Thermo Finnigan LLC

University of Virginia Patent Foundation

John E P Syka

Jae C Schwartz

Scott T Quarmby

Chad R Weisbrod

Christopher Mullen

James L Stephenson, Jr

Michael W Senko

Jesse D Canterbury

August A Specht

Joshua J Coon

Donald F Hunt

Stevan Roy Horning

Robert Malek

Ping F Yip

Andreas Wieghaus

Philip D Compton

Andreas F R Huhmer

A method comprises: (1) making an extract of a biological sample; (2) repeatedly: (a) choosing a respective one of a plurality of pre-determined protein or polypeptide analyte compounds; (b) introducing a portion of the extract into an electrospray ionization source, thereby generating positive ions comprising a plurality of ion species; (c) isolating a plurality of subsets of the ion species comprising respective mass-to-charge (m/z) ratio ranges, each range including an m/z ratio corresponding to a respective protonation state of the chosen compound; (d) reacting the isolated plurality of subsets of first-generation ion species with proton transfer reaction reagent anions for a pre-determined time duration; (e) generating a mass spectrum of the product ion species; and (g) identifying either the presence or absence of the compound based on the mass spectrum; and (3) identifying the presence or absence of the microorganism within the sample based on analytes present.

Methods for mass spectrometry of mixtures of proteins or polypeptides using proton transfer reaction

A method of operating an electrostatic trapping mass analyzer, comprising: introducing a sample of ions into a trapping region of the mass analyzer, wherein a trapping field within the trapping region is such that the ions exhibit radial motion with respect to a central longitudinal axis of the trapping region while undergoing harmonic motion in a dimension defined by the central longitudinal axis, the frequency of harmonic motion of a particular ion being a function of its mass-to-charge ratio; superimposing a modulation field onto the trapping field within the trapping region, the modulation field acting to either increase or reduce the harmonic motion energies of the ions by an amount varying according to the frequency of harmonic motion; and acquiring a mass spectrum of the ions in the trapping region by measuring a signal representative of an image current induced by the harmonic motion of the ions.

Methods for operating electrostatic trap mass analyzers

Applications of ion-ion reaction chemistry are disclosed in which proton transfer reactions (PTR) and real-time data analysis methods are used to (1) simplify complex mixture analysis of samples introduced into a mass spectrometer, and (2) improve resolution and sensitivity for the analysis of large proteins in excess of 50 kDa by removing charge and reducing the collisional cross section.

Methods for top-down multiplexed mass spectral analysis of mixtures of proteins or polypeptides

A method is described that produces product ions for mass analysis, the method comprising the steps of: introducing precursor ions into an RF electric field ion containment device, introducing reagent ions into the RF electric field ion containment device and performing an ion-ion interaction in the RF electric field ion containment device by co-trapping the precursor ions with the reagent ions. Precursor ions and product ions may be retained and/or isolated in the RF electric field ion containment device. The steps above may be repeated until a predetermined amount of reaction completeness is attained. Mass analysis of at least some of the ions in the RF electric field ion containment device may be performed where the ions are mass analyzed either directly from the RF electric field ion containment device.

Methods of performing ion-ion reactions in mass spectrometry

Applications of ion-ion reaction chemistry are disclosed in which proton transfer reactions (PTR) are used to (1) simplify complex mixture analysis of samples introduced into a mass spectrometer, and (2) improve resolution and sensitivity for the analysis of large proteins in excess of 50 kDa by removing charge and reducing the collisional cross section.

Methods for mass spectrometry of mixtures of protein or polypeptides using proton transfer reaction

A method of aligning a light beam within a mass spectrometer includes providing precursor ions along a longitudinal axis of the mass spectrometer at two or more precursor ion locations, the precursor ion locations being spatially separated along the longitudinal axis of the mass spectrometer, the precursor ions forming in-vacuum targets. The method then includes directing a light beam from a light source in a direction along the longitudinal axis of the mass spectrometer, the light beam photo-dissociating the precursor ions, and monitoring a mass spectrometer ion signal from each of the two or more precursor ion locations while adjusting the direction of the light beam, thereby aligning the light beam within the mass spectrometer.

