Thermal cycling device

Abstract

A multi-layer device suitable for thermal cycling is set forth. The device is particularly suitable for performing a polymerase chain reaction (PCR). One embodiment includes a first layer ( 18 ), a second layer ( 20 ) adjacent to the first layer, and a third layer ( 22 ) adjacent to the second layer opposite the first layer. A continuous channel ( 54 ) is formed within the first layer ( 18 ), the second layer ( 20 ), and the third layer ( 22 ). The continuous channel ( 54 ) has a plurality of cycle segments, each of the cycle segments comprises a first portion ( 58 ) disposed within the first layer ( 18 ), a second portion ( 62 ) disposed within the third layer ( 22 ), and a third portion ( 66 ) disposed within the second layer ( 20 ). An integral or separate temperature source or sources ( 14 ), ( 16 ) may be provided to maintain the first layer ( 18 ) at a first temperature and the third layer ( 22 ) at a second temperature. Thermal conduction maintains the third layer ( 22 ) at a temperature between the first temperature and the second temperature.

1 . A method of performing a reaction comprising:
 introducing a sample into a device having a first layer, a second layer proximate the second layer, and a third layer proximate to an opposite side of the second layer from the first layer;   performing a first portion of a cycle in the first layer at a first temperature;   moving the sample to the third layer;   thereafter, performing a second portion of the cycle in the third layer at a second temperature;   moving the sample to a second layer;   thereafter, performing a third portion of a cycle in the second layer at a third temperature; and   repeatedly performing the first portion, the second portion and the third portion for a predetermined number of cycles to perform the reaction.   
     
     
         2 . A method as recited in  claim 1  wherein the second temperature is lower than the first temperature and the third temperature is between the first and second temperature. 
     
     
         3 . A method as recited in  claim 1  wherein the reaction comprises a polymerase chain reaction. 
     
     
         4 . A method as recited in  claim 1  wherein the first portion is a denaturing portion. 
     
     
         5 . A method as recited in  claim 3  wherein the second portion comprises an annealing portion. 
     
     
         6 . A method as recited in  claim 1  wherein the third portion comprises an extension portion. 
     
     
         7 . A method as recited in  claim 1  wherein moving the sample to the third layer comprises moving the sample to the third layer through the second layer. 
     
     
         8 . A method as recited in  claim 1  further comprising providing a first insulator between the first layer and the second layer and a second insulator between the second layer and the third layer. 
     
     
         9 . A method as recited in  claim 1  wherein moving the sample to the third layer comprises moving the sample to the third layer through the second layer, the first insulator and the second insulator. 
     
     
         10 . A method as recited in  claim 1  wherein introducing a sample comprises introducing a sample separated by bubbles and further comprising facilitating mixing within the sample using the bubbles. 
     
     
         11 . A method of performing a PCR comprising:
 providing a thermal cycling element with one or more tests thereon, said thermal cycling element having a first layer, a second layer proximate to the first layer, a third layer proximate to the second layer on an opposite side from the first layer and a continuous channel formed within the first layer, the second layer and the third layer, the continuous channel having a plurality of cycle segments, each cycle segment comprising a first portion disposed within the first layer, a second portion disposed within the third layer and a third portion disposed within the second layer;   selecting one or more of the tests;   preparing a fluidic sample corresponding to the one or more tests;   placing the fluidic sample within the thermal cycling device;   incubating the thermal cycling device; and   circulating the fluidic sample through the continuous channel so that the fluidic sample enters multiple first portions, multiple second portions and multiple third portions.   
     
     
         12 . A method of performing a PCR comprising:
 providing a thermal cycling element having a first layer, a second layer proximate to the first layer, a third layer proximate to the second layer on an opposite side from the first layer and a continuous channel formed within the first layer, the second layer and the third layer, the continuous channel having a plurality of cycle segments, each cycle segment comprising a first portion disposed within the first layer, a second portion disposed within the third layer and a third portion disposed within the second layer;   preparing a fluidic sample having an enzymatic reaction time and an absorption rate;   placing the fluidic sample within the thermal cycling device;   incubating the thermal cycling device; and   circulating the fluidic sample through the continuous channel so that the fluidic sample enters multiple first portions, multiple second portions and multiple third portions, said circulation rate being a function of the absorption rate and the enzymatic reaction time.