Apparatuses and methods for manipulating droplets

• US 9,110,017 B2
• Filed: 11/11/2014
• Issued: 08/18/2015
• Est. Priority Date: 09/24/2002
• Status: Expired due to Fees

• Current Assignee: Duke University
• Original Assignee: Duke University
• Inventors: Pollack, Michael G., Pamula, Vamsee K., Fair, Richard B.
• Primary Examiner(s): Warden, Jill
• Assistant Examiner(s): Handy, Dwayne K
• Application Number:
  US14/538,322
• Publication Number:
  US 20150060284A1
• Time in Patent Office: 280 Days
• Field of Search: 422/501, 422/502, 422/503, 422/504, 435/6.12, 435/91.2, 436/53, 436/180
• US Class Current: 1/1
• 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 2200/0673 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 2200/12 Specific details about manufacturing devices
• CPC Class Codes: B01L 2300/0645 Electrodes
• CPC Class Codes: B01L 2300/0663 Whole sensors
• CPC Class Codes: B01L 2300/0819 Microarrays; Biochips
• 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 2300/0887 Laminated structure
• CPC Class Codes: B01L 2300/089 Virtual walls for guiding liquids
• CPC Class Codes: B01L 2300/12 Specific details about materials
• CPC Class Codes: B01L 2300/1827 using resistive heater
• CPC Class Codes: B01L 2400/0415 electrical forces, e.g. electrokinetic
• CPC Class Codes: B01L 2400/0424 Dielectrophoretic forces
• 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 3/502792 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: B81B 2201/058 Microfluidics not provided for in B81B2201/051 - B81B2201/054
• CPC Class Codes: B81B 3/0021 : Transducers for transforming electrical into mechanical energy or vice versa dynamo-electric machines H02K99/00; electrostatic machines H02N1/00; piezoelectric devices H10N30/00
• CPC Class Codes: B81C 1/00119 : Arrangement of basic structures like cavities or channels, e.g. suitable for microfluidic systems
• CPC Class Codes: C12Q 1/6846 : Common amplification features
• CPC Class Codes: G01N 27/447 : using electrophoresis
• CPC Class Codes: G01N 27/44769 : Continuous electrophoresis, i.e. the sample being continuously introduced, e.g. free flow electrophoresis [FFE]
• CPC Class Codes: G01N 27/44791 : Microapparatus sample containers with integrated microfluidic structures B01L3/5027
• CPC Class Codes: G05D 7/0694 : by action on throttling means or flow sources of very small size, e.g. microfluidics microvalves F16K99/0001; microstructural devices per se B81B
• CPC Class Codes: H01L 21/6715 : Apparatus for applying a liquid, a resin, an ink or the like H01L21/67126 takes precedence
• CPC Class Codes: Y10T 436/2575 : Volumetric liquid transfer

Abstract

Apparatuses and methods for manipulating droplets are disclosed. In one embodiment, an apparatus for manipulating droplets is provided, the apparatus including a substrate, multiple arrays of electrodes disposed on the substrate, wherein corresponding electrodes in each array are connected to a common electrical signal, and a dielectric layer disposed on the substrate first side surface and patterned to cover the electrodes.

Claims

1. An apparatus for manipulating droplets, the apparatus comprising:

(a) a first printed circuit board substrate comprising a first side surface and a second side surface;

(b) an array of drive electrodes disposed on the first printed circuit board substrate first side surface;

(c) a dielectric layer disposed on the first printed circuit board substrate first side covering the drive electrodes;

(d) a second substrate comprising a first side surface and a second side surface, the second substrate being substantially parallel to and spaced apart from the first printed circuit board substrate by a distance to define a space between the second substrate second side surface and the first printed circuit board substrate first side surface, wherein the distance is sufficient to contain a droplet disposed in the space; and

(e) one or more reference elements disposed on the second substrate second side surface.

2. The apparatus according to claim 1 wherein the first printed circuit board substrate comprises a plurality of substrate apertures defined therein and extending from the first side surface of the first printed circuit board substrate to the second side surface of the first printed circuit board substrate and each electrode comprises an electrode aperture, wherein each electrode aperture is aligned with one of the plurality of substrate apertures to define a plurality of via holes through the apparatus.

3. The apparatus according to claim 2 wherein the via holes are filled with a dielectric substance.

4. The apparatus according to claim 2 wherein the via holes are filled with a resin.

5. The apparatus according to claim 4 wherein the resin is a conductive epoxy or an optically transparent epoxy.

6. The apparatus according to claim 1 wherein the first printed circuit board substrate defines at least one droplet inlet port adjacent with at least one of the drive electrodes of the drive electrode array.

7. The apparatus according to claim 6 wherein the at least one droplet inlet port is in communication with a liquid flow source selected from the group consisting of a flexible tube, a syringe, a pipettor, an external fluidic pump, a glass capillary tube, an intra-venous line, and a microdialysis lumen.