Photo-dissociation beam alignment method

The invention provides improvements in reagents for use in electron transfer dissociation ionization techniques for use in mass spectrometry, particularly for sequencing peptides and proteins using mass spectrometric techniques involving electrospray ionization and MS/MS characterization of fragment ions. The novel reagents used in the inventive methods allow for more effective determination of protein sequences, especially of long peptides or post-translationally modified protein fragments. Use of the polycyclic aromatic hydrocarbons azulene, homoazulene, and acenaphthylene, and homodimers and heterodimers thereof, are described.

Reagents for electron transfer dissociation in mass spectrometry analysis

An ion source apparatus for a mass spectrometer comprises a refractory metal filament operable to provide a flow of electrons by thermionic emission; an electrical current source electrically coupled to the filament for heating the filament; a vacuum chamber enclosing the filament; an ionization volume within the vacuum chamber capable of receiving the flow of electrons; a source of an oxygen-providing gas or gases; a restrictive fluidic coupling to the source of oxygen-providing gas or gases; and a gas conduit fluidically coupled to the restrictive fluidic coupling, the restrictive fluidic coupling and conduit operable to provide a flow of the oxygen-providing gas or gases into the vacuum chamber so as to maintain a partial pressure of said gas or gases within the vacuum chamber that is sufficiently high so as to inhibit the otherwise formation of a carbonaceous growth on the filament in the presence of a gaseous carbon-containing material.

Apparatus and method for inhibiting ionization source filament failure

A dual ion trap mass analyzer includes adjacently positioned first and second two-dimensional ion traps respectively maintained at relatively high and low pressures. Functions favoring high pressure (cooling and fragmentation) may be performed in the first trap, and functions favoring low pressure (isolation and analytical scanning) may be performed in the second trap. Ions may be transferred between the first and second trap through a plate lens having a small aperture that presents a pumping restriction and allows different pressures to be maintained in the two traps. The differential-pressure environment of the dual ion trap mass analyzer facilitates the use of high-resolution analytical scan modes without sacrificing ion capture and fragmentation efficiencies.

Differential-pressure dual ion trap mass analyzer and methods of use thereof

Methods and apparatus for data-dependent mass spectrometric MS/MS or MSanalysis are disclosed. The methods may include determination of the charge state of an ion species of interest, followed by automated selection of a dissociation type (e.g., CAD, ETD, or ETD followed by a non-dissociative charge reduction or collisional activation) based at least partially on the determined charge state. The ion species of interest is then dissociated in accordance with the selected dissociation type, and an MS/MS or MSspectrum of the resultant product ions may be acquired.

Data-dependent selection of dissociation type in a mass spectrometer

Ions in a predefined narrow mass to charge ratio range are isolated in an ion trap by adjusting the field and using ejection frequency waveform(s). The ejection waveforms have frequency components in a first and a second dimension, and, are applied across electrodes aligned along a first and a second dimension. Thus the mass-to-charge ratio isolation window is controlled and has an improved resolution without increasing the number of frequency components.

Isolating ions in quadrupole ion traps for mass spectrometry

Ions in a predefined narrow mass to charge ratio range are isolated in an ion trap by adjusting the field and using ejection frequency waveform(s). Thus the mass-to-charge ratio isolation window is controlled and has an improved resolution without increasing the number of frequency components.

Methods and apparatus for trapping or guiding ions. Ions are introduced into an ion trap or ion guide. The ion trap or ion guide includes a first set of electrodes and a second set of electrodes. The first set of electrodes defines a first portion of an ion channel to trap or guide the introduced ions. Periodic voltages are applied to electrodes in the first set of electrodes to generate a first oscillating electric potential that radially confines the ions in the ion channel, and periodic voltages are applied to electrodes in the second set of electrodes to generate a second oscillating electric potential that axially confines the ions in the ion channel.

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Charlottesville, VA, United States of America

John E P Syka