Fluidics cartridge for use in the vertical or substantially vertical position

• US 10,576,471 B2
• Filed: 03/18/2016
• Issued: 03/03/2020
• Est. Priority Date: 03/20/2015
• Status: Active Grant

• Current Assignee: Illumina Incorporated
• Original Assignee: Illumina Incorporated
• Inventors: Osmus, James, Lemoine, Richard L., Gong, Jian, Lin, Sz-Chin Steven
• Primary Examiner(s): Mui, Christine T
• Application Number:
  US15/559,321
• Publication Number:
  US 20180111126A1
• Time in Patent Office: 1,446 Days
• Field of Search: 422502, 422500, 422 50
• CPC Class Codes: B01L 2200/0673 Handling of plugs of fluid surrounded by immiscible fluid
• CPC Class Codes: B01L 2300/0627 Sensor or part of a sensor is integrated
• CPC Class Codes: B01L 2300/0809 rectangular shaped
• CPC Class Codes: B01L 2300/0861 Configuration of multiple channels and/or chambers in a single devices
• CPC Class Codes: B01L 2400/0427 Electrowetting
• CPC Class Codes: B01L 2400/088 by specific surface properties
• 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 3/502784 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: B01L 3/502792 for moving individual droplets on a plate, e.g. by locally altering surface tension
• CPC Class Codes: G01N 33/573 for enzymes or isoenzymes
• CPC Class Codes: G01N 33/6863 Cytokines, i.e. immune system proteins modifying a biological response such as cell growth proliferation or differentiation, e.g. TNF, CNF, GM-CSF, lymphotoxin, MIF or their receptors

Abstract

Disclosed herein are devices, systems and methods for conducting a reaction using electrowetting in a vertical or substantially vertical position. Some embodiments disclosed herein provide fluidic cartridges for use in a substantially vertical position comprising: (a) a front substrate; (b) a back substrate; (c) a droplet operations gap formed between the front substrate and the back substrate; and (d) a plurality of electrodes on the front substrate or the back substrate, wherein the plurality of electrodes are configured to transport a droplet along a substantially vertical plane defined by the front substrate and the back substrate.

Claims

1. A fluidics cartridge for use in a substantially vertical position comprising:

(a) a front substrate;

(b) a back substrate;

(c) a droplet operations gap formed between the front substrate and the back substrate; and

(d) a plurality of electrodes on the front substrate or the back substrate,

wherein the plurality of electrodes is configured to transport a droplet along a substantially vertical plane defined by the front substrate and the back substrate;

wherein the front substrate comprises at least one U-feature which comprises a U-shaped protrusion from an inside surface of the front substrate and which is configured to hold a sample, a reaction mixture, a reagent, a filler fluid, a buffer, or a waste liquid.

2. The fluidics cartridge of claim 1, wherein the front substrate or the back substrate is a printed circuit board (PCB).

3. The fluidics cartridge of claim 1, wherein the back substrate comprises one or more flow paths.

4. The fluidics cartridge of claim 1, comprising one or more reservoirs configured to hold a reagent, a filler fluid, a buffer, or a waste liquid.

5. The fluidics cartridge of claim 4, wherein the one or more reservoirs can hold a volume of 1-100 ml.

6. The fluidics cartridge of claim 4, wherein the one or more reservoirs are integrated into a plate to form a reservoir assembly.

7. The fluidics cartridge of claim 4, wherein each of the one or more reservoirs is in fluid communication with the droplet operations gap through a flow path.

8. The fluidics cartridge of claim 4, wherein each of the one or more reservoirs are in fluid communication with the droplet operations gap through an upper flow path and a lower flow path.

9. The fluidics cartridge of claim 4, wherein the one or more reservoirs comprise a U-shaped portion.

10. The fluidics cartridge of claim 3, wherein the height of the droplet operations gap at the position of a flow path is greater than the height of the droplet operations gap.

11. The fluidics cartridge of claim 1, wherein a U-feature corresponds to a reservoir.

12. The fluidics cartridge of claim 11, wherein each of the one or more U-features comprises a U-shaped protrusion from an inside surface of the front substrate.

13. The fluidics cartridge of claim 12, wherein the U-shaped protrusion is porous.

14. The fluidics cartridge of claim 12, wherein the height of the U-shaped protrusion equals the height of the droplet operations gap.

15. The fluidics cartridge of claim 1, wherein the front substrate or back substrate comprises one or more downward dispensing volumes configured to hold a sample, a reaction mixture, a reagent, or a buffer.

16. The fluidics cartridge of claim 15, wherein the one or more downward dispensing volumes comprise sections having different heights.

17. The fluidics cartridge of claim 1, wherein the plurality of electrodes is configured to transport a droplet from the one or more U-features or the one or more downward dispensing volumes.

18. The fluidics cartridge of claim 17, wherein the plurality of electrodes is configured to form an electrowetting array.

19. The fluidics cartridge of claim 18, wherein the electrowetting array comprises a reagent dispense region, a reaction region, a sample loading region, a waste collection region, and a detection region.

20. The fluidics cartridge of claim 19, wherein the detection region comprises a CMOS detector.

21. The fluidics cartridge of claim 19, wherein the reaction region is configured to conduct a nucleic acid reaction selected from the group consisting of a PCR reaction, a sequencing reaction, a primer extension reaction and a clustering reaction.

22. A method of conducting a reaction using the fluidic cartridge according to claim 1, comprising:

providing a reaction droplet to the droplet operations gap of the fluid cartridge; and

actuating the reaction droplet to move vertically along the operations gap,

wherein the fluidic cartridge is operated in a substantially vertical position.

23. The method of claim 22, comprising drawing the reaction droplet by downward dispensing or upward dispensing.

24. The method of claim 22, comprising activating a CMOS detector to detect a reaction product in the reaction droplet.

25. The method of claim 22, comprising filling the droplet operations gap by passive refill.

26. The method of claim 22, comprising resuspending a plurality of beads in the droplet.

27. A system for conducting a reaction, comprising:

a fluidic cartridge comprising a front substrate, a back substrate, and a plurality of electrodes configured to transport a droplet along a substantially vertical plane defined by the front substrate and the back substrate, wherein the front substrate comprises at least one U-feature which comprises a U-shaped protrusion from an inside surface of the front substrate and which is configured to hold a sample, a reaction mixture, a reagent, a filler fluid, a buffer, or a waste liquid; and

an instrument deck holding the fluidic cartridge in a substantially vertical position.