The Perkin-elmer Corporation

Hoffmann-la Roche Inc.

Applied Biosystems, LLC

Applera Corporation

Richard A Leath

Timothy M Woudenberg

John Girdner Atwood

Robert P Ragusa

Fenton Williams

Albert Carmelo Mossa

Lisa May Goven

Clive Miles

Marcel Margulies

Kary B Mullis

Joseph T Widunas

Louis M Mezei

Timothy J Wennberg

Larry Johnson

Marcel Margoulies

A thermal cycler for automatic performance of the polymerase chain reaction is provided. The thermal cycler comprises a heater control that provides close temperature control of the reaction.

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

An instrument for performing highly accurate PCR employing a sample block in microtiter tray format. The sample block has local balance and local symmetry. A three zone film heater controlled by a computer and ramp cooling solenoid valves also controlled by the computer for gating coolant flow through the block controls the block temperature. Constant bias cooling is used for small changes. Sample temperature is calculated instead of measured. A platen deforms plastic caps to apply a minimum acceptable threshold force for seating the tubes and thermally isolates them. A cover isolates the block. The control software includes diagnostics. An install program tests and characterizes the instrument. A new user interface is used. Disposable, multipiece plastic microtiter trays to give individual freedom to sample tubes are taught.

A two-piece plastic holder for loosely holding microliter sample tubes of a preselected design, each tube having a cylindrically shaped upper section open at its top end, a closed, tapered lower section extending downwardly therefrom, and a circumferential shoulder extending outwardly from the upper section at a position on the upper section spaced from the open end thereof. The holder includes a one-piece tray member and a one-piece retainer. The one-piece tray member including a flat, horizontal plate section containing holes in a rectangular array, a first vertical tray sidewall section around the plate extending upwardly to a height greater than the height of a tube resting in one of the holes, and a second vertical tray sidewall section around the plate extending downwardly approximately to the bottom of the upper section of a tube resting in one of the holes. The one-piece retainer is releasably engageable inside the tray over any sample tubes resting in the tray. The retainer comprises a flat, horizontal plate section containing holes in a rectangular array, and a vertical retainer sidewall section around the retainer plate section extending upwardly from the plate. When the retainer is engaged inside the tray, the retainer plate section lies slightly above the shoulder of a tube resting in the tray and the first tray sidewall section is about as high as the retainer sidewall section, so that tubes resting in the tray are retained loosely both vertically and laterally.

Two piece holder for PCR sample tubes

There is disclosed herein a machine for performing nucleic acid amplification under computer control. The machine utilizes any one of a number of heating and cooling systems under control of a host computer which directs the heating and cooling systems to heat and cool a reaction-chamber-containing heat exchanger at appropriate times in the process. The reaction chambers are pre-loaded with the nucleic acid(s) to be amplified, a thermostable enzyme to catalyze polymerization, specific oligonucleotide primers, and four different nucleotide triphosphates. Also disclosed is the process for the amplification chain reaction implemented by the machine, which utilizes a thermostable enzyme.

System for automated performance of the polymerase chain reaction

Thermal cycler for automatic performance of the polymerase chain

Apparatus and method for performing automated amplification of nucleic

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Berkley, CA, United States of America

Richard A Leath