Ventana Medical Systems, Inc.

Oregon Health & Science University

The United States of America, As Represented by the Secretary, Department of Health and Human Services

University of Rochester

The University of Arizona

University of Nebraska

University of London

British Columbia Cancer Agency Branch

Universität De Barcelona

Oslo University Hospital Hf

Fundacio Clinic

Hospital Clinic De Barcelona

Julius-maximilians-university of Wurzburg

Julius-maximilians-university of Wuerzburg

Hospital Clinic

Thomas M Grogan

William L Richards

Wayne A Showalter

Phillip C Miller

Keith G Copeland

Charles Nathan Hassen

William Ross Humphreys

Michael S Barnes

Charles Daniel Lemme

Esteban Roberts

Joe W Gray

Christophe Chefd'hotel

David Chafin

Benjamin C Stevens

Karl Eric Garsha

Kandavel Shanmugam

Brian Jay Druker

Shalini Singh

Penny Towne

Franklin Ventura

Thomas Jacob

Hiro Nitta

Srinivas Chukka

Anindya Sarkar

Joseph M Connors

Wyndham H Wilson

Kai Fu

Armando Lopez-Guillermo

Jennifer Wong

Christopher Bieniarz

Jerome W Kosmeder, Ii

Michael Patrick Farrell

Brian Daniel Kelly

Anthony L Hartman

Wenjun Zhang

Louis M Staudt

Stacey Stanislaw

Nelson Alexander

Fabien Gaire

Elaine S Jaffe

Erlend B Smeland

Sandeep S Dave

German Ott

Lisa M Rimsza

Wing C Chan

Dennis Weisenburger

Jan Delabie

Alisa Tubbs

Crystal Schemp

Hiroaki Nitta

Damien Ramunno-Johnson

June F Clements

Bruce Tan

Timothy C Greiner

George Wright

Hans-Konrad Muller-Hermelink

Harald Holte

Richard I Fisher

Randy Gascoyne

Thomas Miller

John I Powell

James Armitage

Tothu Tania Vu

Silvia M Bea

Itziar Salaverria

Victor Moreno

Andreas Zettl

Julie Vose

T Andrew Lister

Andreas Rosenwald

Elias Campo Guerri

Catherine Wolf

Lidija Pestic-Dragovich

Tania Vu

Sandeep Dave

Stein Kvaloy

Stein Kvaløy

Lisa Rimsza

Richard Gniewek

Megan Lehrkamp

Mary Padilla

Elias Campo

Emili Montserrat

Philip C Miller

Jacques Cavadenti

Angela Sattler

Charles E Lemme

Erlend Smeland

Elaine Jaffe

Emilio Montserrat

Karl Garsha

Frank Ventura

Leigh A Henricksen

Christophe Chefd´hotel

The present disclosure provides for image processing systems and methods for analyzing digital images of biological samples stained for the presence of protein and/or nucleic acid biomarkers and detecting and quantifying signals corresponding to one or more biomarkers. The present disclosure also provides systems and methods for the clinical interpretation of dual ISH slides where the cells to score are selected (e.g. by using one or more cell detection and identification algorithms. By detecting, identifying, and selecting cells for assessment, it is believed that subjectivity is reduced or eliminated. The systems and methods also allow for an increased number of cells to be considered for scoring as compared with manual dot counting methods, thereby increasing detection sensitivity, ultimately enabling improved patient care and treatment.

Systems for automated in situ hybridization analysis

The present disclosure provides for image processing systems and methods for automatically analyzing digital images of biological samples stained for the presence of protein and/or nucleic acid biomarkers () and automatically detecting and quantifying signals corresponding to one or more biomarkers (). The present disclosure also provides systems and methods for the clinical interpretation of dual ISH slides where the cells to score are automatically selected (e.g. by using one or more cell detection and identification algorithms ()). By automatically detecting, identifying, and selecting cells for assessment, it is believed that subjectivity is reduced or eliminated. The automated systems and methods also allow for an increased number of cells to be considered for scoring as compared with manual dot counting methods, thereby in-creasing detection sensitivity, ultimately enabling improved patient care and treatment.

Methods, systems, and apparatuses for detecting and describing heterogeneity in a cell sample are disclosed herein. A plurality of fields of view (FOV) are generated for one or more areas of interest (AOI) within an image of the cell sample are generated. Hyperspectral or multispectral data from each FOV is organized into an image stack containing one or more z-layers, with each z-layer containing intensity data for a single marker at each pixel in the FOV. A cluster analysis is applied to the image stacks, wherein the clustering algorithm groups pixels having a similar ratio of detectable marker intensity across layers of the z-axis, thereby generating a plurality of clusters having similar expression patterns.

