Flow sorting system and methods regarding same

• US 20030153085A1
• Filed: 01/10/2003
• Published: 08/14/2003
• Est. Priority Date: 01/10/2002
• Status: Active Grant

• Current Assignee: NeuroBioTex Inc., Board of Regents of the University of Texas System (University of Texas System)
• Original Assignee: NeuroBioTex Inc.
• Inventors: Leary, James F., Frederickson, Christopher J.
• Granted Patent: US 7,452,725 B2
• Time in Patent Office: Days
• US Class Current: 436/63
• CPC Class Codes: G01N 15/01 specially adapted for biological cells, e.g. blood cells investigating sedimentation of particle suspensions in blood G01N15/05
• CPC Class Codes: G01N 15/14 Optical investigation techniques, e.g. flow cytometry
• CPC Class Codes: G01N 15/149 specially adapted for sorting particles, e.g. by their size or optical properties

Abstract

A system and method for sorting of objects that includes a pathway network that has a plurality of pathways and one or more branch points. A fluid composition including one or more objects can be transported through the pathway network, where one or more of the objects are analyzed and sorted at one or more branch points based on the analysis of the objects.

Claims

1. A flow sorting method comprising:

transporting a fluid composition comprising a plurality of objects through a pathway network, wherein the pathway network comprises a plurality of pathways and one or more branch points;

analyzing one or more of the objects in pathway network; and

directing at least one of the plurality of objects through the one or more branch points based on the analysis of the objects.

2. The method of claim 1, wherein transporting the fluid composition comprises repeatedly separating the fluid composition into progressively greater numbers of pathways.

3. The method of claim 1, wherein directing at least one of the plurality of objects through the one or more branch points comprises combining a plurality of objects directed through each of two or more branch points prior to directing the combined objects through a subsequent branch point.

4. The method of claim 1, wherein directing at least one of the plurality of objects through the one or more branch points comprises directing a plurality of objects through a branch point prior to directing at least one object of the plurality of objects through a subsequent branch point.

5. The method of claim 1, wherein analyzing one or more of the objects comprises performing at least one of morphology measurements, luminescence measurements, fluorescence measurements, radioactive measurements, light scattering measurements, electrical measurements, or ultrasound measurements for use in determining one or more characteristics of one or more of the objects.

6. The method of claim 1, wherein analyzing one or more of the objects comprises taking two or more different measurements from the objects being analyzed.

7. The method of claim 1, wherein analyzing one or more of the objects comprises:

providing electromagnetic energy to the one or more objects;

detecting electromagnetic energy returned from the one or more objects resulting in a measurement signal; and

providing one or more characteristics of at least one of the one or more objects based on the measurement signal.

8. The method of claim 1, wherein transporting the fluid composition comprises adjusting a flow rate of the transportation of the fluid composition through one or more pathways during analysis of the objects.

9. The method of claim 1, wherein the method further comprises stopping the transportation of the fluid composition through one or more of the plurality of pathways during the analysis of the objects.

10. The method of claim 1, wherein directing at least one of the plurality of objects comprises applying a magnetic field to direct the fluid composition based on the analysis of the objects.

11. The method of claim 1, wherein directing one or more of the objects comprises operating a flow switching structure associated with a branch point based on the analysis of the objects.

12. The method of claim 1, wherein the objects comprise biological objects.

13. The method of claim 1, wherein the objects comprise non-biological objects.

14. The method of claim 13, wherein the non-biological object comprise particles.

15. The method of claim 1, wherein transporting the fluid composition comprises transporting the fluid composition through a plurality of pathways in a fluid tight system.

16. The method of claim 1, wherein the method further comprises providing makeup fluid into one or more of the plurality of pathways.

17. The method of claim 16, wherein the method further comprises changing at least one of a proportion of the makeup fluid and the fluid composition through one or more of the plurality of pathways during the analysis of the objects.

18. The method of claim 1, wherein at least one of one or more branch points is used to provide parallel pathways from a single combined pathway, wherein the single combined pathway is provided by pathways from a plurality of branch points.

19. The method of claim 18, wherein directing at least one of the plurality of objects comprises sorting one or more objects in the single combined pathway by directing the objects through the at least one of the one or more branch points to one or more of the parallel pathways.

