Adaptive Thermal Block Temperature Control Method and System

Abstract

Aspects of the present teachings describe a method and apparatus for automatically controlling a block temperature to reduce undershooting and overshooting of the temperatures of a sample contained in the block and participating in a polymerase chain reaction (PCR). The adaptive thermal block temperature control begins when a sample temperature enters a sample window region between a preliminary setpoint temperature and a target setpoint temperature for the sample. Based on thermodynamic behavior of the sample and the predetermined phase of PCR, predicting a time period measured subsequent to the preliminary setpoint temperature when the sample will reach the target setpoint suitable for the predetermined phase of PCR. During this time period, varying the block temperature ramp rate with a series of cooling and heating changes to ensure the block temperature reaches the target setpoint temperature at approximately the same time as the sample reaches the same. Synchronizing the block temperature and sample temperature to the target setpoint temperature reduces undershooting and overshooting of the sample temperature and increases the speed and efficiency of the overall PCR process as it relates to the thermal cycling operations.

What is claimed is: 
     
         1 . A computer implemented method of controlling a thermal cycler for use in PCR, comprising;
 determining a current temperature ramp rate for a sample being processed in a thermal block;   predicting an expected time interval for the sample to reach a target setpoint temperature based upon the current temperature ramp rate for the sample;   operating the thermal block at a target block ramp rate according to the predicted time interval for the sample to reach the target setpoint temperature;   repeating determination of the current temperature ramp rate for the sample as the thermal protocol for PCR is performed in real-time;   determining whether the predicted time interval for sample to reach target setpoint temperature has changed based on the current temperature ramp rate; and   modifying the predicted time interval and the target block ramp rate to ensure target block and sample both reach target setpoint temperature at approximately same time.   
     
     
         2 . The computer implemented method of  claim 1  wherein repeating the determination of the current temperature ramp rate occurs at a frequency corresponding to control loop time interval. 
     
     
         3 . The computer implemented method of  claim 1  wherein the control loop time interval is approximately 20 times per second. 
     
     
         4 . The computer implemented method of  claim 1  wherein modifying the predicted time interval occurs during an adaptive window for adjusting the target block ramp rate of the thermal block. 
     
     
         5 . The computer implemented method of  claim 4  wherein the adaptive window designates approximately where the sample temperature is predicted to reach the target setpoint temperature and wherein the target block ramp rate is modified so achieve substantially the same sample temperature and block temperature within the range of the adaptive window. 
     
     
         6 . An apparatus for controlled automated performance of polymerase chain reactions, the apparatus comprising:
 at least one sample comprising a PCR mixture to be amplified and contained in a sample vessel whose temperature is varied by association with a thermal block of variable temperature; and   a control module implementing a PCR thermal protocol configured to vary the temperature of the thermal block and further configured to perform the steps of:   determining a current temperature ramp rate for the sample;   predicting an expected time interval for the sample to reach a target setpoint temperature based upon the current temperature ramp rate for the sample;   operating the thermal block at a thermal block ramp rate according to the predicted time interval for the sample to reach the target setpoint temperature;   repeating determination of the current temperature ramp rate for the sample as the thermal protocol for PCR is performed;   determining whether the predicted time interval for sample to reach target setpoint temperature has changed based on the current temperature ramp rate; and   modifying the predicted time interval and the thermal block ramp rate such that the thermal block and sample reach target setpoint temperature at approximately same time.   
     
     
         7 . The apparatus of  claim 6  wherein repeating the determination of the current temperature ramp rate occurs at a frequency corresponding to control loop time interval. 
     
     
         8 . The apparatus of  claim 7  wherein the control loop time interval is approximately 20 times per second. 
     
     
         9 . The apparatus of  claim 6  wherein modifying the predicted time interval occurs during an adaptive window for adjusting the thermal block ramp rate of the thermal block. 
     
     
         10 . The apparatus of  claim 9  wherein the adaptive window designates approximately where the sample temperature is predicted to reach the target setpoint temperature and wherein the target block ramp rate is modified so achieve substantially the same sample temperature and block temperature within the range of the adaptive window. 
     
     
         11 . A method for polymerase chain reaction (PCR) temperature control, the method comprising the steps of;
 determining a current temperature ramp rate for a sample processed in a thermal block;   predicting an expected time interval for the sample to reach a target setpoint temperature based upon the current temperature ramp rate for the sample;   operating the thermal block at a target block ramp rate according to the predicted time interval for the sample to reach the target setpoint temperature;   repeating determination of the current temperature ramp rate for the sample as the thermal protocol for PCR is performed;   determining whether the predicted time interval for sample to reach target setpoint temperature has changed based on the current temperature ramp rate; and   modifying the predicted time interval and the target block ramp rate to ensure target block and sample reach target setpoint temperature at approximately same time.   
     
     
         12 . The method of  claim 11  wherein repeating the determination of the current temperature ramp rate occurs at a frequency corresponding to control loop time interval. 
     
     
         13 . The method of  claim 12  wherein the control loop time interval is approximately 20 times per second. 
     
     
         14 . The method of  claim 11  wherein modifying the predicted time interval occurs during an adaptive window for adjusting the target block ramp rate of the thermal block. 
     
     
         15 . The method of  claim 14  wherein the adaptive window designates approximately where the sample temperature is predicted to reach the target setpoint temperature and wherein the target block ramp rate is modified so achieve substantially the same sample temperature and block temperature within the range of the adaptive window.