Droplet operations platform

• US 9,910,010 B2
• Filed: 01/04/2016
• Issued: 03/06/2018
• Est. Priority Date: 03/30/2010
• Status: Active Grant

• Current Assignee: Advanced Liquid Logic, Inc. (Illumina Incorporated)
• Original Assignee: Advanced Liquid Logic, Inc. (Illumina Incorporated)
• Inventors: Bauer, William Craig
• Primary Examiner(s): Gordon, Brian R
• Application Number:
  US14/987,352
• Publication Number:
  US 20160195492A1
• Time in Patent Office: 792 Days
• CPC Class Codes: B01F 33/3021 the components to be mixed being combined in a single independent droplet, e.g. these droplets being divided by a non-miscible fluid or consisting of independent droplets
• CPC Class Codes: B01F 33/3031 using electro-hydrodynamic [EHD] or electro-kinetic [EKI] phenomena to mix or move the fluids
• CPC Class Codes: B01L 2200/027 for microfluidic devices
• CPC Class Codes: B01L 2200/06 Fluid handling related problems
• CPC Class Codes: B01L 2200/0668 Trapping microscopic beads
• CPC Class Codes: B01L 2200/10 Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
• CPC Class Codes: B01L 2200/16 Reagents, handling or storing thereof
• CPC Class Codes: B01L 2300/0887 Laminated structure
• CPC Class Codes: B01L 2300/12 Specific details about materials
• CPC Class Codes: B01L 2300/18 Means for temperature control
• CPC Class Codes: B01L 2300/1805 Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks
• CPC Class Codes: B01L 2300/1827 using resistive heater
• CPC Class Codes: B01L 2400/0427 Electrowetting
• CPC Class Codes: B01L 2400/043 magnetic forces
• CPC Class Codes: B01L 2400/0677 phase change valves; Meltable, freezing, dissolvable plugs; Destructible barriers
• CPC Class Codes: B01L 2400/0683 mechanically breaking a wall or membrane within a channel or chamber
• CPC Class Codes: B01L 3/502707 characterised by the manufacture of the container or its components by shaping or joining plastic parts B29C59/00, B29C65/00; by laminating B32B37/00; manufacture of microstructural devices in general B81C
• 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: B01L 7/525 : with physical movement of samples between temperature zones
• CPC Class Codes: B01L 7/54 : using spatial temperature gradients
• CPC Class Codes: G01N 27/44734 : by thermal means
• CPC Class Codes: G01N 27/44791 : Microapparatus sample containers with integrated microfluidic structures B01L3/5027

Abstract

The invention relates to a droplet actuator device and methods for integrated sample preparation and analysis of a biological sample. A droplet actuator device is provided for conducting droplet operations. The droplet actuator device may include a bottom substrate and a top substrate separated from each other to form a gap therebetween; an arrangement of droplet operations electrodes arranged on one or both of the bottom and/or top substrates for conducting droplet operations thereon; a reagent storage layer comprising one or more compartments bound to the top substrate; and one or more openings arranged to provide a fluidic path from the one or more compartments into the gap, upon breach of a breachable seal separating the one or more compartments and openings.

Claims

1. A droplet actuator device comprising:

a. a bottom substrate and a top substrate separated from each other to form a gap therebetween;

b. an arrangement of droplet operations electrodes, on one of the bottom substrate and the top substrate, configured for conducting droplet operations thereon;

c. one or more heater elements in proximity to and aligned with one or more of the droplet operations electrodes in a manner which permits establishment of temperature control in the gap in vicinity of the one or more droplet operations electrodes;

d. one or more temperature control zones in the gap, wherein each of the one or more temperature control zones is established by at least one metal layer structure provided within or on a surface of the bottom substrate, and distinct from the droplet operations electrodes, wherein the metal layer structure is distinct from the one or more heater elements and arranged to control distribution of heat in the gap.

