A mass spectrometer is disclosed comprising an on trap and a fragmentation device. Ions are fragmented in the ion trap to form first generation fragment ions. The ion trap has a relatively high mass cut-off. The first generation fragment ions are then transferred to a fragmentation device which is arranged to have a substantially lower low mass cut-off. The first generation fragment ions are fragmented within the fragmentation device any may optionally be stored in an ion accumulation region prior to being passed to a mass analyser for subsequent mass analysis.

A method of mass spectrometry for analyzing a sample within a mass range of interest includes the steps: ionizing the sample to produce a plurality of precursor ions; performing an MS1 scan of the precursor ions comprising mass analyzing the precursor ions across the mass range of interest, to obtain an MS1 mass spectrum of the precursor ions; determining ion intensity values within the MS1 mass spectrum; selecting precursor mass segments within the mass range of interest, and for each precursor mass segment: fragmenting the precursor ions within that precursor mass segment; and performing an MS2 scan of the fragmented ions by: controlling an amount of fragmented ions for that precursor mass segment, based on an intensity value for that precursor mass segment derived from the MS1 spectrum; and mass analyzing the amount of fragmented ions.

Targeted quantification for mass spectrometry is described. In one aspect, a mass spectrometer can generate survey mass spectra and identify the compounds of a sample using the survey mass spectra. Compounds that elute within a same time range and do not form interfering product ions upon fragmentation can be identified, and grouped together for an MS2 scan. A series of MS2 scans can then be generated to acquire MS2 mass spectra.

Systems and methods are used to analyze a sample using variable mass selection window widths. A tandem mass spectrometer is instructed to perform at least two fragmentation scans of a sample with different mass selection window widths using a processor. The tandem mass spectrometer includes a mass analyzer that allows variable mass selection window widths. The selection of the different mass selection window widths can be based on one or more properties of sample compounds. The properties may include a sample compound molecular weight distribution that is calculated from a molecular weight distribution of expected compounds or is determined from a list of molecular weights for one or more known compounds. The tandem mass spectrometer can also be instructed to perform an analysis of the sample before instructing the tandem mass spectrometer to perform the at least two fragmentation scans of the sample.

Systems and methods are provided for analyzing a sample using overlapping measured mass selection window widths. A mass range of a sample is divided into two or more target mass selection window widths using a processor. The two or more target widths can have the same width or variable widths. A tandem mass spectrometer is instructed to perform two or more fragmentation scans across the mass range using the processor. Each fragmentation scan of the two or more fragmentation scans includes a measured mass selection window width. The two or more measured widths of the two or more fragmentation scans can have the same width or variable widths. At least two of the two or more measured mass selection window widths overlap. The overlap in measured mass selection window widths corresponds to at least one target mass selection window width.

The invention relates to methods for the detailed analysis of ion mixtures from complex mixtures of organic substances in time-of-flight mass spectrometers which are equipped with a trapped ion mobility spectrometer, a quadrupole mass selector and a fragmentation cell. The invention proposes to analyze ion signals of a first mass mobility map, fragment ion spectra and the identifications of the associated substances as to whether ion mixtures not resolved according to mass and mobility, for example from isomers or isobars, are possibly present, and to subsequently measure the ion signals of interest with method parameters which allow the ion species to be measured separately by means of high mobility resolution.

A method is described for the analysis of biological polymers, for example, intact proteins or oligonucleotides, by mass spectrometry. This method produces sample ions from a sample containing biological polymers, and ion species are selected that correspond to different charge states of a biological polymer molecule. The ion species are concurrently isolated from the sample ions to generate precursor ions in an ion trap mass spectrometer or in a quadrupole mass filter mass spectrometer. Precursor ions or product ions derived from the precursor ions may then be mass analyzed. The mass analysis step may include fragmenting the precursor ions to form product ions.

A dissociation device fragments a precursor ion, producing at least two different product ions with overlapping m/z values in the dissociation device. The dissociation device applies an AC voltage and a DC voltage creating a pseudopotential that traps ions below a threshold m/z including the at least two product ions. The dissociation device receives a charge reducing reagent that causes the trapped at least two product ions to be charge reduced until their m/z values increase above the threshold m/z set by the AC voltage. The increase in the m/z values of the at least two product ions decreases their overlap. The at least two product ions with increased m/z values are transmitted to another device for subsequent mass analysis by applying the DC voltage to the dissociation device relative to a DC voltage applied to the other device.

A method of data-independent mass spectrometric analysis of compounds of a compound class of interest comprises: determining or retrieving a distribution, over a mass-to-charge (m/z) ratio range of interest, of a number of primary ion species of members of said compound class having m/z ratios within each respective one of a plurality of m/z sub-ranges of the m/z ratio range of interest; defining m/z positions of a set consisting of a number, n.sub.sb, of finite-width bins, within the m/z ratio range of interest, the set of bins excluding m/z sub-ranges within the m/z ratio range of interest that encompass fewer than a threshold number, t.sub.sb, of the primary ion species, wherein the defining based on the determined or received distribution; and performing a plurality of tandem mass analyses, each tandem mass analysis pertaining to primary ion species within a respective one of the defined bins.

A method of determining the structure of a macromolecular assembly (MMA) comprises the steps of (a) generating precursor ions of an MMA species to be investigated; (b) transporting the MMA precursor ions to a fragmentation zone; (c) carrying out pulsed fragmentation of the MMA precursor ions in the fragmentation zone; (d) for a first plurality of MMA precursor ions, detesting both a spatial distribution of the resultant MMA fragment ions, and an m/z distribution of the MMA fragment ions; (e) analyzing the spatial and m/z distributions of fragment ions formed from the said first plurality of precursor ions of the MMA species to be investigated, to determine the relative positions of those fragment ions within the structure of the precursor MMA; and (f) reconstructing the three dimensional (3D) structure of the MMA from the analysis of the spatial and m/z distributions of fragment ions.