Thermal cycler and DNA amplifier method

• US 6,633,785 B1
• Filed: 08/30/2000
• Issued: 10/14/2003
• Est. Priority Date: 08/31/1999
• Status: Expired due to Fees

• Current Assignee: Kabushiki Kaisha Toshiba (Toshiba Corporation)
• Original Assignee: Kabushiki Kaisha Toshiba (Toshiba Corporation)
• Inventors: Iwasaki, Hideo, Kawano, Koichiro, Kasahara, Akihiro
• Primary Examiner(s): Gordon, Paul P.
• Application Number:
  US09/651,085
• Time in Patent Office: 1,140 Days
• Field of Search: 700/73, 700/74, 700/90, 700/299, 700/300, 435/3, 435/285.1, 435/286.1, 435/287.1, 435/287.2, 702/19, 702/20, 702/130
• US Class Current: 700/73
• CPC Class Codes: B01L 2200/147 Employing temperature sensors
• CPC Class Codes: B01L 2300/0829 Multi-well plates; Microtitration plates
• CPC Class Codes: B01L 2300/1827 using resistive heater
• CPC Class Codes: B01L 2300/1844 using fans
• CPC Class Codes: B01L 7/52 with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples amplification or hybridisation processes per se C12Q1/68; controlling sequential reactions for synthesis B01J19/0046

Abstract

A thermal cycler is provided with a number of containing members 10 having a shape in conformity with a shape of micro tubes 6, nozzles 15 for jetting coolant to the respective containing members 10, a blower 5 for supplying the coolant to the nozzles 15, heaters 12 wound around the respective containing members 10, thermocouples 13 provided to be brought into contact with the respective containing members 10 and a control apparatus 14 for generating signals of the heaters 12 based on signals from the thermocouples 13 and outputting the generated signals. By carrying out independent temperature control for the respective micro tubes 6 by the control apparatus 14, accuracy of temperature control of the respective micro tubes 6 is promoted and the processing efficiency is promoted.

Claims

1. A thermal cycler comprising:

a plurality of wells capable of containing micro tubes holding a sample including nucleic acid;

a plurality of heaters provided at the respective wells directly or indirectly heating the micro tubes;

a plurality of temperature sensors, each measuring temperature of the respective micro tubes;

a control apparatus inputted with measured values of the temperature sensors, supplying current to the plurality of heaters based on the measured values and controlling the temperature of the respective micro tubes independently from each other; and

a plurality of nozzles provided at the respective wells jetting a medium to the wells or the micro tubes in order to cool down the micro tubes; and

wherein the control apparatus controls the temperature of the micro tubes by jetting the medium from the nozzles to the wells when the current is supplied to the heaters.

2. The thermal cycler according to claim 1:

wherein the temperature sensors are provided in contact with outer walls of the wells or in noncontact with the micro tubes or the wells at positions capable of measuring the temperature of the sample.

3. The thermal cycler according to claim 1, further comprising:

a plurality of luminance sensors measuring a luminance of the respective sample the wells.

4. The thermal cycler according to claim 1:

wherein the nozzles are separated from the wells and provided to cover outer peripheral faces of the wells.

5. A thermal cycler comprising:

a plurality of wells capable of containing micro tubes holding a sample including nucleic acid and pasted with an indicator which differs in accordance with the respective sample;

a plurality of pick up sensors detecting the respective indicator;

a plurality of heaters provided at the respective wells directly or indirectly heating the micro tubes;

a control apparatus inputted with measured values of the temperature sensors, supplying a current to the respective heaters based on the measured values and controlling the temperature of the respective micro tubes independently from each other by a previously stored temperature pattern in correspondence with the indicator.

6. A DNA amplifier method having a control apparatus controlling to heat a plurality of micro tubes holding a sample including nucleic acid independently from each other by a plurality of heat apparatus provided at the respective micro tubes based on measured values of a plurality of temperature sensors provided at the respective micro tubes and storing a temperature pattern heating the micro tubes, said DNA amplifier method comprising:

a step of reading the temperature pattern set for the respective micro tubes by the control apparatus;

a step of generating a signal for operating the respective heat apparatus based on the measured values and the temperature pattern by the control apparatus;

a step of inputting the generated signal to the respective heat apparatus, heating the respective micro tubes independently from each other based on the signal by the heat apparatus and having a desired reaction carry out in the micro tubes; and

a step of outputting a signal stopping operation of the heat apparatus to the respective heat apparatus based on the temperature pattern by the control apparatus.

7. The DNA amplifier method according to claim 6,

wherein in heating the micro tubes, a medium is jetted from nozzles provided proximately to the respective micro tubes and capable of jetting the medium at the respective micro tubes.

8. A DNA amplifier method having a control apparatus controlling to heat a plurality of micro tubes holding a sample including nucleic acid and pasted with an indicator which differs in accordance with the respective sample independently from each other by a plurality of heat apparatus provided at the respective micro tubes based on measured values of a plurality of temperature sensors provided at the respective micro tubes and storing a temperature pattern heating the micro tubes, said DNA amplifier method comprising:

a step of detecting the indicator and setting the temperature pattern in correspondence with the detected indicator by the control apparatus;

a step of generating a signal operating the respective heat apparatus based on the measured values and the temperature pattern by the control apparatus;

a step of inputting the generated signal to the respective heat apparatus, heating the respective micro tubes independently from each other based on the signal by the heat apparatus and having a desired reaction carry out in the micro tubes; and

a step of outputting a signal stopping operation of the heat apparatus to the respective heat apparatus based on the temperature pattern by the control apparatus.

9. The DNA amplifier method according to claim 8:

wherein the heat apparatus are controlled by the control apparatus such that the micro tubes are heated to about 60°

C. and held for a constant time period, thereafter, the micro tubes are heated to about 95°

C. and held for a constant time period.

10. The DNA amplifier method according to claim 9, further comprising:

a step of measuring a luminance of the sample in the micro tubes after holding the micro tubes at temperature of about 60°

C. for the constant time.