Dh Technologies Development Pte. Ltd.

David Michael Cox

Stephen Alexander Tate

John Lawrence Campbell

Yves Le Blanc

Lyle Lorrence Burton

Chang Liu

Nic G Bloomfield

Eva Duchoslav

Gordana Ivosev

Christie L Hunter

Michael Jarvis

Matthias Glueckmann

Adam San-Ho Lau

An ADE device identifies an identifiable sequence of one or more ejections from at least one sample using a different value or pattern of values for one or more ADE parameters. The identifiable one or more ejections are performed to produce one or more mass peaks that have a different feature value or pattern of feature values for one or more peak features than other mass peaks produced. Ejection times are stored. One or more detected peaks with the different feature values or pattern of feature values are identified as produced by the identifiable one or more ejections. A delay time is calculated from the time of the identifiable ejections and the time of the identified detected peaks and the peaks are aligned with samples using delay time, stored times, and order of the samples.

Identification of a first sample in a series of sequential samples

Each sample of a series of samples is ejected at an ejection time and according to a sample order. Each ejected sample of the series is ionized, producing ion beam. A list of different sets of MRM transitions is received. Each set of the list corresponds to a different sample. A group of one or more different sets is selected from the list. Initially, each set selected for the group corresponds to a different sample of one or more first samples of the series. A mass spectrometer is instructed to execute each transition of each set of the group on the ion beam until a transition of a set of the group is detected, upon which, one or more next sets are selected from the list to be monitored using the set of the detected transition and the sample order.

Simplification of method or system using scout MRM

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

Each of one or more unknown compounds are separated from a sample over a separation time period. Separated compounds are ionized, producing one or more compound precursor ions for each of the unknown compounds and a plurality of background precursor ions. A precursor ion mass spectrum is measured for the combined compound and background precursor ions at each time step of a plurality of time steps spread across the separation time period, producing a plurality of precursor ion mass spectra. One or more background precursor ions are selected from the plurality of precursor ion mass spectra that have a resolving power in a range below a threshold expected resolving power. A separation time is detected for an unknown compound when a decrease in an intensity measurement of the selected background precursor ions over a time period exceeds a threshold decrease in intensity with respect to time.

Agnostic compound elution determination

The resolution of a TOF mass analyzer is maintained despite a loss of resolution in one or more channels of a multichannel ion detection system by selecting the highest resolution channels for qualitative analysis. Ion packets that impact a multichannel detector are converted into multiplied electrons and emitted from two or more segmented electrodes that correspond to impacts in different regions across a length of the detector. The electrons received by each electrode of the two or more segmented electrodes for each ion packet are converted into digital values in a channel of a multichannel digitizer, producing digital values for at least two or more channels. Qualitative information about the ion packets is calculated using digital values of a predetermined subset of one or more channels of the at least two or more channels known to provide the highest resolution.

TOF qualitative measures using a multichannel detector

One or more known compounds of a sample are ionized using an ion source, producing an ion beam of precursor ions. A tandem mass spectrometer receives the ion beam from the ion source, selects one or more precursor ions from the ion beam using a precursor ion mass selection window, fragments precursor ions within the precursor ion mass selection window, and mass analyzes the resulting product ions, producing an unknown product ion mass spectrum. A library product ion mass spectrum for a known compound is retrieved from a memory. Each peak of the unknown spectrum is analyzed for a potential non-halogen isotopic peak using a processor, and if a potential non-halogen isotopic peak is found, it is removed if it does not have a corresponding peak in the library spectrum.

Library search tolerant to isotopes

The present teachings relate to methods, systems, and kits for analyzing a sample containing a glycopeptide of interest that can subject the glycopeptide of interest to a plurality of parallel deglycosylation reactions that differentially cleave the glycan, with the various products resulting from the deglycosylation reactions being differentially labeled (e.g., with isobaric and/or isomeric labeling reagents) to thereby produce labeled glycopeptides or labeled fragments of the glycopeptides. The products of the various deglycosylation reactions can then be mixed together and subject to LC-MS/MS using a single injection of the mixture. In accordance with various aspects, by associating the resulting mass spectral data with a particular deglycosylation reaction (e.g., based on the presence in the MS/MS data of product reporter ions associated with the particular differential labels), the methods and systems described herein can aid in the identification of the glycan structure.

