Dh Technologies Development Pte. Ltd.

Mds Inc.

Applera Corporation

Applied Biosystems, LLC

Life Technologies Corporation

Mds Analytical Technologies

Nic G Bloomfield

Stephen Alexander Tate

Alexandre V Loboda

Takashi Baba

James Walter Hager

John Lawrence Campbell

Yves Le Blanc

Gordana Ivosev

Yves LeBlanc

Frank Londry

David Michael Cox

Chris M Lock

Lyle Lorrence Burton

Igor V Chernushevich

Pavel Ryumin

Eva Duchoslav

Christopher Mark Lock

Stephen A Tate

Michael Murphy

Douglas Arnold Simmons

Adam San-Ho Lau

Igor Chernushevich

A precursor ion transmission window is moved in overlapping steps across a precursor ion mass range. The precursor ions transmitted at each overlapping step by the mass filter are fragmented or transmitted. Intensities or counts are detected for each of the one or more resulting product ions or precursor ions for each overlapping window that form mass spectrum data for each overlapping window. Each unique product ion detected is encoded in real-time during data acquisition. This encoding includes sums of counts or intensities of each unique ion detected the overlapping windows and positions of the windows associated with each sum. The encoding for each unique ion is stored in a memory device rather than the mass spectral data. A deblurring algorithm or numerical method is used to determine a precursor ion of each unique ion from the encoded data.

Method for real time encoding of scanning swath data and probabilistic framework for precursor inference

Method for real time encoding of scanning SWATH data and probabilistic framework for precursor inference

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

Dynamic skimmer pulsing and dynamic equilibration times are used for MS and MS/MS scans. A target percentage transmission of the ion beam is calculated based on a previous percentage transmission and a previous TIC or a previous highest intensity of a previous cycle time. An equilibration time is calculated based on the current percentage transmission and the target percentage transmission. A skimmer of a tandem mass spectrometer is controlled to attenuate the ion beam to the target percentage transmission to prevent saturation of a detector of the tandem mass spectrometer and to increase the dynamic range of the tandem mass spectrometer. The tandem mass spectrometer is controlled to perform an MS scan or an MS/MS scan after the calculated equilibration time to reduce the cycle time.

Dynamic equilibration time calculation to improve MS/MS dynamic range

Intensity measurements made by electron multiplier and image-charge detectors are proportional to charge state. These intensities are used to separate detected ions into different data sets and create mass spectra from the different data sets. Ion measurements are separated by charge state using (i) a single electron multiplier detector, (ii) a single image-charge detector, or (iii) multiple electron multiplier ADC detectors. Using (i), the intensity of a peak calculated from each measured pulse is compared to predetermined intensity ranges and each peak is stored in a corresponding data set. Using (ii), each measured transient time-domain signal is converted to frequency-domain peaks, the intensity of each frequency-domain peak is compared to predetermined intensity ranges, and each peak is stored in a corresponding data set. Using (iii), each detector is adapted to measure a predetermined intensity range and store calculated peaks from the measured pulses in corresponding data sets.

Acquisition strategy for top-down analysis with reduced background and peak overlapping

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

Two-channel electrical and photo-electrical TOF ion detection systems are provided. These systems maintain the resolution and dynamic range advantages of four-channel systems but at a lower cost. Electrodes or light pipes are configured to direct electrons or photons produced by ion impacts into two separate channels. The first channel receives electrons or photons resulting from the inner or central part of the rectangular pattern of each ion impact. The second channel receives electrons or photons resulting from the two outer ends of the rectangular pattern of each ion impact. In a two-channel digitizer, the first channel and the second channel are independently calibrated to align the first digital value and the second digital value in time and account for the convex shape of the ion impacts of each ion packet and/or the curvature of a microchannel plate.

Two-and-a-half channel detection system for time-of-flight (TOF) mass spectrometer

A system is disclosed for identifying a precursor ion of a product ion in a scanning DIA experiment. A precursor ion mass selection window is scanned across a precursor ion mass range of interest, producing a series of overlapping windows across the precursor ion mass range. Each overlapping window is fragmented and mass analyzed, producing a plurality of product ion spectra for the mass range. A product ion is selected from the spectra. Intensities for the selected product ion are retrieved for at least one scan across the mass range producing a trace of intensities versus precursor ion m/z. A matrix multiplication equation is created that describes how one or more precursor ions correspond to the trace for the selected product ion. The matrix multiplication equation is solved for one or more precursor ions corresponding to the selected product ion using a numerical method.

