Particle dispensing apparatus and method

• US 9,678,923 B2
• Filed: 04/11/2013
• Issued: 06/13/2017
• Est. Priority Date: 04/12/2012
• Status: Active Grant

• Current Assignee: Bio-Rad Laboratories Incorporated
• Original Assignee: Bio-Rad Laboratories Incorporated
• Inventors: Guo, Kun, Patt, Paul J
• Primary Examiner(s): Wecker, Jennifer
• Application Number:
  US13/861,143
• Publication Number:
  US 20130270287A1
• Time in Patent Office: 1,524 Days
• CPC Class Codes: B01L 2200/0652 Sorting or classification of particles or molecules
• CPC Class Codes: B01L 2200/0657 Pipetting powder
• CPC Class Codes: B01L 2200/143 Quality control, feedback systems
• CPC Class Codes: B01L 2400/0439 ultrasonic vibrations, vibrating piezo elements
• CPC Class Codes: B01L 2400/0478 pistons
• CPC Class Codes: B01L 2400/0481 squeezing of channels or chambers
• CPC Class Codes: B01L 3/0289 Apparatus for withdrawing or distributing predetermined quantities of fluid B01L3/02 takes precedence; sample taking G01N1/00; sample taking within automatic analysers G01N35/00; volume measuring in general G01F
• CPC Class Codes: G01N 15/02 Investigating particle size or size distribution by measuring osmotic pressure G01N7/10; investigating sedimentation of particle suspensions G01N15/04; investigating individual particles G01N15/10
• CPC Class Codes: G01N 15/0205 by optical means
• CPC Class Codes: G01N 2015/1024 Counting particles by non-optical means
• CPC Class Codes: G01N 2015/1486 Counting the particles
• CPC Class Codes: G06F 17/00 Digital computing or data processing equipment or methods, specially adapted for specific functions information retrieval, database structures or file system structures therefor G06F16/00

Abstract

Particles are dispensed under controlled conditions to achieve an accurate number of particles by passing a suspension of the particles through a particle detecting device, obtaining a cumulative particle count, comparing the cumulative particle count with a target value, and shutting off the suspension flow once the particle count reaches the target value, all performed by automated means.

Claims

1. Apparatus for dispensing a target number of particles from a source of a suspension of said particles into a collection vessel, said apparatus comprising:

a particle detecting device that has a detecting area and that detects particles passing through said detecting area;

a conveyance device for conveying said suspension from said source through said detecting area and into said collection vessel;

a mixing area downstream of said detecting area;

a pump for supplying a dilution liquid from a diluent vessel to said mixing area;

a controller for automated counting of particles passing through said detecting area and thereby obtaining a cumulative number of particles so detected, for comparing said cumulative number with said target number, and for generating a signal when said cumulative number equals said target number; and

a shutoff device for interrupting flow of said suspension into said collection vessel upon receipt of said signal.

2. The apparatus of claim 1 wherein said conveyance device is a syringe pump with a piston, and said shutoff device comprises a component for suspending motion of said piston.

3. The apparatus of claim 1 said conveyance device is a piezoelectric diaphragm pump driven by a power supply, and said shutoff device comprises a component for deactivating said power supply.

4. The apparatus of claim 1, wherein said conveyance device is a pressure pump, and said shutoff device comprises a solenoid valve on either an intake side or a discharge side of said pump;

or

wherein said conveyance device is a peristaltic pump driven by a motor, and said shutoff device comprises a component for deactivating said motor;

or

wherein said conveyance device is an electrophoretic pump driven by an electric field, and said shutoff device comprises a component for removing said electric field;

or

wherein said conveyance device is a surface acoustic wave pump driven by a power source, and said shutoff device comprises a component for deactivating said power source;

or

wherein said conveyance device is a pump arranged to draw said suspension from said source and to discharge said suspension into said particle detecting device;

or

wherein said conveyance device is a pump arranged to draw said suspension from said source through said particle detecting device.

5. The apparatus of claim 1 wherein said particle detecting device is a Coulter principle device detecting perturbations in an electric field caused when a particle enters said field.

