Method, apparatus and article for microfluidic control via electrowetting, for chemical, biochemical and biological assays and the like

• US 20030164295A1
• Filed: 11/26/2002
• Published: 09/04/2003
• Est. Priority Date: 11/26/2001
• Status: Active Grant

• Current Assignee: Keck Graduate Institute
• Original Assignee: Keck Graduate Institute
• Inventors: Sterling, James D.
• Granted Patent: US 7,163,612 B2
• Time in Patent Office: Days
• US Class Current: 204/450
• CPC Class Codes: B01L 2200/06 Fluid handling related problems
• CPC Class Codes: B01L 2300/0819 Microarrays; Biochips
• CPC Class Codes: B01L 2300/089 Virtual walls for guiding liquids
• CPC Class Codes: B01L 2400/0415 electrical forces, e.g. electrokinetic
• CPC Class Codes: B01L 2400/0427 Electrowetting
• 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 3/502738 characterised by integrated valves microvalves F16K99/0001
• CPC Class Codes: B01L 3/502792 for moving individual droplets on a plate, e.g. by locally altering surface tension
• CPC Class Codes: F04B 17/00 Pumps characterised by combination with, or adaptation to, specific driving engines or motors
• CPC Class Codes: F04B 19/006 Micropumps F04B43/043 and F04B43/095 take precedence
• CPC Class Codes: G02B 26/005 based on electrowetting

Abstract

An active matrix microfluidic platform employs thin film transistor active (“TFT”) matrix liquid crystal display technology to manipulate small samples of fluid for chemical, biochemical, or biological assays without moving parts, for example, using a two-dimensional matrix array of drive electrodes. The active matrix microfluidic platform may employ existing active matrix addressing schemes and/or commercial “off-the-shelf” animation software to program assay protocols. A feedback subsystem may determine an actual location of a fluid in the microfluidic structure, and provides location information to for display, for example, on an active matrix display, and/or to control movement of one or more fluid bodies in the microfluidic structure.

Claims

1. A microfluidic structure to move at least one fluid body, comprising:

a first plate having a dielectric overlying at least a portion of the first plate;

a second plate spaced from the first plate to form at least one cavity between the second plate and the dielectric overlying at least the portion of the first plate;

at least a first port providing fluid communication between the cavity and an exterior of the microfluidic structure;

an array of drive electrodes received between the first and the second plates; and

an array of thin film transistors, the thin film transistors coupled to respective ones of the drive electrodes in the array of drive electrodes to control a respective potential applied to respective portions of the dielectric that overlie respective ones of the drive electrodes to move the at least one fluid body from drive electrode to drive electrode.

2. The microfluidic structure of claim 1 wherein the array of drive electrodes is a two-dimensional matrix.

3. The microfluidic structure of claim 1 wherein the first plate and the second plate are substantially planar and parallel to one another.

4. The microfluidic structure of claim 1, further comprising:

a valve coupled to the first port where the valve is selectively actuatable to control a flow of the at least one fluid body through the first port.

5. The microfluidic structure of claim 1 wherein each of the drive electrodes have a dimension less than a lateral dimension of the at least one fluid body.

6. The microfluidic structure of claim 1, further comprising:

at least one ground electrode received between the first and the second plates, the at least one ground electrode spaced relatively from the array of drive electrodes in a direction generally perpendicular to the array of drive electrodes.

7. The microfluidic structure of claim 1 wherein the array of drive electrodes is a generally planar two-dimensional matrix, where successive drive electrodes in the array are activated to apply a different respective potential to the respective portions of the dielectric in the plane of travel of the at least one fluid body.

8. The microfluidic structure of claim 1, further comprising:

at least one hydrophobic layer overlying at least a portion of the dielectric layer.

9. The microfluidic structure of claim 1, further comprising:

at least one electrical connector to electrically couple the drive electrodes of the array of drive electrodes to at least one voltage source via the array of thin film transistors.

10. The microfluidic structure of claim 1 wherein the first port provides fluid communication between the cavity and the exterior of the microfluidic structure after completion of manufacturing of the microfluidic structure.

