Monogram Biosciences, Inc.

Dade Behring Marburg Gmbh

Becton Dickinson and Company Limited

Syntex (u.s.a.) Inc.

Siemens Healthcare Diagnostics Products Gmbh

Behringwerke Aktiengesellschaft

Sepragen Corporation

Wainamics, Inc.

Snytex (u.s.a.) Inc.

Syntex LLC

Daniel B. Wagner

Edwin F. Ullman

Yuri Daniloff

John S. Pease

Hrair Kirakossian

Edwin F Ullman

Sharat Singh

John S Pease

Daniel B Wagner

Hossein Salimi-Moosavi

Carsten Schelp

Tracy J Matray

Gerald J Wallweber

Vincent S Hernandez

Syed Hasan Tahir

Po-Ying Chan-Hui

Michael Trier

Edward M Goldberg

Zbigniew T Bryning

Marcel R Pirio

Torleif Ove Bjornson

Peter J Dehlinger

Diether J Recktenwald

Ming Tan

Chiu C Chang

Liping Yu

Litai Weng

Andreas Wiegand

Mary C Ericson

Richard P Watts

Douglas Petry

Albert W Brown, Jr

Thomas Klopack

William Wevers

Uwe Stöhr

Linda Liu

Dennis Richard Gould

Benjamin R Irvin

Diether Recktenwald

The invention, is directed to devices and methods for low cost and convenient separation, of plasma from whole blood. In some embodiments, devices of the invention comprise an integrated collection of channels and chambers m a body that permit acquisition of a blood sample by capillary action, centrifugal separation of cells from plasma, and manual dispensing of purified plasma by simple pinching of a bellows chamber to force air into plasma-holding channels which thereby expels a predetermined volume of the purified plasma.

Small volume self-metered blood separation device

Compositions, kits, and methods are disclosed for determining one or more target polypeptides in a sample where the target polypeptides have undergone a post-translational modification. The compositions can include a first reagent including a cleavage-inducing moiety and a first binding agent for a binding site that includes a post-translational modification of a target polypeptide.

Methods and compositions for analyzing proteins

The present disclosure provides cytometric methods for the detection of rare target cells in a sample. In certain aspects, the methods and compositions may facilitate the detection of rare target cells, such as circulating tumor cells (CTCs), in a biological sample such as blood. Aspects of the methods include contacting the sample with first and second binding members that specifically bind to a marker of the rare target cell, and cytometrically assaying the sample for the presence of cells comprising bound first and second binding members to detect the rare target cell in the sample. Also provided are systems, compositions, and kits for practicing the subject methods.

Methods and compositions for cytometric detection of rare target cells in a sample

Methods, compositions and kits are disclosed for determining one or more target polypeptides in a sample where the target polypeptides have undergone a post-translational modification.

Compositions for analyzing proteins

A cell culture bioreactor having a culture chamber for cell growth, a culture medium reservoir mounted externally to the culture chamber, a fluid circulation mechanism for moving culture medium from the reservoir through the culture chamber, and an aerating mechanism for introducing air into and removing air from the culture chamber is provided. The cell culture bioreactor comprises a manifold mechanism mounted at the top end of the culture chamber, a fluid circulation mechanism fluidly connected to the culture medium reservoir, for receiving culture medium from the culture medium reservoir and distributing culture medium into the culture chamber. A support matrix is mounted within the culture chamber in fluid communication with the fluid circulation mechanism with at least a portion of the support matrix contacting the culture medium wherein the culture medium flows from the manifold means in a thin film over substantially the entire surface of the support matrix allowing the biological cells to grow on the support matrix.

Cell culture bioreactor

The invention provides a low-cost method for identifying and/or measuring a subpopulation of cells in a biological sample, such as a subpopulation of CD4-positive cells in a whole blood sample. In accordance with the invention, one or more cell surface markers are identified on a subpopulation of interest, which collectively are present in higher numbers on the cells of the subpopulation than on cells not in the subpopulation of interest. A probe comprising a binding compound and a density label are combined with the sample and the resulting mixture is centrifuged or sedimented through a density medium in a capillary. Labeled cells of interest pass through the density medium and stack at the bottom of the capillary where they may be visually detected and quantified by the height of the stack.

Density-based cell detection system

The invention relates to a kit for a homogenous detection method for the quantitative or qualitative detection of an analyte in an assay and adequate reagents therefor, particularly a homogenous binding test. According to the invention, an analyte-specific binding partner R1 comprises more than one specific binding point for a specific binding partner X that is associated with a component of a signal-forming system while a second analyte-specific binding partner R2 comprises more than one specific binding point for a specific binding partner Y which is also associated with a component of a signal-forming system.

Homogeneous detection method

The invention relates to methods for the quantitative or qualitative detection of an analyte in an assay and adequate reagents therefor, particularly a homogeneous binding test. According to the invention, an analyte-specific binding partner R1 comprises more than one specific binding point for a specific binding partner X that is associated with a component of a signal-forming system while a second analyte-specific binding partner R2 comprises more than one specific binding point for a specific binding partner Y which is also associated with a component of a signal-forming system.

