MICROFLUIDIC SYSTEMS AND METHODS FOR THERMAL CONTROL

• US 20110048547A1
• Filed: 06/29/2010
• Published: 03/03/2011
• Est. Priority Date: 06/29/2009
• Status: Active Grant

• Current Assignee: Canon USA, Inc. (Canon Inc.)
• Original Assignee: Canon USA, Inc. (Canon Inc.)
• Inventors: Owen, Gregory H., Inoue, Hiroshi, Hasson, Kenton C., Coursey, Johnathan S.
• Granted Patent: US 9,061,278 B2
• Time in Patent Office: Days
• US Class Current: 137/341
• CPC Class Codes: B01L 2200/14 Process control and prevention of errors
• CPC Class Codes: B01L 2200/147 Employing temperature sensors
• CPC Class Codes: B01L 2300/0645 Electrodes
• CPC Class Codes: B01L 2300/1805 Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks
• CPC Class Codes: B01L 2300/1827 using resistive heater
• CPC Class Codes: B01L 3/502715 characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• 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: B01L 7/525 with physical movement of samples between temperature zones
• CPC Class Codes: C12Q 3/00 Condition responsive control processes apparatus therefor C12M1/36; controlling or regulating in general G05
• CPC Class Codes: H05B 1/02 Automatic switching arrangements specially adapted to apparatus ; Control of heating devices thermally-actuated switches H01H37/00
• CPC Class Codes: Y10T 137/6606 With electric heating element

Abstract

The invention relates to methods and devices for control of an integrated thin-film device with a plurality of microfluidic channels. In one embodiment, a microfluidic device is provided that includes a microfluidic chip having a plurality of microfluidic channels and a plurality of multiplexed resistive thermal detectors (RTDs). Each of the RTDs is associated with one of the microfluidic channels. The RTDs are connected to a power supply through individual electrodes and pairs of common electrodes. Adjacent RTDs may be driven with alternating polarities, and the current in the common electrodes may be minimized using a virtual ground circuit. The compact microfluidic device is capable of fast heating and highly precise thermal control. The compact microfluidic device is also capable using the RTDs to sense temperature without their heating capability.

Claims

1. A microfluidic system comprising:

a microfluidic device comprising;

a plurality of microchannels;

a plurality of resistive temperature detectors (RTDs) each adjacent to a portion of an associated one of the plurality of microchannels;

a first common electrode connected to each of the plurality of RTDs;

a second common electrode connected the first common electrode and to each of the plurality of RTDs; and

a heater control and measurement circuit configured to;

(i) drive the plurality of RTDs with heater control signals having alternating polarities so that adjacent RTDs of the plurality are driven with heater control signals having opposite polarities;

(ii) minimize the current in the first and second common electrodes;

(iii) sense a temperature of each of the plurality of RTDs; and

(iv) update the heater control signals using the sensed temperatures of the plurality of RTDs.

2. The microfluidic system of claim 1, wherein the portions of the associated ones of the plurality of microchannels are located in a polymerase chain reaction (PCR) thermal zone of the microfluidic device or in a thermal melt zone of the microfluidic device.

3. The microfluidic system of claim 1, wherein the heater control and measurement circuit comprises a system controller that is configured to generate the heater control signals based on a polymerase chain reaction (PCR) profile or a temperature ramp profile.

4. The microfluidic system of claim 1, wherein the microfluidic device further comprises:

a second plurality of RTDs;

a third common electrode connected to each of the second plurality of RTDs;

a fourth common electrode connected the third common electrode and to each of the second plurality of RTDs;

wherein the heater control and measurement circuit is further configured to;

(i) drive the second plurality of RTDs with heater control signals having alternating polarities so that adjacent RTDs of the second plurality of RTDs are driven with heater control signals having opposite polarities;

(ii) minimize the current in the third and fourth common electrodes;

(iii) sense a temperature of each of the second plurality of RTDs; and

(iv) update the heater control signals using the sensed temperatures of the second plurality of RTDs.

5. The microfluidic system of claim 4, wherein each of the second plurality of RTDs is adjacent to a second portion of an associated one of the plurality of microchannels.

6. The microfluidic system of claim 5, wherein the portions of the associated ones of the plurality of microchannels are located in a polymerase chain reaction (PCR) thermal zone of the microfluidic device;

and

the second portions of the associated ones of the plurality of microchannels are located in a thermal melt zone of the microfluidic device.

7. The microfluidic system of claim 4, further comprising a second plurality of microchannels, wherein each of the second plurality of RTDs is adjacent to a portion of an associated one of the second plurality of microchannels.

