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1. (WO2019046860) DIGITAL MICROFLUIDICS DEVICES AND METHODS OF USING THEM
Note: Text based on automatic Optical Character Recognition processes. Please use the PDF version for legal matters

CLAIMS

What is claimed is:

1. A cartridge for a digital microfluidics (DMF) apparatus, the cartridge having a bottom and a top, the cartridge comprising:

a sheet of dielectric material having a first side and a second side, the first side

forming an exposed bottom surface on the bottom of the cartridge, wherein at least the second side of the sheet of dielectric material comprises a first hydrophobic surface;

a top plate having a first side and a second side and a thickness therebetween;

a ground electrode on the first side of the top plate;

a second hydrophobic surface on the first side of the top plate covering the ground electrode; and

an air gap separating the first hydrophobic layer and the second hydrophobic layer, wherein the air gap comprises a separation of greater than 280 micrometers.

2. The cartridge of claim 1, wherein the ground electrode comprises a grid pattern forming a plurality of open cells.

3. The cartridge of claim 2, wherein the grid pattern of the ground electrodes is formed of a non-transparent material.

4. The cartridge of claim 1, wherein the ground electrodes is formed of a conductive ink.

5. The cartridge of claim 1, wherein the ground electrodes is formed of silver nanoparticles.

6. The cartridge of claim 2, wherein the minimum width of the grid pattern between the open cells is greater than 50 micrometers.

7. The cartridge of claim 2, wherein the open cells of the plurality of open cells comprise a quadrilateral shape or an elliptical shape.

8. The cartridge of claim 1, wherein the ground electrode extends over more than 50% of the first side of the top plate.

9. The cartridge of claim 1, wherein the top plate comprises a plurality of cavities within the thickness of the top plate, further wherein the cavities are filed with an insulating material having a low thermal mass and low thermal conductivity.

10. The cartridge of claim 9, wherein the insulating material comprises air.

11. The cartridge of claim 1, wherein the sheet of dielectric material is flexible.

12. The cartridge of claim 1, further comprising a microfluidics channel formed one or in the second side of the top plate, wherein the microfluidics channel extends along the second side of the top plate and at least one opening between the microfluidics channel and the air gap.

13. The cartridge of claim 1, wherein the top plate comprises polycarbonate and/or acrylic.

14. The cartridge of claim 1, wherein the sheet of dielectric is less than 30 microns thick.

15. The cartridge of claim 1, wherein the second side of the dielectric material comprises a hydrophobic coating.

16. The cartridge of claim 1, wherein the air gap comprises a separation of greater than 400 micrometers.

17. A cartridge for a digital microfluidics (DMF) apparatus, the cartridge having a bottom and a top, the cartridge comprising:

a flexible sheet of dielectric material having a first side and a second side, the first side forming an exposed bottom surface on the bottom of the cartridge; a first hydrophobic layer on the second side of the sheet of dielectric material;

a top plate having a first side and a second side and a thickness therebetween;

a ground electrode on the first side of the top plate, wherein the ground electrode comprises a grid pattern formed of a non-transparent material forming a plurality of open cells along the first side of the top plate;

a second hydrophobic layer on the first side of the top plate covering the ground electrode; and

an air gap separating the first hydrophobic layer and the second hydrophobic layer, wherein the air gap comprises a separation of greater than 400 micrometers.

18. The cartridge of claim 17, wherein the top plate comprises a plurality of cavities within the thickness of the top plate, further wherein the cavities are filed with an insulating material having a low thermal mass and low thermal conductivity.

19. The cartridge of claim 17, wherein the grid pattern of the ground electrodes is formed of a conductive ink.

20. The cartridge of claim 17, wherein the grid pattern of the ground electrodes is formed of silver nanoparticles.

21. The cartridge of claim 17 wherein the minimum width of the grid pattern between the open cells is greater than 50 micrometers.

22. The cartridge of claim 17, wherein the open cells of the plurality of open cells comprise a quadrilateral shape or an elliptical shape.

23. The cartridge of claim 17, wherein the grid pattern of the ground electrode extends over more than 50% of the first side of the top plate.

