Programmable fluidic processors

• US 10,413,912 B2
• Filed: 03/02/2015
• Issued: 09/17/2019
• Est. Priority Date: 05/28/2004
• Status: Active Grant

• Current Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Original Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Inventors: Gascoyne, Peter R. C., Vykoukal, Jody, Schwartz, Jon
• Primary Examiner(s): Kaur, Gurpreet
• Application Number:
  US14/635,293
• Publication Number:
  US 20160030951A1
• Time in Patent Office: 1,660 Days
• CPC Class Codes: B01F 23/411 using electrical or magnetic fields, heat or vibrations
• CPC Class Codes: B01F 33/051 the energy being electrical energy working on the ingredients or compositions for mixing them
• 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: B01F 33/30351 using hydrophilic/hydrophobic surfaces
• CPC Class Codes: B01L 2200/06 Fluid handling related problems
• CPC Class Codes: B01L 2200/0605 Metering of fluids
• CPC Class Codes: B01L 2200/0673 Handling of plugs of fluid surrounded by immiscible fluid
• CPC Class Codes: B01L 2200/12 Specific details about manufacturing devices
• CPC Class Codes: B01L 2200/14 Process control and prevention of errors
• CPC Class Codes: B01L 2200/143 Quality control, feedback systems
• CPC Class Codes: B01L 2300/0645 Electrodes
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0819 Microarrays; Biochips
• CPC Class Codes: B01L 2300/089 Virtual walls for guiding liquids
• CPC Class Codes: B01L 2300/165 Specific details about hydrophobic, oleophobic surfaces
• CPC Class Codes: B01L 2300/166 Suprahydrophobic; Ultraphobic; Lotus-effect
• CPC Class Codes: B01L 2400/0424 Dielectrophoretic forces
• CPC Class Codes: B01L 3/0268 using pulse dispensing or spraying, eg. inkjet type, piezo actuated ejection of droplets from capillaries
• 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 3/502792 : for moving individual droplets on a plate, e.g. by locally altering surface tension
• CPC Class Codes: B03C 5/005 : Dielectrophoresis, i.e. dielectric particles migrating towards the region of highest field strength
• CPC Class Codes: B03C 5/026 : using open-gradient differential dielectric separation, i.e. using electrodes of special shapes for non-uniform field creation, e.g. Fluid Integrated Circuit [FIC]
• CPC Class Codes: G01N 2035/1034 : Transferring microquantities of liquid

Abstract

Disclosed are apparatuses, systems, and methods for programmable fluidic processors. In one embodiment, the invention involves manipulating droplets across a reaction surface of the processor substantially contact-free of any surfaces. The reaction surface and the electrodes of the processor may include a coating repelling the droplets. Further, the present invention provides for a suitable suspending medium for repelling droplets away from fixed surfaces.

Claims

1. An apparatus, comprising:

a suspending medium comprising a plurality of droplets;

at least one dielectrically-engineered bead to be disposed in at least one droplet of the plurality of droplets, the at least one dielectrically-engineered bead configured for use as a substrate for biological analysis;

a reaction surface providing an interaction site for the plurality of droplets;

at least one electrode coupled to the reaction surface, the at least one electrode comprising an insulating coating for preventing contact between the plurality of droplets and the at least one electrode;

a controller coupled to the at least one electrode for providing dielectrophoretic forces on the plurality of droplets to manipulate the size and shape of the plurality of droplets;

a reservoir defined by a cavity in the apparatus and positioned adjacent to the reaction surface;

a conduit;

an injector in fluid communication with the reservoir via the conduit and configured to build the at least one droplet from the reservoir and to deliver the at least one droplet to the reaction surface, the injector defining;

an injector orifice comprising a conductive orifice tip; and

a sidewall, where the conduit passes through the sidewall from the reaction surface to the reservoir such that the injector orifice is defined by a conductive portion of the sidewall at the reaction surface; and

where the conductive orifice tip is configured to form a droplet that breaks off into the suspending medium, and the suspending medium and the reaction surface are configured to transport the droplet from the conductive orifice tip to the at least one electrode without substantially contacting the reaction surface.

