Dh Technologies Development Pte. Ltd.

Applera Corporation

Mds Inc.

University of Geneva

Mdc Inc.

Applied Biosystems, LLC

Mds Analytical Technologies, a Business Unit of Mds Inc.

Yves Le Blanc

John Lawrence Campbell

David Michael Cox

Ronald Francis Bonner

Takashi Baba

Bruce A Thomson

Mircea Guna

Brendon Seale

Stephen Alexander Tate

Alexandre V Loboda

James Walter Hager

Bradley B Schneider

Bruce Andrew Collings

Nic G Bloomfield

Lyle Lorrence Burton

Igor V Chernushevich

Paul Baker

Eva Duchoslav

Yang Kang

Ron Bonner

Gérard Hopfgartner

Michael Jarvis

Leigh Bedford

Anita Orsolya Ducati

Ron F Bonner

Bruce Colllngs

Before a sample is introduced into a liquid sample delivery device, an ion source device receives aqueous mobile phase solution from the liquid sample delivery device and ionizes compounds of the aqueous mobile phase solution, producing an ion beam. A tandem mass spectrometer performs a first neutral loss scan of the ion beam with a first neutral loss value set to a molecular weight of a first known solvent, producing a first intensity, and performs a second neutral loss scan of the ion beam with a second neutral loss value set to a molecular weight of a second known solvent, producing a second intensity. A ratio of the first intensity to the second intensity is calculated. It is determined if the aqueous mobile phase solution is properly being delivered by the liquid sample delivery device based on the ratio.

Method for mass spectrometry

Before each sample of a series of batch samples is introduced into a liquid sample delivery device, an ion source device receives aqueous mobile phase solution from the liquid sample delivery device and ionizes its compounds, producing an ion beam. A tandem mass spectrometer performs a neutral loss or precursor ion scan on the ion beam to measure intensities of two or more precursor ions corresponding to a known aqueous mobile phase solution compound. Intensity measurements for each of the two or more different precursor ions are compared to previously stored intensities to determine the threshold times at which these measurements indicate orifice contamination. A threshold time is then predicted for a known compound of interest of the batch samples based on the m/z value of the known compound of interest and the m/z value and the threshold time of each of the two or more different precursor ions.

Apparatus is provided and an IDA method is modified to detect and separately dissociate alkali-metal adducts of a compound. An ion source device ionizes one or more compounds of a sample, producing an ion beam. A mass filter selects a mass range of precursor ions from the ion beam, a mass analyzer measures intensities and m/z values of the precursor ions, and one or more of the precursor ions are selected for a peak list. For each pair of precursor ions of the peak list, if an m/z difference between the pair corresponds to an m/z difference between an alkali metal ion and another alkali metal ion or a proton, an ExD device is used to dissociate one precursor ion or both precursor ions of the pair using the processor. A CID device is used to dissociate all other precursor ions of the peak list.

Method of performing IDA with CID-ECD

In some embodiments, a method for optimizing performance of a mass spectrometer comprises using an ion source to generate ions, collisionally cooling the ions within an ion guide, directing said ions from the ion guide through at least one ion lens to a downstream mass analyzer, ramping a DC voltage applied to the ion lens, performing a mass analysis of the ions within the mass analyzer while the DC voltage applied to the ion lens is ramped, estimating performance of the mass spectrometer by measuring one or more characteristics of at least one of an ion signal and the voltage ramp, and adjusting a DC voltage applied to said at least one lens element based on said measured one or more characteristics of at least one of the ion signal and the voltage ramp so as to enhance performance of the mass spectrometer.

Automated ion optics charging compensation

In DM-SWATH a plurality of CoVs and a precursor ion mass range are received. A processor performs an iterative series of steps for each CoV of the plurality of CoVs. For each CoV of the plurality of CoVs, the CoV is applied to the DMS device to select a group of precursor ions. A mass filter is instructed to select precursor ions of the group that are within the precursor ion mass range, producing a subgroup of precursor ions. A fragmentation device is instructed to fragment the subgroup of precursor ions, producing a group of product ions. A mass analyzer is instructed to measure the intensity and m/z of the group of product ions, producing a product ion spectrum for each CoV of the plurality of CoVs. DM-SWATH is further used to validate if a known compound is in a sample.

DM-SWATH acquisition to improve MSMS confidence

An interference in a first MRM transition measurement for a compound of interest is determined by using a second MRM transition that includes an isotope of the precursor ion in the first MRM transition. Both transitions include the same product ion. A first intensity is measured for the first MRM transition and a second intensity is measured for the second MRM transition. A ratio of the first intensity to the second intensity is calculated. A theoretical ratio of the quantity of first precursor ion to the second precursor ion is calculated according to their isotopic relationship. A difference between the ratio and the theoretical ratio is calculated and compared to a threshold value. If the difference is less than the threshold value, the first intensity of the first MRM transition is identified as including an interference for the compound of interest.