Identification of glycosylation forms

Systems and methods are provided for compound identification using multiple spectra that are a function of a variable instrument parameter that affects the intensity of fragment ions. A plurality of acquired fragment ion spectra that are a function of a variable instrument parameter for at least one ion are received from a mass spectrometer using a processor. The at least one ion is identified by comparing rates of change of mass intensity, with respect to the variable instrument parameter, for acquired and known fragment ions using the processor. Specifically, one or more acquired rates of change calculated for acquired fragment ions from the plurality of acquired fragment ion spectra are compared with one or more known rates of change calculated for one or more stored fragment ions of one or more known compounds in a database of known compounds.

Compound identification using multiple spectra at different collision energies

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

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

An m/z range of an ion beam is divided into two or more precursor ion mass selection windows. A pattern of two or more different window m/z ranges to be used during two or more successive cycles for at least one precursor ion mass selection window is determined. The pattern includes an initial window m/z range and one or more successively different window m/z ranges. Each of the one or more successively different window m/z ranges includes at least a portion of the initial window m/z range. A tandem mass spectrometer is instructed to select and fragment the two or more precursor ion mass selection windows during each cycle of a plurality of cycles and to repeatedly use the pattern for each group of two or more successive cycles of the plurality of cycles for the selection and fragmentation of the at least one precursor ion mass selection window.

Deconvolution of mixed spectra

Systems and methods are provided for identifying missing product ions after demultiplexing product ion spectra produced by overlapping precursor ion transmission windows in sequential windowed acquisition tandem mass spectrometry. Overlapping sequential windowed acquisition is performed on a sample. A first precursor mass window and the corresponding first product ion spectrum are selected from a plurality of overlapping stepped precursor mass windows and their corresponding product ion spectra. A product ion spectrum is demultiplexed for each overlapped portion of the first precursor mass window producing two or more demultiplexed first product ion spectra for the first precursor mass window. The two or more demultiplexed first product ion spectra are added together producing a reconstructed summed demultiplexed first product ion spectrum. Missing product ions are identified in the summed demultiplexed first product ion spectrum by comparing the summed demultiplexed first product ion spectrum and the first product ion spectrum.

Data quality after demultiplexing of overlapped acquisition windows in tandem mass spectrometry

MRM triggered MRM, where the triggered MRM transitions make use of mobility device parameter values for the same compound, is performed. A plurality of primary MRM transitions are received and stored together with a mobility device parameter value for each transition as an MRM cycle list. Control information instructs a mobility device and a mass spectrometer to interrogate each MRM transition on the MRM cycle list within an MRM cycle of the mass spectrometer. If a product ion intensity value of an MRM transition exceeds a threshold value for a primary MRM transition, a plurality of secondary MRM transitions of the primary MRM transition with different mobility device parameter values are added to the MRM cycle list. The intensities of the measured secondary MRM transitions provide information on the optimum mobility device parameter for each compound.

Rapid LC mapping of CoV values for SelexION&#x2122; technology using MRM-triggered MRM functionality

Systems and methods are provided for interlacing ramped mass spectrometer parameter values during data acquisition. Ions from a sample are acquired within a cycle time, Ct, using a mass spectrometer. Within each Ct, two or more scans of the acquired ions are performed using two or more ramped values for a parameter of the mass spectrometer. When it is determined that scans for a desired range of ramped parameter values cannot be performed within Ct, the desired range of ramped values is divided into at least two interlaced groups of ramped values. The mass spectrometer is instructed to perform scans for each of the interlaced groups within two or more cycle times. Spectra from the scans for each of the at least two interlaced groups are combined. The ramped parameter values of the combined spectra have the desired range and the desired effective step size.

Interlacing to improve sampling of data when ramping parameters

Systems and methods are provided for scheduled MS. A compound of interest is separated from a sample over a known time period using a separation device. A plurality of sMRM experiments are performed over the known time period on the separating compound of interest using a mass spectrometer. An intensity of a product ion of the compound of interest is produced for each of the plurality of sMRM experiments. Each intensity for the product ion for each of the plurality of sMRM experiments is compared to a threshold intensity level using a processor. When an intensity for the product ion of an sMRM experiment of the plurality of sMRM experiments is equal to or exceeds the threshold intensity level, the mass spectrometer is instructed to perform one or more MSexperiments for the product ion using the processor.

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Toronto, Canada

David Michael Cox