24. The cartridge of claim 17, further comprising a microfluidics channel formed in the second side of the top plate, wherein the microfluidics channel extends along the second side of the top plate and at least one opening between the microfluidics channel and the air gap.

25. The cartridge of claim 17, wherein the top plate comprises polycarbonate and/or acrylic.

26. A cartridge for a digital microfluidics (DMF) apparatus, the cartridge having a bottom and a top, the cartridge comprising:

a sheet of dielectric material having a first side and a second side, the first side

forming an exposed bottom surface on the bottom of the cartridge;

a first hydrophobic layer on the second side of the sheet of dielectric material;

a top plate having a first side and a second side and a thickness therebetween;

a ground electrode on the first side of the top plate;

a second hydrophobic layer on the first side of the top plate covering the ground electrode;

an air gap separating the first hydrophobic layer and the second hydrophobic layer; a microfluidics channel formed in or on the second side of the top plate, wherein the microfluidics channel extends along the second side of the top plate; an opening between the microfluidics channel and the air gap; and

a cover covering the microfluidics channel, wherein the cover includes one or more access ports for accessing the microfluidics channel.

27. The cartridge of claim 26, wherein the microfluidics channel is configured to contain more than 1 ml of fluid within the microfluidics channel.

28. The cartridge of claim 26 wherein the air gap comprises a separation of greater than 500 micrometers.

29. The cartridge of claim 26, wherein the microfluidics channel comprises a first

microfluidics channel and the opening between the microfluidics channel and the air gap comprises a first opening, further comprising a second microfluidics channel formed in the second side of the top plate, wherein the second microfluidics channel extends along the second side of the top plate, and a second opening between the second microfluidics channel and the air gap, wherein the first and second openings are adjacent to each other.

30. The cartridge of claim 29, wherein the first and second openings are within about 2 cm of each other.

31. The cartridge of claim 26, further comprising a window from the top of the cartridge to the air gap through which the air gap is visible.

32. The cartridge of claim 31, wherein the window forms between 2 and 50% of the top of the cartridge.

33. The cartridge of claim 26, wherein the bottom of the cartridge is formed by the first side of the sheet of dielectric material.

34. The cartridge of claim 26, further comprising a plurality of openings into the air gap from the top of the cartridge.

35. The cartridge of claim 26, wherein the top plate comprises polycarbonate and/or acrylic.

36. The cartridge of claim 26, further comprising one or more reagent reservoirs on the

second side of the top plate.

37. The cartridge of claim 26, further comprising one or more freeze-dried reagent reservoirs on the second side of the top plate.

38. The cartridge of claim 26, wherein the sheet of dielectric material is flexible.

39. The cartridge of claim 26, wherein the top plate comprises a plurality of cavities within the thickness of the top plate, further wherein the cavities are filed with an insulating material having a low thermal mass and low thermal conductivity.

40. A cartridge for a digital microfluidics (DMF) apparatus, the cartridge having a bottom and a top, the cartridge comprising:

a sheet of dielectric material having a first side and a second side, the first side

forming an exposed bottom surface on the bottom of the cartridge;

a first hydrophobic layer on the second side of the sheet of dielectric material;

a top plate having first side and a second side and a thickness therebetween;

a ground electrode on first side of the top plate;

a second hydrophobic layer on the first side of the top plate covering the ground electrode;

an air gap separating the first hydrophobic layer and the second hydrophobic layer, wherein the air gap comprises a separation of greater than 500 micrometers; a first microfluidics channel and a second microfluidics channel, wherein the first and second microfluidics channels are formed in the second side of the top plate, wherein the first and second microfluidics channels extend along the second side of the top plate;

a first opening between the first microfluidics channel and the air gap and a second opening between the second microfluidics channel and the air gap, wherein the first and second openings are adjacent to each other within about 2 cm; and a cover covering the microfluidics channel, wherein the cover includes one or more access ports for accessing the microfluidics channel.

