Abstract: Disclosed herein are antibody-nanoparticle conjugates that include two or more nanoparticles (such as gold, palladium, platinum, silver, copper, nickel, cobalt, iridium, or an alloy of two or more thereof) directly linked to an antibody or fragment thereof through a metal-thiol bond. Methods of making the antibody-nanoparticle conjugates disclosed herein include reacting an arylphosphine-nanoparticle composite with a reduced antibody to produce an antibody-nanoparticle conjugate. Also disclosed herein are methods for detecting a target molecule in a sample that include using an antibody-nanoparticle conjugate (such as the antibody-nanoparticle conjugates described herein) and kits for detecting target molecules utilizing the methods disclosed herein.
Type:
Grant
Filed:
April 21, 2015
Date of Patent:
September 13, 2016
Assignee:
Ventana Medical Systems, Inc.
Inventors:
Julia Ashworth-Sharpe, Chol Steven Yun, Zhanna Zhilina, Adrian E. Murillo, Donald D. Johnson, Michael Farrell, Jerome W. Kosmeder, Christopher Bieniarz
Abstract: The disclosure provides methods for characterizing a prostate cancer sample by detecting expression of ERG, PTEN or both, changes in which relative to a normal control are shown herein to be correlated with prostate cancer capsular penetration and more aggressive forms of prostate cancer. Such methods are useful for the prognosis of prostate cancer capsular penetration and for making treatment decisions in patients with prostate cancer that has penetrated the capsule. Also provided are kits that can be used with such methods.
Type:
Grant
Filed:
August 28, 2012
Date of Patent:
September 6, 2016
Assignees:
Ventana Medical Systems, Inc., The Arizona Board of Regents on behalf of the University of Arizona
Inventors:
Gary Pestano, Ray B. Nagle, Connie Cortez, Kristie A. Vanpatten, Amit M. Algotar
Abstract: This disclosure relates to compositions that enhance the deposition of detectable moieties on tissue samples, methods utilizing these compositions and kits including these compositions. The compositions include a deposition enhancer having a formula where R1, R2, R3, and R4 are independently selected from aliphatic, aryl, halogen, a heteroatom-containing moiety, and hydrogen; R1 and/or R3 can be bound to R2 to form a fused, aromatic ring system; R5 is selected from a heteroatom-containing moiety; A is selected from, a carbon atom, a heteroatom, other than sulfur, and any combination thereof; n is 1-5, an enzyme, a specific binding moiety and a detectable moiety.
Type:
Grant
Filed:
October 6, 2014
Date of Patent:
September 6, 2016
Assignee:
Ventana Medical Systems, Inc.
Inventors:
Eric J. May, Adrian E. Murillo, Jerome W. Kosmeder, II
Abstract: The present invention relates to systems and methods for adaptively optimizing broadband reference spectra for a multi-spectral image or adaptively optimizing reference colors for a bright-field image. The methods and systems of the present invention involve optimization techniques that are based on structures detected in an unmixed channel of the image, and involves detecting and segmenting structures from a channel, updating a reference matrix with signals estimated from the structures, subsequently unmixing the image using the updated reference matrix, and iteratively repeating the process until an optimized reference matrix is achieved.
Abstract: A microscope-based system and method for simultaneous imaging of several object planes, of a three-dimensional (3D) sample, associated with different depths throughout the sample. The system includes a polyfocal optical portion, adapted to create a plurality of optical channels each of which is associated with an image of a corresponding object plane, and a spectrally-selective portion, adapted to transform the spectral distribution of the image-forming beam of light to a corresponding spatial distribution. The image, registered by a detector, includes an image of an object plane and an image of the spatially-coded spectral distribution. The method effectuates the simultaneous multispectral imaging of the several object planes. The required data-acquisition time is several fold shorter than that taken by a conventional multispectral microscope-based imaging system.
Abstract: A method and system for spectral demultiplexing of fluorescent species, such as quantum dots, conjugated with a biological tissue. The process of demultiplexing involves a non-liner regression based on curve-fitting of estimated spectra of the quantum dots and confidence intervals describing the parameters of such fitting curve for typical quantum dots.
Type:
Grant
Filed:
May 4, 2012
Date of Patent:
June 28, 2016
Assignee:
VENTANA MEDICAL SYSTEMS, INC.