2. The apparatus of claim 1, the insulating coating being selected from the group consisting of:

silicon dioxide, photopolymer, PDMS, Parylene, barium strontium titinate, epoxy, siloxane, and fluoropolymer, and where the at least one dielectrically-engineered bead is further configured to be manipulated by the dielectrophoretic forces.

3. The apparatus of claim 2, where:

the insulating coating comprising silicon dioxide and photopolymer,

the at least one droplet has a volume between 4 pL and 500 pL, and

based on the dielectrophoretic forces, the at least one dielectrically-engineered bead is configured to be pulled to one side of the at least one droplet to divide the at least one droplet into a first portion including the at least one dielectrically-engineered bead and into a second portion.

4. The apparatus of claim 1, where:

the insulating coating comprises a metal oxide or a thin-film dielectric;

a first droplet of the plurality of droplets has a volume of 4 pL; and

a second droplet of the plurality of droplets has a volume of 500 pL.

5. The apparatus of claim 1, further comprising:

an activation electrode; and

where injection of the at least one droplet from the injector orifice is initiated based on application of an AC voltage between the activation electrode and a fluid in the injector orifice, and

where the insulating coating being selected from the group consisting of;

spin-coated or baked TEFLON and sputtered TEFLON.

6. The apparatus of claim 1, further comprising:

an activation electrode; and

where injection of the at least one droplet from the injector orifice is initiated based on application of a rapidly switching or pulsing voltage to the activation electrode, and

where the suspending medium is more polar than the insulating coating.

7. The apparatus of claim 1, further comprising:

a collecting electrode; and

where the at least one droplet is configured to break off from the injector orifice and move to the collecting electrode responsive to a lateral dielectrophoretic force component, and

where the suspending medium provides buoyancy to substantially eliminate sedimentation forces between the electrodes and the droplets.

8. The apparatus of claim 1, further comprising:

patterned micro-features on the electrodes for reducing the contact area of the electrode; and

where the sidewall defines a boundary of the reaction surface and the suspension medium.

9. The apparatus of claim 1, the insulating coating comprising a layer of between 1 and 10 microns.

10. The apparatus of claim 1, the insulating coating comprising a layer of between 1 and 5 microns.

11. The apparatus of claim 1, the insulating coating comprising a layer with a thickness sufficient to prevent electrical current from passing across the layer.

12. An apparatus, comprising:

a suspending medium comprising droplets;

at least one dielectrically-engineered bead to be disposed in at least one of the droplets, the at least one dielectrically-engineered bead configured for use as a substrate for biological analysis;

a fixed surface comprising a passivation layer and a droplet-repellent coating, the fixed surface provides an interaction site for the droplets;

an injector in fluid communication with a reservoir via a conduit, the injector defining an injector orifice comprising a conductive orifice tip,

a sidewall, where the injector passes through the sidewall from the fixed surface to the reservoir such that the injector orifice is defined by a conductive portion of the sidewall at the fixed surface; and

where the conductive orifice tip is configured to form a droplet that breaks off into the suspending medium, and the suspending medium is configured to transport the droplet to a collecting electrode without substantially contacting the fixed surface; and

a signal generator for applying a signal to the fixed surface for manipulating the droplets.

13. The apparatus of claim 12, the passivation layer being selected from the group consisting of:

silicon dioxide, photopolymer, PDMS, Parylene, barium strontium titinate, spin-coated/baked TEFLON, sputtered TEFLON, epoxy, siloxane, fluoropolymer, metal oxide, and thin-film dielectric.

14. The apparatus of claim 12, where the suspending medium and the droplets are mutually immiscible and have different dielectric properties.

15. The apparatus of claim 14, where the droplets comprise aqueous droplets, the suspending medium and the droplet-repellent coating comprising a hydrophobic suspending medium and a hydrophobic droplet-repellent coating, respectively.