41. A digital microfluidics (DMF) reader device configured to operate with a disposable cartridge having a bottom dielectric surface, a top plate with a ground electrode, and an air gap between the bottom dielectric and the top plate, the device comprising:

a seating surface for seating the disposable cartridge;

a first plurality of drive electrodes on the seating surface, wherein all or some of the drive electrodes comprises an opening therethrough;

a plurality of vacuum ports, wherein each vacuum port is coupled to one or more of the openings through the drive electrodes;

a vacuum pump for applying a vacuum to the vacuum ports; and

a control for applying energy to sequentially activate and de-activate one or more selected drive electrodes to move a droplet within the air gap of the cartridge along a desired path within the air gap,

wherein the DMF reader is configured to apply the vacuum to the vacuum ports to secure each drive electrode to the bottom dielectric of the disposable cartridge when the disposable cartridge is placed on the seating surface.

42. The device of claim 41, further comprising one or more projections extending from the seating surface, wherein the one or more projections are configured to form partitions in the air gap of the cartridge when the vacuum is applied through the openings in the drive electrodes.

43. The device of claim 41, further comprising an optical reader configured to detect an

optical signal from a cartridge seated on the seating surface.

44. The device of claim 41, further comprising a motor configured to move an optical reader configured to detect an optical signal from a cartridge seated on the seating surface.

45. The device of claim 41, further comprising one or more temperature sensors coupled to the seating surface.

46. The device of claim 41, further comprising a resistive heater underlying at least some of the drive electrodes.

47. The device of claim 41, wherein the seating surface comprises a printed circuit board.

48. The device of claim 41, further comprising a magnet underneath one or more of the drive electrodes configured to be activated to apply a magnetic field.

49. The device of claim 41, further comprising one or more Peltier coolers underlying at least some of the drive electrodes configured to cool to less than 10 degrees C.

50. The device of claim 41, further comprising a cartridge tray configured to move the

disposable cartridge onto the seating surface.

51. The device of claim 41, further comprising a housing enclosing the device, wherein the housing is stackable.

52. The device of claim 41, further comprising an output configured to output signals

detected by the device.

53. The device of claim 52, wherein the output comprises a wireless output.

54. The device of claim 41, further comprising a first thermal control configured to cool the seating surface to between 15-25 degrees C.

55. The device of claim 41, further comprising one or more microfluidic vacuum ports positioned above the seating surface and configured to engage with an access ports for accessing a microfluidics channel of the cartridge when the cartridge is seated on the seating surface.

56. The device of claim 41, further comprising a dielectric coating on the outermost surface of the seating surface.

57. The device of claim 41, wherein the first plurality of drive electrodes on the seating surface are each separated from an adjacent electrode in the plurality of electrodes by between 50 and 120 micrometers.

58. The device of claim 41, further comprising a plurality of thermal vias through the seating surface.

59. A digital microfluidics (DMF) reader device configured to operate with a disposable cartridge having a bottom dielectric surface, a top plate with a ground electrode, and an air gap between the bottom dielectric and the top plate, the device comprising:

a seating surface for seating the disposable cartridge;

a plurality of drive electrodes on the seating surface, wherein at least some of the drive electrode comprises an opening therethrough;

a plurality of vacuum ports, wherein each vacuum port is coupled to one or more of the openings through the drive electrodes;

a vacuum pump for applying a vacuum to the vacuum ports; and

a control for applying energy to sequentially activate and de-activate one or more selected drive electrodes to move a droplet within the air gap of the cartridge along a desired path within the air gap,

wherein the DMF reader is configured to apply the vacuum to the vacuum ports to secure each drive electrode to the bottom dielectric of the disposable cartridge to retain the disposable cartridge on the seating surface.

60. A method of preventing droplet evaporation within an air-matrix digital microfluidic (DMF) apparatus, the method comprising:

introducing an aqueous reaction droplet into an air gap of the air-matrix DMF apparatus which is formed between a first plate and a second plate of the air- matrix DMF apparatus;

sequentially energizing driving electrodes on or in the first plate to move the aqueous reaction droplet within the air gap of the air-matrix DMF apparatus so that it combines with a droplet of nonpolar fluid within the air gap of the air- matrix DMF apparatus, forming a coated reaction droplet in which that the nonpolar fluid coats the aqueous reaction droplet and protects the reaction droplet from evaporation; and

sequentially energizing the driving electrodes to move the coated reaction droplet within the air gap of the air-matrix DMF apparatus.