11. A microfluidic system, comprising:

at least one voltage source for supplying at least one voltage;

a microfluidic structure comprising a first plate;

a second plate, spaced from the first plate to form at least one cavity therebetween;

at least a first port providing fluid communication between the cavity and an exterior of the microfluidic structure;

an array of drive electrodes received between the first and the second plates;

a dielectric overlying at least a portion of the array of drive electrodes; and

an array of thin film transistors, the thin film transistors coupled to respective ones of the drive electrodes in the array of drive electrodes to control a respective potential applied to respective portions of the dielectric overlying the drive electrodes to move at least one fluid with respect to the drive electrodes;

a controller programmable to execute a set of driver instructions and coupled to control the thin film transistors of the array of thin film transistors according to a set of driver instructions to supply the at least one voltage from the voltage source to the drive electrodes via the thin film transistors.

12. The microfluidic system of claim 11, further comprising:

a computing system; and

a computer-readable medium having a set of computer animation instructions for causing the computing system to create the set of driver instructions in response to user input.

13. The microfluidic system of claim 11, further comprising:

a computing system; and

a computer-readable medium having a set of computer animation instructions for causing the computing system to create the set of driver instructions in response to user input, where the computer animations instructions comprise a standard, unmodified commercial animation software package.

14. A microfluidic platform for moving microfluidic bodies having a defined minimum lateral dimension, comprising:

a plurality of drive electrodes having a dimension less than the defined minimum lateral dimension of the microfluidic bodies;

a dielectric layer overlying at least a portion of the plurality of electrodes;

a plurality of thin film transistors coupled to the drive electrodes to control a respective potential to respective portions of the dielectric layer to move the fluidic bodies from a portion of the dielectric layer overlying one drive electrode to a portion of the dielectric layer overlying another drive electrode; and

a port providing fluid communications between an interior and an exterior of the microfluidic platform when the microfluidic platform is in use.

15. The microfluidic platform of claim 14 wherein the dimension of the electrodes is less than approximately half of the minimum lateral dimension of the microfluidic bodies.

16. The microfluidic platform of claim 14 wherein the dimension of the electrodes is less than approximately one third of the minimum lateral dimension of the microfluidic bodies.

17. The microfluidic platform of claim 14 wherein there are at least three drive electrodes in an area equivalent to an area that would be electrowetted by the fluid.

18. The microfluidic platform of claim 14, further comprising:

a valve for selectively closing and opening the port when the microfluidic platform is in use.

19. A microfluidic platform for moving microfluidic bodies, comprising:

a two-dimensional matrix array of drive electrodes, the drive electrodes being dimensioned and spaced from one another in the two-dimensional matrix such that there is at least three electrodes in an area corresponding to a surface electrowetted by the microfluidic bodies;

a dielectric overlying at least a portion of the two-dimensional matrix array of drive electrodes;

a plurality of thin film transistors coupled to the drive electrodes to control a potential applied to respective portions of the dielectric overlying the respective drive electrodes to move the microfluidic bodies between successive portions of the dielectric layer; and

a port providing fluid communications between an interior and an exterior of the microfluidic platform when the microfluidic platform is in use.

20. A microfluidic system, comprising:

a microfluidic structure having a number of drive electrodes;

a controller coupled to control of the microfluidic structure; and

a feedback subsystem having a number of feedback sensors for detecting a position of at least one fluidic body, if any, in the microfluidic structure and at least one output for providing feedback position signals corresponding to the detected position.

21. The microfluidic system of claim 20, further comprising:

a display coupled to receive the feedback position signals from the feedback subsystem and configured to display an image corresponding to the detected position of the at least one fluidic body, if any, in the microfluidic structure.

22. The microfluidic system of claim 20 wherein the microfluidic structure, comprises:

a first plate;

a second plate, spaced from the first plate to form at least one cavity therebetween;

a two-dimensional matrix array formed by the drive electrodes received between the first and the second plates, the drive electrodes being separately addressable;

a dielectric layer overlying at least a portion of the two-dimensional matrix array formed by the drive electrodes; and

an array of thin film transistors, the thin film transistors coupled to respective ones of the drive electrodes to control a respective potential-applied by the drive electrode to a portion of the dielectric layer overlying the drive electrode to move the fluid body.

23. The microfluidic system of claim 20 wherein the feedback sensors are capacitively sensitive switches.

24. The microfluidic system of claim 20 wherein the feedback sensors are photosensitive elements of an imager.

25. The microfluidic system of claim 20 wherein the feedback sensors are resistive sensitive switching elements.

26. The microfluidic system of claim 20 wherein the feedback sensors are pressure sensitive switching elements.

27. A microfluidic system, comprising:

a microfluidic structure having a number of drive electrodes;

a feedback subsystem having a number of feedback sensors for detecting a position of at least one fluidic body, if any, in the microfluidic structure and at least one output for providing feedback position signals; and

a controller to produce drive signals and coupled to control of the drive electrodes of the microfluidic structure via the drive signals, and to receive the feedback position signals from the feedback subsystem.