The present invention proves instruments and methods for detecting and/or quantitating an analyte in a fluid sample. The fluid sample is placed in a sample chamber having a small, shallow detection region. The analyte is magnetically labeled using magnetic particles coated with a binding reagent, and is detectably labeled using a fluorescent dye or other detection reagent. The magnetically labeled analyte is concentrated into the detection region using a focusing magnet positioned underneath the sample chamber detection region. Concentrated analyte is measured using excitation optics positioned on top of the sample chamber detection region, adapted to illuminate only the detection region, and detection optics positioned on top of the detection region, adapted to detect only light emitted from the detection region. In a preferred embodiment, the invention provides a simple, rapid assay for measuring the concentration of CD4T cells in a whole blood sample.

Rapid particle detection assay

A method is provided for detecting biomarkers in rare circulating cells by forming an enriched population of cells immunomagnetically followed by biomarker detection using binding compounds having releasable molecular tags. Preferably, biomarkers comprising one or more protein-protein complexes are detected in circulating cancer cells metastasized from a solid tumor. In the presence of biomarkers, the molecular tags of the binding compounds are released and separated from the assay mixture for detection and/or quantification.

Biomarker detection in circulating cells

A photoactivation apparatus () separately delivers light to a plurality of wells of a multiwell plate (). The device-includes a plurality of light emitting diodes () attached to a first surface of a substrate () such that when the photoactivation apparatus is positioned on the multiwell plate each of the light emitting diodes delivers light to one corresponding well. The light emitting diodes () may extend at least partially into the wells of the multiwell plate. A heat sink () and fan may be provided on the device to dissipate heat generated by the light emitting diodes. The components are preferably enclosed in a conveniently-sized housing (). The housing may include one or more grips and air vents. The apparatus includes an interlocking lip () defining a recess which is sized to receive at least a portion of the multiwell plate. A power supply connected to the apparatus and configured to provide an equal voltage across each of the light emitting diodes.

Photoactivation device and method

Methods, compositions and kits are disclosed for determining one or more target polypeptides in a sample where the target polypeptides have undergone a post-translational modification. A mixture comprising the sample and a first reagent comprising a cleavage-inducing moiety and a first binding agent for a binding site on a target polypeptide is subjected to conditions under which binding of respective binding moieties occurs. The binding site is the result of post-translational modification activity involving the target polypeptide. The method may be employed to determine the target polypeptide itself. In another embodiment the presence and/or amount of the target polypeptide is related to the presence and/or amount and/or activity of an agent such as an enzyme involved in the post-translational modification of the target polypeptide. The interaction between the first binding agent and the binding site brings the cleavage-inducing moiety into close proximity to a cleavable moiety, which is associated with the polypeptide and is susceptible to cleavage only when in proximity to the cleavage-inducing moiety. In this way, an electrophoretic tag for each of the polypeptides may be released. Released electrophoretic tags are separated and the presence and/or amount of the target polypeptides are determined based on the corresponding electrophoretic tags.

The present invention is directed to methods and compositions for determining the presence, absence, and/or amounts of one or more membrane-associated analytes in a sample. In accordance with the invention, binding compounds derivatized with releasable molecular tags specifically bind to selected membrane-associated analytes, after which the molecular tags are released upon activation of cleavage moieties, or sensitizers, anchored in the same membrane as the membrane-associated analytes. The released molecular tags are then identified by their distinct separation and detection characteristics.

Multiplex analysis using membrane-bound sensitizers

A polysaccharide coated carrier having a coating of at least two successive layers of polysaccharide. The first polysaccharide layer spontaneously associates with a second polysaccharide layer and, optionally, the carrier. Each successive layer of polysaccharide spontaneously associates with a preceding layer. Spontaneous association occurs due to the presence of oppositely charged functional groups on each layer of polysaccharide or due to a spontaneous reaction between the functional groups the layers. The carrier may be any surface such as a tube, microtitration plate, bead, particle or the like and is suitable for use in diagnostic or therapeutic methods.

Carriers coated with polysaccharides, their preparation and use

Compositions and methods are disclosed for detecting multiple target analytes in a sample using microparticles having molecular tags attached by cleavable linkages. Generally, an assay mixture is formed comprising a sample and a reagent comprising multiple such microparticles under conditions that permit stable complexes to form between binding moieties on the surfaces of the microparticles and the analytes. In one aspect of the invention, the a second binding composition is added so that complexes form among the microparticle-bound binding moieties, the analytes, and second binding moieties of the second binding composition. Such second binding moieties have cleavage-inducing moieties attached that upon activation cause the cleavage of the cleavable linkages and the release of molecular tags. Released molecular tags are separated and the presence and/or amount of the target analytes are determined based on the analysis of the released and separated molecular tags.

Tagged microparticle compositions and methods

Growing community of inventors

San Jose, CA, United States of America

Hrair Kirakossian