61. The method of claim 60, wherein the volume of the nonpolar fluid is less than the volume of the aqueous reaction droplet.

62. The method of claim 60, further comprising combining, within the air gap of the air- matrix DMF apparatus, the coated droplet with one or more additional aqueous droplets.

63. The method of claim 60, further comprising removing the coating of nonpolar fluid by at least partially withdrawing the coated droplet out of the air gap of the air-matrix DMF apparatus into a microfluidic channel.

64. The method of claim 60, further comprising adding the droplet of nonpolar fluid into the air gap of the air-matrix DMF apparatus through an opening in the first or second plate.

65. The method of claim 60, wherein the droplet of nonpolar fluid is liquid at between 10 degrees C and 100 degrees C.

66. A method of preventing droplet evaporation within an air- matrix digital microfluidic (DMF) apparatus, the method comprising:

introducing an aqueous reaction droplet into an air gap of the air-matrix DMF apparatus which is formed between a first plate and a second plate of the air- matrix DMF apparatus;

sequentially energizing driving electrodes on or in the first plate to move the aqueous reaction droplet within the air gap of the air-matrix DMF apparatus so that it combines with a droplet of nonpolar fluid within the air gap of the air- matrix DMF apparatus, forming a coated reaction droplet in which that the

nonpolar fluid coats the aqueous reaction droplet and protects the reaction droplet from evaporation,

wherein the nonpolar fluid is liquid at between 10 degrees C and 100 degrees C, further wherein the volume of the nonpolar fluid is less than the volume of the aqueous reaction droplet; and

sequentially energizing the driving electrodes to move the coated reaction droplet within the air gap of the air-matrix DMF apparatus.

67. A method of dispensing a predetermined volume of fluid into an air gap of an air-matrix digital microfluidics (DMF) apparatus, wherein the air gap is greater than 400 micrometers wide, further wherein the DMF apparatus comprises a plurality of driving electrodes adjacent to the air gap, the method comprising:

flooding a portion of the air gap with the fluid from a port in communication with the air gap;

applying energy to activate a first driving electrode adjacent to the portion of the air gap that is flooded; and

applying suction to withdraw the fluid back into the port while the first electrode is activated, leaving a droplet having a predetermined volume of the fluid in the air gap adjacent to the activated first electrode.

68. The method of claim 67, wherein applying energy to activate the first driving electrode comprises applying energy to activate one or more driving electrodes that are contiguous with the first driving electrode, and further wherein applying suction to withdraw the fluid back into the port while the first driving electrode is activated comprises withdrawing the fluid while the first driving electrode and the one or more driving electrodes that are contiguous with the first driving electrode are active, leaving a droplet of the fluid in the air gap adjacent to the activated first driving electrode and the one or more driving electrodes that are contiguous with the first driving electrode.

69. The method of claim 67, wherein the first driving electrode is separated from the port by a spacing of at least one driving electrode.

70. The method of claim 67, further comprising inactivating one or more driving electrodes adjacent a second portion of the air gap that is within the flooded portion of the air gap, and that is between the port and the first driving electrode.

71. The method of claim 67, wherein the air gap is greater than 500 micrometers.

72. The method of claim 67, wherein flooding the portion of the air gap comprises applying positive pressure to expel fluid from the port.

The method of claim 67, further comprising sequentially energizing driving electrodes adjacent to the air gap to move the droplet within the air gap of the air-matrix DMF apparatus.

The method of claim 67, wherein applying suction to withdraw the fluid back into the port while the first electrode is activated comprises leaving a droplet of the fluid having a volume that is 10 microliters or greater in the air gap adjacent to the activated first electrode.

