Method and apparatus for sorting particles with a moving catcher tube

• US 5,030,002 A
• Filed: 08/11/1989
• Issued: 07/09/1991
• Est. Priority Date: 08/11/1989
• Status: Expired due to Term

• Current Assignee: Becton, Dickinson & Co
• Original Assignee: Becton, Dickinson & Co
• Inventors: North, Howard L. Jr.
• Primary Examiner(s): McGraw, Vincent P.
• Assistant Examiner(s): Keesee, LaCharles P.
• Application Number:
  US07/392,698
• Time in Patent Office: 697 Days
• Field of Search: 356/39, 356/73, 356/341, 250/283, 209/552, 209/606, 209/643, 209/576, 209/577, 209/579, 209/644, 406/1, 406/3
• US Class Current: 356/73
• CPC Class Codes: G01N 15/1404 Handling flow, e.g. hydrodynamic focusing
• CPC Class Codes: G01N 15/149 specially adapted for sorting particles, e.g. by their size or optical properties

Abstract

A sorter with a body member passageway has analysis, pre-analysis and post analysis portions for particles. An elongate catcher tube carried on the body member, and mounted with its axis to be selectively aligned with the analysis portion for intermittently receiving analyzed particles. An operator receives a signal from the analysis portion relative to one or more particle characteristics and selectively aligns the catcher tube in fluid communication with the analysis portion. The signal is an electrical pulse of strength and timing sufficient to cause a driver mounted to the body member and associated with the catcher tube to align the catcher for sorting particles. A resilient support attaches the catcher tube to the body member and provides a pivot for the catcher tube. A method for sorting includes generating a signal representative of one or more characteristics of the particles and applying the signal to a driver to change the position of the catcher tube.

Claims

1. A catcher tube sorter for a flow cytometer comprising:

a body member having a passageway therethrough for the passage of particles which are to be analyzed, the passageway including an analysis portion, a pre-analysis portion and a post analysis portion;

an uptake tube connected in fluid communication with the pre-analysis portion of the passageway and adapted for fluid communication with a source of particles for providing a particle flow path from the source of particles into the analysis portion;

a catcher tube carried on the body member and mounted to be selectively positionable in fluid communication with the analysis portion for intermittently receiving analyzed particles after passage of particles through the analysis portion; and

an operator connected to receive an input signal from the analysis portion relative to one or more particle characteristics and to activate the catcher tube for selectively positioning the catcher tube in fluid communication with the analysis portion.

2. The sorter of claim 1 wherein the analysis portion of the passageway includes a flowcell having an orifice sized to permit the passage of substantially one particle at a time through the analysis portion, and wherein the input signal is an optical response to one or more particle characteristics.

3. The sorter of claim 2 wherein the body member includes means for permitting light to be directed at the orifice at an angle substantially orthogonal to the direction of particle flow through the flowcell.

4. The sorter of claim 3 wherein the means for permitting light includes a recess for positioning a lens adjacent the flowcell.

5. The sorter of claim 2 wherein the operator means produces an electrical pulse of strength and duration sufficient to selectively position the catcher tube in fluid communication with the analysis portion.

6. The sorter of claim 5 wherein a driver mounted to the body member and associated with the catcher tube receives the input signal pulse and selectively positions the catcher tube in at least partial alignment for fluid communication with the analysis portion.

7. The sorter of claim 6 wherein the catcher tube has an axis and is carried on the body member for movement relative to the axis into partial alignment with the analysis portion.

8. The sorter of claim 7 wherein a sheathing liquid is introduced into the pre-analysis portion about an inner end of the uptake tube to provide a sheathed flow of particles along an axis of the passageway toward the analysis portion and the post analysis portion is arranged about the catcher tube to receive and direct away particle flow not selectively caught in the catcher tube.

9. A particle flow through apparatus comprising:

a body member having a passageway therethrough including an analysis region through which substantially one particle at a time may pass in the direction of flow through the analysis region when the apparatus is operating;

a sheathing liquid applied to the supply of particles in the passageway for hydrodynamic focusing the particles relative to the liquid;

catcher tube means supported upon the body member and associated with liquid and particles from the analysis region, the catcher tube positionable in a position substantially in alignment with the particles flowing from the analysis region for culling particles from the analysis region to another position where the catcher tube is not aligned with the particles flowing from the analysis region but is aligned with the fluid flowing from the analysis region; and

control means operatively responsive to particles of one or more preselected types passing through the analysis region, the control means arranged for moving the catcher tube between the positions substantially out of and into alignment with the flowing particles from the analysis region.

10. The apparatus of claim 9 wherein the catcher tube means includes a resilient support which is stressed upon movement of the catcher tube between the positions.

11. The apparatus of claim 10 wherein the control means includes a means responsive to at least one characteristic of one or more particles passing through the analysis region and a driver activated by the means responsive and connected to the catcher tube means for flexing the resilient support from the unaligned position to the aligned position.