8. The microfluidic system of claim 7, wherein the portions of the associated ones of the plurality of microchannels and the portions of the associated ones of the second plurality of microchannels are located in a polymerase chain reaction (PCR) thermal zone of the microfluidic device or a thermal melt zone of the microfluidic device.

9. The microfluidic system of claim 1, wherein the heater control and measurement circuit is configured to update the heater control signals by modulating the amplitude of the heater control signals.

10. The microfluidic system of claim 1, wherein the heater control signals are alternating current signals.

11. The microfluidic system of claim 10, wherein heater control signals have opposite polarities when they are 180 degrees out of phase with each other.

12. A method for individually controlling a plurality of resistive thermal detectors (RTDs) of a microfluidic device of a microfluidic system, wherein the RTDs are each adjacent to a portion of an associated one of the plurality of microchannels;

the method comprising;

generating heater control signals having alternating polarities to drive the plurality of RTDs;

supplying the heater control signals to the plurality of RTDs so that adjacent RTDs of the plurality of RTDs are driven with heater control signals having opposite polarities;

minimizing current in first and second common electrodes, wherein the first and second common electrodes are each connected to each RTD of the plurality of RTDs;

sensing a temperature of each of the plurality of RTDs; and

updating the heater control signals using the sensed temperatures of the plurality of RTDs.

13. The method of claim 12, wherein the heater control signals are generated and updated based on a polymerase chain reaction (PCR) profile or on a temperature ramp profile.

14. The method of claim 12, wherein the minimizing the current in the first and second common electrodes comprises determining a current imbalance between currents of the heating control signals supplied to the plurality of RTDs.

15. The method of claim 14, wherein the minimizing the current in the first and second common electrodes further comprises sourcing/sinking the determined current imbalance.

16. The method of claim 12, further comprising preventing the heater control signals from having a voltage lower than a minimum voltage limit.

17. The method of claim 12, wherein the heater control signals are generated so that deoxyribonucleic acid (DNA) contained in the portions of the associated ones of the plurality of microchannels is amplified through a polymerase chain reaction (PCR).

18. The method of claim 12, wherein the heater control signals are generated so as to ramp the temperature of the first and second RTDs.

19. The method of claim 12, wherein the microfluidic device further comprises a second plurality of RTDs;

the method further comprising;

generating second heater control signals having alternating polarities to drive the second plurality of RTDs;

supplying the second heater control signals to the second plurality of RTDs so that adjacent RTDs of the second plurality of RTDs are driven with second heater control signals having opposite polarities;

minimizing current in third and fourth common electrodes, wherein the third and fourth common electrodes are each connected to each RTD of the second plurality of RTDs;

sensing a temperature of each of the second plurality of RTDs; and

updating the second heater control signals using the sensed temperatures of the second plurality of RTDs.

20. The method of claim 19, wherein each of the second plurality of RTDs is adjacent to a second portion of an associated one of the plurality of microchannels;

the heater control signals that drive the plurality of RTDs are generated so that deoxyribonucleic acid (DNA) contained in the associated ones of the plurality of microchannels is amplified;

the second heater control signals that drive the second plurality of RTDs are generated so as to ramp the temperature of the second plurality of RTDs.

21. The method of claim 20, wherein the DNA amplification is achieved through a polymerase chain reaction (PCR).

22. The method of claim 19, wherein the microfluidic device further comprises a second plurality of microchannels, each of the second plurality of RTDs being adjacent to a portion of an associated one of the second plurality of microchannels;

and

the first and second heater control signals that respectively drive the first and second plurality of RTDs are generated so that deoxyribonucleic acid (DNA) contained in the portions of the associated ones of the plurality of microchannels and the second plurality of microchannels is amplified.

23. The method of claim 22, wherein the DNA amplification is achieved through a polymerase chain reaction (PCR).

24. The method of claim 19, wherein the microfluidic device further comprises a second plurality of microchannels, each of the second plurality of RTDs being adjacent to a portion of an associated one of the second plurality of microchannels;

and

the first and second heater control signals that respectively drive the first and second plurality of RTDs are generated to ramp the temperature of the first and second plurality of RTDs.

25. The method of claim 12, wherein the heater control signals are updated by modulating the amplitude of the heater control signals.

26. The method of claim 12, wherein the heater control signals are alternating current signals.

27. The method of claim 26, wherein the heater control signals have opposite polarities when they are 180 degrees out of phase with each other.

