System for thermal cycling of microfluidic samples

Abstract

A thermal cycler for a microfluidic device includes a controller operable to provide a series of electrical signals, a heat sink, and a heating element in thermal communication with the heat sink and operable to receive the series of electrical signals from the controller. The thermal cycler also includes a thermal chuck in thermal communication with the heating element. The thermal chuck comprises a heating surface operable to make thermal contact with the microfluidic device. The heating surface is characterized by a temperature ramp rate between 2.5 degrees Celsius per second and 5.5 degrees Celsius per second and a temperature difference between a first portion of the heating surface supporting a first portion of the microfluidic device and a second portion of the heating surface supporting a second portion of the microfluidic device is less than 0.25° C.

1 . (canceled) 
     
     
         2 . A system for fluorescent imaging of nucleic acid amplification reactions, the system comprising:
 an optical source optically coupled to a first end of a light guide;   an optical illuminator optically coupled to a second end of the light guide, wherein the optical illuminator directs an excitation optical signal to impinge on a microfluidic device, wherein the microfluidic device comprises a plurality of reaction chambers, wherein each reaction chamber of the plurality of reaction chambers contains a sample, and wherein each sample emits a fluorescent emission along an optical path in response to the excitation optical signal, wherein the optical path includes a first lens system;   a thermal controller operable to provide a series of electrical signals;   a heating element comprising at least one central thermal electric cooler and at least one perimeter heater; and   a detector configured to detect the fluorescent emissions produced by the nucleic acid amplification reactions occurring in the reaction chambers.   
     
     
         3 . The system for fluorescent imaging of  claim 2  further comprising a heat sink comprising a plurality of radiator pins. 
     
     
         4 . The system for fluorescent imaging of  claim 3  further comprising a first thermal pad positioned between the heat sink and the heating element. 
     
     
         5 . The system for fluorescent imaging of  claim 2  further comprising a second thermal pad positioned between the heating element and a thermal chuck. 
     
     
         6 . The system for fluorescent imaging of  claim 5  further comprising at least one resistance temperature detector (RTD) in thermal contact with the thermal chuck. 
     
     
         7 . The system for fluorescent imaging of  claim 2  wherein a temperature difference between a first portion of a heating surface supporting a first portion of the microfluidic device and a second portion of the heating surface supporting a second portion of the microfluidic device is less than 0.25° C. 
     
     
         8 . The system for fluorescent imaging of  claim 2  further comprising a second lens system optically coupled to the first lens system, wherein the second lens system is disposed between the first lens system and the detector. 
     
     
         9 . The system for fluorescent imaging of  claim 8  further comprising an emission shutter disposed between the first lens system and the second lens system. 
     
     
         10 . The system for fluorescent imaging of  claim 9  further comprising an optical filter device disposed between the first lens system and the emission shutter. 
     
     
         11 . The system for fluorescent imaging of  claim 2  wherein a temperature ramp rate is between 2.5 degrees Celsius per second and 5.5 degrees Celsius per second. 
     
     
         12 . A genotyping system for protein crystallization imaging, the genotyping system comprising:
 a microfluidic device disposed on a stage, wherein the microfluidic device comprises a chamber;   an illumination device operable to produce an illumination beam to illuminate objects disposed within the microfluidic device;   a heating element comprising at least one central thermal electric cooler and at least one perimeter heater; and   a lens system operable to focus an image of a protein crystal disposed within the microfluidic device onto a detector.   
     
     
         13 . The genotyping system of  claim 12  further comprising a heat sink comprising a plurality of radiator pins. 
     
     
         14 . The genotyping system of  claim 13  wherein the heat sink further comprises a heat sink sensor. 
     
     
         15 . The genotyping system of  claim 12  wherein the stage ( 20 ) is mechanically coupled to a drive ( 25 ) and the microfluidic device ( 30 ), wherein the stage ( 20 ) has a plurality of fiducial markings. 
     
     
         16 . The genotyping system of  claim 12  further comprising at least one resistance temperature detector (RTD) in thermal contact with a thermal chuck. 
     
     
         17 . The genotyping system of  claim 12  wherein a temperature difference between a first portion of a heating surface supporting a first portion of the microfluidic device and a second portion of the heating surface supporting a second portion of the microfluidic device is less than 0.25° C. 
     
     
         18 . The genotyping system of  claim 12  further comprising a first thermal pad ( 120 ) positioned between a heat sink ( 110 ) and a heating element ( 130 ). 
     
     
         19 . The genotyping system of  claim 18  wherein the genotyping system further comprises a second thermal pad ( 140 ) positioned between the heating element ( 130 ) and a thermal chuck ( 150 ). 
     
     
         20 . The genotyping system of  claim 12  further comprising a computer operable to adjust a location of a focal plane to focus upon a first fiducial marking of a plurality of fiducial markings corresponding to a first xy coordinate image. 
     
     
         21 . The genotyping system of  claim 20  wherein the computer is operable to determine one or more of a stretch or skew based on the first xy coordinate image.