Applied Biosystems, LLC

Perkin-elmer Corp., Applied Biosystems Division

Douglas H Keith

Norman M Whiteley

Lincoln J McBride

Mel N Kronick

Michael W Hunkapiller

John S Shigeura

George Stefan Golda

John A Bridgham

Louis B Hoff

Paul E Mayrand

William J Mordan

Thomas Brennan-Marquez

Melvyn N Kronick

Harry A Guiremand

G Richard Cathcart

Chen-Hanson Ting

Michael L Metzker

Eric Lachenmeier

Marianne Hane

Nucleic acid sequences are detected by a multi-step process, involving labeling sample nucleic acid sequences, duplexing the labeled sample with a probe having a coupling element, immobilizing all of the duplexed probe and target sequence and unduplexed probe, separating specifically immobilized nucleic acid from free and non-specifically immobilized nucleic acid, releasing specifically immobilized nucleic acid, and detecting the presence of the sequence of interest by means of the label. The labeled sequence may be characterized by sizing, e.g. electrophoresis. The method provides for a sensitive and rapid means for accurate detection of sequences of interest in a wide variety of situations.

Nucleic acid detection with separation

A liquid-handling instrument has a worksurface with registration for modular stations to support containers of liquid, pipette apparatus with a pipette tip coupled to a sensing circuit, a robotic translation system for moving the pipette tip, and a control system with an iconic user interface for programming and editing. A gauge block registered on the worksurface provides for calibration using the sensing tip, and register cavities on the worksurface provide for modular stations. There is a wash station fop the pipette tip on the worksurface. An automated laboratory based on the liquid-handling system has heating and cooling and a sealable incubation station as well as a magnetic separation station. Methods are disclosed using the apparatus to convey droplets of liquid, to aspirate with minimum tip contamination, to mix liquids in containers, and to validate the worksurface. A duck-billed closure is disclosed for minimizing evaporation and cross-contamination during processing, and is a part of a container disclosed for storing and transporting liquids.

Automated molecular biology laboratory

Sample DNA is analyzed by joining dsDNA sample fragments to labeling moieties having a primer binding sequence, to provide labeled dsDNA. After denaturation of the labeled dsDNA, strands binding to a probe are separated, conveniently using particles and a specific binding pair, followed by amplification of the sample strands and analysis and/or isolation of the amplified strands.

Restriction/ligation labeling for primer initiated multiple copying of

Termini of restricted double-stranded DNA fragments are modified by ligating the fragments with terminal phosphate-free double-stranded oligonucleotides having a complementary terminus in the presence of a restriction enzyme and a ligase, where joining of the complementary ends results in loss of the restriction enzyme recognition sequence.

Labeling by simultaneous ligation and restriction

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Oakland, CA, United States of America

Douglas H Keith