Abstract: Disclosed herein are various methods and apparatus for performing charge detection mass spectrometry (CDMS). In particular, techniques are disclosed for monitoring a detector signal from a CDMS device to determine how many ions are present in the ion trap (10) of the CDMS device. For example, if no ions are present the measurement can then be terminated early. Similarly, if more than one ion is present, the measurement can be terminated early, or ions can be removed from the trap (10) until only a single ion remains. Techniques are also provided for increasing the probability of there being a single ion in the trap (10). A technique for attenuating an ion beam is also provided.

Abstract: Improved multi-pass time-of-flight mass spectrometers MPTOF, either multi-reflecting (MR) or multi-turn (MT) TOF are proposed with elongated pulsed converters—either orthogonal accelerator or radially ejecting ion trap. The converter 35 is displaced from the MPTOF s-surface of isochronous ion motion in the orthogonal Y-direction. Long ion packets 38 are pulsed deflected in the transverse Y-direction and brought onto said isochronous trajectory s-surface, this way bypassing said converter. Ion packets are isochronously focused in the drift Z-direction within or immediately after the accelerator, either by isochronous trans-axial lens/wedge 68 or Fresnel lens. The accelerator is improved by the ion beam confinement within an RF quadrupolar field or within spatially alternated DC quadrupolar field. The accelerator improves the duty cycle and/or space charge capacity of MPTOF by an order of magnitude.

Abstract: A method of mass spectrometry is disclosed comprising: a) providing temporally separated precursor ions; b) mass analyzing separated precursor ions, and/or product ions derived therefrom, during a plurality of sequential acquisition periods, wherein the value of an operational parameter of the spectrometer is varied during the different acquisition periods; c) storing the spectral data obtained in each acquisition period along with its respective value of the operational parameter; d) interrogating the stored spectral data and determining which of the spectral data for a precursor ion or product ions meets a predetermined criterion, and determining the value of the operational parameter that provides this mass spectral data as a target operational parameter value; and e) mass analyzing again the precursor or product ions whilst the operational parameter is set to the target operational parameter value.

Abstract: A method of mass spectrometry comprising the steps of: providing a library of background ion data including m/z data for multiple background ions in respect of different chromatographic conditions including a change of solvent composition from aqueous (1) to organic (3), chromatographically separating a sample containing analyte components, wherein the chromatographic separation is performed under a chromatographic condition in respect of which background ion data is provided in the library, analysing the sample to obtain sample data comprising m/z values for the sample components as a function of retention time (RT), and calculating one or more error values including ppm error as a function of retention time based on a comparison between background ions identified in the sample data and the library of background ion data. Outliers (4), corrupted measurements and inconsistent measurements at specific retention times are rejected.

Abstract: A method of encoding a parent or precursor ion beam to aid product ion assignment is disclosed. According to an embodiment the energy of parent ions entering a collision cell 3 is progressively increased. Different species of parent ions fragment at different collision energies. Fragment ion intensity profiles are matched with parent ion intensity profiles to correlate fragment ions with corresponding parent ions.

Abstract: Improved pulsed ion sources and pulsed converters are proposed for multi-pass time-of-flight mass spectrometer, either multi-reflecting (MR) or multi-turn (MT) TOF. A wedge electrostatic field (45) is arranged within a region of small ion energy for electronically controlled tilting of ion packets (54) time front. Tilt angle ? of time front (54) is strongly amplified by a post-acceleration in a flat field (48). Electrostatic deflector (30) downstream of the post-acceleration (48) allows denser folding of ion trajectories, whereas the injection mechanism allows for electronically adjustable mutual compensation of the time front tilt angle, i.e. ?=0 for ion packet in location (55), for curvature of ion packets, and for the angular energy dispersion. The arrangement helps bypassing accelerator (40) rims, adjusting ion packets inclination angles ?2 and what is most important, compensating for mechanical misalignments of the optical components.

Abstract: An instrument for analysing ions is disclosed comprising: a first device (4) configured to onwardly transmit ions having a restricted range of physicochemical property values at any given time, and to change said range with time such that the first device (4) is capable of transmitting ions having different physicochemical property values at different times; and an ion mobility separator (6) arranged to receive ions transmitted by the first device (4); wherein the instrument is configured such that the time that any given ion enters the ion mobility separator (6) and begins to be separated from other ions is defined by its time of transmission by the first device.

Abstract: A method of separating ions is disclosed comprising: providing an ion separation device comprising a plurality of electrodes; providing a gas flow (5) so as to urge ions in a first direction along the device; applying voltages to said electrodes so that a plurality of travelling potentials (4) urge the ions in a second opposite direction; and varying at least one operational parameter of the travelling potentials (4) as a function of position along the device such that ions of different mobility or mass to charge ratio become trapped at different locations along the device.

Abstract: A mass spectrometer is disclosed comprising: an ion detector; ion optics for guiding ions to the ion detector; one or more voltage supply for supplying voltages to said ion optics; control circuitry for controlling the one or more voltage supply so as to switch the ion optics between operating in a first mode in which the ion optics are unable to transmit ions having a first mass to charge ratio or first polarity to the ion detector and a second mode in which the ion optics are able to transmit ions having said first mass to charge ratio or first polarity to the ion detector for a time period; and to repeatedly switch between the first and second modes a plurality of times; and a processor and circuitry configured to: (i) determine the intensity of an ion signal detected by the detector at a first time in each of the time periods that the ion optics are in the second mode; and (ii) determine the intensity of the ion signal detected by the detector at a second, later time in each of the time periods that the i

Abstract: A method of mass spectrometry is disclosed comprising: performing a plurality of cycles of operation during a single experimental run, wherein each cycle comprises: mass selectively transmitting precursor ions of a single mass, or range of masses, through or out of a mass separator or mass filter at any given time, wherein the mass separator or mass filter is operated such that the single mass or range of masses transmitted therefrom is varied with time; and mass analysing ions.

