Syntex (u.s.a.) Inc.

Syva Company

Dade Behring Marburg Gmbh

Behringwerke Aktiengesellschaft

Aclara Biosciences, Inc.

Behring Diagnostics Gmbh

Other

Dade Behring Inc.

Discoverx Corporation

Siemens Healthcare Diagnostics Products Gmbh

Snytex (u.s.a.) Inc.

Abbott Laboratories Corporation

Aventis Behring Gmbh

Edwin F Ullman

Sharat Singh

Nurith Kurn

Martin J Becker

Samuel J Rose

Thomas C Goodman

Dariush Davalian

Kenneth E Rubenstein

Pyare L Khanna

Vartan E Ghazarossian

Marcel R Pirio

Cheng-I Lin

David J Litman

Linda M Western

Daniel B Wagner

Carl N Skold

Ian Gibbons

Rajendra Singh

John S Pease

Litai Weng

Mae W Hu

Hrair Kirakossian

Armen B Shanafelt

Arthur C Switchenko

Rajesh D Patel

Thomas L Tarnowski

Donald E Berger, Jr

Moshe Schwarzberg

Karen M Hahnenberger

Mary C Ericson

Christian Neukom

Frank Meneghini

Rohan Peries

Yan Chen

Richard Ray Bott

Robert Mark Caldwell

Maureen H Beresini

Svetlana Alexander

Gerald L Rowley

Christopher Charles Barnett

Richard K Leute

Yuri Daniloff

Avram Goldstein

Alla Lishanski

Mark J Levy

Maureen Laney

Kirk Schulkamp

Jacqueline Sadakian

Joy L Silen

Edward Benjamin Jakobovits

David Calderhead

Zvi Harel

Robert F Zuk

Chiu C Chang

Thomas D Kempe

Remy Cromer

Travis Boone

Thomas M Houts

N Chung Sizto

Yen Ping Liu

James V Freeman

Chen-jung Hsu

Mae Wan-Leng Hu

Paul D Stull

Kesavan Radika

John Jelesko

Yen-Ping Liu

Philip L Felgner

Prithipal Singh

Zbigniew T Bryning

Terry L Burkoth

Torleif Ove Bjornson

Herbert H Hooper

Richard M Eglen

Edward T Maggio

Reuel B Van Atta

John W Vorpahl

F Carl Grumet

Richard D Armenta

Richard P Watts

Barbara S Vold

Dennis R Gould

Floyd W Colvin

Jill McCornack Visor

Linda Kauffman

Joel E Lavine

Harshvardhan B Mehta

Robert K DiNello

Vivian Xiao

Geoffrey A Dafforn

Torlief Bjornson

Steve De Keczer

Anthony Delizza

Hriar Kirakossian

Neil Charter

Ming Wu

Claire Lin

Martin E Packard

Joyce Y Chang

Kenneth G McNeil

Methods, compositions and kits are disclosed. The compositions are light emitting and comprise a polymeric matrix having dissolved therein a photoactive compound. The composition has the characteristic that, after activation of the photoactive compound, the rate of decrease in the intensity of light emission at any time during a 20-fold decrease in the intensity is proportional to the intensity of the light emission. In one embodiment the polymeric matrix is comprised of particles of about 20 nm to about 100 &#x3bc;m in diameter to which is bound a specific binding pair member. The particles generally comprise a polymeric matrix having dissolved therein about 1 to about 20% by weight of a dopant. The compositions may be used in methods for determining an analyte. A combination is provided comprising (1) a medium suspected of containing the analyte, (2) and the aforementioned composition. The photoactive substance is activated and the effect of the activating on the optical properties of the combination is detected. The presence and amount of the effect is related to the presence and amount of the analyte in the medium. Also disclosed are kits for use in an assay.

Particles for diagnostic and therapeutic use

Methods are disclosed for determining minute quantities of an analyte in a medium suspected of containing the analyte. One method comprises treating a medium suspected of containing an analyte under conditions such that the analyte, if present, causes a substrate having an oxidant cleavable linker and a photosensitizer to come into close proximity. The photosensitizer generates singlet oxygen which oxidatively cleaves the linker to form a product which can be detected in a sandwich detection assay such as LOCI. The amount of product detected is related to the amount of analyte in the medium. Compositions, kits, and compounds are also disclosed.

Amplified signal in binding assays

Methods and compositions are provided for determining ADP in the presence of ATP. These comprise including among the assay reagents at least one of the correcting components creatine phosphokinase and phosphocreatine, pyruvate kinase and phosphoenolpyruvate, peroxidase and a non-interfering peroxidase substrate, and catalase. One aspect of the method employs formation of hydrogen peroxide from the ADP by pyruvate kinase, phosphoenolpyruvate and pyruvate oxidase. The hydrogen peroxide is then determined. A combined reagent having all of the reagents may optionally include a peroxidase when the hydrogen peroxide is to be enzymatically determined. A peroxidase substrate is added to the sample in conjunction with the peroxidase substrate reagent, the mixture incubated and depending on whether the peroxidase substrate is a fluorescer or chemiluminescer, the mixture may be illuminated with excitation light and the emitted light determined as a measure of the ADP in the sample.

