Thermal cycling apparatus and method

Abstract

A thermal cycling device and a method of thermal cycling are provided. A thermal cycling device includes a fluid device system, a case, and a cycling head. The fluid delivery system develops a flow of controlled-temperature fluid. The case has a fluid-tight cavity for holding a microfluidic array. The array includes a sheet of material having a pair of opposed surfaces, a thickness, and a plurality of through-holes running through the thickness between the surfaces. The cycling head holds the case and delivers the flow of fluid over the case.

1 .- 88 . (canceled) 
     
     
         89 . A thermal cycling device comprising:
 a fluid delivery system for developing a flow of controlled-temperature fluid;   a case having a fluid-tight cavity for holding a microfluidic array, the array including a sheet of material having a pair of opposed surfaces, a thickness, and a plurality of through-holes running through the thickness between the surfaces; and   a cycling head for holding the case and delivering the flow of fluid over the case.   
     
     
         90 . The thermal cycling device according to  claim 89 , wherein the flow of controlled temperature fluid is selectable between a first controlled temperature and a second controlled temperature. 
     
     
         91 . The thermal cycling device according to  claim 89 , further comprising:
 a thermal sensor for sensing temperature of the flow of fluid.   
     
     
         92 . The thermal cycling device according to  claim 89 , wherein the case includes transparent covers over the microfluidic array, and the cycling head includes transparent windows arranged for imaging of samples in the a microfluidic array. 
     
     
         93 . The thermal cycling device according to  claim 92 , wherein the transparent windows are arranged for one of transmission imaging and epi-flourescence imaging. 
     
     
         94 . The thermal cycling device according to  claim 89 , further including a Peltier device associated with the cycling head for controlling temperature of the fluid. 
     
     
         95 . The thermal cycling device according to  claim 89 , wherein the cycling head is adapted for vertical orientation of the microfluidic array. 
     
     
         96 . The thermal cycling device according to  claim 89 , wherein the case includes a guide rail arrangement for holding the a microfluidic array. 
     
     
         97 . The thermal cycling device according to  claim 89 , wherein the cycling head includes a guide rail arrangement for holding the case. 
     
     
         98 . The thermal cycling device according to  claim 89 , wherein cycling head delivers a laminar flow of fluid delivered over the case. 
     
     
         99 . The thermal cycling device according to  claim 89 , wherein the cycling head includes a flow regulator for promoting uniform flow of fluid over the case. 
     
     
         100 . The thermal cycling device according to  claim 99 , wherein the flow regulator includes a flow restrictor in the cycling head upstream of the case. 
     
     
         101 . The thermal cycling device according to  claim 99 , wherein the flow regulator includes a flow inlet cavity in the cycling head upstream of the case. 
     
     
         102 . The thermal cycling device according to  claim 89 , further comprising:
 a volume of an encapsulation fluid in the case for covering an inserted microfluidic array.   
     
     
         103 . The thermal cycling device according to  claim 102 , wherein the encapsulation fluid is selected from the group consisting of mineral oil, silicon oil, and a fluorinated hydrocarbon. 
     
     
         104 . The thermal cycling device according to  claim 89 , wherein the opposed surfaces include a top surface and a bottom surface, and the case has an associated top cover and bottom cover. 
     
     
         105 . The thermal cycling device according to  claim 104 , wherein the case and the cycling head are adapted so that the flow of fluid is delivered over both the top cover and the bottom cover. 
     
     
         106 . The thermal cycling device according to  claim 89 , wherein the case is adapted to hold a plurality of microfluidic arrays. 
     
     
         107 . A method of thermal cycling comprising:
 developing a flow of controlled-temperature fluid;   holding a microfluidic array in a fluid-tight cavity in a case, the array including a sheet of material having a pair of opposed surfaces, a thickness, and a plurality of through-holes running through the thickness between the surfaces; and   delivering the flow of controlled-temperature fluid over the case.   
     
     
         108 . The method according to  claim 107 , wherein the flow of controlled-temperature fluid is selectable between a first controlled temperature and a second controlled temperature. 
     
     
         109 . The method according to  claim 107 , further comprising:
 sensing the temperature of the flow of fluid over the case.   
     
     
         110 . The method according to  claim 107 , further comprising:
 performing transmission imaging of samples in the microfluidic array.   
     
     
         111 . The method according to  claim 107 , further comprising:
 performing epi-flourescence imaging of sample in the microfluidic array.   
     
     
         112 . The method according to  claim 107 , wherein developing the flow of temperature-controlled fluid uses a Peltier device. 
     
     
         113 . The method according to  claim 107 , wherein the case is adapted for vertical orientation in the flow of fluid. 
     
     
         114 . The method according to  claim 107 , wherein a guide rail arrangement is used for holding the microfluidic array. 
     
     
         115 . The method according to  claim 114 , wherein a guide rail arrangement is used for holding the case. 
     
     
         116 . The method according to  claim 107 , wherein the flow of fluid delivered over-the case is a laminar flow. 
     
     
         117 . The method according to  claim 107 , wherein delivering the flow of controlled-temperature fluid includes promoting uniform flow of fluid over the case with a flow regulator. 
     
     
         118 . The method according to  claim 117 , wherein the flow regulator includes a flow restrictor in the cycling head upstream of the case. 
     
     
         119 . The method according to  claim 117 , wherein the flow regulator includes a flow inlet cavity in the cycling head upstream of the case. 
     
     
         120 . The method according to  claim 107 , further comprising covering the microfluidic array in the cavity with a volume of an encapsulation fluid to avoid sample evaporation. 
     
     
         121 . The method according to  claim 120 , wherein the encapsulation fluid is selected from the group consisting of mineral oil, silicon oil, and a fluorinated hydrocarbon. 
     
     
         122 . The method according to  claim 107 , wherein the opposed surfaces include a top surface and a bottom surface, and the case has an associated top cover and bottom cover. 
     
     
         123 . The method according to  claim 122 , wherein the flow of temperature-controlled fluid is delivered over both the top cover and the bottom cover. 
     
     
         124 .- 309 . (canceled)