28. A microfluidic system comprising:

a microfluidic device comprising;

a first microchannel;

a second microchannel;

a first electrode;

a second electrode;

a first common electrode;

a second common electrode;

a first resistive temperature detector (RTD) adjacent to a portion of the first microchannel and connected to the first electrode and to the first and second common electrodes;

a second RTD adjacent to a portion of the second microchannel and connected to the second electrode and to the first and second common electrodes; and

a heater control and measurement circuit comprising;

a virtual ground circuit associated with the first and second common electrodes and configured to minimize the current in the first and second common electrodes, the virtual ground circuit having;

(i) an input connected to the first common electrode, and

(ii) an output connected to the second common electrode;

a first RTD control circuit having;

(i) an input connected to the first common electrode, and

(ii) an RTD control output connected to the first electrode; and

a second RTD control circuit having;

(i) an input connected to the first common electrode, and

(ii) an RTD control output connected to the second electrode.

29. The microfluidic system of claim 28, wherein the heater control and measurement circuit is configured such that the first and second RTDs are driven with opposite polarities.

30. The microfluidic system of claim 28, further comprising a system controller configured to independently control the first and second electrodes by outputting a first heater control signal for the first RTD and a second heater control signal for the second RTD.

31. The microfluidic system of claim 30, wherein the first and second heater control signals are digital signals and the microfluidic system further comprises a digital to analog converter (DAC) configured to receive the first and second heater control signals, convert the first and second heater control signals into analog signals, and output the analog first and second heater control signals to the heater control and measurement circuit.

32. The microfluidic system of claim 31, wherein the system controller is configured to prevent the analog first and second heater control signals from having a voltage with an absolute value lower than a minimum voltage limit.

33. The microfluidic system of claim 30, wherein the first RTD control circuit is configured to receive the first heater control signal and output to the first electrode a first RTD control signal in accordance with the first heater control signal;

and

the second RTD control circuit is configured to receive the second heater control signal and output to the second electrode a second RTD control signal in accordance with the second heater control signal.

34. The microfluidic system of claim 30, wherein the system controller is further configured to receive first measurement signals generated by the first RTD control circuit and second measurement signals generated by the second RTD control circuit, to calculate a temperature of the first RTD using the first measurement signals, to calculate a temperature of the second RTD using the second measurement signals, to update the first heater control signal in accordance with the calculated temperature of the first RTD, and to update the second heater control signal in accordance with the calculated temperature of the second RTD.

35. The microfluidic system of claim 34, further comprising an analog to digital converter (ADC);

wherein the first and second measurement signals are converted to digital signals by the ADC before being received by the system controller.

36. The microfluidic system of claim 34, wherein the first measurement signals generated by the first RTD control circuit comprise:

a first current measurement signal indicative of a current across the first RTD; and

a first voltage measurement signal indicative of a voltage drop across the first RTD; and

wherein the second measurement signals generated by the second RTD control circuit comprise;

a second current measurement signal indicative of a current across the second RTD; and

a second voltage measurement signal indicative of a voltage drop across the second RTD.

37. The microfluidic system of claim 36, wherein the first current measurement signal is a measure of a voltage drop across a first sense resistor connected in series with said first RTD;

and

wherein the second current measurement signal is a measure of a voltage drop across a second sense resistor connected in series with the second RTD.

38. The microfluidic system of claim 28, wherein the first and second RTD control circuits each comprise:

a first differential amplifier having;

(i) first input, and

(ii) a second input connected to the RTD control output;

a sense resistor connected between the first and second inputs of the first differential amplifier; and

a second differential amplifier having;

(i) a first input connected to the RTD control output, and

(ii) a second input connected to the first common electrode of the first common electrode pair.

39. The microfluidic system of claim 38, wherein the first and second RTD control circuits each further comprises a line driver circuit having an output connected to the first input of the first differential amplifier.

40. The microfluidic system of claim 39, the line driver of the first RTD control circuit is a non-inverting line driver and the line driver of the second RTD control circuit is an inverting line driver.

41. The microfluidic system of claim 28, wherein the virtual ground circuit comprises:

an operational amplifier having an input connected to ground and another input connected to the first common electrode.

42. The microfluidic system of claim 41, wherein the virtual ground circuit further comprises a power buffer having an input connected to an output of the operational amplifier and an output connected to the output of the virtual ground circuit.

43. A method for individually controlling first and second resistive thermal detectors (RTDs) of a microfluidic device of a microfluidic system, wherein the first RTD is adjacent to a portion of a first microchannel of the microfluidic device, and the second RTD is adjacent to a portion of a second microchannel of the microfluidic device;

the method comprising;

generating a first heater control signal for driving the first RTD and a second heater control signal for driving the second RTD;

supplying the first heater control signal to the first RTD using a first electrode connected to the first RTD;

supplying the second heater control signal to the second RTD using a second electrode connected to the second RTD;

minimizing current in first and second common electrodes, wherein the first and second common electrodes are each connected to the first and second RTDs; and

sensing a temperature of the first RTD and a temperature of the second RTD using a signal received from the first common electrode.