20. The method of claim 1, wherein at least one of the one or more branch points are used to provide parallel pathways from a single pathway, wherein the single pathway is provided by a pathway from a single branch point.

21. The method of claim 20, wherein directing at least one of the plurality of objects comprises sorting one or more objects by directing the objects through the at least one of the one or more branch points to one or more of the parallel pathways.

22. The method of claim 1, wherein the pathway network comprising one or more branch points forms a series of pathways, and further wherein directing at least one of the plurality of objects comprises sorting one or more objects by directing the objects down the series of pathways by repeatedly analyzing and directing one or more of the objects through multiple branch points based on the analysis of the objects.

23. The method of claim 22, wherein the analysis of the objects at a branch point uses prior analyzing and directing of the objects in directing one or more of the objects through subsequent branch points.

24. The method of claim 1, wherein the pathway network comprising one or more branch points forms at least a portion of one or more sorting stages, wherein each sorting stage comprises at least one sorting module associated with each of a plurality of branch points.

25. The method of claim 24, wherein analyzing one or more objects comprises analyzing objects during a particular period of time using each of the sorting modules of at least one sorting stage for use in directing the one or more objects through associated branch points.

26. The method of claim 25, wherein analyzing one or more objects comprises analyzing objects at multiple sorting stages.

27. A sorting method, comprising:

providing a pathway network comprising a plurality of pathways and one or more branch points;

analyzing cells suspended in a fluid composition at one or more positions along the pathway network; and

sorting the cells at the one or more branch points based on the analysis of the cells.

28. The method of claim 27, wherein the plurality of pathways and the one or more branch points provide for a progressively greater numbers of pathways.

29. The method of claim 27, wherein sorting the cells comprises combining a plurality of cells directed through each of two or more branch points prior to directing the combined cells through a subsequent branch point.

30. The method of claim 27, wherein sorting the cells comprises directing a plurality of cells through a branch point prior to directing at least one cell of the plurality of cells through a subsequent branch point.

31. The method of claim 27, wherein analyzing the cells comprises performing at least one of morphology measurements, luminescence measurements, fluorescence measurements, radioactive measurements, light scattering measurements, electrical measurements, or ultrasound measurements for use in determining one or more characteristics for one or more of the cells.

32. The method of claim 27, wherein analyzing cells suspended in the fluid composition comprises taking two or more different measurements from the cells being analyzed.

33. The method of claim 27, wherein analyzing the cells suspended in the fluid composition comprises:

providing electromagnetic energy to the one or more cells;

detecting electromagnetic energy returned from the one or more cells resulting in a measurement signal; and

providing one or more characteristics of at least one of the one or more cells based on the measurement signal.

34. The method of claim 27, wherein analyzing the cells suspended in the fluid composition further comprises transporting the fluid composition through one or more pathways.

35. The method of claim 34, wherein transporting the fluid composition further comprises adjusting a flow rate of at least a portion of the fluid composition through one or more pathways during analysis of the cells.

36. The method of claim 34, wherein the method further comprises stopping the transportation of the fluid composition through one or more of the plurality of pathways during the analysis of the cells.

37. The method of claim 34, wherein transporting the fluid composition comprises transporting the fluid composition through a plurality of pathways in a fluid tight system.

38. The method of claim 27, wherein sorting the cells further comprises applying a magnetic field to sort the fluid composition based on the analysis of the cells.

39. The method of claim 27, wherein sorting the cells further comprises operating a flow switching structure associated with a branch point based on the analysis of the cells.

40. The method of claim 27, wherein the method further comprises points is used to provide parallel pathways from a single combined pathway, providing makeup fluid into one or more of the plurality of pathways.

41. The method of claim 27, wherein at least one of one or more branch wherein the single combined pathway is provided by pathways from a plurality of branch points, and further wherein sorting the cells comprises sorting cells in the single combined pathway by directing the cells through the at least one of the one or more branch points to one or more of the parallel pathways.

42. The method of claim 27, wherein at least one of the one or more branch points are used to provide parallel pathways from a single pathway, wherein the single pathway is provided by a pathway from a single branch point, and further wherein sorting the cells comprises sorting the cells by directing one or more cells through the at least one of the one or more branch points to one or more of the parallel pathways.