ADP detection using an enzyme-coupled reaction

A sensitive intracellular calcium assay is disclosed comprising conveniently a reagent comprised of a dye precursor capable of entering cells and being hydrolyzed to a dye, whereby the dye complexes with calcium in the cells and provides a luminescent signal, an antibody specific for the dye and conjugated with a quencher, and a cellular anion exchange enzyme inhibitor. In performing the assay, the reagent is combined with cells expressing a receptor responsive to a ligand resulting in a change in cytosolic calcium. After incubation for the dye precursor to permeate the cells, the calcium may be determined by exciting the dye precursor and determining the peak fluorescence over a time course. The method can be used for measuring the effect of an agent on cytosolic calcium by binding to a cell surface membrane receptor.

Sensitive intracellular calcium assay

Compositions are disclosed comprising (a) a metal chelate wherein the metal is selected from the group consisting of europium, terbium, dysprosium, samarium osmium and ruthenium in at least a hexacoordinated state and (b) a compound having a double bond substituted with two aryl groups, an oxygen atom and an atom selected from the group consisting of oxygen, sulfur and nitrogen wherein one of the aryl groups is electron donating with respect to the other. Such composition is preferably incorporated in a latex particulate material. Methods and kits are also disclosed for determining an analyte in a medium suspected of containing the analyte. The methods and kits employ as one component a composition as described above.

Metal chelate containing compositions for use in chemiluminescent assays

Methods, compositions and kits are disclosed. The methods are directed to determining the presence of one or more analytes in a sample suspected of containing any one of a plurality of the analytes. A combination is provided comprising in a medium (i) the sample, (ii) a binding partner for each of the analytes, (iii) for each of the analytes, a first reagent comprising a member of a signal producing system, a ligand and an analyte analog, and (iv) a second reagent comprising a binding partner for the ligand. The binding of the binding partner for the ligand is affected by the presence of an analyte and alters the amount of signal produced by the member of the signal producing system. The signal thus is modulated if one or more of the analytes are present in the sample. The amount of the signal is determined and is related to the presence of one or more of the analytes in the sample. The method may be homogeneous or heterogeneous.

Simultaneous screening of multiple analytes

Alpha-haloketones are useful alkylating agents for coupling to sulfhydryl-containing biomolecules. However, they react spontaneously with water, alkali and organic bases and therefore cannot be stored for extended periods of time in aqueous solutions, particularly in the presence of proteins at physiological pH. The present invention provides novel solutions to these problems, however, as novel compounds and compositions comprising protected haloketones are disclosed herein. Methods of preparing and using protected haloketones which are useful in a variety of applications&mdash;e.g., in assays and conjugation reactions&mdash;are also disclosed herein.

Protecting groups for biological labeling

Methods, compositions and kits are disclosed. The compositions are light emitting and comprise a polymeric matrix having dissolved therein a photoactive compound. The composition has the characteristic that, after activation of the photoactive compound, the rate of decrease in the intensity of light emission at any time during a 20-fold decrease in the intensity is proportional to the intensity of the light emission. In one embodiment the polymeric matrix is comprised of particles of about 20 nm to about 100 &mgr;m in diameter to which is bound a specific binding pair member. The particles generally comprise a polymeric matrix having dissolved therein about 1 to about 20% by weight of a dopant. The compositions may be used in methods for determining an analyte. A combination is provided comprising (1) a medium suspected of containing the analyte, (2) and the aforementioned composition. The photoactive substance is activated and the effect of the activating on the optical properties of the combination is detected. The presence and amount of the effect is related to the presence and amount of the analyte in the medium. Also disclosed are kits for use in an assay.

Methods and compositions are provided for determining large numbers of single nucleotide polymorphisms in target DNA employing particles having (1) primers complementary to sequences in the target DNA where the next succeeding 3&prime;-nucleotide is a potential single nucleotide polymorphism and coding composition members, where the members are unique for each primer, and (2) differentially labeled terminating nucleotides, where the label permits separation of the terminating nucleotides. Desirably the particles are separated into groups having a common prevalent next succeeding nucleotide. The particles and target DNA are combined under nucleotide extending conditions, the particles separated into groups in accordance with the terminating nucleotide and the coding members identified, so that one knows the sequence and the single nucleotide polymorphism. Various protocols are provided for the determination.

Methods for single nucleotide polymorphism detection

Devices and methods are provided using microfluidic devices for manipulating small volumes and determining a variety of chemical and physical events. The devices rely upon an opening to the atmosphere of a small volume in a zone, where a sample is placed in the zone where evaporation can occur. The zone is maintained in contact with a liquid medium that serves to replenish the liquid in the zone and maintain the composition of the mixture in the zone substantially constant. The diffusion of components in the zone is restricted during the course of the determination by the liquid flux into the zone.

Sample evaporative control

Growing community of inventors

Atherton, CA, United States of America

Edwin F Ullman