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Thermal cycler for automatic performance of the polymerase chain reaction with close temperature control

  • US 5,602,756 A
  • Filed: 12/08/1995
  • Issued: 02/11/1997
  • Est. Priority Date: 11/29/1990
  • Status: Expired due to Term
First Claim
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1. A method for computer control of automated performance of polymerase chain reactions in at least one sample tube containing a known volume of liquid sample mixture by means of a computer-controlled themocycler including a computing apparatus, a sample block having at least one well for said at least one sample tube, a block temperature sensor thermally coupled to said sample block, and heating and cooling means controlled by said computing apparatus for changing the temperature of said sample block, comprising the steps ofa. reading by said computing apparatus via said temperature sensor the block temperature at predetermined times,b. determining by said computing apparatus the temperature of said liquid sample mixture as a function of the temperature of said sample block over time, andc. controlling said heating and cooling means as a function of said sample temperature by said computing apparatuswherein said step of determining the temperature of said liquid sample comprises the steps of(i) determining a first thermal time constant for said at least one sample tube and said volume of liquid sample mixture,(ii) determining a second thermal time constant for said block temperature sensor, and(iii) determining the sample temperature in a sample interval at a current time n according to the formula


  • space="preserve" listing-type="equation">T.sub.samp.sbsb.n =T.sub.samp.sbsb.n-1 +(T.sub.B.sbsb.n -T.sub.samp.sbsb.n-1)*t.sub.interval /tau
where tsamp.sbsb.n is equal to the sample temperature at time n, the time at said current sample interval, Tsamp.sbsb.n-1 is equal to the sample temperature at an immediately preceding sample interval having occurred at time n-1, TB.sbsb.n is equal to the block temperature at time n, tinterval is a time in seconds between sample intervals, and tau is said first thermal time constant minus said second thermal time constant.

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