Non-poissonian droplet partitioning using feedback

Patent metadata

Field	Value
Publication number	US-11944973-B2
Application number	US-202117396819-A
Country	US
Kind code	B2
Filing date	Aug 9, 2021
Priority date	Jan 8, 2019
Publication date	Apr 2, 2024
Grant date	Apr 2, 2024

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.

First claim

What is claimed is:

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.

Assignees

• Sharp Life Science Eu Ltd

Inventors

• Huang Laura
• Hadwen Benjamin James
• Wilson Adam Christopher

Classifications

• B01L3/502792 Primary

  for moving individual droplets on a plate, e.g. by locally altering surface tension · CPC title

• B01L3/502746

  characterised by the means for controlling flow resistance, e.g. flow controllers, baffles or throttle valves · CPC title

• G01N15/1031

  by measuring electrical or magnetic effects · CPC title

• G01N15/1484

  microstructural devices · CPC title

• B01L2200/06

  Fluid handling related problems · CPC title