16. The apparatus of claim 14, where the droplets comprise hydrophobic droplets, the suspending medium and the droplet-repellent coating comprising a hydrophilic suspending medium and a hydrophilic droplet-repellent coating, respectively.

17. The apparatus of claim 16, the hydrophilic suspending medium being selected from the group consisting of:

water, DMF, ethanol, acetone, methanol, 1-bromodecane, and DMSO.

18. The apparatus of claim 16, the hydrophilic droplet-repellent coating being selected from the group consisting of:

polylysine, PEG, silicon oil, and carboxylated agents.

19. The apparatus of claim 12, where the suspending medium is more polar than the droplet-repellent coating.

20. The apparatus of claim 12, the fixed surface further comprising a plurality of electrodes.

21. The apparatus of claim 20, the signal generator configured to provide an electrical signal to the plurality of electrodes to create a dielectrophoretic force on the droplets.

22. A system, comprising:

a semiconductor chip;

a reaction surface coupled to the semiconductor chip;

an array of electrodes coupled to the reaction surface for droplet manipulation;

an injector comprising a conductive orifice tip, where the conductive orifice tip is configured to form at least one droplet that breaks off into a suspending medium;

a sidewall, where the injector passes through the sidewall from the reaction surface to a reservoir such that the conductive orifice tip is defined by a conductive portion of the sidewall at the reaction surface; and

a controller coupled to the array of electrodes, the controller selecting a phase of a signal to apply to each electrode in the array of electrodes; and

where the reaction surface comprises a droplet-repellent coating; and

where the array of electrodes is configured to cause the at least one droplet to move without substantially contacting the reaction surface in response to a lateral dielectrophoretic force component.

23. The system of claim 22, the droplet-repellent coating comprising a layer being selected from the group consisting of:

silicon dioxide, photopolymer, PDMS, Parylene, barium strontium titinate, spin-coated/baked TEFLON, sputtered TEFLON, epoxy, siloxane, fluoropolymer, metal oxide, and thin-film dielectric.

24. The system of claim 23, the layer comprises a layer of about 1 to 10 micrometer.

25. The system of claim 22, the droplet-repellent coating further comprising a monolayer of a compound including microparticles.

26. The system of claim 22, the reaction surface comprising a passivated SOI reaction surface.

27. The system of claim 22, the signal comprising an inhomogeneous AC signal for providing a dielectrophoretic force on the droplets, manipulating the droplets.

28. The system of claim 27, the droplets traveling across the reaction surface substantially contact-free from the reaction surface.

29. The system of claim 22, the semiconductor chip comprising a complementary metal on silicon (CMOS) chip.

30. A method, comprising:

providing a fluidic processor comprising a fixed surface with a droplet-repellent coating;

injecting a droplet from a conductive orifice tip defined by a conductive portion of a sidewall at the fixed surface onto the fixed surface;

providing at least one dielectrically-engineered bead to be disposed in the droplet, the at least one dielectrically-engineered bead configured for use as a substrate for biological analysis; and

providing an inhomogeneous AC field to the fixed surface creating a dielectrophoretic force on the droplet, the droplet manipulated substantially contact-free of the fixed surface.

31. The method of claim 30, the step of injecting a droplet further comprising injecting a droplet of a desired volume.

32. The method of claim 31, the step of injecting a droplet of a desired volume further comprising triggering a signal from the fluidic processor when the desired volume is reached.

33. The method of claim 30, the step of providing an inhomogeneous AC field to the fixed surface further comprising providing an AC field to a plurality of electrodes of the fluidic processor.

34. The method of claim 30, the step of providing an inhomogeneous AC field further comprising applying switching configurations to transport a droplet to a desired location or bring two droplets together for mixing.

35. The method of claim 30, the droplet-repellent coating being selected from the group consisting of:

hydrophobic coatings and hydrophilic coatings.