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

2020 Genesystems Inc.

University System of Maryland

The United States of America

Other

Michael R Emmert-Buck

Rodrigo F Chuaqui

Robert F Bonner

Lance A Liotta

Michael Anthony Tangrea

Thomas J Pohida

David B Krizman

Paul D Smith

Seth R Goldstein

John I Peterson

W Marston Linehan

Dan-Paul Hartmann

Vladimir Knezevic

Jeffry M Trent

Benjamin Shapiro

Francis S Collins

Stephen M Hewitt

Zhengping Zhuang

Allen M Spiegel

Irina A Lubensky

Larisa V Debelenko

Sunita K Agarwal

A Lee Burns

Stephen J Marx

Kristina A Cole

Nicole Simone

Emmanuel F Petricoin Iii

Galina Baibakova

Settara Chandrasekharappa

Capre Denise Mitchell

Siradanahalli Guru

Kevin Gardner

Pachiappan Manickam

Systems and methods are disclosed for directing magnetizable particles comprising therapeutic agents to a target volume, or for guiding magnetizable particles comprising therapeutic agents from a first target volume to a second target volume, at a distance using a magnetic field, to enable the treatment of diseased areas including areas deep inside a patient's body. The methods may be used to diagnose or treat diseased areas within a patient, for example tumors of the lungs, intestines, and liver, and is also useful in enhancing the permeability of solid tumors to chemotherapeutic agents.

Methods and systems for using therapeutic, diagnostic or prophylactic magnetic agents

The present disclosure provides methods, devices and kits that permit large numbers of target biomolecules to be detected simultaneously in samples originating from a multi-sample holder, such as a multi-well plate. One specific example method is a method of making multiple substantial replicas of a biomolecular content of a multi-well sample holder. Devices and kits for carrying out the described methods are also provided.

Method and device for analyzing biomolecules with track-etched polymeric layers

A method of removing a target from a biological sample which involves placing a transfer surface in contact with the biological sample, and then focally altering the transfer surface to allow selective separation of the target from the biological sample. In disclosed embodiments, the target is a cell or cellular component of a tissue section and the transfer surface is a film that can be focally altered to adhere the target to the transfer surface. Subsequent separation of the film from the tissue section selectively removes the adhered target from the tissue section. The transfer surface is activated from within the target to adhere the target to the transfer surface, for example by heating the target to adhere it to a thermoplastic transfer surface. Such in situ activation can be achieved by exposing the biological sample to an immunoreagent that specifically binds to the target (or a component of the target). The immunoreagent can alter the transfer surface directly (for example with a heat generating enzyme carried by the immunoreagent), or indirectly (for example by changing a characteristic of the target). In some embodiments, the immunoreagent deposits a precipitate in the target that increases its light absorption relative to surrounding tissue, such that the biological specimen can be exposed to light to selectively heat the target. Alternatively, the immunoreagent is an immunofluorescent agent that carries a fluorophore that absorbs light and emits heat.

Target activated microtransfer

A device for performing target activated transfer that includes a mounting surface for mounting a tissue sample; and a light source positioned to substantially uniformly irradiate both stained and unstained regions of the tissue sample with light energy that activates the reagent to selectively adhere the stained regions to a transfer surface. Also described is an automated system for transferring tissue from a tissue sample to a transfer substrate. The system includes means for holding a tissue section that includes targets specifically stained with an absorptive stain thereby resulting in a stained tissue surface, and a flexible transfer film that includes a lower thermoplastic layer in sufficient thermal contact with the stained tissue surface; an irradiating assembly configured to provide a predetermined uniform light dose to the entire tissue section; and means for applying a constant pressure to the transfer film during irradiation.

This invention relates to methods and apparati for performing multiple simultaneous manipulations of biomolecules in a two-dimensional array, such as a gel, membrane, tissue biopsy, etc. Such manipulations particularly include assays and nucleic acid amplification protocols.

Method and apparatus for performing multiple simultaneous manipulations of biomolecules in a two dimensional array

Methods, devices and kits for multiplex blotting of biological samples from multi-well plates

The invention relates to the discovery of a novel tumor suppressor gene which is associated with multiple endocrine neoplasia type 1. The gene has been designated MEN1 and the gene product is menin. The absence of this protein and associated mutations in the corresponding gene have been identified in individuals suffering from multiple endocrine neoplasia type 1. The identification of this marker for multiple endocrine neoplasia type 1 has diagnostic uses as well as for gene therapy.

