Droplet velocity detection

Patent metadata

Field	Value
Publication number	US-10215771-B2
Application number	US-201514932537-A
Country	US
Kind code	B2
Filing date	Nov 4, 2015
Priority date	Nov 6, 2014
Publication date	Feb 26, 2019
Grant date	Feb 26, 2019

Abstract

Methods and systems are provided for measuring a velocity of a droplet passing through a microfluidic channel.

First claim

What is claimed is:

1. A method of measuring a velocity of a droplet passing through a microfluidic channel, wherein:
the microfluidic channel is interposed between a laser and a detector, and comprises a transparent illumination site;
the laser is directed at the illumination site and the detector; and
the detector comprises a plurality of physically separated detection regions and is configured to generate a signal for each region, the signal being proportional to the intensity of light incident on the region,
and the method comprising:
while the droplet is absent from the illumination site,
shining a laser beam emitted by the laser through the illumination site and onto the detector, wherein the laser beam is incident on a first region and a second region of the detector,
measuring a first baseline signal for the first region, and
measuring a second baseline signal for the second region;
while the droplet passes through the illumination site,
shining the laser beam through the illumination site and onto the detector,
measuring a first signal for the first region, and
measuring a second signal for the second region;
determining a first departure time at which the first signal initially departs from the first baseline signal by a first predetermined amount;
determining a second departure time at which the second signal initially departs from the second baseline signal by a second predetermined amount;
calculating a difference between the first departure time and the second departure time to obtain an elapsed time;
determining a velocity based on the elapsed time,
determining a first recovery time at which the first signal initially recovers to the first baseline signal to within a first predetermined tolerance, the first recovery time occurring after the first departure time;
calculating a difference between the first departure time and the first recovery time to obtain a first passage time; and
multiplying the first passage time by the velocity to obtain a width of the droplet thereby measuring the velocity and width of the droplet passing through the microfluidic channel.

2. The method of claim 1 , wherein the first region of the detector or the second region of the detector comprises a single pixel or photodiode.

3. The method of claim 1 , wherein:
the first signal initially departs from the first baseline signal by falling below the first baseline signal by the first predetermined amount, or
the second signal initially departs from the second baseline signal by falling below the second baseline signal by the second predetermined amount.

4. The method of claim 1 , wherein:
the first signal initially departs from the first baseline signal by exceeding the first baseline signal by the first predetermined amount, or
the second signal initially departs from the second baseline signal by exceeding the second baseline signal by the second predetermined amount.

5. The method of claim 1 , wherein the first predetermined amount is about equal to the second predetermined amount.

6. The method of claim 1 , wherein the first predetermined tolerance is at most 1,000,000 count(s).

7. The method of claim 1 , further comprising:
determining a second recovery time at which the second signal initially recovers to the second baseline signal to within a second predetermined tolerance,
calculating a difference between the first recovery time and the second recovery time to obtain an additional elapsed time; and
determining an additional velocity of the droplet based on the additional elapsed time.

8. The method of claim 7 , wherein the first predetermined tolerance is about equal to the second predetermined tolerance.

9. The method of claim 7 , wherein determining an additional velocity of the droplet comprises dividing an appropriate distance by the additional elapsed time.

10. A method of measuring a velocity of a droplet passing through a microfluidic channel, wherein:
the microfluidic channel is interposed between a laser and a detector, and comprises a transparent illumination site;
the laser is directed at the illumination site and the detector;
the detector comprises a plurality of physically separated detection regions and is configured to generate a signal for each region, the signal being proportional to the intensity of light incident on the region,
and the method comprising:
shining a laser beam emitted by the laser through the illumination site and onto the detector;
identifying a first non-incident region and a second non-incident region of the detector, wherein the laser beam is not incident on either non-incident region when the droplet is absent from the illumination site;
while the droplet passes through the illumination site,
measuring a first signal for the first non-incident region, and
measuring a second signal for the second non-incident region;
determining a first increase time at which the first signal initially exceeds a first predetermined threshold;
determining a second increase time at which the second signal initially exceeds a second predetermined threshold;
calculating a difference between the first increase time and the second increase time to obtain an elapsed time; and
determining a velocity based on the elapsed time, thereby measuring the velocity of the droplet passing through the microfluidic channel.

11. The method of claim 10 , wherein the first non-incident region or the second non-incident region comprises a single pixel or photodiode.

12. The method of claim 10 , further comprising:
while the droplet is absent from the illumination site, measuring a first dark signal for the first non-incident region, and measuring a second dark signal for the second non-incident region;
wherein the first predetermined threshold is based on the first dark signal, and the second predetermined threshold is based on the second dark signal.

13. The method of claim 12 , wherein:
the first predetermined threshold is a multiple of at least 1.1 of the first dark signal, or
the second predetermined threshold is a multiple of at least 1.1 of the second dark signal.

14. The method of claim 10 , wherein the first predetermined threshold is about equal to the second predetermined threshold.

15. The method of claim 10 , wherein determining a velocity comprises dividing an appropriate distance by the elapsed time.

16. The method of claim 15 , wherein the appropriate distance is a function of the distance between the first non-incident region and the second non-incident region of the detector.

17. The method of claim, 9 , wherein the appropriate distance is about equal to the width of the illumination site.

18. The method of claim 1 , wherein the laser beam is focused at the illumination site.

19. A system for measuring the velocity of a droplet passing through a microfluidic channel, the system comprising a laser, a microfluidic channel, and a detector, wherein:
the microfluidic channel comprises a transparent illumination site and is interposed between the laser and the detector;
the laser is directed at the microfluidic channel and the detector, such that a laser beam emitted by the laser intersects the microfluidic channel at the illumination site and is transmitted by the microfluidic channel to the detector;
the detector comprises a plurality of physically separated detection regions and is configured to generate a signal for each region, the signal being proportional to the intensity of light incident on the region; and
in the absence of a droplet at the illumination

Assignees

• Bio Rad Laboratories

Inventors

• Weber Aaron
• Hung Tony
• Kiani Sepehr

Classifications

• G01P5/20

  using particles entrained by a fluid stream (G01P5/22 takes precedence) · CPC title

• G01P5/18 Primary

  by measuring the time taken to traverse a fixed distance · CPC title

• G01P5/26

  by measuring the direct influence of the streaming fluid on the properties of a detecting optical wave · CPC title