43. The method of claim 27, wherein the pathway network comprising one or more branch points forms a series of pathways, and further sorting the cells comprises sorting the cells by directing the cells down the series of pathways by repeatedly analyzing and directing one or more of the cells through multiple branch points based on the analysis of the objects.

44. The method of claim 27, wherein the pathway network comprising one or more branch points forms at least a portion of one or more sorting stages, wherein each sorting stage comprises at least one sorting module associated with each of a plurality of branch points.

45. The method of claim 44, wherein analyzing cells comprises analyzing cells during a particular period of time using each of the sorting modules of at least one sorting stage for use in directing one or more of the cells through associated branch points.

46. The method of claim 45, wherein analyzing cells comprises analyzing cells at multiple sorting stages.

47. The method of claim 27, wherein each of one or more branch points are used to form parallel pathways from a single pathway, and further wherein sorting at least one of the cells comprises sorting directing the cells through the one or more branch points to one or more of the parallel pathways.

48. A sorting system comprising:

a pathway network comprising a plurality of pathways operable to receive a fluid composition comprising a plurality of objects, wherein pathway network further comprises one or more branch points;

one or more analyzer devices at one or more positions of the pathways for use in analyzing one or more of the plurality of objects that flow in the pathways; and

one or more fluid flow controllers, wherein at least one fluid flow controller associated with at least one of the one or more branch points is operable to direct fluid composition in the plurality of pathways based on analysis of the objects.

49. The system of claim 48, further comprising a control apparatus, wherein the control apparatus is operable to receive a measurement signal from at least one analyzer device and determine at least one characteristic of an object based on the measurement signal, and further wherein the control apparatus is operable to provide a control signal to a fluid flow controller based on the at least one characteristic of the object.

50. The system of claim 49, wherein the control apparatus is operable to receive previous measurement signals from one or more analyzer devices, and further wherein the control apparatus is operable to provide the control signal to a fluid flow controller based on at least one of the at least one characteristic of the object and the previous measurement signals.

51. The system of claim 48, wherein at least one of one or more branch points is used to provide parallel pathways from a single combined pathway, wherein the single combined pathway is provided by pathways from a plurality of branch points.

52. The system of claim 48, wherein at least one of the one or more branch points are used to provide parallel pathways from a single pathway, wherein the single pathway is provided by a pathway from a single branch point.

53. The system of claim 48, wherein the pathway network comprises a single pathway separated into two or more additional pathways by at least one of the one or more branch points.

54. The system of claim 48, wherein the pathway network comprising one or more branch points comprises a series of pathways, each branch point from the series of pathways has at least one analyzer device and at least one fluid flow controller associated therewith to allow for a sequential analysis and sorting of objects through a progression of branch points.

55. The system of claim 48, wherein each of a plurality of branch points have at least one analyzer device and at least one fluid flow controller associated therewith to allow for a parallel analysis and sorting of objects simultaneously.

56. The system of claim 48, wherein at least one analyzer device and at least one fluid flow controller are associated to form a sorting module associated with each of a plurality of one or more branch points, wherein at least one group of the sorting modules is arranged and operable for parallel analysis and sorting of objects, wherein each group of sorting modules forms a sort stage.

57. The system of claim 56, wherein the sorting system comprises two or more sort stages.

58. The system of claim 48, wherein the one or more analyzer devices are operable for use in analyzing biological objects that flow in the pathways.

59. The system of claim 58, wherein the biological objects comprise cells, and further wherein the one or more analyzer devices are operable for use in analyzing the cells that flow in the pathways.

60. The system of claim 48, wherein the one or more analyzer devices are operable for use in analyzing non-biological objects that flow in the pathways.

61. The system of claim 60, wherein the non-biological objects comprise particles.

62. The system of claim 48, wherein the one or more analyzer devices are positioned at or before one or more branch points of the plurality of pathways.

63. The system of claim 48, wherein the one or more analyzer devices are operable to perform at least one of optical measurements, luminescence measurements, fluorescence measurements, light scattering measurements, radioactive measurements, electrical measurements, and ultrasound measurements.

64. The system of claim 48, wherein the one or more analyzer devices comprise at least one exciter.

65. The system of claim 64, wherein the one or more analyzer devices comprise at least one exciter tuned at a specific wavelength to cause fluorescent markers to fluoresce.

