Vanderbilt University

Picoliter Inc.

Katholieke Universiteit Leuven, Ku Leuven R&d

Frontier Diagnostics, LLC

Protein Discovery, Inc.

Richard Caprioli

Jeremy L Norris

Richard N Ellson

Mitchell Wayne Mutz

Ned A Porter

Nathan S Lewis

John P Wikswo

Dean G Hafeman

Eric P Skaar

Charles E Witkowski, Ii

Bart De Moor

Raf Van De Plas

Etienne Waelkens

Dana Borden Lacy

Kilian Dill

David Anderson

Jason B Robbins

John McLean

Nico Verbeeck

Faizan Zubair

Stacy Sherrod

Erin H Seeley

Douglas S Masterson

Paul Edward Laibinis

James Pino

Huiyong Yin

Eric Spivey

Melissa Farrow

Shawn Levy

Danielle Gutierrez

James B Harkins

Junhai Yang

Nicole D Muszynski

Daniel Kuban

This disclosure relates to apparatus and methods for sublimation and deposition of chemicals. In particular aspects, this disclosure relates to apparatus and methods for patterned sublimation and deposition of chemicals for use in matrix assisted laser desorption ionization imaging mass spectrometry (MALDI IMS). In specific aspects, the apparatus comprises a vacuum chamber and a template comprising a planar surface containing the chemical to be sublimed, where the template is located within the vacuum chamber.

Apparatus and methods of sublimation for repeatable uniform or patterned deposition of matrix crystals on solid substrates

Pre-coated analysis substrates, and methods of making the substrates and using them to analyze animal tissue, are described. The pre-coated analysis substrates can be made by forming a matrix surface on an analysis substrate; adding a protease to the matrix surface to form a pre-coated analysis substrate; and placing an animal tissue specimen on the matrix surface. The animal tissue can then be analyzed by allowing the protease to partially digest the animal tissue specimen; and analyzing the partially digested animal tissue specimen by mass spectrometry.

Pre-coated surfaces for imaging biomolecules

The present invention is directed to a mass spectrometry approach to identifying non-Spitzoid melanoma, and distinguishing non-Spitzoid nevi from non-Spitzoid malignant melanoma.

Imaging mass spectrometry and uses thereof

The present disclosure provides for rapid identification of mechanism of action (MOA) for drugs and toxins, and does so in a rapid (30 days or less) fashion. The methods use a combination of high throughput bioinformatics and pathway analysis that examine a wide variety of biological parametics.

High-throughput, multi-omics approach to determine and validate de novo global mechanisms of action for drugs and toxins

Imaging mass spectrometry (IMS) has become a prime tool for studying the distribution of biomolecules in tissue. Although IMS data sets can become very large, computational methods have made it practically feasible to search these experiments for relevant findings. However, these methods lack access to an important source of information that many human interpretations rely upon: anatomical insight. In this work, this need is addressed by (1) integrating a curated anatomical data source with an empirically acquired IMS data source, establishing an algorithm-accessible link between them; and (2) demonstrating the potential of such an IMS-anatomical atlas link by applying it toward automated anatomical interpretation of ion distributions in tissue.

System for interpretation of image patterns in terms of anatomical or curated patterns

Systems and methods are provided for generating a model relating parameters generated via a first molecular imaging modality to parameters generated via a second molecular imaging modality. First and second feature extractors extract, from images of a region of interest obtained via respective first and second molecular imaging modalities, respective sets of parameters for respective first and second sets of locations. A mapping component associates respective locations of the first and second sets of locations according to their spatial relationship within the region of interest to produce a training set. Each example in the training set comprises a set of parameters associated with a location in the first set of locations and a set of parameters associated with a location in the second set. A modeling component generates a predictive model relating the parameters associated with the first modality with at least one parameter associated with the second modality.

Predictive modeling relating molecular imaging modalities

The present invention provides for a mass spectrometry proteomic approach to distinguishing Spitz nevi from Spitzoid malignant melanoma. Histology directed mass spectral profiling allows for targeted analysis of sites of melanocytic lesion within formalin-fixed, paraffin embedded excisional biopsies. The classification system identified 5 peptide peaks, of which two have been identified as originating from vimentin and actin. A sensitivity and specificity for Spitz nevi of 97% and 90%, respectively, were achieved.

Method for differentiating spitz nevi from spitzoid malignant melanoma

Methods and apparatuses for analyzing proteins and other biological materials and xenobiotics within a sample. A specimen is generated, which may include an energy absorbent matrix. The specimen is struck with laser beams such that the specimen releases proteins. The atomic mass of the released proteins over a range of atomic masses is measured. An atomic mass window of interest within the range of atomic masses is analyzed to determine the spatial arrangement of specific proteins within the sample, and those specific proteins are identified as a function of the spatial arrangement. By analyzing the proteins, one may monitor and classify disease within a sample.

Methods and apparatuses for analyzing biological samples by mass spectrometry

The present invention includes a cleavable surfactant/detergent compound of the following formula: wherein the variables are defined herein. Embodiments of the cleavable surfactant/detergent compound are useful, for example, in methods for isolating a hydrophobic molecule that include providing a plasma comprising a hydrophobic molecule, applying the cleavable surfactant to the plasma so that the surfactant engages the hydrophobic molecule, cleaving the surfactant from the hydrophobic molecule, and analyzing said hydrophobic molecule.

Cleavable surfactants and methods of use thereof

The present invention provides for the simultaneous assessment of a plurality of tissue regions or microregions, the benefit being homogeneity of the sampling, both in terms of tissue content and timing. Discrete regions of a tissue sample, such as those demarcated by microwells formed within the tissue itself or tissue plugs removed from the tissue in a spatially referenced fashion, can be treated with one or more physical or chemical treatments to liberate target molecules of interest. Subsequent analysis of said target molecules by, e.g., mass spectroscopy, permits identification of a variety of biological parameters, including those associated with disease or therapy.

In situ analysis of tissues

A method of modifying protein samples that comprises combining the sample with a peroxycarbonate solution and inserting the sample into a mass spectrometer. The present invention also includes methods of N-terminus characterization.

MS based peptide and protein sequencing via reactions of lysine residues with peroxycarbonate compounds

The present invention provides for a proteomic approach to grading gliomas, and for predicting patient survival. In addition to employing global protein expression patterns, such as by mass spectrometry, particular target proteins whose expression is altered in various gliomas can be used to predict the stage/classification of a glioma, as well as to indicate whether a given patient will be a short- or long-term survivor.

Diagnosing and grading gliomas using a proteomics approach

The present invention provides mass tag complexes that permit simultaneously obtaining information of a plurality of biological molecules. The biological molecules may be RNA or protein, and the information includes both level of expression as well as spatial disposition within a cell or tissue. The mass tag comprise a core structure, a target binding structure (e.g., nucleic acid or peptide binding structure), a cleavable linker and a mass tag that exhibits a unique mass spectroscopy signal.

Multiplex spatial profiling of gene expression

Analytical methods and devices are disclosed for separating low abundance analytes by electrophoretically driving the analytes through a sieving matrix to first remove high molecular weight species. Subsequently the remaining low abundance analytes are electrophoretically focused onto a capture membrane where the analytes become bound within a small capture site. After this step the capture membrane may be allowed to dry and then attached to a conductive MALDI sample plate.

Methods and devices for concentration and purification of analytes for chemical analysis including matrix-assisted laser desorption/ionization(MALDI) mass spectrometry (MS)

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Brentwood, TN, United States of America

Richard Caprioli