Abstract: A method of analysing ions is disclosed comprising: (i) subjecting ions of an analyte molecule to different activation levels at different times so as to cause the ions to have different mobilities at said different times, wherein the activation level is varied in a plurality of cycles, and wherein the activation level is varied between said different levels during each of the cycles. The method uses an ion mobility separator or scanned ion mobility filter to determine the mobilities of the ions for said different activation levels; and correlates the determined mobilities with their respective activation levels so as to thereby obtain a fingerprint for the analyte molecule.

Abstract: A method of analysis using mass spectrometry and/or ion mobility spectrometry is disclosed. The method comprises: using a first device to generate smoke, aerosol or vapour from a target comprising or consisting of a microbial population; mass analysing and/or ion mobility analysing said smoke, aerosol or vapour, or ions derived therefrom, in order to obtain spectrometric data; and analysing said spectrometric data in order to analyse said microbial population.

Abstract: A method of identifying and/or characterising ions comprises separating analyte ions according to a first physico-chemical property (ion-mobility), selecting first ions of the analyte ions, and activating, fragmenting or reacting the first ions to produce first product ions, separating the first product ions according to the first physico-chemical property, and determining a pattern of the first product ions. The first ions are identified and/or characterised using the pattern of the first product ions.

Abstract: Improved ion mirrors 30 (FIG. 3) are proposed for multi-reflecting TOF MS and electrostatic traps. Minor and controlled variation by means of arranging a localized wedge field structure 35 at the ion retarding region was found to produce major tilt of ion packets time fronts 39. Combining wedge reflecting fields with compensated deflectors is proposed for electrically controlled compensation of local and global misalignments, for improved ion injection and for reversing ion motion in the drift direction. Fine ion optical properties of methods and embodiments are verified in ion optical simulations.

Abstract: Provided herein are methods and systems directed to stable, isotopically labeled internal calibrators for use in mass spectrometry analysis for quantifying a target analyte in a sample. The present disclosure relates more particularly to mass spectrometry analysis where a single sample includes at least three isotopically labeled internal calibrators and the target analyte. The methods and systems described herein allows accommodation of isotope interferences arising from the use of isotopically labeled internal calibrators in quantification a target analyte. As a result, smaller quantities (e.g., lesser concentration) of isotopically labeled internal calibrators are utilized in the present technology in the generation of a calibration curve to quantify a target analyte.

Abstract: A method of ionising a sample is disclosed comprising nebulising a sample which includes first biomolecules such as bovine insulin comprising one or more disulphide (S—S) bonds. A stream of droplet or charged droplets comprising one or more disulphide (S—S) bonds is directed so as to impact upon a target (106) or electrode so as to cause the breaking of a portion of the disulphide bonds. Alternatively, charged droplets may pass through an electric field region determined by an electrode (106) arranged downstream of a nebuliser or electrospray probe and an ion inlet (104) of a mass spectrometer so as to cause the breaking of a portion of the disulphide bonds.

Abstract: The present disclosure provides a method comprising providing a sample to be analysed, separating successive populations of ions from said sample in a separator, wherein said populations of ions are introduced into said separator at regular intervals, and the intervals are timed such that at least some ions in a subsequent population of ions overlap ions in a preceding population of ions, varying one or more parameters of said separator such that different populations of ions experience different separation conditions, detecting ions from said populations of ions and obtaining a convolved data set, and de¬ convolving said convolved data set using the known variance of the parameters and outputting data corresponding to the successive populations of ions.

Abstract: A method of analysis using mass spectrometry and/or ion mobility spectrometry is disclosed comprising: (a) using a first device to generate smoke, aerosol or vapour from a target in vitro or ex vivo cell population; (b) mass analysing and/or ion mobility analysing said smoke, aerosol or vapour, or ions derived therefrom, in order to obtain spectrometric data; and (c) analysing said spectrometric data in order to identify and/or characterise said target cell population or one or more cells and/or compounds present in said target cell population.

Abstract: Improved multi-pass time-of-flight mass spectrometers MPTOF, either multi-reflecting (MR) or multi-turn (MT) TOF are proposed with elongated pulsed converters—either orthogonal accelerator or radially ejecting ion trap. The converter 35 is displaced from the MPTOF s-surface of isochronous ion motion in the orthogonal Y-direction. Long ion packets 38 are pulsed deflected in the transverse Y-direction and brought onto said isochronous trajectory s-surface, this way bypassing said converter. Ion packets are isochronously focused in the drift Z-direction within or immediately after the accelerator, either by isochronous trans-axial lens/wedge 68 or Fresnel lens. The accelerator is improved by the ion beam confinement within an RF quadrupolar field or within spatially alternated DC quadrupolar field. The accelerator improves the duty cycle and/or space charge capacity of MPTOF by an order of magnitude.

Abstract: An impact ionisation spray or electrospray ionisation ion source comprising a nebuliser (30) having a first conduit (11) for providing a liquid sample and a second conduit (10) for providing a nebulisation gas in order to nebulise the liquid sample is disclosed. The first conduit (11) and second conduit (10) are of unitary construction with each other and may be made from glass. The ion source can provide a consistent and/or predictable spray profile for the nebulised sample.