Microfluidic devices with integrated resistive heater electrodes including systems and methods for controlling and measuring the temperatures of such heater electrodes

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 heater electrodes, wherein the heater electrodes are part of a multiplex circuit including a common lead connecting the heater electrodes to a power supply, each of the heater electrodes being associated with one of the microfluidic channels. The microfluidic device also includes a control system configured to regulate power applied to each heater electrode by varying a duty cycle, the control system being further configured to determine the temperature each heater electrode by determining the resistance of each heater electrode.

What is claimed is: 
     
         1 . A microfluidic device incorporating thin-film heaters within a plurality of microfluidic channels to effect a biological reaction, said device comprising:
 a microfluidic chip comprising a first zone and a second zone wherein said first zone and said second zone comprise a plurality of microfluidic channels, a plurality of thin-film heaters disposed beneath said microfluidic channels; and   control circuitry configured to generate PWM control signals for each of the thin-film heaters in said first and second zones,   wherein the control circuitry is configured to calibrate the PWM signals so that said PWM signals are optimized for each of the thin-film heaters.   
     
     
         2 . The device of  claim 1 , wherein the control circuitry is configured to calibrate the PWM signals by:
 applying electrical power to all heater electrodes;   measuring a voltage drop across each of the heater electrodes to determine individual electrode resistance values;   computing a heater power based on the individual heater electrode resistance values;   applying the heater power to heater electrodes for a pre-determined calibration pulse time;   collecting heater electrode resistance measurements for a predetermined collection time at a predetermined sampling rate;   using said measurements to compute a thermal decay time constant; and   computing an optimal pulse width modulation frequency based on the decay time information.   
     
     
         3 . The device of  claim 2 , wherein the control circuitry is configured to compute the heater power by using a look-up table to find the heater power associated with a particular resistance value. 
     
     
         4 . The device of  claim 1 , wherein the microfluidic chip is removable. 
     
     
         5 . The device of  claim 1 , wherein the control circuitry is configured to produce multiplexed PWM control signals. 
     
     
         6 . The device of  claim 1 , wherein the control circuitry is configured to produce differential PWM control signals that alternate between a first set of PWM signals and a second set of PWM signals. 
     
     
         7 . The device of  claim 1 , wherein the first zone is used for conducting a polymerase chain reaction and the second zone is used for biological monitoring. 
     
     
         8 . The device of  claim 7 , wherein biological monitoring is thermal melt. 
     
     
         9 . The device of  claim 7 , wherein the biological monitoring is end point PCR fluorescence. 
     
     
         10 . A method of calibrating a pulse width modulation thin-film heater control system for an integrated thin-film device with a plurality of microfluidic channels, each channel having at least one heater electrode, comprising:
 applying electrical power to said at least one heater electrode in said each channel;   measuring a voltage drop across each of the heater electrodes to determine individual electrode resistance values;   computing a heater power based on the individual heater electrode resistance values;   applying the heater power to heater electrodes for a pre-determined calibration pulse time;   collecting heater electrode resistance measurements for a predetermined collection time at a predetermined sampling rate;   using said measurements to compute a thermal decay time constant; and   computing an optimal pulse width modulation frequency based on the decay time information for each heater electrode in said each channel; and   varying the duty cycle of said optimal pulse width modulation frequency for said each heater electrode for controlling the temperature of said each heater electrode.   
     
     
         11 . The method of  claim 10 , wherein the calibration pulse time is between approximately 10 μs to 10 ms. 
     
     
         12 . The method of  claim 11 , wherein the calibration pulse time is between approximately 200 μs to 2 ms. 
     
     
         13 . The method of  claim 12 , wherein the calibration pulse time is approximately 500 μs. 
     
     
         14 . The method of  claim 10 , wherein the collection time is between approximately 1 μs to 1000 μs. 
     
     
         15 . The method of  claim 14 , wherein the collection time is between approximately 10 μs to 100 μs. 
     
     
         16 . The method of  claim 15 , wherein the collection time is approximately 25 μs. 
     
