IP Library Granted Patent US 11,944,973
Granted Patent B2
US 11,944,973 · App. 17/396,819 · Granted Apr 2, 2024

Non-poissonian droplet partitioning using feedback

Inventors: Laura Huang (Oxford, GB); Benjamin James Hadwen (Oxford, GB); Adam Christopher Wilson (Oxford, GB)
Assignee: Sharp Life Science (EU) Limited
B01L3/502792B01L3/502746G01N15/1031G01N15/1484B01L2200/06B01L2200/061B01L2400/0427B01L2400/084G01N2015/1043G01N2015/1481G01N2015/1486
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Quick Facts
Patent No.
US 11,944,973
App. No.
17/396,819
Granted
Apr 2, 2024
Kind
B2
Abstract

A microfluidic device performs a method of partitioning droplets from a fluid reservoir containing particles that provides a non-Poissonian distribution of dispensed droplets containing a desired number of particles. Using an electrowetting on dielectric (EWOD) device, droplets are dispensed having a Poissonian distribution of dispensed droplets containing a desired number of particles, and the droplets are interrogated to determine whether each dispensed droplet has a desired number of particles. Droplets that contain the desired number of particles are moved by EWOD operation to a reaction area on the EWOD device, and droplets that do not contain the desired number of particles are rejected and moved by EWOD operation to a holding area on the EWOD device that is different and spaced apart from the reaction area. The result is that droplets in the reaction area have a non-Poissonian distribution of droplets containing the desired number of particles.

Claims (26)

1. A microfluidic system comprising:

an electro-wetting on dielectric (EWOD) device comprising an element array configured to receive liquid droplets, the element array comprising a plurality of individual array elements and wherein one of said liquid droplets comprises a fluid reservoir containing particles that is inputted into the EWOD device;

a detector for detecting a property of a liquid droplet dispensed onto the element array; and

a control system configured to perform electrowetting operations by controlling actuation voltages applied to the element array to perform manipulation operations as to liquid droplets present on the element array;

wherein the control system is configured to perform the steps of:

performing an electrowetting operation to dispense a plurality of dispensed droplets from the fluid reservoir, the dispensed droplets having a Poisson distribution of droplets containing a desired number of particles;

interrogating each dispensed droplet with the detector and determining whether each dispensed droplet has the desired number of particles;

selecting dispensed droplets that contain the desired number of particles and performing an electrowetting operation to move the selected dispensed droplets to a reaction area on the EWOD device, the selected dispensed droplets having a non-Poisson distribution of droplets containing the desired number of particles; and

rejecting dispensed droplets that do not contain the desired number of particles and performing an electrowetting operation to move the rejected dispensed droplets to a holding area on the EWOD device that is different and spaced apart from the reaction area.

2. The microfluidic system of claim 1 , wherein the control system further is configured to perform an electrowetting operation to merge a portion of the rejected droplets from the holding area back into the fluid reservoir.

3. The microfluidic system of claim 1 , further comprising a data logger that records a droplet history of the selected and rejected droplets; and the control system further is configured to perform the steps of:

reading the droplet history from the data logger; and

performing an electrowetting operation based on the droplet history to merge a portion of the rejected droplets from the holding area back into the fluid reservoir to maintain a particle concentration in the fluid reservoir having an increased probability of dispensing droplets with the desired number of particles.

4. The microfluidic system of claim 1 , wherein the detector includes a sensor that is external to the element array of the EWOD device.

5. The microfluidic system of claim 1 , wherein the detector includes sensing circuitry that is integrated into array element circuitry of each of the array elements of the EWOD device.

6. The microfluidic system of claim 1 , wherein the detector includes a sensor configured to interrogate a dispensed droplet by optically observing the droplet, determining an electrical property of the droplet, and/or determining a mass of the droplet.

7. A non-transitory computer-readable medium storing program code which is executed by a processing device for controlling actuation voltages applied to array elements of an element array of an electro-wetting on dielectric (EWOD) device comprising an element array configured to receive liquid droplets, the element array comprising a plurality of individual array elements and wherein one of said liquid droplets comprises a fluid reservoir containing particles that is inputted into the EWOD device;

the program code being executable by the processing device to perform the steps of:

performing an electrowetting operation to dispense a plurality of dispensed droplets from the fluid reservoir, the dispensed droplets having a Poisson distribution of droplets containing a desired number of particles;

interrogating each dispensed droplet with a detector and determining whether each dispensed droplet has the desired number of particles;

selecting dispensed droplets that contain the desired number of particles and performing an electrowetting operation to move the selected dispensed droplets to a reaction area on the EWOD device, the selected dispensed droplets having a non-Poisson distribution of droplets containing the desired number of particles; and

rejecting dispensed droplets that do not contain the desired number of particles and performing an electrowetting operation to move the rejected dispensed droplets to a holding area on the EWOD device that is different and spaced apart from the reaction area.

8. The non-transitory computer-readable medium of claim 7 , wherein the program code further is executable by the processing device to perform an electrowetting operation to merge a portion of the rejected droplets from the holding area back into the fluid reservoir.

9. The non-transitory computer-readable medium of claim 7 , wherein the EWOD device further comprises a data logger that records a droplet history of the selected and rejected droplets; and the program code further is executable by the processing device to perform the steps of:

reading the droplet history from the data logger; and

performing an electrowetting operation based on the droplet history to merge a portion of the rejected droplets from the holding area back into the fluid reservoir to maintain a particle concentration in the fluid reservoir having an increased probability of dispensing droplets with the desired number of particles.

Assignments (1)
CHANGE OF APPLICANT'S ADDRESS Recorded Feb 3, 2022
From: SHARP LIFE SCIENCE (EU) LIMITED
To: SHARP LIFE SCIENCE (EU) LIMITED
Reel/Frame 058948/0187 →
Continuity (2)
Division 16242078 · Jan 8, 2019
Related Publication 20210362160A1 · Nov 25, 2021