Rapid thermocycler system for rapid amplification of nucleic acids and related methods

A method for operating a thermocycler instrument, comprising the steps of:

• a) supplying power to a thermocycler instrument that includes;
• (i) at least two thermoelectric devices which are generally opposing and spaced apart;
• (ii) a sample holder located between the at least two thermoelectric devices and having one or more bores to complementarily receive a sample tube;
• and
• (iii) a pair of heat exchangers, each heat, exchanger associated with at least one of the at least two thermoelectric devices and projecting away from the sample holder;
• b) applying a voltage signal having a positive polarity and a negative polarity to the at least two thermoelectric devices of the thermocycler instrument via at least one circuit;
• c ) optionally, applying a voltage signal to an air mover circuit for rotating an impeller of an air mover to convectively expel air from the thermocycler instrument;
• d) controlling the polarity of the voltage signal that is applied to the at least two thermoelectric devices to repeatedly alternate the operation of the thermoelectric devices between a first condition of supplying heat to the sample holder and a second condition removing heat from the sample holder;
• e) obtaining a first sample holder electrical signal corresponding with a temperature within the sample holder;
• and
• f) obtaining a second electrical signal corresponding with a temperature from at least one of the pair of heat exchangers and external of the sample holder;
• g) employing the first sample holder electrical signal and the second electrical signal for determining values for controlling power delivery to be delivered to the thermoelectric devices:
• and
• wherein substantially real time temperature condition information is employed and processed for delivering the power which is suitable to rapidly heat and cool a sample.

A method for controlling operation of a thermocycler instrument for amplification by polymerase chain reaction, comprising the steps of:

• a) introducing at least one biological sample into a thermocycler instrument that includes:
• i) at least one pair of thermoelectric devices which are opposed and spaced apart, each thermoelectric device having at least one heat exchanger;
• ii) at least one sample holder which is solid metal having at least one first bore defined therein to receive at least one sample contained in a tube, and at least one second bore to receive an temperature sensor within the at least one sample holder, the at least one sample holder being disposed in thermal conducting relation with and between the at least one pair of thermoelectric devices;
• iii) at least one first temperature sensor that is located in the at least one first bore and is adapted to monitor a first temperature of the at least one sample holder;
• iv) at least one second temperature sensor located externally of the at least one sample holder and in a sensing relationship with at least one of the heat exchangers to monitor at least one second temperature;
• b) receiving at least one first setpoint temperature of at least about 85° C., to which the at least one biological sample is to be heated in the sample holder for polymerase chain reaction denaturation, and at least one second setpoint temperature of below about 70° C. to which the biological sample held in the sample holder is to be cooled for annealing of the at least one biological sample;
• c) maintaining a heating rate of at least about 8° C./second until a first offset temperature amount of no more than about 7.5° C. below the first setpoint temperature is reached for the sample holder;
• d) when the first offset temperature is reached, pulse cooling the sample holder to slow the heating rate until the sample holder is within about 1° C. of the first setpoint temperature;
• e) maintaining a cooling rate of at least about 6° C./second until a second offset temperature no more than about 7.5° C. above) the second setpoint temperature is reached for the sample holder;
• f) when the second offset temperature is reached, pulse heating the sample holder to slow the cooling rate until the sample holder is within about 1° C. of the second setpoint temperature;
• g) monitoring a first temperature corresponding with a temperature of the sample holder and a second temperature corresponding with a temperature of the heat exchanger;
• h) adjusting an amount of time, a temperature or both at which the steps of pulse cooling, the pulse heating or both commence based upon the first temperature and the second temperature;
• and
• i)detecting amplification in a real-time manner and repeating steps (b)-(h) for a predetermined number of cycles until the amplification desired by the user is achieved.