Microfluidic systems and methods for thermal control

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.

What is claimed is: 
     
         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 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. 
 
   
     
     
         13 . The microfluidic system of  claim 12 , wherein the heater control and measurement circuit is configured such that the first and second RTDs are driven with opposite polarities. 
     
     
         14 . The microfluidic system of  claim 12 , 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. 
     
     
         15 . The microfluidic system of  claim 14 , 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. 
     
     
         16 . The microfluidic system of  claim 15 , 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. 
     
     
         17 . The microfluidic system of  claim 14 , 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.   
     
     
         18 . The microfluidic system of  claim 14 , 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. 
     
     
         19 . The microfluidic system of  claim 18 , 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.   
     
     
         20 . The microfluidic system of  claim 18 , 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.   
     
     
         21 . The microfluidic system of  claim 20 , 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.   
     
     
         22 . The microfluidic system of  claim 12 , 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. 
   
     
     
         23 . The microfluidic system of  claim 22 , 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. 
     
     
         24 . The microfluidic system of  claim 23 , 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. 
     
     
         25 . The microfluidic system of  claim 12 , wherein the virtual ground circuit comprises:
 an operational amplifier having an input connected to ground and another input connected to the first common electrode.   
     
     
         26 . The microfluidic system of  claim 25 , 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. 
     
     
         27 . 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.   
     
     
         28 . The method of  claim 27 , wherein the first and second RTDs are driven with opposite polarities. 
     
     
         29 . The method of  claim 27 , 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.   
     
     
         30 . The method of  claim 27 , 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. 
     
     
         31 . The method of  claim 27 , 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.   
     
     
         32 . The method of  claim 31 , 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.   
     
     
         33 . The method of  claim 31 , 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.   
     
     
         34 . The method of  claim 31 , 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.   
     
     
         35 . The method of  claim 27 , wherein the current in the first and second common electrodes is minimized by driving the first and second common electrodes to near zero potential. 
     
     
         36 . The method of  claim 35 , 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. 
     
     
         37 . 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. 
   
     
     
         38 . 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.   
     
     
         39 . 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. 
   
     
     
         40 . 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.