Analyzing system using sheath flow of sample

• US 5,079,959 A
• Filed: 09/08/1989
• Issued: 01/14/1992
• Est. Priority Date: 09/19/1988
• Status: Expired due to Term

• Current Assignee: Hitachi, Ltd.
• Original Assignee: Hitachi, Ltd.
• Inventors: Miyake, Ryo, Sakuraba, Shinichi, Yasuda, Kaori, Ohki, Hiroshi, Yamazaki, Isao, Kaneko, Toshio, Horiuchi, Hideyuki
• Primary Examiner(s): NOLAND, THOMAS
• Application Number:
  US07/404,559
• Time in Patent Office: 858 Days
• Field of Search: 422/64, 422/65, 422/100, 73/864.81-864.87, 73/864.91, 73/864.11-864.35, 73/864.73, 73/864.24, 73/61 R, 436/180
• US Class Current: 73/864.85
• CPC Class Codes: G01N 15/1404 Handling flow, e.g. hydrodynamic focusing
• CPC Class Codes: G01N 2035/1086 Cylindrical, e.g. variable angle
• CPC Class Codes: G01N 35/1004 Cleaning sample transfer devices
• CPC Class Codes: G01N 35/1083 with one horizontal degree of freedom

Abstract

Particles contained in a liquid sample are analyzed by moving the particles along a detection passage past a detector using a liquid flow in the detection passage. To reduce the time required for analysis of each sample, the sample is delivered at an input location at the upstream end of the detection passage by movement of a movable container carrying the sample to the input location. Immediately after the commencement of the delivery of the liquid sample, liquid flow is caused to occur in the detection passage. Washing liquid is supplied to the input location by a liquid supplier different from the movable container which carries the sample.

Claims

1. A method of analyzing particles contained in at least one liquid sample by moving the particles along a detection passage past a detector by means of a liquid flow in said passage, which method includes the steps of

(a) delivering one liquid sample, of said at least one liquid sample, containing the particles to an input location at an upstream end of said detection passage by moving a movable container carrying said sample to said input location, and forming a seal between the movable container and said input location, the input location being immediately upstream of the detection passage so as to be directly connected thereto, wherein said movable container has an output nozzle for said one liquid sample, the one liquid sample being delivered to said input location from said movable container through said output nozzle,

(b) supplying a carrying liquid to said detection passage so as to cause sheath flow in said detection passage in which the flowing carrying liquid entrains the one liquid sample as a thin stream in the carrying liquid, whereby the sample is carried past the detector in said sheath flow,

(c) immediately after commencement of the delivery of the one liquid sample to the input location by the movable container, causing said liquid flow to occur in said detection passage so as to move the particles from the input location past said detector and analyzing the particles by means of the detector, and

(d) supplying washing liquid to said input location by means different from said movable container which carries the sample.

2. A method according to claim 1 wherein said carrying liquid forms said washing liquid for the input location.

3. A method according to claim 1 wherein a plurality of liquid samples respectively containing particles, in a plurality of sample holders, are sequentially carried by said pipette to said input location for analysis.

4. A method according to claim 3 wherein one of the plurality of liquid samples is carried to said input location, the steps (a), (b), (c) and (d) are performed on said one of the plurality of liquid samples, and, thereafter, a following one of the plurality of liquid samples is carried to said input location and the steps (a), (b), and (c) and (d) are performed on said following one of the plurality of liquid samples.

5. A method according to claim 3 wherein said plurality of liquid samples are held in a plurality of holding containers, respectively, prior to carrying a respective liquid sample to said input location for analysis.

6. A method according to claim 1 including the step of washing said movable container independently of the washing of the input location.

7. A method according to claim 1 wherein said moving container is a pipette tube.

8. A method according to claim 1 wherein said input location has a resilient seal which seals against said moving container.

9. A method according to claim 1 wherein the detection passage has the upstream end thereof in a flow cell, the input location being immediately upstream of the upstream end of the detection passage.

10. Apparatus according to claim 9 wherein said pipette comprises a tube for containing said liquid sample, said tube having an inside diameter of not more than 1 mm and a resilient seal mounted on said tube for forming sealing engagement with said input location.

11. Apparatus for analyzing particles contained in a liquid sample, comprising

(i) a detector for the particles,

(ii) a detection passage for liquid flow extending past said detector, so that said particles passing along said detection passage are detected by said detector for analysis, said detection passage having an input end at which said sample enters the passage,

(iii) an input chamber at said input end of said passage, having an inlet for delivery of said sample to said chamber, a first output port connecting directly to said detection passage and a second outlet port for outflow of washing liquid,

(iv) means for causing liquid flow along said detection passage so as to move the liquid sample from said input chamber past said detector, the means for causing liquid flow including a means for causing sheath flow in the detection passage in which a carrying liquid entrains the liquid sample as a thin stream in the carrying liquid, to carry the liquid sample past the detector in sheath flow, and

(v) means for supplying said washing liquid to said input chamber.

12. Apparatus according to claim 11 further having a movable container for carrying said sample to the input chamber by movement of the container relative to the input chamber, said movable container having a discharge location in said chamber and said second outlet being upstream of said discharge location in the flow direction of said liquid sample.

13. Apparatus according to claim 11 further having suction means connected to said second outlet port for sucking washing liquid from said input chamber.