28. The microfluidic system of claim 27 wherein the controller is configured to modify the drive signals based on the feedback signals.

29. The microfluidic system of claim 27 wherein the controller is configured to modify the drive signals based on the feedback signals, by:

determining a difference between the determined position of the at least one fluidic body and a desired position of the at least one fluidic body; and

adjusting the control of the drive electrodes based on the determined difference between the determined position of the at least one fluidic body and a desired position of the at least one fluidic body.

30. The microfluidic system of claim 27 wherein the feedback sensors are capacitively sensitive switches.

31. The microfluidic system of claim 27 wherein the feedback sensors are photosensitive elements of an imager.

32. The microfluidic system of claim 27 wherein the feedback sensors are resistive sensitive switching elements.

33. The microfluidic system of claim 27 wherein the feedback sensors are pressure sensitive switching elements.

34. A method of controlling a microfluidic structure having at least one cavity, a two-dimensional matrix array of drive electrodes;

a dielectric overlying at least a portion of the two-dimensional matrix array of drive electrodes; and

an array of thin film transistors electrically coupled to the drive electrodes, the method comprising;

introducing at least one fluid into the cavity of the microfluidic structure;

executing a set of executable instructions to produce a set of drive signals for each drive electrode in the two-dimensional matrix array of drive electrodes including drive electrodes in a desired flow path of the fluid and drive electrodes out of the desired flow path of the fluid;

applying the set of drive signals to the thin film transistors of the array of thin film transistors;

applying a potential to the drive electrodes in response to the set of drive signals applied to the thin film transistors; and

applying a respective potential to respective portions of the dielectric overlying respective ones of the drive electrodes to move the at least one fluid from at least one drive electrode to at least another drive electrode, along the desired flow path.

35. The method of claim 34 wherein applying the set of drive signals to the thin film transistors of the array of thin film transistors includes applying two different potential to successive portions of the dielectric in a direction planar with the desired flow path of the fluid.

36. The method of claim 34, further comprising:

evacuating the fluid from the cavity of the microfluidic structure after the applying the respective potential to the respective portions of the dielectric.

37. A method of controlling a microfluidic structure having at least one cavity, an array of drive electrodes and an array of thin film transistors coupled to the drive electrodes to selectively apply voltage across at least one fluid, the method comprising:

creating a set of executable instructions corresponding to an animated sequence using a standard, unmodified, animation software package;

introducing the at least one fluid into the cavity of the microfluidic structure;

executing the set of executable instructions to produce a set of drive signals;

applying the drive signals to the thin film transistors; and

selectively applying a potential to the drive electrodes via the thin film transistors to move the fluid from at least one of the drive electrodes to another one of the drive electrodes.

38. The method of claim 37 wherein creating a set of executable instructions corresponding to an animated sequence using a standard, unmodified, animation package includes selecting animation commands from a graphical user interface of the standard, unmodified, animation software package.

39. The method of claim 37 wherein the array of drive electrodes is a two-dimensional matrix array and creating a set of executable instructions corresponding to an animated sequence using a standard, unmodified, animation package includes:

manually selecting animation commands from a graphical user interface of the standard, unmodified, animation software package; and

automatically producing a respective drive signal for each of the drive electrodes in the two-dimensional matrix array of drive electrodes once each frame period.

40. The method of claim 37, further comprising:

providing the drive signals to an active matrix display to display the animated sequence on the active matrix display before the applying the drive signals to the thin film transistors of the microfluidic structure.

41. The method of claim 37, further comprising:

providing the drive signals in unaltered form to an active matrix display to display the animated sequence on the active matrix display before the applying the drive signals to the thin film transistors of the microfluidic structure.

42. The method of claim 37, further comprising:

providing the drive signals to an active matrix display to display the animated sequence on an active matrix display at approximately the same time as the applying the drive signals to the thin film transistors of the microfluidic structure.

43. The method of claim 37, further comprising:

providing the drive signals in unaltered form to an active matrix display to display the animated sequence on an active matrix display at approximately the same time as the applying the drive signals to the thin film transistors of the microfluidic structure.

44. A method of forming a microfluidic structure, the method comprising:

providing a first plate;

providing a second plate;

spacing the second plate from the first plate to create at least one cavity therebetween;

forming at an array of drive electrodes and an array of thin film transistors overlying at least a portion of the first plate, the thin film transistors electrically coupled to control the drive electrodes; and

providing a port between an exterior of the microfluidic structure and the cavity.

