Low cost optical high speed discrete measurement system

Patent metadata

Field	Value
Publication number	US-9766261-B2
Application number	US-201414289982-A
Country	US
Kind code	B2
Filing date	May 29, 2014
Priority date	May 29, 2013
Publication date	Sep 19, 2017
Grant date	Sep 19, 2017

Abstract

Systems and methods are provided for determining a velocity or an inflation rate of a droplet in a microfluidic channel. The droplet is exposed to two or more temporally separated flashes of light, each flash including light of one wavelength band, and imaged using a detector configured to distinguish light in the wavelength bands. Two or more images of the droplet are acquired, each corresponding to one of the flashes, and all within a single video frame or photographic exposure. The images can be processed separately and the position or size of the droplet in each image is calculated. A velocity or inflation rate is then determined by dividing the change in position or size by the amount of time allowed to pass between the flashes.

First claim

What is claimed is:

1. A method for determining a velocity, an inflation rate, or both of a droplet passing through a microfluidic channel formed of a translucent material, the method comprising:
illuminating the droplet with a first flash of light emitted by a multicolor light source, wherein the multicolor light source is configured to emit light in two or more different wavelength bands and as temporally separated flashes, wherein each flash comprises light of only one of said wavelength bands, and wherein the first flash of light comprises light of a first wavelength band;
acquiring a first image of the droplet when the droplet is illuminated with the first flash of light with a detector configured to detect and distinguish between light in said wavelength bands, wherein the multicolor light source, the detector, and the microfluidic channel are positioned such that light emitted by the multicolor light source is incident upon the microfluidic channel, and the droplet passing through the microfluidic channel and illuminated by the multicolor light source is imaged on the detector;
allowing an amount of time to pass;
illuminating the droplet with a second flash of light emitted by the multicolor light source, wherein the second flash of light comprises light of a second wavelength band different from the first wavelength band;
acquiring a second image of the droplet when the droplet is illuminated with the second flash of light, wherein the first image and the second image are acquired (i) using the detector and (ii) as part of the same video frame or the same photographic exposure;
calculating a change in position of the droplet, a change in size of the droplet, or both, between the first image and the second image by separating the first image from the second image in the video frame or the photographic exposure; and
dividing the change in position of the droplet, the change in size of the droplet, or both, by the amount of time, thereby determining a velocity of the droplet, an inflation rate of the droplet, or both, respectively, passing through the microfluidic channel between the first image and the second image.

2. The method of claim 1 wherein determining a velocity of the droplet further comprises calculating the change in position of the droplet by determining a first centroid position of the droplet in the first image and a second centroid position of the droplet in the second image.

3. The method of claim 1 comprising determining an inflation rate of the droplet, wherein calculating a change in size of the droplet between the first image and the second image comprises determining a first diameter of the droplet in the first image and a second diameter of the droplet in the second image.

4. The method of claim 1 , wherein the system further comprises a pressure source coupled to the microfluidic channel, and the method further comprises adjusting the pressure source based upon the velocity or the inflation rate of the droplet.

5. The method of claim 1 , further comprising:
illuminating the droplet with a third flash of light emitted by the multicolor light source;
acquiring a third image of the droplet when the droplet is illuminated with the third flash of light, wherein the image is acquired using the detector;
selecting a reference image, wherein the reference image is either the first image or the second image;
calculating an additional change in position of the droplet, an additional change in size of the droplet, or both, between the reference image and the third image;
determining an elapsed time between acquisition of the reference image and acquisition of the third image; and
dividing the additional change in position of the droplet, the additional change in size of the droplet, or both, respectively, by the elapsed time to determine a velocity, an inflation rate, or both of the droplet in the microfluidic channel between the reference image and the third image.

6. The method of claim 5 , wherein the third flash of light comprises light of a third wavelength band different from the first wavelength band and the second wavelength band.

7. The method of claim 5 , wherein the third image and the reference image are acquired as part of the same video frame or the same photographic exposure.

8. The method of claim 5 , wherein the elapsed time between acquisition of the reference image and acquisition of the third image differs by a factor of at least 2 from the amount of time allowed to pass between acquisition of the first image and acquisition of the second image.

9. A method for determining a velocity, an inflation rate, or both of a droplet passing through a microfluidic channel formed of a translucent material, the method comprising:
illuminating the droplet with a first flash of light emitted by a multicolor light source, wherein the multicolor light source is configured to emit light in two or more different wavelength bands and as temporally separated flashes, wherein each flash comprises light of only one of said wavelength bands, and, wherein the first flash of light comprises light of a first wavelength band;
acquiring a first image of the droplet when the droplet is illuminated with the first flash of light with a detector configured to detect and distinguish between light in said wavelength bands, wherein the multicolor light source, the detector, and the microfluidic channel are positioned such that light emitted by the multicolor light source is incident upon the microfluidic channel, and the droplet passing through the microfluidic channel and illuminated by the multicolor light source is imaged on the detector;
allowing an amount of time to pass;
illuminating the droplet with a second flash of light emitted by the multicolor light source, wherein the second flash of light comprises light of a second wavelength band different from the first wavelength band;
acquiring a second image of the droplet when the droplet is illuminated with the second flash of light, wherein the first image and the second image are acquired using the detector and as part of the same video frame or the same photographic exposure;
calculating a change in position of the droplet, a change in size of the droplet, or both, between the first image and the second image, wherein calculating the change in position of the droplet comprises determining a first centroid position of the droplet in the first image and a second centroid position of the droplet in the second image; and
dividing the change in position of the droplet, the change in size of the droplet, or both, by the amount of time, thereby determining a velocity of the droplet centroid position, an inflation rate of the droplet, or both, respectively, passing through the microfluidic channel between the first image and the second image.

10. The method of claim 9 , wherein calculating a change in position of the droplet or a change in size of the droplet between the first image and the second image comprises separating the first image from the second image in the video frame or the photographic exposure.

11. The method of claim 9 comprising determining an inflation rate of the droplet, wherein calculating a change in size of the droplet between the first image and the second image comprises determining a first diameter of the droplet in the first image and a second diameter of the droplet in the second image.

12. The method of claim 9 , wherein the system further comprises a pressure source coupled to the microfluidic channel, and the method further comprises adjusting the pressure source based upon the velocity or the inflation rate of the droplet.

13. The method of claim 9 , further

Assignees

• Gnubio Inc
• Bio Rad Laboratories Inc

Inventors

• Tracy David H
• Weber Aaron
• Stokes Peter

Classifications

• B01L2400/082

  Active control of flow resistance, e.g. flow controllers · CPC title

• G01N15/1484

  microstructural devices · CPC title

• G01N35/08

  using a stream of discrete samples flowing along a tube system, e.g. flow injection analysis · CPC title

• G01P5/20 Primary

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

• B01L3/502784

  specially adapted for droplet or plug flow, e.g. digital microfluidics · CPC title