     
         17 . The method of  claim 10 , wherein the sampling rate is between approximately 0.1 μs to 1000 μs. 
     
     
         18 . The method of  claim 17 , wherein the sampling rate is between approximately 1 μs to 10 μs. 
     
     
         19 . The method of  claim 18 , wherein the sampling rate is approximately 2.5 μs. 
     
     
         20 . The method of  claim 10 , further comprising the step of storing said optimal pulse width modulation frequency in a memory array. 
     
     
         21 . A method of calibrating a PWM thin-film heater control system to effect a biological reaction in a microfluidic device, wherein the microfluidic device includes a plurality of thin-film heaters that heat a plurality of microfluidic channels, said method comprising:
 determining a thin-film heater resistance in between PWM energy cycles;   computing a microfluidic channel temperature based on said thin-film heater resistance;   applying a controlled current pulse to the thin-film heaters;   measuring a thermal decay time constant of the thin-film heaters after application of the controlled current pulse;   calculating an optimal PWM frequency for the thin-film heaters based on the time constant; and   adjusting the PWM frequency to said optimal frequency.   
     
     
         22 . The method of  claim 21 , wherein the step of determining a thin-film heater resistance comprises measuring a voltage drop across the thin-film heater. 
     
     
         23 . The method of  claim 21 , wherein the biological reaction is a polymerase chain reaction. 
     
     
         24 . The method of  claim 21 , wherein the biological reaction is a high resolution thermal melt. 
     
     
         25 . The method of  claim 21 , wherein the PWM signal is multiplexed between the plurality of thin-film heaters within the microfluidic channels. 
     
     
         26 . The method of  claim 21 , wherein the step of generating a set of calibration data comprises:
 applying electrical power to all heater electrodes;   measuring a voltage drop across each of the heater electrodes to determine individual electrode resistance values;   computing a nominal heater power based on the individual heater electrode resistance values;   applying the nominal heater power to said heater electrodes for a pre-determined calibration pulse time;   collecting heater electrode resistance measurements for a predetermined collection time at a predetermined sampling rate;   using said measurements to compute a thermal decay time constant; and   computing an optimal pulse width modulation frequency based on the decay time information.   
     
     
         27 . A method of controlling a microfluidic device comprising a plurality of thin-film heaters that heat a plurality of microfluidic channels to effect a biological reaction, said method comprising:
 a. measuring a thin-film heater resistance in between pulse width modulation energy cycles so as to measure the microfluidic channel temperature;   b. measuring a thermal decay time constant of the thin-film heaters after application of a controlled current pulse; and   c. adjusting the pulse width modulation frequency to be optimal for the thermal decay time constant of the thin-film heaters.   
     
     
         28 . The method of  claim 27 , wherein the biological reaction is polymerase chain reaction. 
     
     
         29 . The method of  claim 27  wherein the biological reaction is a thermal melt. 
     
     
         30 . A microfluidic device for performing biological reactions comprising:
 a microfluidic chip comprising a first zone having a plurality of microfluidic channels and a second zone having a plurality of microfluidic channels, wherein said microfluidic channels in said first and second zones are in fluid communication, said microfluidic chip further comprising a thin-film heater in thermal communication with each of said microfluidic channels in said first and second zones;   a control system configured to independently control the temperature of each of the thin-film heaters using PWM control signals that are optimized for each of the thin-film heaters.   
     
     
         31 . The microfluidic device of  claim 30 , wherein the control system provides PWM control signals to the thin-film heaters corresponding to the first zone configured to effect a polymerase chain reaction and wherein the control system provides PWM control signals to the thin-film heaters corresponding to the second zone configured to effect biological monitoring. 
     
     
         32 . The microfluidic device of  claim 30 , wherein the biological monitoring is thermal melt. 
     
     
         33 . The microfluidic device of  claim 30 , wherein the biological monitoring is PCR fluorescence. 
     
     
         34 . The microfluidic device of  claim 30 , wherein the control system comprises a closed-loop control system configured to adjust the duty cycle of the PWM signal in order to maintain a desired temperature.