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A novel gene, PB39, that is up-regulated, or over-expressed, in prostate cancer has been identified. The gene has been identified by means of its cDNA obtained by reverse transcription of the corresponding mRNA. Microdissection of prostate glands that had been surgically removed from prostate cancer patients revealed a novel up-regulated transcript in an aggressive prostate carcinoma. Differential analysis for the presence of this gene was carried out from the same glands by comparing transcription in microdissected normal prostatic epithelium versus that in microdissected invasive tumor. The transcript was over-expressed in 5 of 10 prostate carcinomas examined. A variant transcript was over-expressed in 4 of 4 prostate carcinomas, and was found in 1 of 4 normal samples. The invention provides a purified and isolated nucleic acid that includes the sequence of PB39 or its complement, the sequence of a variant of PB39 or its complement, and a primer or probe, that includes a sequence that is a fragment of these sequences. Additionally, the polypeptide encoded by these genes, an antibody to the polypeptide, and methods of detection of PB39 or its gene product are provided.

PB 39, a gene dysregulated in prostate cancer, and uses thereof

The present invention involves methods, systems, and devices for analyzing a biological material, such as a cellular or other specimen. The method includes placing the specimen on a substrate having different capture regions, such as contiguous layers, wherein the different capture regions of the substrate contain different identification molecules, and transferring components of the specimen through the capture regions under conditions that allow the components to interact with different identification molecules in the different regions of the substrate. The components of the specimen can be transferred through the different layers (or other regions) of the substrate by capillary action of a solution moving through the cellular specimen or by electrophoresis. The transfer of components of the specimen through the substrate may occur while maintaining a geometric correspondence to the specimen, such as the cytoarchitecture of a cellular specimen, for example by moving the components through parallel layers having positions that correspond to positions within the specimen. When the cellular architecture of the specimen is maintained, a correlation between the different identification molecules and the components of the cellular specimens may be made. The analysis can occur with one or more different discrete (for example cellular) specimens on a surface of the substrate. Examples of cellular specimens include, but are not limited to tissue sections, particularly tumor tissue sections. The cellular specimen can also include cultured cells or a cytology sample. Cytostat tissue sections cut slightly thicker than usual, that is about 25 to about 50 &#x3bc;m, improves the ability to detect molecules of moderate and low level abundance.

Layered device with capture regions for cellular analysis

The present invention describes devices and methods for performing protein analysis on laser capture microdissected cells, which permits proteomic analysis on cells of different populations. Particular disclosed examples are analysis of normal versus malignant cells, or a comparison of differential protein expression in cells that are progressing from normal to malignant. The protein content of the microdissected cells may be analyzed using techniques such as immunoassays, 1D and 2D gel electrophoresis characterization, Western blotting, liquid chromatography quadrapole ion trap electrospray (LCQ-MS), Matrix Assisted Laser Desorption Ionization/Time of Flight (MALDI/TOF), and Surface Enhanced Laser Desorption Ionization Spectroscopy (SELDI). In addition to permitting direct comparison of qualitative and quantitative protein content of tumor cells and normal cells from the same tissue sample, the methods also allow for investigation of protein characteristics of tumor cells, such as binding ability and amino acid sequence, and differential expression of proteins in particular cell populations in response to drug treatment. The present methods also provide, through the use of protein fingerprinting, a rapid and reliable way to identify the source tissue of a tumor metastasis.

Methods for the isolation and analysis of cellular protein content

The present disclosure is directed to devices, arrays, kits and methods for detecting biomolecules in a tissue section (such as a fresh or archival sample, tissue microarray, or cells harvested by an LCM procedure) or other substantially two-dimensional sample (such as an electrophoretic gel or cDNA microarray) by creating 'carbon copies' of the biomolecules eluted from the sample and visualizing the biomolecules on the copies using one or more detector molecules (e.g., antibodies or DNA probes) having specific affinity for the biomolecules of interest. Specific methods are provided for identifying the pattern of biomolecules (e.g., proteins and nucleic acids) in the samples. Other specific methods are provided for the identification and analysis of proteins and other biological molecules produced by cells and/or tissue, especially human cells and/or tissue. The disclosure also provides a plurality of differentially prepared and/or processed membranes that can be used in described methods, and which permit the identification and analysis of biomolecules.

Methods, devices, arrays and kits for detecting and analyzing biomolecules

A method of microdissection which involves forming an image field of cells of the tissue sample utilizing a microscope, identifying at least one zone of cells of interest from the image field of cells which at least one zone of cells of interest includes different types of cells than adjacent zones of cells, and extracting the at least one zone of cells of interest from the tissue sample. The extraction is achieved by contacting the tissue sample with a transfer surface that can be selectively activated so that regions thereof adhere to the zone of cells of interest to be extracted. The transfer surface includes a selectively activatable adhesive layer which provides, for example, chemical or electrostatic adherence to the selected regions of the tissue sample. After the transfer surface is activated, the transfer surface and tissue sample are separated. During separation, the zone of cells of interest remains adhered to the transfer surface and is thus separated from the tissue sample, the zone of cells of interest may then be molecularly analyzed.

Isolation of cellular material under microscopic visualization

Growing community of inventors

Easton, MD, United States of America

Michael R Emmert-Buck