75. A method of dispensing a predetermined volume of fluid into an air gap of an air-matrix digital microfluidics (DMF) apparatus, wherein the air gap is greater than 400 micrometers wide, further wherein the DMF apparatus comprises a plurality of driving electrodes adjacent to the air gap, the method comprising:

flooding a portion of the air gap with the fluid from a port in communication with the air gap;

applying energy to activate a first driving electrode or a first group of contiguous driving electrodes adjacent to the portion of the air gap that is flooded, wherein the first driving electrode or the first group of contiguous driving electrodes are spaced apart from the port by one or more driving electrodes that are not activated; and

applying suction to withdraw the fluid back into the port while the first electrode or first group of contiguous electrodes are activated, leaving a droplet of the fluid in the air gap adjacent to the first electrode or first group of contiguous electrodes.

A method for controlling a digital microfluidics (DMF) apparatus, the method comprising:

providing a graphical user interface comprising a menu of fluid handling control commands, including one or more of: move, heat, remove, cycle, wait, breakoff, mix and dispense;

receiving a fluid handling protocol comprising user-selected fluid handling control commands;

calculating a path for moving fluid within an air gap of the DMF apparatus based on the fluid handling protocol, wherein the path minimizes the amount of overlap in the path to avoid contamination; and

executing the fluid handing protocol using the DMF apparatus based on the calculated path.

77. The method of claim 76, wherein the fluid handling control commands comprise at least: move, heat, remove, wait, and mix.

78. The method of claim 76, wherein receiving the fluid handling protocol comprises

receiving a string of fluid handling control commands.

79. The method of claim 76, wherein calculating the path comprises calculating the path based on the arrangement of heating and cooling zones in the DMF apparatus.

80. The method of claim 76, wherein calculating the path comprises determining the shortest path that does not cross over itself.

81. The method of claim 76, wherein executing the fluid handling protocol on the DMF apparatus comprises executing the fluid handling protocol in a disposable cartridge coupled to the DMF apparatus.

82. A digital microfluidics (DMF) reader device configured to operate with a disposable cartridge having a bottom dielectric surface, a top plate with a ground electrode, and an air gap between the bottom dielectric and the top plate, the device comprising:

a seating surface for seating the disposable cartridge on an upper surface;

a first plurality of drive electrodes on the seating surface, wherein all or some of the drive electrodes comprises an opening therethrough;

a thermal control for applying thermal energy to a first region of the seating surface; a plurality of thermal vias, wherein the thermal vias comprise a thermally conductive material and are in thermal communication with the first region of the seating surface but are electrically isolated from the subset of electrodes and further wherein the thermal vias are in thermal communication with the thermal control; a plurality of vacuum ports, wherein each vacuum port is coupled to one or more of the openings through the drive electrodes;

a vacuum pump for applying a vacuum to the vacuum ports; and

a control for applying energy to sequentially activate and de-activate one or more selected drive electrodes to move a droplet within the air gap of the cartridge along a desired path within the air gap.

83. The device of claim 82, wherein the thermal vias each have a diameter of between 0.5 and 1.5 mm

84. The device of claim 82, wherein there are between 5-15 thermal vias associated with a region corresponding to a single electrode in the first region.

85. The device of claim 82, wherein the thermal vias are each filled with a thermally

conductive metal.

86. The device of claim 82, further comprising a resistive heater underlying at least some of the drive electrodes.

87. The device of claim 82, wherein the seating surface comprises a printed circuit board.

88. The device of claim 82, further comprising a magnet underneath one or more of the drive electrodes configured to be activated to apply a magnetic field.

89. The device of claim 82, further comprising one or more Peltier coolers underlying at least some of the drive electrodes configured to cool to less than 10 degrees C.

90. A method of detecting the location and identity of a material in an air gap of a digital microfluidics (DMF) cartridge, the method comprising:

disconnecting a reference electrode on a first side of the air gap of the DMF cartridge from a driving circuit;

setting the voltage of one or more drive electrodes of an array of drive electrodes on a second side of the air gap to a high voltage while setting all other drive electrode of the array of drive electrodes to ground;

sensing the voltage at the reference electrode;

determining a capacitance between the first side of the air gap and the second side of the air gap based on the voltage sensed at the reference electrode; and

Identifying the material in the air gap adjacent to the one or more drive electrodes based on the determined capacitance.

