Thermo Finnigan LLC

Wisconsin Alumni Research Foundation

Harvard College

Graeme C McAlister

Joshua J Coon

Michael W Senko

Steven P Gygi

Wilhelm Haas

Shannon Eliuk Dixon

Romain M Huguet

Marc W Kirschner

Michael S Westphall

Jesse D Canterbury

Christopher Laurence Etienne

Chad R Weisbrod

Martin Helmut Wuhr

Derek James Bailey

Douglas H Phanstiel

Leonid Peshkin

Ramin Rad

Michael P Goodwin

A mass spectrometer system, comprises: an ion source; a first and a second multipole apparatus; one or more ion gates or ion lenses between the first and second multipole apparatuses; at least one power supply configured to provide voltages to electrodes of the ion source, the mass analyzer, the first and second multipole apparatuses and the one or more ion gates or ion lenses; and a computer or electronic controller electrically coupled to the at least one power supply, wherein the computer or electronic controller comprises computer-readable instructions that are operable to cause the at least one power supply to supply voltages to the electrodes that cause transfer of ions from the first multipole apparatus to the second multipole apparatus, wherein a duration of a time allotted for completion of the transfer of the ions is dependent upon one or more properties of the ions being transferred.

Methods for transferring ions between trapping devices of variable internal pressure

Isobaric mass spectrometry tags (e.g., TMT) are susceptible to ratio compression, which arises from the co-isolation and co-fragmentation of interfering species that also contribute to the final reporter ion ratios. Additional stages of ion activation/transformation (e.g., MSn and PTR) have been shown to decrease ratio compression. Embodiments of the present invention include a mass spectrometry cleavable moiety on the isobaric mass tags. The cleavable moiety allows for a predictable mass loss, and results in an improved tag reporter ion purity.

Methods of mass spectrometry quantitation using cleavable isobaric tags and neutral loss fragmentation

A method includes obtaining a first mass spectrum; selecting a first peak of the first mass spectrum; isolating precursor ions in an isolation window including the first peak; fragmenting and analyzing the isolated ions to obtain a second mass spectrum; performing a real-time search of the second mass spectrum for both the target precursor and near isobaric precursors ions that are co-isolated with the target precursor in an isolation window; adding the precursor ions that produced an identification during the real-time search to the exclusion list; selecting a second peak present in the first mass spectrum and not on the exclusion list; and fragmenting and analyzing ions of the second peak to obtain a third mass spectrum.

Feeding real time search results of chimeric MS2 spectra into the dynamic exclusion list

A method includes obtaining a first mass spectrum; selecting a first peak of the first mass spectrum; fragmenting and analyzing ions of the first peak to obtain a second mass spectrum; performing a real-time spectral search for compounds corresponding to peaks in the second mass spectrum; identifying fragments for the compounds identified based on the real-time spectral search; adding mass-to-charge ratios for the fragments to an exclusion list; selecting a second peak present in the first mass spectrum and not on the exclusion list; and fragmenting and analyzing ions of the second peak to obtain a third mass spectrum.

Using real time search results to dynamically exclude product ions that may be present in the master scan

A mass spectrometry method comprises: generating ions; directing the ions through an ion optical component within a first chamber having a first vacuum pressure, the ion optical component maintained at a first electrical potential; transferring the ions through an ion guide within a second chamber having a second vacuum pressure less than the first vacuum pressure, the ion guide maintained at a second electrical potential, wherein a difference between the first and second potentials imparts kinetic energy that causes collision-induced ion fragmentation within the second chamber that removes adduct species; and transferring the ions into another ion guide within a third chamber having a third vacuum pressure less than the second vacuum pressure, the other ion guide maintained at a third electrical potential, wherein a difference between the third and second potentials reduces a portion of the imparted kinetic energy of the ions passing into the third chamber.

Methods and system for optimizing ion transmission through a mass spectrometer

A method for parallel accumulation and serial fragmentation of ions, wherein ions are injected into a device capable of serial ejection using a pseudopotential barrier created by an RF voltage. In all instances, the ions may be filtered prior to accumulation in the device capable of serial ejection. In some cases this filtering may take the form of discrete isolation windows using isolation waveforms with multiple notches. In some cases these waveforms may be applied to a quadrupole mass filter. Following accumulation of the precursor ions, the initial population may be serially ejected using a pseudopotential barrier created by an RF voltage. Following serial ejection, the individual precursor ion populations are analyzed. In some cases, this analysis might involve additional rounds of ion isolation and manipulation (e.g., MSn, CID, ETD, etc.).

