Flow sorting system and methods regarding same

• US 7,452,725 B2
• Filed: 01/10/2003
• Issued: 11/18/2008
• Est. Priority Date: 01/10/2002
• Status: Expired due to Fees

• Current Assignee: NeuroBioTex Inc., Board of Regents of the University of Texas System (University of Texas System)
• Original Assignee: NeuroBioTex Inc., Board of Regents of the University of Texas System (University of Texas System)
• Inventors: Leary, James F., Frederickson, Christopher J.
• Primary Examiner(s): Warden; Jill
• Assistant Examiner(s): Moss; Keri A
• Application Number:
  US10/340,520
• Publication Number:
  US 20030153085A1
• Time in Patent Office: 2,139 Days
• Field of Search: 436/63, 422/73, 422/58, 422/82.05, 422/82.08, 435/288.7, 435/287.3, 738/658
• 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 groups of multiple objects of the plurality of objects being transported in a pathway of the pathway network to detect objects of interest, wherein analyzing each group of multiple objects comprises analyzing simultaneously the multiple objects of the group together by providing a measurement taken on multiple objects of the group together in the pathway, the measurement for use in determining a pathway of the pathway network down which the group is to be directed; and

directing at least a few of the groups of the multiple objects through one branch point of the one or more branch points down at least one pathway of the plurality of pathways based on the analysis of the groups of multiple objects such that a distance between multiple objects of the few groups is increased and directing other groups of multiple objects down a pathway different than the at least one pathway to increase the percentage of objects of interest in the at least one pathway relative to other objects present therein, wherein the method further comprises;

analyzing objects of the few groups directed down the at least one pathway with increased distance between multiple objects thereof to detect objects of interest, wherein analyzing the objects of the few groups comprises analyzing simultaneously multiple objects together in a pathway by providing at least a measurement taken on the multiple objects together, the measurement for use in determining a pathway of the pathway network down which one or more of the objects of the few groups is to be directed; and

directing one or more of the objects of the few groups through another of the one or more branch points down another pathway of the pathway network based on the analysis of objects of the few groups to further increase the percentage of objects of interest therein relative to other objects present therein.

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 the few of the groups of multiple objects or directing one or more of the objects of the few groups 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 the few of the groups of multiple objects or directing one or more of the objects of the few groups 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 the groups of multiple objects or the objects of the few groups 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 the objects being analyzed.

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

7. The method of claim 1, wherein analyzing the groups of multiple objects or the objects of the few groups comprises:

providing electromagnetic energy to the objects being analyzed;

detecting electromagnetic energy returned from the objects being analyzed resulting in a measurement signal; and

providing one or more characteristics of the objects being analyzed 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 the few of the groups of multiple 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 at least the few of the groups of multiple 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 to increase the distance between multiple objects of the few groups.

17. 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 1, wherein directing at least the few of the groups of multiple objects comprises sorting objects in a pathway by directing the objects through the at least one of the one or more branch points to one or more pathways having smaller cross sections such that the distance between multiple objects of the few groups is increased.

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, wherein directing at least the few of the groups of multiple objects or directing one or more of the objects of the few groups comprises sorting objects in the single 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.

21. The method of claim 1, wherein the method further comprises performing single object analysis on a plurality of sorted objects, wherein the plurality of sorted objects are a result of directing objects in the plurality of pathways based on group analysis of multiple objects.

22. The method of claim 1, wherein the pathway network comprising one or more branch points forms a series of pathways, and wherein the method comprises repeatedly analyzing objects and directing one or more of the objects through multiple branch points based on the analysis of the objects to increase the percentage of objects of interest in the series of pathways relative to other objects present therein.

23. The method of claim 22, wherein analysis of the objects uses prior analysis 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 the groups of multiple objects or the objects of the few groups 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 objects through associated branch points.

26. The method of claim 25, wherein analyzing the 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 groups of cells suspended in a fluid composition at one or more positions along a pathway of the pathway network to detect cells of interest, wherein analyzing each group of cells comprises analyzing simultaneously the cells of the group together by providing a measurement taken on the cells of the group together, the measurement for use in determining a pathway of the pathway network down which the group is to be directed; and

sorting the groups of cells, wherein sorting the groups of cells comprises directing at least a few of the groups of cells through one branch point of the one or more branch points down at least one pathway of the plurality of pathways based on the analysis of the groups of cells such that a distance between cells of the few groups is increased and directing other groups of cells down a pathway different than the at least one pathway to increase the percentage of cells of interest in the at least one pathway relative to other cells present therein, wherein the method further comprises analyzing cells of the few groups directed down the at least one pathway with increased distance between cells thereof to detect cells of interest, wherein analyzing the cells of the few groups comprises analyzing simultaneously multiple cells of the few groups together in a pathway by providing a measurement taken on the multiple cells of the few groups together in the pathway, the measurement for use in determining a pathway of the pathway network down which one or more of cells of the few groups is to be directed, and directing one or more of the cells of the few groups through another of the one or more branch points down another pathway of the pathway network based on the analysis of the cells of the few groups to further increase the percentage of cells of interest therein relative to other cells present therein.

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

29. The method of claim 27, wherein directing at least the few groups of cells or directing one or more of the cells of the few groups 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 directing at least the few groups of cells or directing one or more of the cells of the few groups 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 groups of cells or the cells of the few groups 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 the cells being analyzed.

32. The method of claim 27, wherein analyzing the groups of cells or the cells of the few groups 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 groups of cells or the cells of the few groups suspended in the fluid composition comprises:

providing electromagnetic energy to the cells being analyzed;

detecting electromagnetic energy returned from the cells being analyzed resulting in a measurement signal; and

providing one or more characteristics of the cells being analyzed based on the measurement signal.

34. The method of claim 27, wherein the method 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 directing at least the few groups of cells or directing one or more of the cells of the few groups comprises applying a magnetic field to sort the fluid composition based on the analysis of the cells.

39. The method of claim 27, wherein directing at least the few groups of cells or directing one or more of the cells of the few groups 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 providing makeup fluid into one or more of the plurality of pathways to increase the distance between cells of the few groups.

41. The method of claim 27, 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, and further wherein directing at least the few groups of cells or directing one or more of the cells of the few groups comprises sorting cells in the single combined pathway 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.

42. The method of claim 27, wherein directing at least the few groups of cells or directing one or more of the cells of the few groups comprises sorting the cells in a pathway by directing one or more cells through the at least one of the one or more branch points to one or more pathways having a smaller cross sections such that the distance between multiple cells of the few groups is increased.

43. The method of claim 27, wherein the pathway network comprising one or more branch points forms a series of pathways, and further wherein the method comprises repeatedly analyzing cells and directing one or more of the cells through multiple branch points based on the analysis of the cells to increase the percentage of cells of interest in the series of pathways relative to other cells present therein.

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 the groups of cells or the cells of the few groups 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 the cells through associated branch points.

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

47. The method of claim 27, wherein the method comprises performing single cell analysis on a plurality of sorted cells, wherein the plurality of sorted cells are a result of directing cells in the plurality of pathways based on group analysis of the cells.