8. The apparatus according to claim 6 wherein the first printed circuit board substrate defines at least one droplet outlet port adjacent with at least one of the drive electrodes of the drive electrode array.

9. The apparatus according to claim 8 wherein the at least one droplet outlet port is in communication with a liquid flow source selected from the group consisting of a flexible tube, a syringe, a pipettor, an external fluidic pump, a glass capillary tube, an intra-venous line, and a microdialysis lumen.

10. The apparatus according to claim 1 wherein the dielectric substance is a soldermask material, spin-on material, dip-coatable material, brush or spray-coatable, vapor depositable, or sputtered material.

11. The apparatus according to claim 10 wherein the soldermask material is selected from the group consisting of liquid photoimageable soldermask (LPI) and dry film soldermask (DFSS).

12. The apparatus according to claim 1 further comprising an electronic component operatively connected to the first printed circuit board substrate, the electronic component being selected from the group consisting of microcontrollers, relays, high voltage multiplexers, voltage converters, light emitting diodes (LEDs), photodiodes, photo-multiplier tubes (PMT), heating elements, thermistors, resistance temperature devices (RTDs), and electrochemical measurement electrodes.

13. The apparatus according to claim 1 wherein the dielectric layer disposed on the first printed circuit board substrate first side surface comprises a hydrophobic surface or coating.

14. The apparatus according to claim 1 wherein the one or more reference elements disposed on the second substrate second side surface comprises a hydrophobic surface or coating.

15. The apparatus according to claim 1 wherein the space comprises oil.

16. The apparatus according to claim 1 wherein the space is filled with oil.

17. The apparatus according to claim 1 wherein the space comprises oil and a droplet in the oil.

18. The apparatus according to claim 1 wherein the space is filled with oil and comprises a droplet in the oil.

19. An apparatus for manipulating droplets, the apparatus comprising:

(a) a first printed circuit board substrate comprising a first side surface and a second side surface;

(b) an array of drive electrodes disposed on the first printed circuit board substrate first side surface;

(c) a dielectric substance layer disposed on the first printed circuit board substrate first side surface covering the drive electrodes;

(d) a second substrate comprising a first side surface and a second side surface, the second substrate being substantially parallel to and spaced apart from the first printed circuit board substrate by a distance to define a space between the second substrate second side surface and the first printed circuit board substrate first side surface, wherein the distance is sufficient to contain a droplet disposed in the space; and

(e) one or more reference elements settable to a common reference potential disposed in at least substantially co-planar relation to the drive electrode array.

20. The apparatus according to claim 19 wherein the first printed circuit board substrate comprises a plurality of substrate apertures defined therein and extending from the first side surface of the first printed circuit board substrate to the second side surface of the first printed circuit board substrate and each drive electrode comprises an electrode aperture, wherein each drive electrode aperture is aligned with one of the plurality of substrate apertures to define a plurality of via holes through the apparatus.

21. The apparatus according to claim 20 wherein the via holes are filled with the dielectric substance.

22. The apparatus according to claim 20 wherein the via holes are filled with a resin.

23. The apparatus according to claim 22 wherein the resin is a conductive epoxy or an optically transparent epoxy.

24. The apparatus according to claim 19 wherein the first printed circuit board substrate defines at least one droplet inlet port adjacent with at least one of the drive electrodes of the drive electrode array.

25. The apparatus according to claim 24 wherein the at least one droplet inlet port is in communication with a liquid flow source selected from the group consisting of a flexible tube, a syringe, a pipettor, an external fluidic pump, a glass capillary tube, an intra-venous line, and a microdialysis lumen.

26. The apparatus according to claim 24 wherein the first printed circuit board substrate defines at least one droplet outlet port adjacent with at least one of the drive electrodes of the drive electrode array.

27. The apparatus according to claim 26 wherein the at least one droplet outlet port is in communication with a liquid flow source selected from the group consisting of a flexible tube, a syringe, a pipettor, an external fluidic pump, a glass capillary tube, an intra-venous line, and a microdialysis lumen.

28. The apparatus according to claim 19 wherein the one or more reference elements comprises a grid of elongate structures.

29. The apparatus according to claim 28 wherein the height of the grid of elongate structures is at least equal to the height of the droplet disposed on the substrate first side surface.

30. The apparatus according to claim 19 wherein the dielectric substance is a soldermask material, spin-on material, dip-coatable material, brush or spray-coatable, vapor depositable, or sputtered material.

31. The apparatus according to claim 30 wherein the soldermask material is selected from the group consisting of liquid photoimageable soldermask (LPI) and dry film soldermask (DFSS).

