Applied Biosystems, LLC

The Perkin-elmer Corporation

Hewlett-packard Company

Perkin-elmer Corp., Applied Biosystems Division

John A Bridgham

Michael W Hunkapiller

Timothy G Geiser

Paul O Ramstad

Stephen B Kent

Paul D Hoeprich, Jr

John Brandis

John Leong

Eric S Nordman

Roger A O'Neill

Mark P Marriott

Charles L Sloan

John S Shigeura

Paul E Stoft

Louis B Hoff

Barry G Willis

William J Mordan

Moshe A Fostick

Melvyn N Kronick

Jacob Y Wong

Robert L Chaney

Charles M Hill

John K Lazier

George Stefan Golda

Charles R Connell

Charles E Bryson, Iii

Norman M Whiteley

Paul E Mayrand

Lincoln J McBride

Douglas H Keith

John D Lytle

Thomas Brennan-Marquez

P Eric Mayrand

Charles Andre

Mark P Marplott

Sam H Eletr

Chen-Hanson Ting

Michael L Metzker

Eric Lachenmeier

Marianne Hane

Harry A Guiremand

G Richard Cathcart

Cloning systems useful for the isolation of recombinant nucleic acid are disclosed in which the recombination of cloning-system nucleic acid and foreign nucleic acid is linked to the expression of a moiety on the surface of a host organism, the moiety being a first member of a binding pair. When recombination occurs between the nucleic acid and the foreign nucleic acid, the moiety is expressed on the surface of the host organism. The isolation of recombinant nucleic acid is then performed by attaching a second member of the binding pair to a solid support and contacting the host organism with the support. When the first member of the binding pair is expressed on the surface of the host organism, the host organism binds to the second member of the binding pair attached to the solid support, thereby selectively isolating those organisms.

Recombinant clone selection system

Cloning systems useful for the isolation of recombinant nucleic acid are disclosed in which the recombination of cloning-system nucleic acid and foreign nucleic acid is linked to the expression of a moiety on the surface of a host organism, the moiety being a first member of a binding pair. When recombination occurs between the nucleic acid and the foreign nucleic acid, the moiety is expressed on the surface of the host organism. The isolation of recombinant nucleic acid is then performed by attaching a second member of the binding pair to a solid support and contacting the host organism with the support. When the first member of the binding pair is expressed on the surface of the host organism, the host organism binds to the second member of the binding pair attached to the solid support, thereby selectively isolating those organisms. Other aspects of the invention include devices for the isolation of individual cells that differentially express binding moieties on their surface. The devices may be adapted for polynucleotide sequencing and analysis of polynucleotides in the isolated cells. Additional aspects of the invention include methods of using the devices for single cell isolation and analysis.

Host organism capture

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

An electrophoresis apparatus has a gel film cast between two plates and buffer reservoirs at each end of the film with electrodes connectable to an external power supply for providing electromotive force for driving electrophoresis. The reservoirs are configured to wet the ends of the gel film and submerge the electrodes with the apparatus positioned either horizontally or vertically, so gel films can be cast horizontally with sample wells formed in the end of the gel between the plates. Samples may be added to the wells and run into the gel with the apparatus positioned vertically, and the analytical separation may be performed with the apparatus again positioned horizontally, such as in an automatic scanning apparatus.

Horizontal polyacrylamide gel electrophoresis

An automated system for providing a preselected sequence of chemicals to a reaction. This apparatus includes a track on which a set of cartridges are placed in a preselected order corresponding to an order in which they are to be used in a reaction process. These cartridges are moved past a point at which these chemicals are extracted for use in the process. The chemicals are preferably in liquid form and are contained in containing having a top seal through which a needle can penetrate to extract chemicals for use in the process. These containers preferably contain the aliquot portion needed for the process, thereby providing a mechanism for providing accurate amounts of each chemical to the process.

Automated system for providing a sequence of chemicals to a reaction

An apparatus is provided for automatically constructing a polypeptide of high purity, up to 50 amino acids in length, using only single couplings. The apparatus includes an activation system for receiving protected amino acids, one kind at a time, having a common vessel (an activator vessel) in which to activate each of the amino acids. Also included is a reaction vessel for containing a resin used in solid-phase peptide synthesis for attaching a peptide chain thereto. A transfer system is also provided, which operates under control of a computer, to transfer the activated species from the activation system to the reaction vessel and to transfer amino acids, reagents, gases, and solvents from one part of the apparatus to another. The activator system also includes a temperature controlled concentrator vessel in which an activator solvent is replaced by a coupling solvent to enhance the coupling of the activated species to the peptide chain in the reaction vessel. Also included in the synthesizer system is a vortexer for affecting total washing of materials in the reaction vessel and the reaction vessel itself, an automated peptide resin sampling system, and an autodelivery system for providing individual containers of amino acid to the synthesizer in the order desired in the peptide sequence. A liquid sensor system is also included to monitor transitions between gases and liquids in specific tubes in the synthesizer in order to provide input signals to the computer system for control purposes. The computer system software which controls the operation of the synthesizer is organized according to a series of menus which allows the user of the system to select individual cycles of operation for each vessel in the synthesizer. In addition, an algorithm has been developed which provides for optimum efficiency in tbe production of a peptide for any given selection of cycles.