Methods and apparatus for improved tandem mass spectrometry duty cycle

A method and corresponding apparatus are disclosed for analysis of a peptide-containing sample. The sample is prepared by adding isotopically-labeled peptides corresponding to endogenous peptides of interest, and the prepared sample is analyzed by liquid chromatography-mass spectrometry (LCMS). Detection in a high-resolution, accurate mass (HRAM) MS1 spectrum of a precursor ion matching an isotopically-labeled peptide triggers acquisition of an MS/MS spectrum (preferably acquired in an ion trap or other fast mass analyzer) to determine if a product ion is present matching a characteristic product ion (e.g., the yion) of the isotopically-labeled peptide. If the characteristic product ion is present, then a HRAM MS/MS spectrum is acquired for detection and quantitation of the corresponding endogenous peptide.

Analyzing a complex sample by MS/MS using isotopically-labeled standards

Embodiments are directed to a method, a computer readable medium encoded with instructions that, when executed, perform a method, and a system for performing mass spectrometry analysis. Molecules of different samples may be labeled with a chemical tag, allowing a multiplexed analysis of multiple samples. The labeled molecules may be fragmented, each fragmented molecule creating at least two separate ions. The relative abundance of each of the heavier ions, which may comprise the original molecule from the sample, may be measured. A relative abundance of the labeled molecules in each of the samples may be determined from the measured relative abundances of the heavier ions.

Accurate and interference-free multiplexed quantitative proteomics using mass spectrometry

An ion source filter for use in the source region is disclosed. The ion source filter includes four rod electrodes having circular cross sections. The rod electrodes of the ion source filter are sized and positioned such that the ratio r/rof the rod radius to the inscribed circle radius is considerably reduced relative to conventional RF/DC mass filters. The reduced r/rgeometry has been observed to lessen the diminishment of resolution with increasing pressure relative to prior art devices.

Ion source filter

Described herein are methods and systems related to the use of the pre-existing ion injection pathway of a mass spectrometer to perform beam-type collision-activated dissociation, as well as other dissociation methods. The methods can be practiced using a wide range of mass spectrometer configurations and allows MSexperiments to be performed on very basic mass spectrometers, even those without secondary mass analyzers and/or collision cells. Following injection and selection of a particular ion type or population, that population can be fragmented via beam-type collision-activated dissociation (CAD), as well as other dissociation methods, using the pre-existing ion injection pathway or inlet of a mass spectrometer. For CAD applications, this is achieved by transmitting the ions back along the ion injection pathway with a high degree of kinetic energy. As the ions pass into the higher pressure regions located in or near the atmospheric pressure inlet, the ions are fragmented and then trapped. Following fragmentation and trapping, the ions can either be re-injected into the primary ion selection device or sent on to a secondary mass analyzer.

Method to perform beam-type collision-activated dissociation in the pre-existing ion injection pathway of a mass spectrometer

A method of performing a mass spectrometry analysis includes labeling each of a plurality of samples with a corresponding chemical tag; forming a first plurality of ions from molecules in the samples; selecting a subset of the first plurality of ions, the subset being selected by isolating ions of the first plurality of ions in a plurality of ranges of mass-to-charge; forming a second plurality of ions by fragmenting ions in the subset; and measuring information indicative of a quantity of each of the plurality of chemical tags present in each of the plurality of samples.

Mass spectrometry for multiplexed quantitation using multiple frequency notches

Described herein are mass spectrometry systems and methods which utilize a dynamic a new data acquisition/instrument control methodology. These systems and methods employ novel artificial intelligence algorithms to greatly increase quantitative and/or identification accuracy during data acquisition. In an embodiment, the algorithms can adapt the instrument methods and systems during data acquisition to direct data acquisition resources to increase quantitative or identification accuracy of target analytes, such as proteins, peptides, and peptide fragments.

Precursor selection using an artificial intelligence algorithm increases proteomic sample coverage and reproducibility

Described herein are methods and systems related to the use of the pre-existing ion injection pathway of a mass spectrometer to perform beam-type collision-activated dissociation, as well as other dissociation methods. Following injection and selection of a particular ion type or population, that population can be fragmented using the pre-existing ion injection pathway or inlet of a mass spectrometer. This is achieved by transmitting the ions back along the ion injection pathway. As the ions pass into the higher pressure regions located in or near the atmospheric pressure inlet, the ions are fragmented and then trapped. Following fragmentation and trapping, the ions can either be re-injected into the primary ion selection device or sent on to a secondary mass analyzer.

Growing community of inventors

San Jose, CA, United States of America

Graeme C McAlister