14. Apparatus according to claim 11 having a valve for controlling flow of washing liquid via said second outlet port.

15. Apparatus for analyzing particles contained in at least one liquid sample, comprising

(i) a detector for the particles,

(ii) a detection passage for liquid flow extending past said detector, so that said particles passing along said detection passage are detected by said detector for analysis, the detection passage being provided as part of a flow cell,

(iii) an input location for the at least one liquid sample at an upstream end of said detection passage,

(iv) means for causing said liquid flow along said detection passage so as to move the at least one liquid sample from said input location,

(v) at least one liquid sample holder for holding the at least one liquid sample,

(vi) a movable container for carrying the at least one liquid sample to the input location from said at least one sample holder, by movement of the movable container relative to the input location, wherein said movable container is a pipette, and there are a plurality of sample holders each accessible by said pipette,

(vii) means, different from said movable container, for supplying washing liquid to said input location, and (viii) means for supplying carrying liquid to said detection passage so as to establish therein sheath flow in which the flowing carrying liquid entrains the liquid sample as a thin stream in the carrying liquid, to carry the liquid sample past the detector, said means for supplying carrying liquid including at least one carrying liquid inlet of the flow cell connected to said detection passage and a connector external to the flow cell for supply of carrying liquid, said connector being adapted to be sealingly and detachably engaged with said carrying liquid inlet.

16. Apparatus according to claim 15 wherein said plurality of sample holders are arranged on a movable carrier, for sequential presentation to said pipette.

17. Apparatus according to claim 16 wherein said pipette is adapted to sequentially carry the plurality of liquid samples to said input location from the respective sample holders.

18. Apparatus according to claim 15 wherein said connector is adapted to make a plug-type engagement with said carrying liquid inlet, and one of said connector and said input has a resilient ring seal for making sealing engagement with the other.

19. Apparatus according to claim 15 wherein the means for causing said liquid flow along said detection passage so as to move said at least one liquid sample from said input location is suction means for applying suction pressure to said detection passage to cause liquid flow.

20. Apparatus for analyzing particles contained in at least one liquid sample, comprising

(i) a detector for the particles,

(ii) a detection passage for liquid flow extending past said detector, so that said particles passing along said detection passage are detected by said detector for analysis,

(iii) an input location for the at least one liquid sample at an upstream end of said detection passage, said input location having a nozzle from which the at least one liquid sample exits into a carrying liquid, said carrying liquid passing to said input location to act as washing liquid by reverse flow through the nozzle, the input location having an output passage for said washing liquid,

(iv) means for causing said liquid flow along said detection passage so as to move the at least one liquid sample from said input location, including means for supplying said carrying liquid to said detection passage such that the carrying liquid provides sheath flow along the detection passage entraining the at least one liquid sample as a thin stream in the flowing carrying liquid,

(v) at least one liquid sample holder for holding the at least one liquid sample,

(vi) a movable container for carrying the at least one liquid sample to the input location from said at least one sample holder, by movement of the movable container relative to the input location, and

(vii) means, different from said movable container, for supplying the washing liquid to said input location, said means for supplying a carrying liquid constituting said means for supplying washing liquid, whereby said carrying liquid acts as said washing liquid.

21. Apparatus for analyzing particles contained in a liquid sample, comprising

(i) a detector for the particles,

(ii) a detection passage for liquid flow extending past said detector, so that said particles passing along said detection passage are detected by said detector for analysis, said detection passage having an input end at which said sample enters the passage,

(iii) an input chamber at said input end of said passage, having an inlet for delivery of said sample to said chamber, a first outlet port connecting directly to said detection passage and a second outlet port for outflow of washing liquid,

(iv) means for causing liquid flow along said detection passage so as to move the liquid sample from said input chamber past said detector, wherein said means for causing liquid flow along said detection passage is adapted to supply a carrying liquid which creates sheath flow in said detection passage entraining the liquid sample emerging from said first outlet port as a thin stream in the carrying liquid, said carrying liquid also acting as said washing liquid by reverse flow through said first outlet port, and

(v) means for supplying said washing liquid to said input chamber.

22. Apparatus for analyzing particles contained in at least one liquid sample, comprising

(i) a detector for the particles,

(ii) a detection passage for liquid flow extending past said detector, so that said particles passing along said detection passage are detected by said detector for analysis,

(iii) an input location for the at least one liquid sample at an upstream end of said detection passage,

(iv) means for causing said liquid flow along said detection passage so as to move the at least one liquid sample from said input location,

(v) at least one liquid sample holder for holding the at least one liquid sample,

(vi) a movable container for carrying the at least one liquid sample to the input location from said at least one sample holder, by movement of the movable container relative to the input location, wherein said movable container is a pipette, and there are a plurality of sample holders each accessible by said pipette,

(vii) means, different from said movable container, for supplying washing liquid to said input location,

(viii) a sample input to said detection passage, adapted to receive delivery of said liquid sample from the movable container, the sample inlet including a deformable mouth portion for engagement with the movable container, and

(ix) at least one carrying liquid inlet to said detection passage for supply of carrying liquid so as to establish sheath flow in said detection passage in which the flowing carrying liquid entrains the liquid sample to a thin stream in the carrying liquid.