Automated polypeptide synthesis apparatus

An apparatus is provided for automatically constructing a polypeptide of high purity, up to 50 amino acids in length, using only single couplings. The apparatus includes an activation system for receiving protected amino acids, one kind at a time, having a common vessel (an activator vessel) in which to activate each of the amino acids. Also included is a reaction vessel for containing a resin used in solid-phase peptide synthesis for attaching a peptide chain thereto. A transfer system is also provided, which operates under control of a computer, to transfer the activated species from the activation system to the reaction vessel and to transfer amino acids, reagents, gases, and solvents from one part of the apparatus to another. The activator system also includes a temperature controlled concentrator vessel in which an activator solvent is replaced by a coupling solvent to enhance the coupling of the activated species to the peptide chain in the reaction vessel. Also included in the synthesizer system is a vortexer for affecting total washing of materials in the reaction vessel and the reaction vessel itself, an automated peptide resin sampling system, and an autodelivery system for providing individual containers of amino acid to the synthesizer in the order desired in the peptide sequence. A liquid sensor system is also included to monitor transitions between gases and liquids in specific tubes in the synthesizer in order to provide input signals to the computer system for control purposes. The computer system software which controls the operation of the synthesizer is organized according to a series of menus which allows the user of the system to select individual cycles of operation for each vessel in the synthesizer. In addition, an algorithm has been developed which provides for optimum efficiency in the production of a peptide for any given selection of cycles.

Automated polypeptide synthesis process

A real-time, automated, nucleic acid sequencing apparatus that offers high speed, definitive sequencing on many samples at the same time. The apparatus permits more than one clone to be sequenced at a time, thus vastly decreasing the time required to sequence longer fragments and reducing sequencing costs accordingly. The apparatus detects electromagnetic radiation from a plurality of lanes in an electrophoresis system wherein the plurality of lanes are arranged in a planar array. The apparatus includes an optical system for detecting the radiation at a plurality of wavelengths and is made up of a collection element, a filter for selectively transmitting the plurality of wavelengths received from the collection element, and a detection system for measuring intensity of the radiation received from the filter means. A translational stage is used for mounting the optical system and for moving the optical system parallel to the planar array in order to move the collection element back and forth across the lanes in order to receive radiation from the lanes, one lane at a time during electrophoresis. Also included is a computer system for controlling the filter and the stage, and for receiving intensity data from the detector and correlating that data with the corresponding lane and corresponding wavelengths transmitted by the filter in substantially real time.

Real time scanning electrophoresis apparatus for DNA sequencing

An apparatus is provided for automatically constructing a polypeptide of high purity, up to 50 amino acids in length, using only single couplings. The apparatus includes an activation system for receiving protected amino acids, one kind at a time, having a common vessel (an activator vessel) in which to activate each of the amino acids. Also included is a reaction vessel for containing a resin used in solid-phase peptide synthesis for attaching a peptide chain thereto. A transfer system is also provided, which operates under control of a computer, to transfer the activated species from the activation system to the reaction vessel and to transfer amino acids, reagents, gases, and solvents from one part of the apparatus to another.

A device is provided for measuring the concentration of oxygen in a sample utilizing the differential absorption by oxygen (O.sub.2) of two closely spaced ultraviolet (UV) radiation lines. The two UV lines are preferably isotope-shifted Hg lines in the vicinity of the Hg atomic transistion line at 1849.5A.

Measurement of oxygen by differential absorption of UV radiation

A gas analyzer is provided which is particularly suited for making transcutaneous measurement of the CO.sub.2 concentration in the blood. In accordance with one embodiment of the invention, sample gases from the body are circulated in a cavity of the device. A rotating wheel in the cavity includes two reference cells and a sample cell which are sequentially rotated into the optical path between a source and a detector. Three signals are thereby provided which may be combined to give an output indication of the CO.sub.2 concentration in the body fluids. In a preferred embodiment, the sample cell is an 'inverted cell' being in open communication with the sample gas circulating in the device so that the gas in the sample cell is a portion of the circulating gas which also surrounds the two reference cells. An output indication is thereby obtained which is insensitive to contaminants in the sample. In accordance with another embodiment, the sample cell is isolated from the region surrounding the wheel and positioned so as to be presented in series with the reference cells in the optical detection path. In preferred embodiments, the rotating wheel contains a number of permanent magnets which interact with a number of electromagnets driven in sequence to provide rotation of the wheel.

Medical-analytical gas detector

Growing community of inventors

Hillsborough, CA, United States of America

John A Bridgham