Apparatus and methods for infrared calorimetric measurements

Abstract

Apparatus and methods for performing calorimetry. The apparatus include optical devices for detecting thermal processes and multiwell sample plates for supporting samples for use with such optical devices. The methods include measurement strategies and data processing techniques for reducing noise in measurements of thermal processes. The apparatus and methods may be particularly suitable for extracting thermal data from small differential measurements made using an infrared camera and for monitoring chemical and physiological processes.

We claim:  
     
         1 . A plate for holding a plurality of samples, comprising: 
 a frame; and    a plurality of sample wells disposed in the frame for holding a corresponding plurality of samples, each sample well having at least one infrared-transmissive surface configured to transmit thermal infrared radiation emitted by a sample positioned within the well.    
     
     
         2 . The plate of  claim 1 , the frame being substantially rectangular, where the length of the frame ranges between about 125 mm and about 130 mm, and where the width of the frame ranges between about 80 mm and about 90 mm.  
     
     
         3 . The plate of  claim 1 , where the number of sample wells in the plate is selected from the group consisting of 96, 384, 768, 1536, 3456, and 9600.  
     
     
         4 . The plate of  claim 1 , where the density of sample wells in the plate is at least about 1 well per 81 mm 2 .  
     
     
         5 . The plate of  claim 1 , where the volume of each sample well in the plate is less than about 500 microliters.  
     
     
         6 . The plate of  claim 1 , where the infrared-transmissive surface is composed at least in part of an infrared-transmissive polymer.  
     
     
         7 . The plate of  claim 6 , where the infrared-transmissive polymer is polyethylene.  
     
     
         8 . The plate of  claim 1 , where at least a portion of the infrared-transmissive surface transmits at least about half of incident thermal infrared radiation having wavelengths between about 3 micrometers and about 5 micrometers.  
     
     
         9 . The plate of  claim 8 , where at least a portion of the infrared-transmissive surface transmits at least about 80% of incident thermal infrared radiation having wavelengths between about 3 micrometers and about 5 micrometers.  
     
     
         10 . The plate of  claim 1 , where at least a portion of the infrared-transmissive surface transmits at least about half of incident thermal infrared radiation having wavelengths between about 7 micrometers and about 14 micrometers.  
     
     
         11 . The plate of  claim 10 , where at least a portion of the infrared-transmissive surface transmits at least about 80% of incident thermal infrared radiation having wavelengths between about 7 micrometers and about 14 micrometers.  
     
     
         12 . The plate of  claim 1 , each sample well having a bottom and a side, where the infrared-transmissive surface includes at least a portion of the bottom.  
     
     
         13 . The plate of  claim 12 , where at least a portion of the bottom is substantially planar.  
     
     
         14 . The plate of  claim 12 , where the sample wells are frustoconical in shape.  
     
     
         15 . The plate of  claim 1 , where the frame and the sample wells each include an optically transmissive surface configured so that the optical reader can detect electromagnetic radiation transmitted from a sample through both the optically transmissive surface of the corresponding sample well and the optically transmissive surface of the frame.  
     
     
         16 . The plate of  claim 1 , further comprising a cover configured to cover the sample wells, reducing evaporation from samples contained within the sample wells.  
     
     
         17 . The plate of  claim 1 , further comprising a thermal reference region disposed about the sample wells in the frame, where thermal infrared radiation detected from a sample positioned in at least one of the sample wells may be calibrated using thermal infrared radiation detected from an adjacent thermal reference region.  
     
     
         18 . The plate of  claim 17 , the sample wells having a central axis, where the thermal reference region includes an annular emissive reference surface positioned about the central axis of each sample well.  
     
     
         19 . A plate for holding a plurality of samples, comprising: 
 a frame; and    a plurality of sample wells disposed in the frame for holding a corresponding plurality of samples; 
 where the frame and the sample wells each include an optically transmissive surface configured so that an optical reader can detect electromagnetic radiation transmitted from a sample through both the optically transmissive surface of the corresponding sample well and the optically transmissive surface of the frame.  
   
     
     
         20 . A method of detecting thermal infrared radiation, comprising: 
 providing a sample plate having a plurality of sample wells containing a corresponding plurality of samples, each sample well having at least one infrared-transmissive surface configured to transmit thermal infrared radiation emitted by a sample positioned within the well;    providing an optical device configured preferentially to detect thermal infrared radiation; and    detecting thermal infrared radiation transmitted from a sample through the infrared-transmissive surface of at least one of the sample wells in the sample plate using the optical device.    
     
     
         21 . The method of  claim 20 , further comprising correlating the detected radiation with the progress of a chemical or physiological reaction occurring within the sample.  
     
     
         22 . The method of  claim 20 , the frame being substantially rectangular, where the length of the frame ranges between about 125 mm and about 130 mm, and where the width of the frame ranges between about 80 mm and about 90 mm.  
     
     
         23 . The method of  claim 20 , where the number of sample wells in the sample plate is selected from the group consisting of 96, 384, 768, 1536, 3456, and 9600.  
     
