Apparatuses and methods for time-of-flight mass spectrometry providing effective pulsed conversion of continuous ion beams into pulsed ion packets is disclosed. Bunching of energetic continuous ion beams forms ion packets, which are filtered by a subsequent isochronous energy filter. The bunching method is particularly suitable for ion sources with relatively large spatial emittance, otherwise unable to fir the acceptance of orthogonal accelerators. The method is particularly suitable for multi-reflecting TOF MS, which accommodates small size ion packets and where the duty cycle advantage of orthogonal accelerators is minor.

A method, apparatus and algorithms are disclosed for operating an open electrostatic trap (E-trap) or a multi-pass TOF mass spectrometer with an extended flight path. A string of start pulses with non equal time intervals is employed for triggering ion packet injection into the analyzer, a long spectrum is acquired to accept ions from the entire string and a true spectrum is reconstructed by eliminating or accounting overlapping signals at the data analysis stage while using logical analysis of peak groups. The method is particularly useful for tandem mass spectrometry wherein spectra are sparse. The method improves the duty cycle, the dynamic range and the space charge throughput of the analyzer and of the detector, so as the response time of the E-trap analyzer. It allows flight extension without degrading E-trap sensitivity.

A method of time-of-flight mass spectrometry is disclosed comprising: providing two ion mirrors (42) that are spaced apart in a first dimension (X-dimension) and that are each elongated in a second dimension (Z-dimension) orthogonal to the first dimension; introducing packets of ions (47) into the space between the mirrors using an ion introduction mechanism (43) such that the ions repeatedly oscillate in the first dimension (X-dimension) between the mirrors (42) as they drift through said space in the second dimension (Z-dimension); oscillating the ions in a third dimension (Y-dimension) orthogonal to both the first and second dimensions as the ions drift through said space in the second dimension (Z-dimension); and receiving the ions in or on an ion receiving mechanism (44) after the ions have oscillated multiple times in the first dimension (X-dimension); wherein at least part of the ion introduction mechanism (43) and/or at least part of the ion receiving mechanism (44) is arranged between the mirrors (42).

A Time of Flight mass analyzer is disclosed comprising an annular ion guide having a longitudinal axis and comprising a first annular ion guide section and a second annular ion guide section. Ions are introduced into the first annular ion guide section so that the ions form substantially stable circular orbits within the first annular ion guide section about the longitudinal axis. An ion detector is disposed within the annular ion guide. Ions are orthogonally accelerated in a first axial direction from the first annular ion guide section into the second annular ion guide section. An axial DC potential is maintained along at least a portion of the second annular ion guide section so that the ions are reflected in a second axial direction which is substantially opposed to the first axial direction. The ions undergo multiple axial passes through the second annular ion guide section before being detected by the ion detector.

Disclosed herein is a multi-reflection mass spectrometer comprising two ion mirrors spaced apart and opposing each other in an X direction, each mirror elongated along a drift direction Y orthogonal to the direction X, and an ion injector for injecting ions as an ion beam into the space between the ion mirrors at an inclination angle to the X direction. Along a first portion of their length in the drift direction Y the ion mirrors converge with a first degree of convergence, and along a second portion of their length in the drift direction Y the ion mirrors converge with a second degree of convergence or are parallel, the first portion of their length being closer to the ion injector than the second portion and the first degree of convergence being greater than the second degree of convergence.

A method of separating ions according to their time of flight is provided comprising: a. providing an analyzer comprising two opposing ion mirrors, each mirror comprising inner and outer field-defining electrode systems elongated along an analyzer axis with the outer field-defining electrode system surrounding the inner field-defining electrode system and creating therebetween an analyzer volume; b. injecting ions into the analyzer volume or creating ions within the analyzer volume so that they separate according to their time of flight as they travel along a main flight path while undergoing a plurality of axial oscillations in the direction of the analyzer axis and a plurality of radial oscillations while orbiting about one or more inner field-defining electrodes; c. the plurality of axial oscillations and plurality of radial oscillations causing the separated ions to intercept an exit port after a predetermined number of orbits. Also provided is an analyzer for performing the method, comprising: the two opposing ion mirrors which abut at a first plane, wherein the outer field-defining electrode system of one mirror comprises two sections, the sections abutting at a second plane, comprising a first section between the first plane and the second plane, and a second section adjacent the first section and wherein the first section has at least a portion which extends radially from the analyzer axis a greater extent than an adjacent portion of the second section at the second plane.

A method and apparatus are disclosed for improving resolution and duty-cycle of a multi-reflecting TOF mass spectrometer (MR-TOF) by arranging a cylindrical analyzer having an appropriate radial deflection means, means for limiting ion divergence in the tangential direction and a pulsed source providing ion packet divergence of less than 1 mm*deg. There are disclosed embodiments for fifth-order focusing cylindrical ion minors. Separate embodiments provide parallel tandem MS-MS within a single cylindrical MR-TOF.

There is described a multi-reflection time-of-flight (MR-ToF) mass analyser for a mass spectrometer, comprising a first and second mirror electrodes respectively configured to operate at a first polarity and at a second polarity. The mass analyser is configured for polarity switching and further comprises: a first regulator coupled to one or more first HV switches and configured to provide an electric potential to the first mirror electrode; and one or more second regulators each coupled to one or more second HV switches, each of the one or more second regulators configured to provide an electric potential to a respective second mirror electrode. The first and second HV switches are configured to swap the polarity supplied to the first regulator and the one or more second regulators. There is further described a regulator comprising a feedback circuit arranged to monitor one or more voltages indicative of a regulated HV voltage supplied at an output, the feedback circuit comprising a first feedback path configured to monitor AC coupled currents on the output and a second feedback path configured to monitor the DC level on the output.

A multi-reflection time of flight mass spectrometer comprises two ion-optical mirrors elongated along a drift (Y) direction and separated in the Z direction and tilted so that their separation in the Z direction decreases with distance along the Y direction. Correction electrodes extend along the Y direction in or adjacent the space between the mirrors. Each correction electrode has a surface parallel to the Y-Z plane shaped such that its separation from one of the mirrors varies along the Y direction. The correction electrodes are biased to produce a combined voltage offset which varies as a function of distance along the Y direction. A first component corrects for an intended aberration arising from the mirror tilt and a second component to correct for unintended aberrations arising from perturbations to the ideal time of flight extending from maximum to minimum perturbations.

A method of determining a calibration model for an analytical instrument comprises receiving mass spectral data, wherein the mass spectral data is generated by analysing one or more calibration samples using an analytical instrument; processing the mass spectral data to produce processed data indicative of one or more properties of the analytical instrument; and determining a calibration model for the analytical instrument by performing Gaussian Process Regression (GPR) on the processed data.