66. The system of claim 64, wherein the exciters comprise light emitting diodes, laser diodes and/or vertical cavity surface emitting lasers.

67. The system of claim 64, wherein at least one of the one or more analyzer devices comprises at least one detector.

68. The system of claim 67, wherein the detector comprise a charge-coupled device (CCD) detector.

69. The system of claim 67, wherein the detector comprises a photosensitive diode.

70. The system of claim 48, wherein at least one of the one or more fluid flow controllers is operable to stop the one or more objects in a pathway.

71. The system of claim 48, wherein the one or more fluid flow controllers are operable to adjust a flow rate of the objects in the plurality of pathways.

72. The system of claim 48, wherein at least one of the fluid flow controllers comprises a flow switching structure operable to direct fluid composition in the pathways.

73. The system of claim 72, wherein the flow switching structure comprises at least one of a mechanical multi-way valve, a rotary valve, a magnetic solenoid shuttle valve, and an elastomeric valve.

74. The system of claim 48, wherein the fluid composition comprises nano-size magnetic particles at a concentration sufficient to allow the fluid composition to be directed in the pathways through the application of an electromagnetic field.

75. The system of claim 74, wherein the controller is operable to apply magnetic fields to direct the fluid composition comprising the nano-size magnetic particles in the pathways based on analysis of the objects.

76. The system of claim 48, wherein the plurality of pathways form a portion of a fluid tight sealed system.

77. The system of claim 48, wherein the system further comprises a fluid manifold containing fluid and one or more makeup fluid ports, wherein the one or more makeup fluid ports connect the fluid manifold and the pathways to allow for fluid to be provided to one or more of the pathways of the sorting system from the fluid manifold.

78. The system of claim 48, wherein at least one of one or more branch points is operable to receive fluid composition from multiple branch points via multiple pathways and provide fluid composition to one or more pathways.

79. The system of claim 48, wherein at least one of the one or more branch points is operable to receive fluid composition from a single branch point via a single pathway and provide fluid composition to one or more pathways.

80. The system of claim 48, wherein each of a plurality of the one or more branch points and at least portions of associated pathways are provided as a separate branch point module, wherein the separate branch point module is configured to be assembled for use as at least a portion of the pathway network.

81. The system of claim 80, wherein two or more separate branch point modules are configured to be assembled for use as at least a portion of the pathway network.

82. The system of claim 80, wherein each of the two or more separate branch point modules may be configured with at least a portion of a different analyzer device.

83. The system of claim 80, wherein each of the two or more branch point modules are configured to be inserted into a holding frame for use as at least a portion of the pathway network.

84. The system of claim 80, wherein at least one of the two or more separate branch point modules has a different flow path configuration than another of the plurality of branch point modules.

85. A cell sorting system comprising:

a pathway network comprising a plurality of pathways and one or more branch points, the pathway network operable to receive a fluid composition comprising a plurality of cells;

one or more analyzer devices at one or more positions of the pathways for use in analyzing one or more of the plurality of cells that flow in the pathways; and

one or more fluid flow controllers, wherein at least one fluid flow controller associated with at least one of the one or more branch points is operable to sort the plurality of cells in the plurality of pathways based on analysis of the cells.

86. The system of claim 85, further comprising a control apparatus, wherein the control apparatus is operable to receive a measurement signal from at least one analyzer device and determine at least one characteristic of at least one cell based on the measurement signal, and further wherein the control apparatus is operable to provide a control signal to a fluid flow controller based on the at least one characteristic of the at least one cell.

87. The system of claim 85, wherein at least one of one or more branch points is used to provide parallel pathways from a single combined pathway, wherein the single combined pathway is provided by pathways from a plurality of branch points.

88. The system of claim 85, wherein at least one of the one or more branch points are used to provide parallel pathways from a single pathway, wherein the single pathway is provided by a pathway from a single branch point.

89. The system of claim 85, wherein the pathway network comprises a single pathway separated into two or more additional pathways by at least one of the one or more branch points.

90. The system of claim 85, wherein the pathway network comprising one or more branch points comprise a series of pathways, each branch point in the series of pathways has at least one analyzer device and at least one fluid flow controller associated therewith to allow for a sequential analysis and sorting of cells through a progression of branch points.

