Dh Technologies Development Pte. Ltd.

University of Geneva

Lyle Lorrence Burton

Stephen Alexander Tate

David Michael Cox

Eva Duchoslav

Ronald Francis Bonner

Gordana Ivosev

John Lawrence Campbell

Nic G Bloomfield

Yves Le Blanc

Gérard Hopfgartner

Ron Bonner

Adam San-Ho Lau

Ron F Bonner

At least one molecule is ionized and a mass spectrometer mass analyzes an m/z range, producing an m/z mass spectrum. A range of N sequential charge states is received. A copy of the m/z mass spectrum is created for each of the N charge states, producing N m/z spectra. Each spectrum of the N spectra is converted to a neutral mass mass spectrum using a different charge state of the N charge states, producing N neutral mass mass spectra. The N neutral mass mass spectra are aligned by neutral mass. When two or more spectra of the N neutral mass mass spectra corresponding to two or more different and sequential charge states include a neutral mass peak above a predetermined intensity threshold at a neutral mass value within a predetermined neutral mass tolerance, the neutral mass value is identified as a neutral mass of the at least one molecule.

Effective use of multiple charge states

First, an MS scan of a mass range of a control sample that does not include a metabolite is performed () producing background peak m/z and intensity values for background precursor ions (). Background peaks are selected for an exclusion list and in the exclusion list an m/z value and an intensity value are included for each background peak (). Next, an MS scan of the mass range of an experimental sample that does include a metabolite is performed () producing peak m/z and intensity values for precursor ions (). Peaks are selected for a peak list and in the peak list an m/z value and an intensity value are included for each peak (). Finally, each peak of the peak list that has both an m/z value and an intensity value that correspond to an m/z value and an intensity value of a background peak of the exclusion list is excluded from the peak list ().

Threshold-based IDA exclusion list

A separation device is instructed to separate a compound from a sample over a time period. A mass spectrometer is instructed to measure a plurality of intensities of at least one ion of the separated compound over the time period, producing a chromatogram. At least one peak of the at least one ion is identified from the chromatogram using a peak-finding algorithm. Two or more different peak integration areas are calculated for the at least one peak by applying the peak-finding algorithm with two or more different values for at least one peak-finding parameter. Two or more plots of the at least one peak that each shows graphically a different peak integration area are displayed on a display device at the same time. In response, data is received from a user selection device that indicates user selection of one of the two or more plots.

Peak integration correction without parameter adjustment

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

Systems and methods are disclosed for determining if the dynamic range of quantitation in mass spectrometry can be extended. A DIA method is performed on a sample for a compound of interest at each acquisition time of a plurality of acquisition times. A plurality of product ion spectra are produced for each window of two or more precursor ion mass selection windows. A known product ion of the compound of interest is selected. Two or more XICs are calculated from two or more different precursor ion windows for the known product ion. A ratio of one XIC of the two or more XICs to at least one other XIC of the two or more XICs is calculated. If the ratio is above a threshold, the XIC is used in the quantitation. If not, two or more XICs can be combined into a single XIC that is used for the quantitation.

Swath&#xae; to extend dynamic range

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

At least one product ion mass spectrum produced by a tandem mass spectrometer is received. A chemical structure of a compound that corresponds to the at least one product ion mass spectrum is received. One or more elemental compositions are assigned to at least one peak in the at least one product ion spectrum based on the chemical structure using the processor. At least one elemental composition of the one or more assigned elemental compositions is selected for the at least one peak using the processor. The mass of the at least one peak is converted to the mass of the selected at least one elemental composition using the processor, producing a product ion mass spectrum with higher mass accuracy.

Method for converting mass spectral libraries into accurate mass spectral libraries

One or more known compounds of a sample are ionized. At least one precursor ion corresponding to a compound of the one or more known compounds is selected and fragmented, producing a product ion mass spectrum for the precursor ion. An m/z tolerance probability function that varies from 1 to 0 with increasing values of an m/z difference between two mass peaks and that includes one or more values between 1 and 0 is received. A library product ion mass spectrum for the at least one compound is retrieved from a memory. An m/z difference between at least one experimental product ion mass peak in the product ion mass spectrum and at least one library product ion mass peak in the library product ion mass spectrum is calculated. An m/z tolerance probability that determines if the two peaks are corresponding peaks is calculated from the m/z difference using the probability function.

Probability-based library search algorithm (ProLS)

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

A scan of a separating sample is received by a mass spectrometer at each interval of a plurality of intervals. The spectrometer performs at each interval one or more mass spectrometry scans. The scans have one or more sequential mass window widths in order to span an entire mass range at each interval and produce a collection of spectra for the entire mass range for the plurality of intervals. One or more peaks at one or more different intervals in the collection of spectra are identified for a fragment ion. A mass spectrum of the entire mass range is retrieved for each interval of each peak. Values for one or more ion characteristics of a mass-to-charge ratio peak in the mass spectrum corresponding to each peak are compared to one or more known values for the fragment ion. Each peak is scored based on the comparison.

Use of windowed mass spectrometry data for retention time determination or confirmation

Systems and methods for analyzing compounds in a sample. In one embodiment, the present technology is directed towards a method of analyzing a sample, comprising: emitting ions from the sample; selecting the emitted ions for a designated ion; fragmenting the designated ions; scanning for a plurality of designated ion fragments; determining a designated fragment chromatographic trace for each designated ion fragment; and generating a combined chromatographic trace corresponding to a non-linear combination of a plurality of designated fragment chromatographic traces.

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Woodbridge, Canada

Lyle Lorrence Burton