Applied Biosystems, LLC

The Perkin-elmer Corporation

Applera Corporation

Life Technologies Corporation

Charles M Wittmer

John Girdner Atwood

Adrian Fawcett

Keith Ferrara

Richard W Noreiks

Douglas E Olsen

Paul M Hetherington

John R Widomski

Ronald J Swanson

Keith S Ferrara

Paul M Hetzerington

Adrain Fawcett

An instrument for performing highly accurate PCR employing an assembly, a heated cover, and an internal computer, is provided. The assembly is made up of a sample block, a number of Peltier thermal electric devices, and a heat sink, clamped together. A control algorithm manipulates the current supplied to thermoelectric coolers such that the dynamic thermal performance of a block can be controlled so that pre-defined thermal profiles of sample temperature can be executed. The sample temperature is calculated instead of measured using a design specific model and equations. The control software includes calibration diagnostics which permit variation in the performance of thermoelectric coolers from instrument to instrument to be compensated for such that all instruments perform identically. The block/heat sink assembly can be changed to another of the same or different design. The assembly carries the necessary information required to characterize its own performance in an on-board memory device, allowing the assembly to be interchangeable among instruments while retaining its precision operating characteristics.

Thermal cycler for PCR

An instrument for performing highly accurate PCR employing an assembly, a heated cover and an internal computer. The assembly is made up of a sample block, a number of Peltier thermal electric devices and heat sink, clamped together. The sample block temperature is changed exclusively by the thermoelectric devices controlled by the computer. The sample block is of low thermal mass and is constructed of silver. The Peltier devices are designed to provide fast temperature excursions over a wide range. The heat sink has a perimeter trench to minimize edge losses and is adjacent to a continuously variable fan. A perimeter heater is used to improve the thermal uniformity across the sample block to approximately &#xb1;0.2&#xb0; C. A heated platen pushes down onto the tube caps to apply a minimum acceptable force for seating the tubes into the block, ensuring good thermal contact with the block. The force is applied about the periphery of the tube caps to prevent distortion of the caps during thermal cycling. The platen is heated to provided thermal isolation from ambient conditions and to prevent evaporation from the surface of the sample into the upper portion of the sample tube. A control algorithm manipulates the current supplied to the thermoelectric coolers such that the dynamic thermal performance of the block can be controlled so that pre-defined thermal profiles for the sample temperature can be executed. The sample temperature is calculated instead of measured using a design specific model and equations. The control software includes calibration diagnostics which permit variation in the performance of thermoelectric coolers from instrument to instrument to be compensated for such that all instruments perform identically. The block/heat sink assembly can be changed to another of the same or different design. The assembly carries the necessary information required to characterize its own performance in an on-board memory device, allowing the assembly to be interchangeable among instruments while retaining its precision operating characteristics. The instrument has a graphical user interface. The instrument monitors the thermoelectric devices and warns of changes in resistance that may result in failure.

An apparatus comprising an assembly and a cover. The assembly comprises a sample block configured to receive a microtiter tray having a plurality of vials, each vial comprising a cap having a surface and a perimeter. The cover comprises a platen, vertically and horizontally displaceable in relationship to the sample block, the platen having a plurality of recesses. Each recess corresponds to a respective vial and is shaped and arranged to clear the surface of its respective cap when the cover is displaced onto the sample block. The cover includes a skirt in contact with and surrounding a perimeter of the platen. The skirt is configured for mating with a perimeter of a microtiter tray when a microtiter tray is received in the sample block, and also configured such that the cover contacts a microtiter tray when a microtiter tray is received in the sample block.

A method for performing highly accurate PCR employing an assembly, a heated cover and an internal computer. The assembly is made up of a sample block, a number of Peltier thermal electric devices and heat sink, clamped together. The sample block temperature is changed exclusively by the thermoelectric devices controlled by the computer. The control software includes calibration diagnostics which permit variation in the performance of thermoelectric coolers from instrument to instrument to be compensated for such that all instruments perform identically. The block heat sink assembly can be changed to another of the same or different design. The assembly carries the necessary information required to characterize its own performance in an on-board memory device, allowing the assembly to be interchangeable among instruments while retaining its precision operating characteristics. The instrument monitors the thermoelectric devices and warns of changes in resistance that may result in failure.

