Apparatuses and methods for manipulating droplets on a printed circuit board

• US 20060194331A1
• Filed: 01/30/2006
• Published: 08/31/2006
• Est. Priority Date: 09/24/2002
• Status: Active Grant

• Current Assignee: Duke University
• Original Assignee: Duke University
• Inventors: Pamula, Vamsee K., Pollack, Michael G., Fair, Richard B.
• Granted Patent: US 8,349,276 B2
• Time in Patent Office: Days
• US Class Current: 436/150
• 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 on a printed circuit board (PCB) are disclosed. Droplets are actuated upon a printed circuit board substrate surface by the application of electrical potentials to electrodes defined on the PCB. The use of soldermask as an electrode insulator for droplet manipulation as well techniques for adapting other traditional PCB layers and materials for droplet-based microfluidics are also disclosed.

Claims

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

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

(b) an array of electrodes disposed on the substrate first side surface;

(c) a dielectric layer disposed on the substrate first side surface and patterned to cover the electrodes; and

(d) an electrode selector for dynamically creating a sequence of array electrode activation whereby a droplet disposed on the substrate first side surface is electrically manipulated.

2. The apparatus according to claim 1 wherein the printed circuit board substrate comprises a plurality of substrate apertures defined therein and extending from the substrate first side surface to the substrate second side surface 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 substrate defines at least one droplet inlet port adjacent with at least one of the electrodes of the 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 substrate defines at least one droplet outlet port adjacent with at least one of the electrodes of the 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 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. An apparatus for manipulating droplets, the apparatus comprising:

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

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

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

(d) a dielectric substance layer disposed on the substrate first side surface and patterned to cover the drive electrodes; and

(e) an electrode selector for dynamically creating a sequence of array electrode activation whereby a droplet disposed on the substrate first side surface is electrically manipulated.

14. The apparatus according to claim 13 wherein the printed circuit board substrate comprises a plurality of substrate apertures defined therein and extending from the substrate first side surface to the substrate second side surface 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.

15. The apparatus according to claim 14 wherein the via holes are filled with the dielectric substance.

16. The apparatus according to claim 14 wherein the via holes are filled with a resin.

17. The apparatus according to claim 16 wherein the resin is a conductive epoxy or an optically transparent epoxy.

18. The apparatus according to claim 13 wherein the substrate defines at least one droplet inlet port adjacent with at least one of the electrodes of the electrode array.

19. The apparatus according to claim 18 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.

20. The apparatus according to claim 18 wherein the substrate defines at least one droplet outlet port adjacent with at least one of the electrodes of the electrode array.

21. The apparatus according to claim 20 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.

22. The apparatus according to claim 13 wherein the array of reference elements comprises a grid of elongate structures.

23. The apparatus according to claim 22 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.

24. The apparatus according to claim 13 wherein the dielectric substance is a soldermask material, spin-on material, dip-coatable material, brush or spray-coatable, vapor depositable, or sputtered material.

25. The apparatus according to claim 24 wherein the soldermask material is selected from the group consisting of liquid photoimageable soldermask (LPI) and dry film soldermask (DFSS).

26. The apparatus according to claim 13 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.

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

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

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

(c) an elongate reference element substantially parallel to and spaced apart from the substrate first side surface by a distance to define a space between the reference element and the substrate first side surface, wherein the distance is sufficient to contain a droplet disposed in the space;

(d) a dielectric substance layer disposed on the substrate first side surface and patterned to cover the drive electrodes; and

(e) an electrode selector for dynamically creating a sequence of array electrode activation whereby a droplet disposed on the substrate first side surface is electrically manipulated.

28. The apparatus according to claim 27 wherein the printed circuit board substrate comprises a plurality of substrate apertures defined therein and extending from the substrate first side surface to the substrate second side surface 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.

29. The apparatus according to claim 28 wherein the via holes are filled with the dielectric substance.

30. The apparatus according to claim 28 wherein the via holes are filled with a resin.

31. The apparatus according to claim 30 wherein the resin is a conductive epoxy or an optically transparent epoxy.

32. The apparatus according to claim 27 wherein the substrate defines at least one droplet inlet port adjacent with at least one of the electrodes of the electrode array.

33. The apparatus according to claim 32 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.

34. The apparatus according to claim 32 wherein the substrate defines at least one droplet outlet port adjacent with at least one of the electrodes of the electrode array.

35. The apparatus according to claim 34 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.

36. The apparatus according to claim 27 wherein the elongate reference element is an array of one or more wires.

37. The apparatus according to claim 27 wherein the elongate reference element is a plate.

38. The apparatus according to claim 37 wherein the reference element plate comprises a plate surface facing the substrate surface, and the plate surface is hydrophobic.

39. The apparatus according to claim 27 wherein the dielectric substance is a soldermask material, spin-on material, dip-coatable material, brush or spray-coatable, vapor depositable, or sputtered material.

40. The apparatus according to claim 39 wherein the soldermask material is selected from the group consisting of liquid photoimageable soldermask (LPI) and dry film soldermask (DFSS).