6. The apparatus of claim 1 wherein said particle detecting device is a flow cytometer.

7. The apparatus of claim 1 wherein said particle detecting device is an optical camera.

8. The apparatus of claim 1 wherein said controller is a microcontroller or a printed circuit board.

9. The apparatus of claim 1 wherein said particle detecting device is defined as a first particle detecting device, said detecting area is defined as a first detecting area, and said signal is defined as a first signal, said apparatus further comprising:

a second particle detecting device having a second particle detecting area arranged to receive said suspension emerging from said first particle detecting device;

a second controller for automated counting of particles passing through said second detecting area and thereby obtaining a confirmatory cumulative number of particles so detected, for comparing said confirmatory cumulative number with said target number, and for generating a second signal when said confirmatory cumulative number equals said target number; and

a second device for diluting said suspension with a diluting liquid upstream of said first particle detecting area and for further diluting said suspension with said diluting liquid between said first particle detecting area and said second particle detecting area;

and wherein said shutoff device is actuated by either said first signal or said second signal.

10. A method for dispensing a target number of particle(s) into a collection vessel from a suspension of said particles in a suspending liquid, said method comprising:

(a) passing said suspension through a detecting area of a particle detecting device, and detecting said particle(s) as said particle(s) pass through said detecting area,

(b) cumulatively recording by a controller the number of particles so detected and comparing the cumulative number so recorded with said target number,

(c) mixing said suspension with a dilution liquid downstream of said detecting area,

(d) collecting all particles so detected in said collection vessel, and

(e) by said controller, interrupting flow of said suspension into said collection vessel when said cumulative number equals said target number, thereby limiting said particles in said collection vessel to said target number.

11. The method of claim 10 wherein step (a) comprises pumping said suspension by a syringe pump through motion of a piston in said syringe pump, and step (e) comprises interrupting said flow by suspending motion of said piston;

or

wherein step (a) comprises pumping said suspension by a piezoelectric diaphragm pump driven by a power supply, and step (e) comprises interrupting said flow by deactivating said power supply;

or

wherein step (a) comprises pumping said suspension by a pressure pump, and step (e) comprises interrupting said flow by closing a solenoid valve on either an intake side or a discharge side of said pump;

or

wherein step (a) comprises pumping said suspension by a peristaltic pump driven by a motor, and step (e) comprises interrupting said flow by deactivating said motor;

or

wherein step (a) comprises pumping said suspension by an electrophoretic pump driven by an electric field, and step (e) comprises interrupting said flow by removing said electric field;

or

wherein step (a) comprises pumping said suspension by a surface acoustic wave pump driven by a power source, and step (e) comprises interrupting said flow by deactivating said power source;

or

wherein step (a) comprises pumping said suspension from a source vessel by a pump arranged to draw said suspension from said source vessel and to discharge said suspension into said particle detecting device;

or

wherein step (a) comprises pumping said suspension from a source vessel through said particle detecting device by a pump arranged to draw said suspension from said source vessel through said particle detecting device.

12. The method of claim 10 wherein said particle detecting device is a Coulter principle device detecting perturbations in an electric field caused when a particle enters said field.

13. The method of claim 10 wherein said particle detecting device is a flow cytometer, and step (a) comprises detecting said particles with a photomultiplier tube.

14. The method of claim 10 wherein said particle detecting device is a digital optical camera, and step (a) comprises detecting said particles with a CCD or a CMOS.

15. The method of claim 10 wherein said controller is a microcontroller or a printed circuit board.

16. The method of claim 10 wherein said step of mixing said suspension is performed by continuously feeding said dilution liquid into said suspension downstream of said detecting area.

17. The method of claim 10 further comprising diluting said suspension with a dilution liquid prior to passing said suspension through said detecting area.

18. The method of claim 10 wherein said detecting area is defined as a first detecting area and said particle detecting device is defined as a first particle detecting device, said method further comprising:

(a′

) passing said suspension emerging from said first detecting area through a second detecting area of a second particle detecting device, and detecting said particles as they pass through said second detecting area prior to collecting said particles in said collection vessel,

(a″

) diluting said suspension with a dilution liquid prior to passing said suspension through said first detecting area, and

(a′

″

) further diluting said suspension with said dilution liquid between said first detection area and said second detection area,

and wherein step (b) comprises cumulatively recording by said controller the number of particles detected by said second particle detecting device.