Microparticle sorting apparatus and delay time determination method

Patent metadata

Field	Value
Publication number	US-10876954-B2
Application number	US-201815907805-A
Country	US
Kind code	B2
Filing date	Feb 28, 2018
Priority date	Mar 30, 2012
Publication date	Dec 29, 2020
Grant date	Dec 29, 2020

Abstract

A microparticle sorting apparatus includes a detection unit which detects microparticles flowing through a flow path; an imaging device which images a droplet containing the microparticles which is discharged from an orifice provided on an edge portion of the flow path; a charge unit which applies a charge to the droplets; and a control unit which determines a delay time as from a time that the microparticles are detected by the detection unit to the time at which a number of bright spots in a standard region, which is set beforehand, of image information imaged by the imaging device reaches the maximum, making it possible for the charge unit to apply a charge to the microparticles once the delay time has lapsed after the microparticles are detected by the detection unit.

First claim

What is claimed is:

1. A microparticle sorting apparatus comprising:
a detector configured to detect microparticles flowing through a flow path;
an imaging device configured to obtain a plurality of images of a droplet containing at least one of the microparticles, wherein the droplet is discharged from an orifice provided on an edge portion of the flow path; and
a controller configured to:
control the imaging device to obtain the plurality of images, the plurality of images having a common region in respective images of the plurality of images; and
determine a delay phase by comparing a brightness characteristic within the common region between a first image of the plurality of images and at least one second image of the plurality of images, wherein the brightness characteristic is indicative of an amount of pixels having a brightness higher than a threshold.

2. The microparticle sorting apparatus of claim 1 , wherein the controller is further configured to set a timing for applying charge to droplets based on the delay phase.

3. The microparticle sorting apparatus of claim 1 , wherein the controller is further configured to determine the delay phase by comparing a brightness characteristic in at least one comparison region to a brightness characteristic in the common region for an image of the plurality of images, wherein the at least one comparison region is adjacent to the common region along a discharge direction of the droplets in the image.

4. The microparticle sorting apparatus of claim 3 , wherein the at least one comparison region includes a first comparison region and a second comparison region arranged on opposite sides of the common region, and wherein the controller is configured to determine the delay phase based on a brightness characteristic in the first comparison region and a brightness characteristic in the second comparison region.

5. The microparticle sorting apparatus of claim 4 , wherein the controller is further configured to:
calculate a first time at which a brightness characteristic of the first comparison region reaches a predetermined percentage of a maximum value;
calculate a second time at which a brightness characteristic of the second comparison region reaches a predetermined percentage of the maximum value; and
determine a time for the common region as (the first time+the second time)/2.

6. The microparticle sorting apparatus of claim 4 , wherein the controller is further configured to adjust a discharge frequency of the droplets based on the delay phase, and determine an optimal discharge frequency of the droplets to be the discharge frequency at which a point where the droplets are formed is proximate the orifice.

7. The microparticle sorting apparatus of claim 1 , further comprising:
a pair of deflection plates disposed opposite one another to interpose the droplets imaged by the imaging device, which change a progression direction of the droplets using an electrical force which acts between the deflection plates and a charge applied to the droplets.

8. The microparticle sorting apparatus of claim 1 , wherein the microparticle sorting apparatus is a microchip-type flow cytometer in which the orifice and the flow path are provided in a microchip.

9. The microparticle sorting apparatus of claim 1 , wherein the controller is further configured to control the imaging device to obtain the plurality of images based on a time when one of the microparticles is detected by the detector.

10. A delay phase determination method comprising:
detecting, using a microparticle sorting device, microparticles flowing through a flow path;
obtaining, using the microparticle sorting device, a plurality of images of a droplet including at least one of the microparticles, the plurality of images having a common region in respective images of the plurality of images; and
determining a delay phase by comparing a brightness characteristic within the common region between a first image of the plurality of images and at least one second image of the plurality of images, wherein the brightness characteristic is indicative of an amount of pixels having a brightness higher than a threshold.

11. The delay phase determination method of claim 10 , the method further comprising setting a timing for applying charge to droplets based on the delay phase.

12. The delay phase determination method of claim 10 , wherein determining the delay phase further comprises comparing a brightness characteristic in at least one comparison region to a brightness characteristic in the common region for an image of the plurality of images, wherein the at least one comparison region is adjacent to the common region along a discharge direction of the droplets in the image.

13. The delay phase determination method of claim 12 , wherein the at least one comparison region includes a first comparison region and a second comparison region arranged on opposite sides of the common region, and
determining the delay phase further comprises determining the delay phase based on a brightness characteristic in the first comparison region and a brightness characteristic in the second comparison region.

14. The delay phase determination method of claim 13 , the method further comprising:
calculating a first time at which a brightness characteristic of the first comparison region reaches a predetermined percentage of a maximum value;
calculating a second time at which a brightness characteristic of the second comparison region reaches a predetermined percentage of the maximum value; and
determining a time for the common region as (the first time+the second time)/2.

15. The delay phase determination method of claim 13 , the method further comprising:
adjusting a discharge frequency of the droplets based on the delay phase; and
determining an optimal discharge frequency of the droplets to be the discharge frequency at which a point where the droplets are formed is proximate to the orifice.

16. The delay phase determination method of claim 10 , wherein obtaining the plurality of images further comprises obtaining the plurality of images based on a time when one of the microparticles is detected by the microparticle sorting device.

17. The microparticle sorting apparatus of claim 1 , wherein the brightness characteristic is representative of one or more microparticles contained within one or more droplets.

18. The microparticle sorting apparatus of claim 1 , wherein the delay phase corresponds to a time relative to a discharge time interval between droplets.

19. The microparticle sorting apparatus of claim 1 , wherein the droplet is in the common region for at least one of the plurality of images and the droplet is not in the common region for at least one of the plurality of images.

20. The microparticle sorting apparatus of claim 1 , wherein the common region is at the same section along a discharge direction of the droplet.

Assignees

• Sony Corp

Inventors

• Muraki Yosuke
• Tsuji Akiko
• Miyata Takashi

Classifications

• G01N2015/1481

  Optical analysis of particles within droplets (sorting particles within droplets G01N15/1492) · CPC title

• G01N15/1425 Primary

  using an analyser being characterised by its control arrangement · CPC title

• G01N15/1492

  within droplets · CPC title

• G01N15/1404 Primary

  Handling flow, e.g. hydrodynamic focusing · CPC title

• G01N15/1429

  Signal processing · CPC title