12. A catcher tube sorter for a flow cytometer comprising:

a body member having a passageway therethrough for the passage of particles which are to be analyzed, the passageway including an analysis portion, a pre-analysis portion and post-analysis portion, all of which lie substantially on the same axis through the body member;

an uptake tube having an inner end positioned in the pre-analysis portion of the passageway adjacent the analysis portion and outer end extending outwardly of the body member for insertion into a pressurized sample supply containing liquid and particles, the uptake tube having a lumen extending therethrough for the passage of the particles toward the analysis portion of the passageway;

a flowcell included in the analysis portion and having an orifice sized to permit the passage of substantially one particle at a time through the analysis portion;

a catcher tube movable into fluid communication with the axis extending through the pre-analysis portion, analysis portion and the post-analysis portion; and

regulating means on the body member and operatively associated with the catcher tube for substantially aligning the catcher tube with the axis.

13. The sorter of claim 12 wherein the catcher tube is elongate with an axis and a flexible support moveably attaches the catcher tube to the body member for carrying the catcher tube in a position for realignment of the catcher tube axis with the passageway axis so that the axes are substantially coaxial with one another.

14. The sorter of claim 13 wherein the catcher tube includes a pair of ends and a central section therebetween and the flexible support attaches the central section of the catcher tube to the body member permitting pivotal movement about a point located along the catcher tube axis into the position for realignment of the catcher tube axis with the passageway axis so that the axes are displaced relative to one another.

15. The sorter of claim 14 wherein the catcher tube includes a driver located between an end of the catcher tube and the body member for moving an opposite end on the catcher tube into displaced alignment with the passageway axis.

22. The sorter of claim 15 wherein said driver is a piezo electric device responsive to voltage.

16. A flow cytometer for determining one or more characteristics of particles or the like flowing in a liquid stream comprising:

means for moving particles in a liquid flow stream;

a body member having a passageway therethrough including an analysis region through which the moving particles pass substantially one at a time in the direction of flow;

a catcher tube sorting means having an elongate catcher tube operative to selectively receive flow from the passageway when the elongate catcher tube is longitudinal aligned with the passageway;

means for providing a beam of light to illuminate the particles passing through the analysis region;

means for detecting light with respect to each moving particle and for associating the detected light with one or more characteristics of each particle and to generate a signal responsive to the particle characteristics; and

means for receiving the signal and in response thereto to operatively position the elongate catcher tube in alignment with the passageway.

17. A method for sorting particles passing through a particle analysis apparatus for transporting a sample of particles carried in a liquid including the following steps;

generating a signal representative of one or more characteristics of the particles passing through an analysis region of the analysis apparatus,

applying the signal to a driver for changing the position of a catcher tube so that the catcher tube is moved to receive the particles having one or more of the characteristics.

18. The method of claim 17 wherein the step of applying the signal to a driver for changing the position of the catcher tube includes flexing a support for the catcher tube to bring the catcher tube into substantial alignment with the particles passing through the particle analysis apparatus and having one or more of the characteristics.

19. The method of claim 17 wherein the step of generating a signal representative of one or more characteristics of the particles passing through an analysis region includes using light to analyze the particles passing one at a time through the analysis region and to provide an electrical signal.

20. The method of claim 19 wherein the step of using light to analyze the particles passing one at a time through the analysis region and to provide an electrical signal includes as a step thereof applying the signal to a driver for changing the position of a catcher tube.

21. The method of claim 18 wherein the step of positioning the catcher tube to bring the catcher tube into substantial alignment with the particles includes as a step thereof pivoting the catcher tube about a point located between the ends of the catcher tube.

23. A catcher tube sorter for a flow cytometer comprising:

a body member haivng a passageway therethrough for the passage of particles which are to be analyzed, the passageway including an analysis portion, a pre-analysis portion and post-analysis portion, all of which lie substantially on the same axis through the body member;

an uptake tube having an inner end positioned in the pre-analysis portion of the passageway adjacent the analysis portion and outer end extending outwardly of the body member for insertion into a sample supply containing liquid and particles, the uptake tube having a lumen extending therethrough for the passage of the particles toward the analysis portion of the passageway;

a flowcell included in the analysis portion and having an orifice sized to permit the passage of substantially one particle at a time through the analysis portion;

a catcher tube movable into fluid communication with the axis extending through the pre-analysis portion, analysis portion and the post-analysis portion; and

regulating means on the body member and operatively associated with the catcher tube for substantially aligning the catcher tube with the axis.

24. The sorter of claim 23 wherein the catcher tube is elongate with an axis and a flexible support moveably attaches the catcher tube to the body member for carrying the catcher tube in a position for realignment of the catcher tube axis with the passageway axis so that the axes are substantially coaxial with one another.

25. The sorter of claim 24 wherein the catcher tube includes a pair of ends and a central section therebetween and the flexible support attaches the central section of the catcher tube to the body member permitting pivotal movement about a point located along the catcher tube axis into the position for realignment of the catcher tube axis with the passageway axis so that the axes are displaced relative to one another.

26. The sorter of claim 25 wherein the catcher tube includes a driver located between an end of the catcher tube and the body member for moving an opposite end on the catcher tube into displaced alignment with the passageway axis.

27. The sorter of claim 26 wherein said driver is a piezo electric device responsive to voltage.