44. The method of claim 43, wherein the first and second RTDs are driven with opposite polarities.

45. The method of claim 43, wherein the microfluidic device further comprises third and fourth RTDs, the second RTD is adjacent to the first and third RTDs, and the third RTD is adjacent to the second and fourth RTDs;

the first and third RTDs are driven with signals having a first polarity; and

the second and fourth RTDs are driven with signals having a second polarity that is opposite to the polarity of the first polarity.

46. The method of claim 43, further comprising generating an updated first heater control signal using the sensed temperature of the first RTD and generating an updated second heater signal using the sensed temperature of the second RTD.

47. The method of claim 43, wherein the sensing the temperature of the first RTD comprises:

(i) measuring a current across the first RTD, and

(ii) measuring a voltage drop across the first RTD; and

the sensing the temperature of the second RTD comprises;

(i) measuring a current across the second RTD, and

(ii) measuring a voltage drop across the second RTD.

48. The method of claim 47, wherein a first sense resistor is connected in series with the first RTD;

a second sense resistor is connected in series with the second RTD;

the current across the first RTD is measured by measuring a voltage drop across the first sense resistor; and

the current across the second RTD is measured by measuring a voltage drop across the second sense resistor.

49. The method of claim 47, wherein the voltage drop across the first RTD is measured by measuring the voltage difference between the first electrode and the first common electrode;

and

the voltage drop across the second RTD is measured by measuring the voltage difference between the second electrode and the first common electrode.

50. The method of claim 47, wherein the sensing the temperature of the first RTD further comprises converting the measured current and voltage drop across the first RTD into a temperature;

and

the sensing the temperature of the second RTD further comprises converting the measured current and voltage drop across the second RTD into a temperature.

51. The method of claim 43, wherein the current in the first and second common electrodes is minimized by driving the first and second common electrodes to near zero potential.

52. The method of claim 51, wherein the first and second common electrodes are driven to near zero potential by inverting a voltage at the first common electrode and supplying a signal indicative of the inverted voltage to the second common electrode.

53. A microfluidic system comprising:

a microfluidic device comprising;

a plurality of microchannels;

a plurality of resistive temperature detectors (RTDs) each adjacent to a portion of an associated one of the plurality of microchannels;

a first common electrode connected to each of the plurality of RTDs; and

a second common electrode connected the first common electrode and to each of the plurality of RTDs; and

a RTD measurement circuit configured to;

(i) invert a drive signal into an inverted drive signal;

(ii) drive every other RTD of the plurality of RTDs with the drive signal;

(iii) drive the RTDs of the plurality of RTDs that are not driven with drive signal with the inverted drive signal;

(iv) minimize the current in the first and second common electrodes; and

(v) sense a temperature of each of the plurality of RTDs.

54. A method for sensing the temperature of a plurality of resistive thermal detectors (RTDs) of a microfluidic device of a microfluidic system, wherein the RTDs are each adjacent to a portion of an associated one of the plurality of microchannels;

the method comprising;

generating a drive signal;

inverting the drive signal into an inverted drive signal;

driving every other RTD of the plurality of RTDs with the drive signal;

driving the RTDs of the plurality of RTDs that are not driven with drive signal with the inverted drive signal;

minimizing current in first and second common electrodes, wherein the first and second common electrodes are each connected to each RTD of the plurality of RTDs; and

sensing a temperature of each of the plurality of RTDs.

55. A microfluidic system comprising:

a microfluidic device comprising;

a plurality of microchannels;

a plurality of resistive temperature detectors (RTDs) each adjacent to a portion of an associated one of the plurality of microchannels; and

a common electrode connected to each of the plurality of RTDs; and

a heater control and measurement circuit configured to;

(i) drive the plurality of RTDs with heater control signals having alternating polarities so that adjacent RTDs of the plurality are driven with heater control signals having opposite polarities;

(ii) sense a temperature of each of the plurality of RTDs; and

(iii) update the heater control signals by modulating the amplitude of the heater control signals in accordance with the sensed temperatures of the plurality of RTDs.

56. A method for individually controlling a plurality of resistive thermal detectors (RTDs) of a microfluidic device of a microfluidic system, wherein the RTDs are each adjacent to a portion of an associated one of the plurality of microchannels;

the method comprising;

generating heater control signals having alternating polarities to drive the plurality of RTDs;

supplying the heater control signals to the plurality of RTDs so that adjacent RTDs of the plurality of RTDs are driven with heater control signals having opposite polarities;

sensing a temperature of each of the plurality of RTDs; and

updating the heater control signals by modulating the amplitude of the heater control signals in accordance with the sensed temperatures of the plurality of RTDs.