41. The apparatus according to claim 27 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.

42. 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 and patterned to cover the drive electrodes;

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

(e) an array of drive electrodes and an array of one or more reference elements disposed on the second printed circuit board substrate second side surface; and

(f) an electrode selector for dynamically creating a sequence of array electrode activation whereby a droplet disposed between the first printed circuit board substrate first side surface and the second printed circuit board substrate second side surface is electrically manipulated.

43. A method for actuating a droplet, the method comprising the steps of:

(a) providing a droplet on a surface of a printed circuit board substrate, the surface comprising an array of electrodes, wherein the droplet is initially disposed on a first one of the electrodes and is adjacent to a second one of the electrodes separated from the first electrode by a first gap;

(b) biasing the first electrode to a first voltage and the second electrode to a second voltage different from the first voltage whereby the droplet moves towards the second electrode.

44. The method according to claim 43 wherein the second voltage is a ground state.

45. The method according to claim 43 wherein the applied bias is either DC or AC.

46. A method for actuating a droplet, the method comprising:

(a) providing a droplet on a surface of a printed circuit board substrate, the surface comprising an array of drive electrodes and an at least substantially co-planar array of one or more reference elements, wherein the droplet is disposed on a first one of the drive electrodes; and

(b) biasing the first drive electrode to move the droplet from the first drive electrode to a second drive electrode.

47. The method according to claim 46 wherein the second electrode is adjacent to the first electrode along a first direction, the electrode array comprises one or more additional electrodes adjacent to the first electrode along one or more additional directions, the droplet is adjacent to the one or more additional electrodes, and the method comprises the steps of:

(a) selecting the first direction as a desired direction along which the droplet is to move; and

(b) selecting the second electrode for biasing based on the selection of the first direction.

48. A method for actuating a droplet, the method comprising:

(a) providing a droplet between a surface of a printed circuit board substrate and an elongate reference element substantially parallel to and spaced apart from the printed circuit board surface, wherein the printed circuit board surface comprises an array of drive electrodes and the droplet is disposed on a first one of the drive electrodes; and

(b) biasing the first drive electrode to move the droplet from the first drive electrode to a second drive electrode.

49. A method for actuating a droplet, the method comprising:

(a) providing a droplet between a surface of a first printed circuit board substrate and a surface of a second printed circuit board substrate substantially parallel to and spaced apart from the printed circuit board, wherein the first printed circuit board surface comprises an array of drive electrodes and the droplet is disposed on a first one of the drive electrodes, and further wherein the second printed circuit board surface comprises an array of drive electrodes and an array of one or more reference elements; and

(b) biasing the first drive electrode to move the droplet from the first drive electrode to a second drive electrode.

50. A method for merging two or more droplets into one droplet, comprising the steps of:

(a) providing first and second droplets on a surface of a printed circuit board substrate, the surface comprising an array of electrodes, wherein the electrode array comprises at least three electrodes comprising a first outer electrode, a medial electrode adjacent to the first outer electrode, and a second outer electrode adjacent to the medial electrode, the first droplet is disposed on the first outer electrode and is adjacent to the medial electrode, and the second droplet is disposed on the second outer electrode and is adjacent to the medial electrode;

(b) selecting one of the three electrodes as a destination electrode;

(c) selecting two or more of the three electrodes for activation and de-activation based on the selection of the destination electrode; and

(d) activating and de-activating the electrodes selected to move one of the first and second droplets toward the other droplet or both of the first and second droplets toward each other, whereby the first and second droplets merge together to form a combined droplet on the destination electrode.

51. A method for splitting a droplet into two or more droplets, comprising the steps of:

(a) providing a starting droplet on a surface of a printed circuit board substrate, the surface comprising an array of electrodes, wherein the electrode array comprises at least three electrodes comprising a first outer electrode, a medial electrode adjacent to the first outer electrode, and a second outer electrode adjacent to the medial electrode, and the starting droplet is initially disposed on at least one of the three electrodes and is adjacent to at least one other of the three electrodes;

(b) biasing each of the three electrodes to a first voltage to position the starting droplet across the three electrodes; and

(c) biasing the medial electrode to a second voltage different from the first voltage to split the starting droplet into first and second split droplets, whereby the first split droplet is formed on the first outer electrode and the second split droplet is formed on the second outer electrode.

52. A method for splitting a droplet into two or more droplets, comprising the steps of:

(a) providing a starting droplet on a surface of a printed circuit board substrate, the surface comprising an array of electrodes, wherein the electrode array comprises at least three electrodes comprising a first outer electrode, a medial electrode adjacent to the first outer electrode, and a second outer electrode adjacent to the medial electrode, and the starting droplet is initially disposed on at least one of the three electrodes and at least partially overlaps at least one other of the three electrodes;

(b) biasing the medial electrode to a first voltage to position the starting droplet, whereby the starting droplet at least partially overlaps the three electrodes; and

(c) biasing the medial electrode to a second voltage and at least one of the first and second outer electrodes to a third voltage, the second and third voltages different than the first voltage, to split the initial droplet into first and second split droplets, whereby the first split droplet is formed on the first outer electrode and the second split droplet is formed on the second outer electrode.