2. The droplet actuator device of claim 1, wherein the bottom substrate comprises a PCB.

3. The droplet actuator device of claim 2, wherein the PCB comprises a dielectric layer.

4. The droplet actuator device of claim 2, wherein the arrangement of droplet operations electrodes is arranged on the PCB, and the at least one metal layer structure and the arrangement of droplet operations electrodes are provided on a same layer on the PCB.

5. The droplet actuator device of claim 1, wherein the at least one metal layer structure is constructed from copper.

6. The droplet actuator device of claim 1, wherein the at least one metal layer structure is positioned adjacent to the one or more droplet operations electrodes.

7. The droplet actuator device of claim 1, wherein the arrangement of droplet operations electrodes is arranged in a layer on the PCB, and the at least one metal layer structure is provided on a different layer on the PCB than the arrangement of droplet operations electrodes.

8. The droplet actuator device of claim 7, wherein the at least one metal layer structure is provided on a layer on a backside of the PCB that is opposite to the layer of the arrangement of droplet operations electrodes.

9. The droplet actuator device of claim 7, wherein the at least one metal layer structure is provided on a layer on the PCB adjacent to the arrangement of droplet operations electrodes arranged on the PCB.

10. The droplet actuator device of claim 1, comprising at least two temperature control zones, wherein at least two of the at least one metal layer structure are respectively co-located with the at least two temperature control zones and are configured to control distribution of heat flowing in the gap of the at least two temperature control zones to heat the at least two temperature control zones to a same temperature.

11. The droplet actuator device of claim 10, wherein the at least two temperature control zones heated to the same temperature are thermally coupled.

12. The droplet actuator device of claim 1, wherein the gap comprises oil.

13. The droplet actuator device of claim 1, wherein the gap comprises silicone oil.

14. The droplet actuator device of claim 1, wherein the arrangement of droplet operations electrodes comprises electrowetting electrodes.

15. The system of claim 1, wherein the one or more heater elements are positioned adjacent to the at least one metal layer structure.

16. The system of claim 1, wherein the one or more heater elements provide heat to the at least one metal layer structure.

17. The system of claim 1, wherein the one or more heater elements comprise a resistive heater.

18. The system of claim 1, wherein the one or more heater elements comprise thermoelectric heat pumps.

19. The system of claim 1, further comprising at least one thermistor to monitor the temperature of the at least one metal layer structure.

20. The system of claim 1, wherein the at least one metal layer structure is shaped to form a temperature gradient along a path of the droplet operations electrodes.

21. The system of claim 20, wherein the at least one metal layer structure is shaped in the form of a “

V”

such that a substantially linear temperature gradient is formed along the path of the droplet operations electrodes, wherein one of the one or more heater elements is positioned at the narrow end of the “

V”

shaped heat spreader.

22. The system of claim 20, wherein the heat spreader is shaped in the form of a “

U” and

arranged such that a temperature gradient is formed along the path of the droplet operations electrodes, wherein one of the one or more heater elements is coupled to the “

U”

shaped heat spreader.

25. The droplet actuator device of claim 1, wherein the at least one metal layer structure comprises a metal layer structure surface area larger than a surface area of a droplet operations electrode of the droplet operations electrodes.

23. A system comprising:

i) a droplet actuator device comprising;

a. a bottom substrate and a top substrate separated from each other to form a gap therebetween;

b. an arrangement of droplet operations electrodes comprising electrowetting electrodes, on one of the bottom substrate and the top substrate, configured for conducting droplet operations thereon;

c. one or more temperature control zones in the gap, wherein each of the one or more temperature control zones is established by at least one metal layer structure provided within or on a surface of the bottom substrate, and distinct from the droplet operations electrodes; and

ii) one or more heater elements in proximity to and aligned with one or more of the droplet operations electrodes in a manner which permits establishment of temperature control in the gap in vicinity of the one or more droplet operations electrodes, wherein the one or more heater elements provide heat to the at least one metal layer structure, wherein the at least one metal layer structure is distinct from the one or more heater elements and arranged to control distribution of heat flowing in the gap.

24. The system of claim 23, further comprising at least one thermistor to monitor the temperature of the at least one metal layer structure.