91. The system of claim 85, wherein each of a plurality of branch points have at least one analyzer device and at least one fluid flow controller associated therewith to allow for a parallel analysis and sorting of cells simultaneously.

92. The system of claim 85, wherein at least one analyzer device and at least one fluid flow controller are associated to form a sorting module associated with each of a plurality of one or more branch points, wherein at least one group of the sorting modules is arranged and operable for parallel analysis and sorting of cells, wherein each group of sorting modules forms a sort stage.

93. The system of claim 92, wherein the sorting system comprises two or more sort stages.

94. The system of claim 92, wherein the one or more analyzer devices are positioned at or before one or more branch points of the plurality of pathways.

95. The system of claim 85, wherein the one or more analyzer devices are operable to perform at least one of optical measurements, luminescence measurements, fluorescence measurements, light scattering measurements, radioactive measurements, electrical measurements, and ultrasound measurements.

96. The system of claim 85, wherein the one or more analyzer devices comprise at least one exciter.

97. The system of claim 96, wherein at least one of the one or more analyzer devices comprises at least one detector.

98. The system of claim 85, wherein at least one of the one or more fluid flow controllers is operable to stop the one or more cells in a pathway.

99. The system of claim 85, wherein the one or more fluid flow controllers are operable to adjust a flow rate of one or more of the cells in the plurality of pathways.

100. The system of claim 85, wherein at least one of the fluid flow controllers comprises a flow switching structure operable to direct fluid composition in the pathways.

101. The system of claim 100, wherein the flow switching structure comprises at least one of a mechanical multi-way valve, a rotary valve, a magnetic solenoid shuttle valve, and an elastomeric valve.

102. The system of claim 85, wherein the fluid composition comprises nano-size magnetic particles at a concentration sufficient to allow the fluid composition to be directed in the pathways through the application of an electromagnetic field.

103. The system of claim 102, wherein the controller is operable to apply magnetic fields to direct the fluid composition comprising the nano-size magnetic particles in the pathways based on analysis of the cells.

104. The system of claim 85, wherein the plurality of pathways form a portion of a fluid tight sealed system.

105. The system of claim 85, wherein the system further comprises a fluid manifold containing fluid and one or more makeup fluid ports, wherein the one or more makeup fluid ports connect the fluid manifold and the pathways to allow for fluid to be provided to one or more of the pathways of the sorting system from the fluid manifold.

106. The system of claim 85, wherein each of a plurality of the one or more branch points and at least portions of associated pathways are provided as a separate branch point module, wherein the separate branch point module is configured to be assembled for use as at least a portion of the pathway network.

107. The system of claim 106, wherein two or more separate branch point modules are configured to be assembled for use as at least a portion of the pathway network.

108. The system of claim 107, wherein each of the two or more separate branch point modules may be configured with at least a portion of a different analyzer device.

109. A sorting system comprising:

a pathway network comprising a plurality of pathways operable to receive a fluid composition comprising a plurality of objects, wherein pathway network further comprises one or more branch points, and further wherein at least one of the one or more branch points and at least portions of associated pathways is provided as a separate branch point module, wherein the separate branch point module is configured to be assembled for use as at least a portion of the pathway network;

one or more analyzer devices associated with the separate branch point module for use in analyzing one or more of the plurality of objects that flow in the pathways; and

one or more fluid flow controllers associated with the separate branch point module operable to direct fluid composition therein.

110. The system of claim 109, wherein two or more separate branch point modules are configured to be assembled for use as at least a portion of the pathway network.

111. The system of claim 110, wherein each of the two or more separate branch point modules may be configured with at least a portion of a different analyzer device.

112. The system of claim 110, wherein each of the two or more separate branch point modules are configured to be inserted into a holding frame for use as at least a portion of the pathway network.

113. The system of claim 110, wherein at least one of the two or more separate branch point modules has a different flow path configuration than another of the plurality of branch point modules.

114. The system of claim 110, wherein at least one of two or more separate branch point modules is operable, when assembled, to receive fluid composition from multiple branch points via multiple pathways and provide fluid composition to one or more pathways.

115. The system of claim 110, wherein at least one of the two or more separate branch point modules is operable, when assembled, to receive fluid composition from a single branch point via a single pathway and provide fluid composition to one or more pathways.