45. The method of claim 44, further comprising:

providing a valve for controlling a flow of fluid through the port when the microfluidic structure is in use.

46. The method of claim 44, further comprising:

forming a first fluid compatibility coating overlying the array of drive electrodes.

47. The method of claim 44, further comprising:

forming a first hydrophobic coating overlying the array of drive electrodes, the first hydrophobic coating forming at least a portion of at least one surface of the cavity; and

forming a second hydrophobic coating overlying the second plate, the second hydrophobic coating forming at least a portion of at least one surface of the cavity.

48. The method of claim 44 wherein forming at an array of drive electrodes and an array of thin film transistors overlying at least a portion of the first plate, the thin film transistors electrically coupled to control the drive electrodes includes forming a two-dimensional matrix array of electrodes and a two-dimensional matrix array of thin film transistors electrically coupled to respective ones of the drive electrodes.

49. A computer readable medium containing instructions for causing computer to move fluids in a microfluidic structure having a two-dimensional matrix array of drive electrodes;

a dielectric overlying at least a portion of the two-dimensional matrix array of drive electrodes; and

an array of thin film transistors coupled to the drive electrodes, by;

producing a set of drive signals for each drive electrode in the two-dimensional matrix array of drive electrodes, including drive electrodes in a desired flow path of at least one fluid and drive electrodes out of the desired flow path of the at least one fluid;

applying the set of drive signals to the thin film transistors of the array of thin film transistors;

applying a potential to the drive electrodes in response to the set of drive signals applied to the thin film transistors; and

applying a respective potential to respective portions of the dielectric overlying respective ones of the drive electrodes to move the at least one fluid from at least one drive electrode to at least another drive electrode, along the desired flow path.

50. A method of operating a microfluidic system having a controller, a number of position feedback sensors, and a microfluidic structure including an array of selectively addressable drive electrodes, the method comprising:

providing drive signals to drive selected ones of the drive electrodes;

receiving position feedback signals from the position feedback sensors, the position feedback signals representing an actual position of at least one fluid body with respect to the drive electrodes; and

displaying a representation of the actual position of the at least one fluid body on an active matrix display in response to the position feedback signals.

51. The method of claim 50 wherein receiving position feedback signals from the position feedback sensors, the position feedback signals representing an actual position of at least one fluid body with respect to the drive electrodes includes receiving signals from an array of capacitive sensitive sensors.

52. The method of claim 50 wherein receiving position feedback signals from the position feedback sensors, the position feedback signals representing an actual position of at least one fluid body with respect to the drive electrodes includes receiving signals from an array of imager sensors.

53. The method of claim 50, further comprising:

displaying a representation of a desired position of the at least one fluid body on the active matrix display.

54. The method of claim 50, further comprising:

displaying a representation of at least one desired flow path of the at least one fluid body on the active matrix display.

55. A method of operating a microfluidic system having a controller, a number of position feedback sensors, and a microfluidic structure including an array of selectively addressable drive electrodes, the method comprising:

providing drive signals to drive selected ones of the drive electrodes;

receiving position feedback signals from the position feedback sensors, the position feedback signals representing an actual position of at least one fluid body with respect to the drive electrodes; and

providing further drive signals based at least in part on the position feedback signals.

56. The method of claim 55 wherein providing further drive signals based at least in part on the position feedback signals includes providing further drive signals for moving a first fluid body to a desired positioned before providing further drive signals for moving a second fluid body.

57. The method of claim 55 wherein providing further drive signals based at least in part on the position feedback signals includes adjusting a next set of drive signals in response to the position feedback signals.

58. The method of claim 55 wherein providing further drive signals based at least in part on the position feedback signals includes determining a next set of drive signals based on a respective actual position and respective desired position of at least two fluid bodies with respect to a time.

59. The method of claim 55, further comprising:

determining a difference between an actual position and a desired position of the at least one fluid body, and wherein providing further drive signals based at least in part on the position feedback signals includes compensating for the determined difference.

60. The method of claim 55 wherein providing further drive signals based at least in part on the position feedback signals includes providing further drive signals to a first set of drive electrodes along a first flow path to adjust a rate of movement of a first fluid body along a first flow path and providing further drive signals to a second set of drive electrodes along a second flow path to adjust a rate of movement of a second fluid body along a second flow path.