Agilent Technologies, Inc.

Hewlett-packard Company

Memorial Sloan Kettering Cancer Center

Steven Michael Fischer

Darrell L Gourley

Charles William Russ, Iv

James L Bertsch

Robert Keith Crawford

Jian Bai

J Michael Flanagan

Patricia H Cormia

Glen F Ingle

Paul C Goodley

William Daniel Frazer

Christine A Miller

Karl A Hanold

Timothy Herbert Joyce

Harvey D Loucks, Jr

Kent D Henry

Curt Alan Flory

Arthur Schleifer

Jean-Luc Truche

Robert Lee, Jr

Mark H Werlich

James Alexander Apffel, Jr

Patrick D Perkins

Harry F Prest

Dean R Thompson

Kristin Briana Bernick

Jerry T Dowell

Robert G Nordman

Justin Cross

Eugene M Wong

William E Barry

Jian Bal

Genevieve Van De Bittner

Stephen P Madden

Julie B Riccomini

Nora W Gee

Hans-Peter Zimmerman

Justin R Cross

William Barry

Charles W Russ Iv

Darell L Gourley

A method for analyzing samples utilizing stable label isotope tracing includes receiving mass spectrometry (MS) data generated by an MS system performing untargeted data acquisition on a plurality of samples, performing untargeted feature extraction on the unlabeled compound data to generate a data set of first extracted features, generating a plurality of empirical molecular formulas respectively corresponding to the first extracted features, performing targeted isotopologue extraction on the labeled compound data to generate a data set of second extracted features, wherein the targeted isotopologue extraction is based on the empirical molecular formula and retention time of each first extracted feature, and identifying one or more groups of isotopologues from the second extracted features.

Stable label isotope tracing for untargeted data

Reagents and methods for extracting and stabilizing metabolites at room temperature and methods in which metabolites and one or more of proteins, lipids and nucleic acids are extracted from a single sample in a unified workflow.

Room temperature methods for preparing biological analytes

Provided herein, among other things, is a method of ionizing a first stream of liquid by an electrospray ion source having a nebulizer, wherein the first stream of liquid may comprise an analyte. In some embodiments, the method may comprise: a) providing the first stream of liquid to the nebulizer; b) adding a second stream of liquid to the first stream of liquid, wherein the second stream of liquid comprises a co-solvent that has a relatively high boiling point and an enhancement solvent that a relatively high boiling; and c) nebulizing and ionizing the resulting liquid.

Method for enhancing electrospray

A method of identifying a biopolymer in a sample that includes one or more biopolymers. The biopolymers may be polypeptides, polynucleotides, or polysaccharides. The method makes use of mass spectral datasets. A first dataset includes measured masses of the one or more biopolymers that are in the sample. A second dataset includes measured masses of a collection of fragments of the one or more biopolymers. The method selects a mass from the first dataset and then matches masses from the second dataset with the selected mass. The matched masses represent fragments of the biopolymer with the selected mass. Once the masses in the second dataset have been matched they are compared to determine a monomer sequence for the biopolymer with the selected mass. The method may be repeated with additional masses in the first dataset.

Methods and devices for identifying biopolymers using mass spectroscopy

A mass spectrometer having a matrix-assisted laser desorption ionization (MALDI) source which operates at ambient pressure is disclosed. The apparatus and method are disclosed to analyze at least one sample which contains at least one analyte using matrix-assisted laser desorption ionization (MALDI), which apparatus comprises: The present invention relates to an apparatus and a method for ionizing at least one analyte in a sample for delivery to a mass analysis device, comprising: 

Ambient pressure matrix-assisted laser desorption ionization (MALDI) apparatus and method of analysis

A method of obtaining ions of an analyte is disclosed. The method includes aerosolizing a sample using a thermal liquid jetting device or a piezoelectric liquid jetting device to obtain an aerosol without ionizing the sample. The sample includes the analyte in a solvent. The method further includes drying the aerosol to obtain gas phase solvent and gas phase analyte, and ionizing the gas phase analyte to obtain ions thereof. An ion source using the method for obtaining ions of an analyte is also disclosed.

Method and an ion source for obtaining ions of an analyte

A method of facilitating analysis of a peptide in a mass spectrometer comprising derivatizing the C-terminus of the peptide with an amino acid residue via a reaction with a carbodiimide reagent, yielding a derivative peptide, ionizing the derivative peptide with a double charge, and fragmenting the ionized derivative peptide in a mass spectrometry system, wherein binary fragments of the ionized derivative each include a charge, facilitating sequence analysis of the peptide.

