of the reservoirs is temperature.

68. The method of claim 67 wherein the property to be determined for the fluid in each of the reservoirs is fluid composition.

69. The method of claim 63 wherein steps (a)-(h) are performed for all of the reservoirs on the substrate.

70. The method of claim 69 wherein the property to be determined for the fluid in the reservoir is temperature.

71. The method of claim 70 wherein the property to be determined for the fluid in the reservoir is fluid composition.

72. The method of claim 63 wherein step (h) is used to determine a property of the substrate.

73. The method of claim 72 wherein the property to be determined for the substrate is temperature.

74. The method of claim 54, wherein the reservoir is empty, and in step (b′

) the acoustic energy is reflected from an upper surface of the reservoir, in step (c′

) the acoustic radiation reflected from the upper surface of the reservoir is delivered to an analyzer to determine the transit time of acoustic energy through the reservoir, and in step (d′

) the transit time obtained in step (c′

) and provided to the analyzer is used to determine a property of the reservoir.

75. The method of claim 74 wherein the property to be determined for the reservoir is temperature.

76. The method of claim 74 wherein there are multiple reservoirs contained in, disposed in, or contained on a substrate, and steps (a)-(d) are performed for selected reservoirs on the substrate.

77. The method of claim 76 wherein the property to be determined for each of the reservoirs is temperature.

78. The method of claim 74 wherein steps (a)-(d) are performed for all of the reservoirs on the substrate.

79. The method of claim 78 wherein the property to be determined for each of the reservoirs is temperature.

80. The method of claim 74, including the steps of:

(e) positioning an acoustic radiation generator in acoustic coupling relationship to the substrate adjacent to the reservoir;

(f) actuating the acoustic radiation generator to generate acoustic radiation, then transmitting the generated acoustic radiation through the substrate adjacent to the reservoir, to be reflected from an upper surface of the substrate

(g) delivering the generated acoustic radiation reflected from the upper surface of the substrate adjacent to the reservoir to an analyzer to determine the transit time of reflected acoustic energy through the substrate; and

(h) using the transit time obtained in steps (c) and (g), and provided to the analyzer, to determine a property of the reservoir.

81. The method of claim 80 wherein the property to be determined for the reservoir is temperature.

82. The method of claim 80 wherein step (h) is used to determine a property of the substrate.

83. The method of claim 82 wherein the property to be determined for the substrate is temperature.

84. The method of claim 80 wherein there are multiple reservoirs contained in, disposed in, or contained on a substrate, and steps (a)-(h) are performed for selected reservoirs on the substrate.

85. The method of claim 84 wherein the property to be determined for each of the reservoirs is temperature.

86. The method of claim 84 wherein step (h) is used to determine a property of the substrate.

87. The method of claim 86 wherein the property to be determined for the substrate is temperature.

88. The method of claim 80 wherein steps (a)-(h) are performed for all of the reservoirs on the substrate.

89. The method of claim 88 wherein the property to be determined for each of the reservoirs is temperature.

90. The method of claim 88 wherein step (h) is used to determine a property of the substrate.

91. The method of claim 90 wherein the property to be determined for the substrate is temperature.

92. A method for acoustically determining a property of a fluid in a reservoir adapted to contain a fluid, the reservoir contained in or located on a solid surface of a substrate, the method comprising the steps of:

(a) positioning an acoustic radiation generator in acoustic coupling relationship to the reservoir;

(b) actuating the acoustic radiation generator to generate acoustic radiation, then transmitting the generated acoustic radiation through the reservoir, to be reflected from an interface between the fluid and the reservoir;

(c) delivering the acoustic radiation reflected from the interface to an analyzer to determine a characteristic thereof;

(d) selecting the characteristic to be analyzed to provide information about a property of the fluid in the reservoir.

93. A method for acoustically determining the properties of a fluid in a reservoir contained in or located on a substrate, the reservoir comprising a solid surface of the substrate adapted to contain a fluid, the method comprising the steps of:

(a) positioning an acoustic radiation generator in acoustic coupling relationship to the reservoir;

(b) actuating the acoustic radiation generator to generate acoustic radiation, then transmitting the generated acoustic radiation through the substrate and into the reservoir, to be reflected from an interface between the substrate and the reservoir;

(c) delivering the acoustic radiation reflected from the interface to an analyzer for processing; and

(d) processing the reflected acoustic radiation to determine a characteristic thereof that provides information about a property of the fluid in the reservoir.

94. A method for acoustically determining the properties of a substrate wherein a reservoir is contained in or located on the substrate, the reservoir comprising a solid surface of the substrate adapted to contain a fluid, the method comprising the steps of:

(b) positioning an acoustic radiation generator in acoustic coupling relationship to the reservoir;

(c) actuating the acoustic radiation generator to generate acoustic radiation, then transmitting the generated acoustic radiation through the substrate, to be reflected from the fluid in the reservoir;

(d) delivering the acoustic radiation reflected from the fluid in the reservoir to an analyzer to process the fluid-reflected acoustic energy;

(e) positioning an acoustic radiation generator in acoustic coupling relationship to a portion of the substrate adjacent to the selected reservoir;

(f) actuating the acoustic radiation generator to generate acoustic radiation, then transmitting the generated acoustic radiation through the substrate adjacent to the reservoir, to be reflected from a surface of the adjacent substrate

(g) delivering the generated acoustic radiation reflected from the surface of the adjacent substrate to an analyzer to process the substrate reflected acoustic energy;

(h) processing the reflected acoustic energy obtained in steps (d) and (g), provided to the analyzer, to analyze a characteristic thereof, wherein the characteristic selected provides information about a property of the substrate.