An instrument for PCR comprising an assembly, a heated cover, and a computer. The assembly can include a sample block, Peltier devices, and a heat sink, clamped together. The sample block temperature can be changed by controlling the Peltier devices with the computer. A perimeter heater can be used to in prove thermal uniformity. A heated platen can push down onto tube caps to apply a minimum force for seating the tubes. The force can be applied about the periphery of the tube caps to prevent distortion of the caps. The platen can be heated to provide thermal isolation and prevent evaporation from the surface of the sample. The software can include diagnostics to compensate for variation in thermoelectric coolers such that all instruments can perform identically.

A circuit for synchronizing digital signals with alternating current includes a first counter that repetitively starts a first counting sequence at a predetermined phase point in each AC line cycle and effects the sequence at a high frequency rate thereby generating a total count during each line cycle. The total count is then divided by a dividing integer to produce a count number. A second counter repetitively starts a second counting sequence at the predetermined phase point and effects the second sequence at the high frequency rate up to the count number continuously during each line cycle. A decoder responsive to the second counter produces a digital output signal at one or more predetermined points in preselected second counting sequences during each line cycle.

Synchronization of digital signals with alternating current

The system includes a synchronous voltage-to-frequency converter connected to receive an analog input signal voltage and to generate a train of output pulses. A counter is connected to receive and count the output pulses and a digital register is connected to the counter for periodically receiving and storing the count in the counter. A conversion interval timer circuit is connected to control the operation of the counter and the register to determine a conversion interval during which the output pulses from the synchronous voltage-to-frequency converter are accumulated in the counter and then stored in the register. The conversion interval timer circuit is operable to determine the end of a prior conversion interval and the beginning of a new conversion interval in response to a predetermined phase of a predetermined cycle of the ac power line voltage. A timer is provided for exact measurement of the duration of each conversion interval and a multiplier is provided for multiplying the number stored in the register by a function which is a reciprocal of the exact duration measurement from the timer to thereby contact the number for variations in the conversion interval.

Line frequency slaved voltage-to-frequency converter system

A digital gain controlled current to voltage amplifier having particular utility for interfacing with and forming part of a spectrophotometer system with a photomultiplier tube being responsive to light for producing an analog current proportional to the intensity thereof. The digital gain controlled current to voltage amplifier incorporates a current switched multiplying digital-to-analog converter inside its feedback loop. In this manner, the feedback loop impedance may be maintained constant as its gain is varied under control of a software programmed microcomputer.

Digital gain controlled current to voltage amplifier

A sequential spectrophotometer system having a light source, a scanning type monochromator, a stepper motor means for changing the monochromator wavelength over a light spectrum being scanned, a photomultiplier for measuring the intensity of light absorption or passage through a sample being tested and generating a signal corresponding thereto, data acquisition means for compiling data corresponding to said signals and means for recording such data generally as a function of light measured for each wavelength, the improvement comprising: a method and means to effect the data acquisition conversion at or about each desired wavelength during a respective stepper motor rotor displacement period, i.e., during each corresponding period of diffraction grating vibration or oscillation following a stepper motor disposition thereof to another wavelength position angle.

Synchronous wavelength drive and data acquisition conversion for a

This invention relates to a spectrophotometer which includes a burner adapted for burning a gaseous fuel and for atomizing a sample to be analyzed in a burner compartment, mechanical elements or electrical circuitry serving to periodically pass a beam of light through the burner compartment, a detector, electrical circuitry for energizing the detector during the period of absence of the beam of light through the burner compartment, said detector being adapted when energized to produce an electronic signal representative of the presence of a flame in the burner compartment; and control elements responsive to the electronic signal for controlling the feeding of fuel to the burner.

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Trumbull, CT, United States of America

Charles M Wittmer