Filler fluids for droplet operations

• US 8,980,198 B2
• Filed: 12/15/2006
• Issued: 03/17/2015
• Est. Priority Date: 04/18/2006
• Status: Active Grant

• Current Assignee: Duke University, Advanced Liquid Logic, Inc. (Illumina Incorporated)
• Original Assignee: Duke University, Advanced Liquid Logic, Inc. (Illumina Incorporated)
• Inventors: Srinivasan, Vijay, Pollack, Michael G., Paik, Philip Y., Pamula, Vamsee K., Fair, Richard B.
• Primary Examiner(s): Gordon, Brian R
• Application Number:
  US11/639,594
• Publication Number:
  US 20070242105A1
• Time in Patent Office: 3,014 Days
• Field of Search: 422/100, 422/501, 422502-504, 422/509, 422/518
• US Class Current: 422/504
• 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 2200/0647 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 2200/10 Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
• CPC Class Codes: B01L 2200/147 Employing temperature sensors
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0861 Configuration of multiple channels and/or chambers in a single devices
• CPC Class Codes: B01L 2300/089 Virtual walls for guiding liquids
• CPC Class Codes: B01L 2300/1827 using resistive heater
• CPC Class Codes: B01L 2400/0427 Electrowetting
• CPC Class Codes: B01L 2400/0448 Marangoni flow; Thermocapillary effect
• 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 3/502792 for moving individual droplets on a plate, e.g. by locally altering surface tension
• CPC Class Codes: B01L 7/52 with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples amplification or hybridisation processes per se C12Q1/68; controlling sequential reactions for synthesis B01J19/0046
• 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: B03C 5/02 : Separators
• CPC Class Codes: B81B 1/00 : Devices without movable or flexible elements, e.g. microcapillary devices
• CPC Class Codes: G01N 2035/1046 : Levitated, suspended drops
• CPC Class Codes: G01N 27/447 : using electrophoresis

Abstract

The present invention relates to filler fluids for droplet operations. According to one embodiment of this aspect, a droplet microactuator is provided and includes: (a) a first substrate comprising electrodes configured for conducting droplet operations on a surface of the substrate; (b) a second substrate spaced from the surface of the substrate by a distance sufficient to define an interior volume between the first substrate and second substrate, wherein the distance is sufficient to contain a droplet disposed in the space on the first substrate; and (c) a droplet arranged in the interior volume and arranged with respect to the electrodes in a manner which permits droplet operations to be effected on the droplet using the electrodes.

Claims

1. A droplet microactuator comprising:

(a) a first substrate comprising electrodes configured to effect electrowetting mediated droplet operations on a surface of the first substrate;

(b) a second substrate spaced from the surface of the first substrate by a distance sufficient to define an interior volume between the first substrate and the second substrate; and

(c) a droplet and a filler fluid in the interior volume, wherein the droplet is surrounded by the filler fluid, and arranged with respect to the electrodes in a manner which permits electrowetting mediated droplet operations to be effected on the droplet using the electrodes, wherein the filler fluid comprises an oil and a surfactant, and wherein the surfactant is provided in an amount which ranges from about 0.001 to about 10% w/w.

2. The droplet microactuator of claim 1 wherein the filler fluid comprises one or more silicone oils.

3. The droplet microactuator of claim 1 wherein the filler fluid comprises one or more fluorosilicone oils.

4. The droplet microactuator of claim 1 wherein the filler fluid comprises one or more hydrocarbons.

5. The droplet microactuator of claim 1 wherein the filler fluid comprises one or more alkanes.

6. The droplet microactuator of claim 1 wherein the filler fluid comprises a component selected from the group consisting of decane, undecane, dodecane, tridecane, tetradecane, pentadecane, hexadecane.

7. The droplet microactuator of claim 1 wherein the filler fluid comprises a component selected from the group consisting of aromatic alkanes.

8. The droplet microactuator of claim 1 wherein the filler fluid comprises a mineral oil.

9. The droplet microactuator of claim 1 wherein the filler fluid comprises a paraffin oil.

10. The droplet microactuator of claim 1 wherein the filler fluid is solid at room temperature of about 25°

C.

11. The droplet microactuator of claim 1 further comprising a second filler fluid surrounding or in contact with the filler fluid.

12. The droplet microactuator of claim 1 wherein the surfactant is a nonionic low HLB surfactant or a nonionic lipophile surfactant.

13. The droplet microactuator of claim 1 wherein the oil comprises a silicone oil and the surfactant comprises a nonionic lipophile surfactant.

14. The droplet microactuator of claim 1 wherein the surfactant is provided in an amount which ranges from about 0.001 to about 1% w/w.

15. The droplet microactuator of claim 1 wherein the surfactant is provided in an amount which ranges from about 0.001 to about 0.1% w/w.

16. The droplet microactuator of claim 1 wherein the filler fluid comprises silicone oil and the surfactant is a nonionic lipophile surfactant.

17. The droplet microactuator of claim 1 wherein the filler fluid comprises silicone oil and the surfactant is a nonionic lipophile surfactant in an amount which ranges from about 0.001 to about 1% w/w.

18. The droplet microactuator of claim 1 wherein the filler fluid comprises silicone oil and the surfactant is a nonionic lipophile surfactant in an amount which ranges from about 0.001 to about 0.1% w/w.

19. The droplet microactuator of claim 1 wherein the surfactant comprises nonionic low hydrophile-lipophile balanced (HLB) surfactant.

20. The droplet microactuator of claim 19 wherein the HLB is less than about 10.

21. The droplet microactuator of claim 19 wherein the HLB is less than about 5.

22. The droplet microactuator of claim 19 wherein the droplet comprises whole blood and the surfactant has an HLB which is less than about 2.

23. The droplet microactuator of claim 1, wherein the droplet is one of a set of droplets comprising reagent droplets for executing an immunoassay protocol.

24. The droplet microactuator of claim 23, wherein the reagent droplets comprise one or more wash droplets.

25. The droplet microactuator of claim 23, wherein the reagent droplets comprise a droplet comprising an antibody immobilized on a surface of a magnetically responsive bead comprised in the droplet.

26. The droplet microactuator of claim 23, wherein the reagent droplets comprise reagents for executing an immunoassay protocol, one or more of the droplets comprising a magnetically responsive bead having antibodies immobilized thereon;

the droplets further comprising one or more wash droplets for washing the magnetically responsive antibody-capture bead and wherein each of the droplets is subject to one or more of the electrowetting droplet operations.