Thermocycler and sample vessel for rapid amplification of dna

Abstract

A thermocycler apparatus and method for rapidly performing the PCR process employs at least two thermoelectric modules which are in substantial spatial opposition with an interior space present between opposing modules. One or more multiple sample vessels are placed in between the module such that the vessels are subjected to temperature cycling by the modules. The sample vessels have a minimal internal dimensional that is substantially perpendicular to the modules that facilitates rapid temperature cycling. In embodiments of the invention the sample vessels may be deformable between: a) a shape having a wide mouth to facilitate filling and removing of sample fluids from the vessel, and b) a shape which is thinner for conforming to the sample cavity or interior space between the thermoelectric modules of the thermocycler for more rapid heat transfer.

What is claimed is: 
     
         1 . A thermocycler for subjecting one or a plurality of samples to rapid thermal cycling comprising at least one pair of thermoelectric modules each having an interior module face for heating and cooling one or a plurality of sample vessels each containing a sample, wherein the thermoelectric modules of each pair are positioned such that the module faces of the thermoelectric module pair are in substantial opposition to each other with an interior space between the opposing module faces for receiving said one or a plurality of sample vessels, at least one heat sink for dissipating heat, and a controller electrically connected to each pair of thermoelectric modules which controls the temperature of the thermoelectric modules. 
     
     
         2 - 37 . (canceled) 
     
     
         38 . The thermocycler of  claim 1 , wherein a direct current supply is electronically connected to the power input of an H-bridge electronic circuit. 
     
     
         39 . The thermocycler of  claim 1 , wherein a heat sink compound or thermal paste is applied to facilitate good contact between the heat sink, thermoelectric modules and machined interior metal. 
     
     
         40 . The thermocycler of  claim 1 , wherein one or more fans are present to aid in heat dissipation from the at least one heat sink. 
     
     
         41 . The thermocycler of  claim 1 , which includes one or multiple temperature measurement devices which provide information to the controller. 
     
     
         42 . The thermocycler of  claim 41 , wherein the one or multiple temperature measurement devices are thermocouples. 
     
     
         43 . The thermocycler of  claim 42 , wherein the thermocouples are located in a sample vessel, a sample vessel holder, a module laminate, or combinations thereof. 
     
     
         44 . The thermocycler of  claim 1 , which includes on-line optical detection to combine rapid polymerase chain reaction thermocycling with real-time product detection. 
     
     
         45 . The thermocycling instrument of  claim 1 , wherein the temperature within the sample holder is cycled between a low temperature range of about 55° C. to about 72° C. and a high temperature range of about 85° C. to about 98° C. 
     
     
         46 . The thermocycler of  claim 1 , which can be subjected to independent polymerase chain reaction protocols simultaneously. 
     
     
         47 . A thermocycling instrument comprising:
 at least one pair of thermoelectric modules for heating and cooling one or a plurality of sample vessels each containing a sample;   a sample holder between the opposing modules for receiving said one or a plurality of sample vessels;   first and second temperature sensors; and   a controller electrically connected to each pair of thermoelectric modules which controls the temperature of the thermoelectric modules   wherein the sample undergoes polymerase chain reaction amplification by repeated cycling between heating and cooling stages.   
     
     
         48 . The thermocycling instrument of  claim 47 , wherein the pair thermoelectric modules each have at least one heat exchanger. 
     
     
         49 . The thermocycling instrument of  claim 47 , wherein the sample holder is composed of a solid metal. 
     
     
         50 . The thermocycling instrument of  claim 47 , wherein the sample holder includes a plurality of bores. 
     
     
         51 . The thermocycling instrument of  claim 47 , wherein the first temperature sensor is located internal to the sample holder. 
     
     
         52 . The thermocycling instrument of  claim 47 , wherein the second temperature sensor is located external to the sample holder. 
     
     
         53 . The thermocycling instrument of  claim 48 , wherein there is a sensing relationship between the heat exchangers and the temperature sensors. 
     
     
         54 . The thermocycling instrument of  claim 47 , wherein the temperature within the sample holder is cycled between a low temperature range of about 55° C. to about 72° C. and a high temperature range of about 85° C. to about 98° C. 
     
     
         55 . The thermocycling instrument of  claim 47 , which includes at least one thermocycling element which may heat and cool the sample holder. 
     
     
         56 . The thermocycling instrument of  claim 47 , which can be subjected to independent polymerase chain reaction protocols simultaneously.