Peptide derivatization method to increase fragmentation information from MS/MS spectra

The present invention provides novel systems for sequencing nucleic acid molecules using dNTPs that are 3' end labeled with cleavable tags that block further extension and uniquely identify the bases to which they are attached. Removal of the tags liberates the 3&#x2032; ends of the extension products for further extension. In related embodiments, oligonucleotides containing sequence-related cleavable tags are employed in a ligation reaction to determine the sequence of a particular DNA sample.

Method of DNA sequencing using cleavable tags

The invention provides a system apparatus and methods for fragmenting various molecules. In particular, the invention may be employed for fragmenting biomolecules like peptides to determine sequence information. The invention provides a mass spectrometry system for photo-activated collision induced dissociation. The mass spectrometry system or device includes an ion source for producing ions, a photon source adjacent to the ion source for photo-activating ions produced by the ion source, an electrical element adjacent to the photon source for creating an electric field for accelerating ions produced by the ion source and photo-activated by the photon source; wherein ions are produced by the ion source, photo-activated by the photon source and accelerated into a surface to cause dissociation of the activated ions; and a detector downstream from the ion source for detecting the collision induced and dissociated ions.

Photoactivated collision induced dissociation (PACID) (apparatus and method)

The present invention provides a new and improved method for quantitative determination and/or identification of proteins in a sample. In one aspect, the invention provides a mass spectroscopic method for comparing protein levels in two or more samples by differentially isotopically labeling each sample's proteins' N- or C-termini. In another aspect, the invention provides a mass-spectroscopic method for identifying a sample as source for a protein from a mixture of two or more samples by differentially isotopically labeling each sample's proteins' N- or C-termini.

Mass spectroscopic method for comparing protein levels in two or more samples

A tandem mass spectrometer and method for calibrating a tandem mass spectrometer. The tandem mass spectrometer comprises first and second mass analyzers. The first and second mass analyzers form an ion path. The second mass analyzer is positioned downstream from the first mass analyzer and is arranged to receive ions from the first mass analyzer. An electrode arrangement positioned between the first and second mass analyzers. The electrode assembly is configured to selectively deflect ions from the ion path.

Mass spectrometry system having ion deflector

A method of analyzing a sample comprising multiple protein species is provided. The proteins are separated by species such that the multiple protein species emerge in a sequential order and are then digested in the sequential order in which they emerge from the separation process. The digested proteins are introduced into a mass spectrometer in the same sequential order so that, within a given time window, the digested proteins introduced into the mass spectrometer are covariant.

Linear high-throughput proteomics

The present invention provides an apparatus and method for use with a mass spectrometer. The multimode ionization source of the present invention provides one or more atmospheric pressure ionization sources (e.g., electrospray, atmospheric pressure chemical ionization and/or atmospheric pressure photoionization) for ionizing molecules. A method of producing ions using the multimode ionization source is also disclosed. The apparatus and method provide the advantages of the combined ion sources without the inherent disadvantages of the individual sources. In an embodiment, the multimode ionization source includes an infrared emitter enclosed in an inner chamber for drying a charged aerosol. ESI/APCI multimode sources may include a corona needle shield and/or an auxiliary electrode.

Multimode ionization source

An ion sampling apparatus for use in a mass spectrometry system. The ion sampling apparatus includes a target support for receiving a sample, an irradiation source for emitting energetic radiation or particles toward the target support, and a conduit having a curved end and a longitudinal axis, the curved end having an inlet with a central axis, the conduit being adjacent to the target support. The longitudinal axis of the conduit and the central axis of the inlet intersect to define an angle that is between about 20 degrees and about 210 degrees.

Curved conduit ion sampling device and method

The present invention provides a new and improved method for reducing the complexity of a proteomic sample, and preferably also for allowing identification of proteins in the sample. In one aspect, the invention provides a highly efficient method for identifying proteins in a proteomic sample by characterizing a single N-terminal peptide per protein. In another aspect, the invention provides a method for identifying proteins in a proteomic sample by characterizing a single C-terminal peptide per protein. In another aspect, the present invention provides a method for quantitative determination of differential protein expression and/or modification in different samples. In another aspect, the invention relates to kits useful for conveniently performing a method in accordance with the invention.

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Hayward, CA, United States of America

Steven Michael Fischer