32. The apparatus according to claim 19 further comprising an electronic component operatively connected to the first printed circuit board substrate, the electronic component being selected from the group consisting of microcontrollers, relays, high voltage multiplexers, voltage converters, light emitting diodes (LEDs), photodiodes, photo-multiplier tubes (PMT), heating elements, thermistors, resistance temperature devices (RTDs), and electrochemical measurement electrodes.

33. The apparatus according to claim 19 wherein the dielectric layer disposed on the first printed circuit board substrate first side surface comprises a hydrophobic surface or coating.

34. The apparatus according to claim 19 wherein the one or more reference elements disposed on the second substrate second side surface comprises a hydrophobic surface or coating.

35. The apparatus according to claim 19 wherein the space comprises oil.

36. The apparatus according to claim 19 wherein the space is filled with oil.

37. The apparatus according to claim 19 wherein the space comprises oil and a droplet in the oil.

38. The apparatus according to claim 19 wherein the space is filled with oil and comprises a droplet in the oil.

39. An apparatus for manipulating droplets, the apparatus comprising:

(a) a first printed circuit board substrate comprising a first side surface and a second side surface;

(b) an array of drive electrodes disposed on the first printed circuit board substrate first side surface;

(c) a dielectric substance layer disposed on the first printed circuit board substrate first side surface covering the drive electrodes;

(d) a second substrate comprising a first side surface and a second side surface, the second substrate being substantially parallel to and spaced apart from the first printed circuit board substrate by a distance to define a space between the second substrate second side surface and the first printed circuit board substrate first side surface, wherein the distance is sufficient to contain a droplet disposed in the space; and

(e) an elongated reference element disposed on the second substrate second side surface.

40. The apparatus according to claim 39 wherein the first printed circuit board substrate comprises a plurality of substrate apertures defined therein and extending from the first side surface of the first printed circuit board substrate to the second side surface of the first printed circuit board substrate and each drive electrode comprises an electrode aperture, wherein each drive electrode aperture is aligned with one of the plurality of substrate apertures to define a plurality of via holes through the apparatus.

41. The apparatus according to claim 40 wherein the via holes are filled with the dielectric substance.

42. The apparatus according to claim 40 wherein the via holes are filled with a resin.

43. The apparatus according to claim 42 wherein the resin is a conductive epoxy or an optically transparent epoxy.

44. The apparatus according to claim 39 wherein the first printed circuit board substrate defines at least one droplet inlet port adjacent with at least one of the drive electrodes of the drive electrode array.

45. The apparatus according to claim 44 wherein the at least one droplet inlet port is in communication with a liquid flow source selected from the group consisting of a flexible tube, a syringe, a pipettor, an external fluidic pump, a glass capillary tube, an intra-venous line, and a microdialysis lumen.

46. The apparatus according to claim 44 wherein the first printed circuit board substrate defines at least one droplet outlet port adjacent with at least one of the drive electrodes of the drive electrode array.

47. The apparatus according to claim 46 wherein the at least one droplet outlet port is in communication with a liquid flow source selected from the group consisting of a flexible tube, a syringe, a pipettor, an external fluidic pump, a glass capillary tube, an intra-venous line, and a microdialysis lumen.

48. The apparatus according to claim 39 wherein the elongated reference element comprises one or more wires.

49. The apparatus according to claim 39 wherein the elongated reference element comprises a plate.

50. The apparatus according to claim 49 wherein the reference element plate comprises a plate surface facing the first printed circuit board substrate first side surface, and the plate surface is hydrophobic.

51. The apparatus according to claim 39 wherein the dielectric substance is a soldermask material, spin-on material, dip-coatable material, brush or spray-coatable, vapor depositable, or sputtered material.

52. The apparatus according to claim 51 wherein the soldermask material is selected from the group consisting of liquid photoimageable soldermask (LPI) and dry film soldermask (DFSS).

53. The apparatus according to claim 39 further comprising an electronic component operatively connected to the printed circuit board substrate, the electronic component being selected from the group consisting of microcontrollers, relays, high voltage multiplexers, voltage converters, light emitting diodes (LEDs), photodiodes, photo-multiplier tubes (PMT), heating elements, thermistors, resistance temperature devices (RTDs), and electrochemical measurement electrodes.

54. The apparatus according to claim 39 wherein the dielectric layer disposed on the first printed circuit board substrate first side surface comprises a hydrophobic surface or coating.

55. The apparatus according to claim 39 wherein the elongated reference element disposed on the second substrate second side surface comprises a hydrophobic surface or coating.

56. The apparatus according to claim 39 wherein the space comprises oil.

57. The apparatus according to claim 39 wherein the space is filled with oil.

58. The apparatus according to claim 39 wherein the space comprises oil and a droplet in the oil.

59. The apparatus according to claim 39 wherein the space is filled with oil and comprises a droplet in the oil.