Methods, systems, and apparatuses for quantitative analysis of heterogeneous biomarker distribution

Disclosed herein are methods for identifying a subject as having NSCLC that is predicted or is likely to respond to treatment with an ALK inhibitor, for example crizotinib. The methods include identifying a sample including NSCLC tumor cells as ALK-positive or ALK-negative using immunohistochemistry (IHC) and scoring methods disclosed herein. A subject is identified as having NSCLC likely to respond to treatment with an ALK inhibitor if the sample is identified as ALK-positive and is identified as having NSCLC not likely to respond to treatment with an ALK inhibitor if the sample is identified as ALK-negative. According to certain embodiments of the methods, subjects predicted to respond to an ALK inhibitor may then be treated with an ALK inhibitor such as crizotinib.

Method of identifying treatment responsive non-small cell lung cancer using anaplastic lymphoma kinase (ALK) as a marker

Gene expression data provides a basis for more accurate identification and diagnosis of lymphoproliferative disorders. In addition, gene expression data can be used to develop more accurate predictors of survival. The present invention discloses methods for identifying, diagnosing, and predicting survival in a lymphoma or lymphoproliferative disorder on the basis of gene expression patterns. The invention discloses a novel microarray, the Lymph Dx microarray, for obtaining gene expression data from a lymphoma sample. The invention also discloses a variety of methods for utilizing lymphoma gene expression data to determine the identity of a particular lymphoma and to predict survival in a subject diagnosed with a particular lymphoma. This information will be useful in developing the therapeutic approach to be used with a particular subject.

Methods for identifying, diagnosing, and predicting survival of lymphomas

Disclosed herein are methods for identifying a subject as having NSCLC that is predicted or is likely to respond to treatment with an ALK inhibitor, for example crizotinib. The methods include identifying a sample including NSCLC tumor cells as ALK-positive or ALK-negative using immunohistochemistry (IBC) and scoring methods disclosed herein. A subject is identified as having NSCLC likely to respond to treatment with an ALK inhibitor if the sample is identified as ALK-positive and is identified as having NSCLC not likely to respond to treatment with an ALK inhibitor if the sample is identified as ALK-negative. According to certain embodiments of the methods, subjects predicted to respond to an ALK inhibitor may then be treated with an ALK inhibitor such as crizotinib.

The present invention provides a method and kit for detection of two or more target molecules in a single tissue sample, such as for gene and protein dual detection in a single tissue sample. Methods comprise treating a tissue sample with a first binding moiety that specifically binds a first target molecule. Methods further comprise treating the tissue sample with a solution containing a soluble electron-rich aromatic compound prior to or concomitantly with contacting the tissue sample with a hapten-labeled binding moiety and detecting a second target molecule. In one example, the first target molecule is a protein and the second is a nucleic acid sequence, the first target molecule being detected by immunohistochemistry and the second by in situ hybridization. The disclosed method reduces background due to non-specific binding of the hapten-labeled specific binding moiety to an insoluble electron rich compound deposited near the first target molecule.

Method for chromogenic detection of two or more target molecules in a single sample

The present disclosure provides methods of diagnosing cervical dysplasia and cervical cancer by detecting Na, K-ATPase expression. For example, it is demonstrated herein that expression of the Na, K-ATPase &#x3b2;1-subunit increases in cervical dysplasia and cervical cancer, relative to normal cervical tissue. Also provided are methods of treating cervical dysplasia and cervical cancer by decreasing the biological activity of the Na, K-ATPase. For example, therapeutically effective amounts of one or more Na, K-ATPase inhibitors can be applied to the cervix to treat cervical dysplasia and cervical cancer.

[object Object]

An automated immunostaining apparatus having a reagent application zone and a reagent supply zone. The apparatus has a carousel slide support supporting a plurality of slide supports thereon, and drive means engaging the carousel slide support for consecutively positioning each of a plurality of slide supports in the reagent application zone. The apparatus also has a carousel reagent support having a plurality of reagent container supports thereon, and drive means engaging the carousel for rotating the carousel and positioning a preselected reagent container support in the reagent supply zone. The apparatus also has a reagent delivery actuator means positioned for engaging a reagent container positioned on a container support in the reagent delivery zone and initiating reagent delivery from the reagent container to a slide supported on a slide support in the reagent receiving zone.

Automated biological reaction apparatus

An automated immunostaining apparatus having a reagent application zone and a reagent supply zone. The apparatus has a carousel slide support supporting a plurality of slide supports thereon, and drive engaging the carousel slide support for consecutively positioning each of a plurality of slide supports in the reagent application zone. The apparatus also has a carousel reagent support having a plurality of reagent container supports thereon, and drive engaging the carousel for rotating the carousel and positioning a preselected reagent container support in the reagent supply zone. The apparatus also has a reagent delivery actuator positioned for engaging a reagent container positioned on a container support in the reagent delivery zone and initiating reagent delivery from the reagent container to a slide supported on a slide support in the reagent receiving zone.

Automated biological reaction method

Growing community of inventors

Tucson, AZ, United States of America

Thomas M Grogan