Systems and methods for identifying precursor and product ion pairs in scanning SWATH data

A sample is ionized using an ion source and the ion beam is received using a tandem mass spectrometer. An m/z range is divided into two or more precursor ion isolation windows. Two or more values for a fragmentation parameter are selected. A first value of the two or more values for the fragmentation parameter has a level that fragments a minimal amount of ions of the ion beam. The one or more additional values have increasingly aggressive levels that produce increasingly more fragmentation of the ions of the ion beam. For each precursor ion isolation window, the tandem mass spectrometer is instructed to perform a selection and fragmentation of the ion beam using the precursor ion isolation window and the first value and is instructed to perform one or more additional selections and fragmentations of the ion beam using the precursor ion isolation window and using the one or more additional values.

Rapid scanning of wide quadrupole RF windows while toggling fragmentation energy

A transmission window that has a constant rate of precursor ion transmission for each precursor ion is stepped across a mass range, producing a series of overlapping transmission windows across the mass range. The precursor ions produced at each step are fragmented. Resulting product ions are analyzed, producing a product ion spectrum for each step of the transmission window and a plurality of product ion spectra for the mass range. For at least one product ion of the plurality of product ion spectra, a function that describes how an intensity of the at least one product ion from the plurality of product ion spectra varies with precursor ion mass as the transmission window is stepped across the mass range is calculated. A precursor ion of the at least one product ion is identified from the function. An elution profile can also be determined from the function.

Systems and methods for identifying precursor ions from product ions using arbitrary transmission windowing

The present teachings are directed to methods and systems for the selection of ions for subsequent ion fragmentation in the analysis of a sample. Rather than select the most intense subset of precursor ions for further analysis in an attempt to maximize the number of high quality, identifiable MS/MS spectra, in some settings, systems and methods for analyzing and 5 identifying precursor ions for further processing can benefit from a discovery approach in which precursor ions are selected randomly/stochastically.

Methods and systems for selecting ions for ion fragmentation

Sample molecules are ionized producing a beam of ions using an ion source. A plurality of ion extractions are performed on the beam of ions using a TOF mass spectrometer. Electrical detections from each extraction are measured using an ADC, producing a mass sub-spectrum for each extraction. An ion m/z from the plurality of mass sub-spectra is selected. For each mass sub-spectrum, the amplitude and m/z of an ion within a m/z tolerance of the ion m/z is assigned to the corresponding amplitude band of a plurality of predetermined amplitude bands, producing a plurality of amplitude and m/z values for the each amplitude band. For each amplitude band of the plurality of predetermined amplitude bands, the plurality of amplitude and m/z values are combined into a peak, resulting in a plurality of peaks corresponding to the plurality of predetermined amplitude bands.

Grouping amplitudes of TOF extractions to detect convolution due to resolution saturation

Systems and methods are provided for shaping an effective transmission window used to select precursor ions for a precursor mass range of a sequential windowed acquisition experiment. For at least one precursor mass range, an ion transfer function is selected that is a function of mass using a processor. A quadrupole mass filter that transmits ions from a sample is instructed to produce two or more transmission windows over time using the processor. The two or more transmission windows are produced to cumulatively create an effective transmission window for the at least one precursor mass range with a shape described by the ion transfer function.

Systems and methods for arbitrary quadrupole transmission windowing

Systems and methods are used to band-pass filter ions from a mass range. A full spectrum is received for a full scan of a mass range using a tandem mass spectrometer. A mass selection window of the full spectrum is selected and a set of tuning parameter values is selected. The tandem mass spectrometer is instructed to perform a scan of the mass selection window using the set of tuning parameter values. A spectrum is received for the scan from the tandem mass spectrometer. A band-pass filtered spectrum is created for the mass range that includes values from the spectrum for the mass selection window of the mass range. Systems and methods are also used to band-pass filter ions from two or more mass selection windows across the mass range and to filter out ions from a mass selection window between two band-pass mass selection windows.

Removal of ions from survey scans using variable window band-pass filtering to improve intrascan dynamic range

Systems and methods are provided for correcting uniform detector saturation. In one method, a mass analyzer analyzes N extractions of an ion beam. A nonzero amplitude from an ADC detector subsystem is counted as one ion, producing a count of one for each ion of each sub-spectrum. The ADC amplitudes and counts of the N sub-spectra are summed, producing a spectrum that includes a summed ADC amplitude and a total count for each ion of the spectrum. A probability that the total count arises from single ions hitting the detector is calculated. For each ion of the spectrum where the probability exceeds a threshold value, an amplitude response is calculated, producing amplitude responses for ions found to be single ions hitting the detector. Amplitude responses are combined, producing a combined amplitude response. The total count is dynamically corrected using the combined amplitude response and the summed ADC amplitude.

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Newmarket, Canada

Nic G Bloomfield