Assessing MRM peak purity with isotope selective MSMS

A system and method is described for characterizing glycopeptides which includes a first quadrupole mass filter, a multipole rod set of an ion guide, a lens electrode, an ExD device and a mass analyzer. The multipole rod set is adapted to receive a radial radio frequency (RF) trapping voltage and a radial dipole direct current (DC) voltage The lens electrode is adapted to receive an axial trapping alternating current (AC) voltage and a DC voltage. The ExD device performs electron capture dissociation or electron transfer dissociation, the ExD device being positioned so that an entrance of the ExD device is disposed on the other side of the lens electrode opposite the multipole rod set. The mass analyzer is positioned at an exit of the ExD device for receiving ions from the ExD device.

Apparatus and method for glycopeptide analysis

A method and apparatus for analyzing samples using mass spectrometry are disclosed. The apparatus includes a reaction device configured to dissociate sample ions into fragments by reacting the sample ions with a charged species (e.g., electrons) such as through ECD, EID, or EIEIO. The kinetic energy of the charged species is such that the fragments may be detected and produce spectra that allow for the determination of isomeric species in the sample and the location of double bonds and/or the orientation of those double bonds within the sample molecules. The fragments may include radical fragments and non-radical fragments. Spectra resulting from analysis of the fragments may allow for the determination of the oxygen-radical fragments resulting from the dissociation of the sample molecules as confirmation of the presence of those radical fragments.

Method and apparatus for analyzing samples using mass spectrometry

Methods and systems are provided herein for varying the CoV about a nominal CoV-apex while monitoring the ion of interest corresponding to the nominal CoV-apex as it is transmitted by a DMS. In various aspects, the CoV can be swept or stepped across a series of values during the injection of ions into the DMS such that a composite spectra of the ion of interest transmitted by the DMS (or its product ions following one or more stages of fragmentation) can be generated so as to include the transmission of the particular ion at a CoV with optimum sensitivity (i.e., if distinct from the CoV-apex), thereby improving the robustness, accuracy, and/or selectivity during experimental conditions relative to known DMS techniques, which typically used a fixed CoV value for each ion of interest.

Differential mobility spectrometry method

Systems and methods are provided for providing a DMS precursor ion survey scan. An ion source configured to receive a sample is instructed to ionize the sample using a processor. A DMS device configured to receive ions from the ion source is instructed to separate precursor ions received from the ion source and transmit precursor ions using two or more CoVs using the processor. A mass analyzer configured to receive transmitted precursor ions from the DMS device is instructed to measure the m/z intensities of the transmitted precursor ions across an m/z range at each CoV of the two or more CoVs using the processor. The measured m/z intensities of the transmitted precursor ions received from the mass analyzer are stored as a function of m/z value and CoV using the processor. This produces a stored two-dimensional mapping of m/z intensities of the precursor ions of the sample.

Dynamic orthogonal analysis method

Methods and systems are provided herein for on-line preparation of a sample for mass spectrometry. In accordance with various aspects of applicant's teachings, the methods and systems can provide for the reduction of a polypeptide, for example, on a liquid chromatography column and can reduce or eliminate the need to incubate the reducing agent with the polypeptide and/or expose the reduced polypeptide to an alkylating agent.

Methods for protein and peptide reduction

Systems and methods are provided for enabling or disabling a DMS device during an IDA method. Each cycle of the method includes a survey scan step, producing a precursor ion mass spectrum, and an MS/MS scan step. During the MS/MS scan step, one or more user-defined MS/MS scans are performed that correspond to compounds of interest found in the precursor ion mass spectrum. With each user-defined MS/MS scan, a DMS enable parameter that determines if the DMS device is enabled or disabled and one or more DMS parameters necessary to enable the DMS device for the corresponding compound of interest are received. During the MS/MS scan step, for each user-defined MS/MS scan, the DMS device is enabled or disabled according to the DMS enable parameter and one or more parameters of the DMS device are set according to the one or more DMS parameters.

Method to improve MS/MS spectral quality from MRM triggered IDA

In a first location of a mass spectrometer, a plurality of ionized molecules of an ion source are selected that have mass-to-charge ratios within a mass-to-charge ratio window width. The plurality of selected ionized molecules are transmitted from a first to a second location. Reagent ions are transmitted to the second location to reduce a charge state of one or more of the plurality of selected ionized molecules. A mass analyzer is used to analyze the plurality of reduced ionized molecules and produce a mass spectrum. A compound is identified from a peak of the spectrum that has a mass-to-charge ratio less than or equal to the highest mass-to-charge ratio in the window width if the noise is multiply charged and greater than the highest mass-to-charge ratio in the window width if the noise is singly charged.

Windowing combined with ion-ion reactions for chemical noise elimination

A method is provided for mass spectrometry. The method includes generating precursor ions from a sample; transmitting the precursor ions into a collision cell; generating product ions in the collision cell; detecting the precursor and product ions; applying modulation to one or more of the precursor ion intensity and the product ion intensity; and identifying precursor ion and product ion relationships by analyzing intensity profiles defined by the modulation.

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Newmarket, Canada

Yves Le Blanc