     
         24 . The method of  claim 20 , where the density of sample wells in the sample plate is at least about 1 well per 81 mm 2 .  
     
     
         25 . The method of  claim 20 , where the volume of each sample well in the sample plate is less than about 500 microliters.  
     
     
         26 . The method of  claim 20 , the sample plate comprising an insert portion containing the sample wells and a frame portion for supporting the insert, further comprising forming the sample plate by mating the insert portion with the frame portion.  
     
     
         27 . The method of  claim 20 , where the optical device comprises: 
 an examination site; and    a detector configured to receive and preferentially to detect thermal infrared radiation transmitted from a sample positioned within a sample well at the examination site.    
     
     
         28 . The method of  claim 20 , the sample wells having a central axis, the optical device having an optical axis, further comprising aligning the central axis and the optical axis prior to the steps of detecting thermal infrared radiation.  
     
     
         29 . The method of  claim 20 , further comprising shielding the sample from incident radiation to reduce the proportion of the sample signal arising from transmission, reflection, and/or photoluminescence from the sample.  
     
     
         30 . The method of  claim 20 , further comprising filtering the radiation transmitted from the sample to extract thermal infrared radiation prior to the step of detecting thermal infrared radiation.  
     
     
         31 . The method of  claim 20 , where at least about half of the thermal infrared radiation detected by the optical device has a wavelength between about 3 micrometers and about 5 micrometers.  
     
     
         32 . The method of  claim 20 , where at least about half of the thermal infrared radiation detected by the optical device has a wavelength between about 7 micrometers and about 14 micrometers.  
     
     
         33 . The method of  claim 20 , each sample well having a bottom that transmits thermal infrared radiation, where the step of detecting thermal infrared radiation includes the step of detecting the thermal infrared radiation through the bottom of the sample well.  
     
     
         34 . The method of  claim 33 , where at least a portion of the bottom is substantially planar.  
     
     
         35 . The method of  claim 20 , further comprising: 
 detecting thermal infrared radiation transmitted from a reference region adjacent the sample; and    constructing a sample signal characteristic of the thermal infrared radiation detected from the sample based on the thermal infrared radiation detected from the sample and the adjacent reference region.    
     
     
         36 . The method of  claim 35 , the sample wells having a central axis, where the thermal reference region includes an annular emissive reference surface positioned about the central axis of each sample well.  
     
     
         37 . The method of  claim 20 , further comprising detecting thermal infrared radiation transmitted from a plurality of samples contained in a corresponding plurality of sample wells in the sample plate using the optical device.  
     
     
         38 . The method of  claim 37 , where the thermal infrared radiation is detected simultaneously from the plurality of samples.  
     
     
         39 . The method of  claim 37 , where the thermal infrared radiation is detected sequentially from the plurality of samples.  
     
     
         40 . The method of  claim 20 , further comprising computing a quantity related to a characteristic of the thermal infrared radiation transmitted from the sample.  
     
     
         41 . The method of  claim 40 , where the quantity is representative of the temperature of the sample.  
     
     
         42 . The method of  claim 40 , further comprising: 
 computing the quantity for a plurality of samples; and    displaying the quantities graphically in a manner representative of the arrangement of the corresponding sample wells in the sample plate.    
     
     
         43 . The method of  claim 20 , further comprising covering the sample wells to reduce evaporation from the samples.  
     
     
         44 . The method of  claim 20 , further comprising: 
 placing the samples in the sample wells such that the samples occupy at least about half of the volume of the sample wells; and    covering the sample wells to reduce evaporation from the samples.    
     
     
         45 . The method of  claim 20 , further comprising: 
 converting the detected thermal infrared radiation to a signal; and    processing the signal to reduce the proportion of the signal that is attributable to noise.    
     
     
         46 . The method of  claim 45 , where the step of processing the signal includes the step of computing a quantity based on distinguishable components of the signal representing thermal infrared radiation detected from the same sample at different times.  
     
     
         47 . The method of  claim 45 , where the step of processing the signal includes the step of computing a quantity based on distinguishable components of the signal representing thermal infrared radiation detected from different portions of the same sample.  
     
     
         48 . The method of  claim 20 , further comprising: 
 detecting thermal infrared radiation transmitted from a plurality of samples contained in the sample wells using the optical device;    converting the thermal infrared radiation detected from each sample to a corresponding signal; and    adjusting the signals so that each has the same preselected value at the same preselected time.    
     
     
         49 . The method of  claim 48 , where the preselected value is zero.  
     
     
         50 . The method of  claim 48 , where the preselected time is zero.  
     
     
         51 . A system for detecting thermal infrared radiation, comprising: 
 a sample plate having a plurality of sample wells for holding a corresponding plurality of samples, each sample well having at least one infrared-transmissive surface configured to transmit thermal infrared radiation emitted by a sample positioned within the well; and    an optical device configured preferentially to detect thermal infrared radiation transmitted from a sample through the infrared-transmissive surface of the corresponding sample well.