Inventors:
Pascal Bamford, Michael Otter, Ronald T. Kurnik
Abstract: An imaging system (100) is capable of detecting of tissue situated on a microscope slide (180). The imaging system (100) includes a light source (150), an image capturing device (160) including a camera, and an imaging lens (170). The light source (150) directs light (154) towards one or more of the edges of the slide (180) such that the light (154) undergoes total internal reflection between a surface of the slide (180) and a coverslip (182) carried by the slide (180). The light (154) has a wavelength or waveband designed to stimulate one or more specimens carried on the slide (180). The imaging lens (170) is positioned to direct radiation emitted from the tissue and/or fluorophore onto the camera. The image capturing device (160) can capture an image of the whole slide (180) or a portion thereof.
Type:
Application
Filed:
May 28, 2014
Publication date:
May 12, 2016
Applicant:
VENTANA MEDICAL SYSTEMS, INC.
Inventors:
Pascal Bamford, Lou Dietz, Elizabeth Little
Abstract: Antibody/signal-generating moiety conjugates are disclosed that include an antibody covalently linked to a signal-generating moiety through a heterobifunctional polyalkyleneglycol linker. The disclosed conjugates show exceptional signal-generation in immunohistochemical and in situ hybridization assays on tissue sections and cytology samples. In one embodiment, enzyme-metallographic detection of nucleic acid sequences with hapten-labeled probes can be accomplished using the disclosed conjugates as a primary antibody without amplification.
Type:
Grant
Filed:
January 2, 2014
Date of Patent:
April 19, 2016
Assignee:
Ventana Medical Systems, Inc.
Inventors:
Christopher Bieniarz, Jennifer Wong, Mark Lefever, Jerome W. Kosmeder, II, Julia Ashworth-Sharpe, Casey A. Kernag
Abstract: Multiple modality contrast can be used to produce images that can be combined and rendered to produce images similar to those produced with wavelength absorbing stains viewed under transmitted white light illumination. Images obtained with other complementary contrast modalities can be presented using engineered color schemes based on classical contrast methods used to reveal the same anatomical structures and histochemistry, thereby providing relevance to medical training and experience. Dark-field contrast images derived from refractive index and fluorescent DAPI counterstain images are combined to produce images similar to those obtained with conventional H&E staining for pathology interpretation.
Type:
Grant
Filed:
October 7, 2010
Date of Patent:
April 12, 2016
Assignee:
VENTANA MEDICAL SYSTEMS, INC.
Inventors:
Karl Garsha, Gary Pestano, Michael Otter, Alexandra Dea Nagy, Ray B. Nagle, Phillip Miller, Jan Froehlich, William Day
Abstract: A method is disclosed for making a conjugate of two molecules using a hydrazide thiol linker. In a particular working embodiment, an Fc-specific antibody-enzyme conjugate is made using the method and demonstrated to provide exceptional staining sensitivity and specificity in immunohistochemical and in situ hybridization assays.
Type:
Grant
Filed:
February 14, 2014
Date of Patent:
April 12, 2016
Assignee:
Ventana Medical Systems, Inc.
Inventors:
Christopher Bieniarz, Julia Ashworth-Sharpe, Casey A. Kernag, Jerome W. Kosmeder, Mark Lefever
Abstract: Particular disclosed embodiments disclosed herein concern using a one or more various mass tags, which can be specifically deposited at targets through direct or indirect enzymatic-catalyzed transformation, to provide a method for identifying targets in tissue samples. The mass tags may be labeled with stable isotopes to produce mass tags having the same chemical structure but different masses. Mass codes produced by ionizing the mass tags are detected and/or quantified using mass spectrometry. The method can be used for multiplexed detection of multiple targets in a particular sample. In some embodiments, a map divided into sections representing sections of the tissue sample may be prepared, with the map sections including data corresponding to quantification data wherein the size of a mass peak is determined and correlated with the amount of a target for the corresponding tissue sample section.
Type:
Grant
Filed:
July 1, 2011
Date of Patent:
March 22, 2016
Assignee:
VENTANA MEDICAL SYSTEMS, INC.
Inventors:
Rui Hong, Hong Wang, Mark Lefever, Jan Froehlich, Christopher Bieniarz, Brian Kelly, Phillip Miller
Abstract: A transfer device (100) comprises a housing (110) defining a chamber (130), carriers (120), and an adjustable spacing mechanism (124). The carriers (120) can be positioned in the chamber (130) and have receiving openings (158). The spacing mechanism (124) is configured to move carriers (120) relative to one another along a chamber (130) to a desired spatial arrangement. Items, such as microscope slides (260), can be transferred between slide holder devices by using the transfer device (100). The pitch of the carriers (120) can be adjusted to receive and dispense slides (260).
Type:
Grant
Filed:
August 21, 2012
Date of Patent:
November 24, 2015
Assignee:
Ventana Medical Systems, Inc.