91. The method of claim 90, further comprising reconnecting the reference electrode to the driving circuit, and driving a droplet within the air gap by applying a voltage between the reference electrode and one the drive electrodes.

92. The method of claim 90, wherein disconnecting the reference electrode comprises

allowing the reference electrode to float.

93. The method of claim 90, wherein setting the voltage of the one or more of drive electrodes to a high voltage comprises setting the one or more of the drive electrodes to between 10 and 400V.

94. The method of claim 90, further comprising determining a total capacitance for the air gap by setting the voltage of all of the drive electrodes of the array of drive electrodes to the high voltage while the reference electrode is disconnected from the driving circuit and sensing the voltage a the reference electrode to determine the total capacitance.

95. The method of claim 94, further comprising determining the total capacitance using one or more reference capacitors connected to the reference electrode when the reference electrode is disconnected from the driving circuit.

96. The method of claim 94, wherein determining the capacitance between the first side of the air gap and the second side of the air gap based on the voltage sensed at the reference electrode further comprises using the total capacitance.

97. The method of claim 94, wherein identifying the material in the air gap comprises using a reference database comprising a plurality of ranges of capacitance to identify the material in the air gap based on the determined capacitance.

98. A cartridge for a digital microfluidics (DMF) apparatus, the cartridge having a bottom and a top, the cartridge comprising:

a sheet of dielectric material having a first side and a second side, the first side

forming an exposed bottom surface on the bottom of the cartridge, wherein at least the second side of the sheet of dielectric material comprises a first hydrophobic surface;

a tensioning frame holding the sheet of dielectric material in tension so that it is

substantially flat;

a top plate having a first side and a second side and a thickness therebetween;

a ground electrode on the first side of the top plate;

a second hydrophobic surface on the first side of the top plate covering the ground electrode; and

an air gap separating the first hydrophobic layer and the second hydrophobic layer, wherein the air gap comprises a separation of greater than 280 micrometers.

99. The cartridge of claim 98, further comprising a lip extending around and proud of the sheet of dielectric material.

100. The cartridge of claim 98, wherein the tensioning frame comprises an outer frame and an inner frame, further wherein the sheet is held between the outer and inner frames.

101. The cartridge of claim 98, wherein the ground electrode comprises a grid pattern

forming a plurality of open cells.

102. The cartridge of claim 101, wherein the grid pattern of the ground electrodes is formed of a non-transparent material.

103. The cartridge of claim 98, wherein the ground electrodes is formed of a conductive ink.

104. The cartridge of claim 98, wherein the ground electrodes is formed of silver

nanoparticles.

105. The cartridge of claim 101, wherein the minimum width of the grid pattern between the open cells is greater than 50 micrometers.

106. The cartridge of claim 101, wherein the open cells of the plurality of open cells

comprise a quadrilateral shape or an elliptical shape.

107. The cartridge of claim 98, wherein the ground electrode extends over more than 50% of the first side of the top plate.

108. The cartridge of claim 98, wherein the top plate comprises a plurality of cavities within the thickness of the top plate, further wherein the cavities are filed with an insulating material having a low thermal mass and low thermal conductivity.

109. The cartridge of claim 109, wherein the insulating material comprises air.

110. The cartridge of claim 98, wherein the sheet of dielectric material is flexible.

111. The cartridge of claim 98, further comprising a microfluidics channel formed one or in the second side of the top plate, wherein the microfluidics channel extends along the second side of the top plate and at least one opening between the microfluidics channel and the air gap.

112. The cartridge of claim 98, wherein the top plate comprises polycarbonate and/or

acrylic.

113. The cartridge of claim 98, wherein the sheet of dielectric is less than 30 microns thick.

114. The cartridge of claim 98, wherein the second side of the dielectric material comprises a hydrophobic coating.

115. The cartridge of claim 98, wherein the air gap comprises a separation of greater than 400 micrometers.