Droplet Actuator Devices and Methods Employing Magnetic Beads

• US 20190324026A1
• Filed: 06/27/2019
• Published: 10/24/2019
• Est. Priority Date: 02/09/2007
• Status: Active Application

• Current Assignee: Duke University, Advanced Liquid Logic, Inc. (Illumina Incorporated)
• Original Assignee: Advanced Liquid Logic, Inc. (Illumina Incorporated)
• Inventors: Sista, Ramakrishna, Pamula, Vamsee K., Pollack, Michael G., Srinivasan, Vijay, Eckhardt, Allen E., Fair, Richard B.
• Application Number:
  US16/455,506
• Publication Number:
  US 20190324026A1
• Time in Patent Office: Days
• CPC Class Codes: B01L 2200/025 Align devices or objects to ensure defined positions relative to each other
• CPC Class Codes: B01L 2200/028 Modular arrangements
• CPC Class Codes: B01L 2200/0647 Handling flowable solids, e.g. microscopic beads, cells, particles
• CPC Class Codes: B01L 2200/0673 Handling of plugs of fluid surrounded by immiscible fluid
• CPC Class Codes: B01L 2200/141 Preventing contamination, tampering
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0864 comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
• CPC Class Codes: B01L 2300/0867 Multiple inlets and one sample wells, e.g. mixing, dilution
• CPC Class Codes: B01L 2400/0427 Electrowetting
• CPC Class Codes: B01L 2400/043 magnetic forces
• CPC Class Codes: B01L 3/502715 characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: B01L 3/50273 characterised by the means or forces applied to move the fluids micropumps F04B19/006, of the membrane type F04B43/043
• CPC Class Codes: B01L 3/502761 specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads, for physically stretching molecules investigating characteristics of particles G01N15/00
• CPC Class Codes: B01L 3/502784 specially adapted for droplet or plug flow, e.g. digital microfluidics automatic analysis using a stream of discrete samples in a tube system G01N35/08
• CPC Class Codes: C12M 25/01 Drops
• CPC Class Codes: C12M 25/16 Particles; Beads; Granular material; Encapsulation chemical or physical processes conducted in the presence of fluids and solid particles B01J8/00
• CPC Class Codes: G01N 2035/1046 Levitated, suspended drops
• CPC Class Codes: G01N 27/44717 Arrangements for investigating the separated zones, e.g. localising zones
• CPC Class Codes: G01N 27/44786 of the magneto-electrophoresis type
• CPC Class Codes: G01N 33/54326 Magnetic particles
• CPC Class Codes: G01N 33/54386 : Analytical elements
• CPC Class Codes: G01N 35/0098 : involving analyte bound to insoluble magnetic carrier, e.g. using magnetic separation magnetic particles used in immunoassays G01N33/54326; magnetic separation in general B03C

Abstract

A method comprising effecting a change in a shape of a droplet, wherein the droplet is disposed over a substrate in sensing proximity to a sensor and the droplet has a starting surface area exposed to the sensor; and producing an expanded surface area of the droplet in the sensing proximity exposed to the sensor, wherein the expanded surface area exposed to the sensor is greater than the starting surface area exposed to the sensor.

Claims

1. A method comprising:

effecting a change in a shape of a droplet, wherein the droplet is disposed over a substrate in sensing proximity to a sensor and the droplet has a starting surface area exposed to the sensor; and

producing an expanded surface area of the droplet in the sensing proximity exposed to the sensor, wherein the expanded surface area exposed to the sensor is greater than the starting surface area exposed to the sensor.

2. The method of claim 1, further comprising activating one or more electrodes associated with the substrate.

3. The method of claim 1, wherein the producing an expanded surface area comprises an electrowetting mediated effect.

4. The method of claim 1, wherein the sensor comprises a photon sensor, and the droplet comprises a substance that emits photons.

5. The method of claim 1, wherein the change in the droplet'"'"'s shape produces a slug.

6. The method of claim 1, wherein the change in the droplet'"'"'s shape produces a series of sub-droplets.

7. The method of claim 1, wherein in the expanded surface area of the droplet, the droplet is spread across multiple electrodes.

8. The method of claim 1 wherein the droplet comprises one or more magnetically responsive beads.

9. A method comprising:

activating one or more electrodes associated with a substrate to effect a change in a shape of a droplet, wherein the droplet is disposed over a substrate in sensing proximity to a photon sensor, and the droplet has a starting surface area exposed to the sensor; and

producing an expanded surface area of the droplet in sensing proximity to the photon sensor, wherein the expanded surface area exposed to the sensor is greater than the starting surface area exposed to the sensor.

10. The method of claim 9 wherein in the expanded surface area of the droplet, the droplet is spread across multiple electrodes.

11. The method of claim 9, wherein the droplet comprises one or more magnetically responsive beads.

12. The method of claim 9, further comprising detecting photons emitted from the droplet using a photomultiplier tube (PMT) or photon-counting PMT located in a droplet detection region of the substrate, wherein the photon sensor comprises the photomultiplier tube (PMT) or photon-counting PMT.

13. A method comprising:

transporting a first droplet from a set of two or more droplets into sensing proximity with a sensor while retaining at least one remainder droplet of the set in a buffer zone; and

transporting the first droplet away from the sensing proximity with the sensor and transporting a second droplet of the at least one remainder droplet of the set from the buffer zone into the sensing proximity with the sensor.

14. The method of claim 13 further comprising repeating the transporting with respect to one or more additional droplets, wherein the set has three or more droplets.

15. The method of claim 13 wherein the first and second droplets are buffered and transported on a droplet actuator.

16. The method of claim 15, wherein:

the droplet actuator comprises two substrates separated to form a gap;

the droplets are positioned in the gap;

the sensor is configured in proximity to one of the substrates; and

the sensing proximity of the sensor is limited by a mask on one or both of the substrates.

17. The method of claim 16, further comprising detecting photons emitted from the droplet using a photomultiplier tube (PMT) or photon-counting PMT located in a droplet detection region of one of the substrates, wherein the sensor comprises the photomultiplier tube (PMT) or photon-counting PMT.

18. The method of claim 16, wherein the transporting of the first droplet and the transporting of the second droplet comprises the use of a plurality of electrodes on one of the substrates.

19. The method of claim 16, wherein the droplet comprises one or more magnetically responsive beads.

20. The method of claim 19, wherein the droplet actuator further includes a magnet that is arranged in proximity to the arrangement of electrodes.