Compound calibrator for thermal sensors

Abstract

The present invention, in one aspect, provides a method for calibrating thermal control elements in situ using a single compound calibrator. In some embodiments, the present invention uses a compound calibrator to calibrate thermal control elements on a microfluidic device. In non-limiting embodiment, the compound calibrator can be a droplet, plug, slug, segment or continuous flow of any appropriate solution that, when heated, yields a thermal response profile with a plurality of features (e.g., maxima, minima, inflection points, linear regions, etc.).

What is claimed is: 
     
         1 . A method for calibrating a plurality of thermal control elements in a thermal device, comprising:
 a) providing a compound calibrator in a first thermal zone, wherein the first thermal zone is in thermal contact with a first of said plurality of thermal control elements;   b) utilizing said first thermal control element to perform a thermal variation, generating a first thermal response profile for said compound calibrator;   c) identifying a first feature of said first thermal response profile and generating a first relation between a known temperature of said first feature and a first measurement value of said first thermal control element;   d) identifying a second feature of said first thermal response profile and generating a second relation between a known temperature of said second feature and a second measurement value of said first thermal control element;   e) calculating one or more calibration coefficients for said first thermal control element based on at least said first and second relations;   f) repeating steps a-e using the compound calibrator in a second thermal zone, wherein the second thermal zone is in thermal contact with a second thermal control element.   
     
     
         2 . The method of  claim 1 , further comprising repeating steps a-e for each additional thermal control element in the thermal device. 
     
     
         3 . The method of  claim 1 , wherein the thermal device is a microfluidic channel in thermal communication with a plurality of thermal control elements. 
     
     
         4 . The method of  claim 1 , wherein said first thermal zone is thermally isolated from the second thermal zone. 
     
     
         5 . The method of  claim 4 , wherein said first thermal zone and said second thermal zone are calibrated in parallel. 
     
     
         6 . The method of  claim 5 , wherein said first thermal zone and said second thermal zone are calibrated in series. 
     
     
         7 . The method of  claim 4 , wherein the compound calibrator is a mixture of two or more amplicons. 
     
     
         8 . A method for calibrating a plurality of thermal control elements in a thermal device, comprising:
 a) providing a compound calibrator in a first thermal zone, wherein the first thermal zone is in thermal contact with a first of said plurality of thermal control elements;   b) utilizing said first thermal control element to perform a thermal variation, generating a first thermal response profile for said compound calibrator;   c) identifying a first feature of said first thermal response profile and generating a first relation between a known temperature of said first feature and a first measurement value of said first thermal control element;   d) identifying a second feature of said first thermal response profile and generating a second relation between a known temperature of said second feature and a second measurement value of said first thermal control element;   e) identifying a third relation between a known ambient temperature and measurement value of said first thermal control element;   f) calculating one or more calibration coefficients for said first thermal control element based on at least said first, second, and third relations;   g) repeating steps a-f using the compound calibrator in a second thermal zone, wherein the second thermal zone is in thermal contact with a second thermal control element.   
     
     
         9 . A method for serially calibrating a plurality of thermal control elements in a microfluidic channel, comprising:
 providing a compound calibrator in thermal contact with a first of said plurality of thermal control elements;   utilizing said first thermal control element to perform a thermal ramp, generating a first melt curve for said compound calibrator;   identifying a first feature of said first melt curve and generating a first relation between a known temperature of said first feature and a first measurement value of said first thermal control element;   identifying a second feature of said first melt curve and generating a second relation between a known temperature of said second feature and a second measurement value of said first thermal control element;   calculating one or more calibration coefficients for said first thermal control element based on at least said first and second relations;   providing said compound calibrator in thermal contact with a second of said plurality of thermal control elements;   utilizing said second thermal control element to perform a thermal ramp, generating a second melt curve for said compound calibrator;   identifying a third feature of said second melt curve and generating a third relation between a known temperature of said third feature and a third measurement value of said second thermal control element;   identifying a fourth feature of said second melt curve and generating a fourth relation between a known temperature of said second feature and a fourth measurement value of said second thermal control element;   calculating one or more calibration coefficients for said second thermal control element based on at least said third and fourth relations.   
     
     
         10 . A method for calibrating a thermal control element, comprising:
 pre-selecting one or more initial calibration coefficients for a calibration equation defining relationship between a temperature of a thermal control element and a measured resistance of said thermal control element;   providing a compound calibrator in thermal contact with said thermal control element, the compound calibrator characterized by first and second features associated with first and second known melt temperatures of the compound calibrator, respectively;   utilizing said thermal control element to perform a thermal ramp, generating a melt curve for said compound calibrator;   identifying the first and second features and associated first and second measured melt temperatures from said melt curve;   calculating a first resistance and a second resistance of the thermal control element as a function of the first and second identified melt temperatures, respectively, and the one or more initial calibration coefficients;   generating a first calibration equation with one or more unknown calibration coefficients providing a relation between the first known melt temperature and the first resistance of said thermal control element;   generating a second calibration equation with the one or more unknown calibration coefficients providing a relation between the second known melt temperature and the second resistance of said thermal control element; and   calculating the one or more unknown calibration coefficients for said thermal control element based on at least said first and second relations.