Thermo Finnigan LLC

Other

Intrinsic Bioprobes, Inc.

Prakash, Amol

David A Sarracino

Amol Prakash

Philip M Remes

Scott M Peterman

Sebastien F Gallien

Randall W Nelson

Dennis Sgroi

Paul Oran

Bryan E Krastins

Taha Rezai

Peter Leopold

Mary Frances Lopez

Darryl E Palmer-Toy

A Liquid Chromatography Mass Spectrometry system comprises: a chromatograph; a mass spectrometer configured to ionize separated fractions of a sample received from the chromatograph; and a programmable processor operable to repeatedly execute the steps of: (i) causing the mass spectrometer to perform a data-independent analysis of the precursor ion species using a mass analyzer of the mass spectrometer; (ii) calculating one or more degree-of-matching scores that relate to detection of an internal standard; and (iii) if each of the degree-of-matching scores meets a respective degree-of-matching condition, performing a quantitative tandem mass spectrometric analyses of both the internal standard and the analyte; the programmable processor further operable to calculate a quantity of the analyte in the sample by comparison between intensities of one or more mass spectral signals generated by the quantitative tandem mass spectrometric analyses of the analyte and the internal standard.

Methods and apparatus for targeted mass spectral proteomic analyses

A method for determining a quantity of an analyte in a liquid sample, comprises: adding a known quantity of an internal standard comprising an isotopically labeled version of the analyte to the sample; (b) providing a continuous stream of the sample having the internal standard to an inlet of a Liquid Chromatography Mass Spectrometry (LCMS) system; and repeatedly performing the steps of: performing a data-independent analysis of the precursor ion species using a mass analyzer, whereby mass spectra of a plurality of fragment-ion species are acquired; calculating one or more degree-of-matching scores that relate to either a number of ions of the internal standard that overlap between results of the data-independent analysis and tabulated mass spectral data of the internal standard; and performing quantitative tandem mass spectrometric analyses of the internal standard and the analyte if each of the degree-of-matching scores meets a respective degree-of-matching condition.

A variable data dependent acquisition/dynamic exclusion (vDDA/DE) method selects target m/z range utilizing a MS1 precursor topography map over the most recently acquired MS spectrum to identify the precursor m/z values and MS/MS acquisition parameters to improve the selection of the next data-dependent MS/MS acquisition. The topography used to define the next set of DDA scan events is defined by previous tandem MS scan events defined by precursor quadrupole isolation windows as well as all detected compounds contained within the specific tandem MS events. At least some of the parameters used for MS/MS data acquisition are dynamic so as to exhaustively sample the user specified MS mass range with MS/MS information. These parameters include the quadrupole MS isolation width and symmetry around the targeted m/z value. Using this approach, a greater proportion of the precursor m/z space is effectively and efficiently sampled per chromatographic peak width.

Variable data-dependent acquisition and dynamic exclusion method for mass spectrometry

Methods are described for monitoring the amounts of PTH variants in a biological sample by digesting the sample to produce surrogate peptides specific to the targeted PTH variants, and detecting and quantifying the surrogate peptides by selective reaction monitoring (SRM) mass spectrometry, using a set of precursor-to-product ion transitions optimized for sensitivity and selectivity. The PTH variants, or a portion thereof, may be concentrated in the sample by means of immunoaffinity capture or other suitable technique. The mass spectrometric method described herein enables the concurrent measurement of peptides representative of a plurality of targeted PTH variants in a single assay.

Assay for monitoring parathyroid hormone (PTH) variants by tandem mass spectrometry

A highly specific and sensitive technique for exploring cell physiology is disclosed. The method includes laser capture microdissection (LCM) for selecting small clusters of cells of interest from sections of tissue and matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS) for characterizing simultaneously a broad variety of biological molecules present in the small cluster of cells.

Methods and apparatus for cell analysis

Growing community of inventors

Andover, MA, United States of America

David A Sarracino