Inventors:
David Diepersloot, Raphael Hebert, David Moriconi
Abstract: The present disclosure provides nucleic acid probes, as well as kits that include such probes. Methods for producing and using (for example in chromosomal in situ hybridization) the probes are also provided. Such probes in some examples are used to detect chromosomal abnormalities or the presence of a pathogen.
Abstract: Embodiments of substrates and processes for chromogenic detection, and in particular pyrazolyl dihydrogen phosphate compounds, are disclosed.
Type:
Grant
Filed:
August 12, 2011
Date of Patent:
September 8, 2015
Assignee:
Ventana Medical Systems, Inc.
Inventors:
Brian Daniel Kelly, Christopher Bieniarz, Hiro Nitta, Fabien Gaire
Abstract: Certain disclosed embodiments of the present invention concern the synthesis, derivatization, conjugation to immunoglobulins and signal amplification based on discrete, relatively short polymers having plural reactive functional groups that react with plural molecules of interest. Reactive functional groups, such as hydrazides, may be derivatized with a variety of detectable labels, particularly haptens. The remaining reactive functional groups may be conjugated directly to a specific binding molecule, such as to the oxidized carbohydrate of the Fc region of the antibody. Disclosed conjugates display large signal amplification as compared to those based on molecules derivatized with single haptens, and are useful for assay methods, particularly multiplexed assays.
Type:
Grant
Filed:
May 30, 2013
Date of Patent:
August 11, 2015
Assignee:
Ventana Medical Systems, Inc.
Inventors:
Jerry W. Kosmeder, II, Casey A. Kernag, Donald Johnson, Christopher Bieniarz
Abstract: Provided herein are methods of staining biological material for the purpose of detecting, and in some examples also identifying, microorganisms. Methods of Gram staining bacteria using a slow-acting decolorizing formulation, such as one that includes 1,2-propandiol or ethylene glycol, can be used to extend the time of the decolorizing step, and thus permit automation of the Gram staining method. Also provided are compositions and kits for performing automated Gram staining on microscope slides.
Abstract: In general, the presently disclosed technology relates to identification of cancer subtypes. More specifically, the technology relates to methods for determining molecular drivers of cancer and/or progression using a multivariate image data and statistical analysis of in-situ molecular markers and morphological characteristics in the same cells of a biological sample suspected of b cancer. This analysis takes place after a single acquisition that obtains the molecular and anatomic morphology data in parallel. The analysis compares specific morphological and molecular markers to known samples exhibiting particular genetic drivers of the cancer. This method provides statistical information that allows for an increased confidence in the identification of specific molecular drivers of the cancer.
Type:
Application
Filed:
April 23, 2013
Publication date:
July 16, 2015
Applicants:
CORNELL UNIVERSITY, VENTANA MEDICAL SYSTEMS, INC.
Inventors:
Francesca Demichelis, Karl Garsha, Phillip C. Miller, Ray B. Nagle, Michael Otter, Gary Anthony Pestano, Mark Rubin
Abstract: Disclosed herein are antibody-nanoparticle conjugates that include two or more nanoparticles (such as gold, palladium, platinum, silver, copper, nickel, cobalt, iridium, or an alloy of two or more thereof) directly linked to an antibody or fragment thereof through a metal-thiol bond. Methods of making the antibody-nanoparticle conjugates disclosed herein include reacting an arylphosphine-nanoparticle composite with a reduced antibody to produce an antibody-nanoparticle conjugate. Also disclosed herein are methods for detecting a target molecule in a sample that include using an antibody-nanoparticle conjugate (such as the antibody-nanoparticle conjugates described herein) and kits for detecting target molecules utilizing the methods disclosed herein.
Type:
Grant
Filed:
April 27, 2011
Date of Patent:
May 26, 2015
Assignee:
Ventana Medical Systems, Inc.
Inventors:
Julia Ashworth-Sharpe, Chol Steven Yun, Zhanna Zhilina, Adrian E. Murillo, Donald D. Johnson, Michael Farrell, Jerome W. Kosmeder, Christopher Bieniarz
Abstract: Systems and techniques for an optical scanning microscope and/or other appropriate imaging system includes components for scanning and collecting focused images of a tissue sample and/or other object disposed on a slide. The focusing system described herein provides for determining best focus for each snapshot as a snapshot is captured, which may be referred to as “on-the-fly focusing.” The devices and techniques provided herein lead to significant reductions in the time required for forming a digital image of an area in a pathology slide and provide for the creation of high quality digital images of a specimen at high throughput.
Type:
Grant
Filed:
April 11, 2012
Date of Patent:
May 19, 2015
Assignee:
Ventana Medical Systems, Inc.
Inventors:
Gregory C. Loney, Glenn Stark, Chris Todd, Bikash Sabata