A hybrid mass spectrometer comprising: an ion source for generating ions from a sample, a first mass spectral system comprising a nanoelectromechanical mass spectral (NEMS-MS) system, a second mass spectral system including at least one mass analyzer adapted to separate the charged particles according to their mass-to-charge ratios, and an integration zone coupling the first and second mass spectral systems, the integration zone including at least one directional device for controllably routing the ions to a selected one or both of the first and second mass spectral systems for analysis thereby. The second system can be an orbital electrostatic trap system. The ion beam can be electrically directed to one or the other system by ion optics. A chip with resonators can be used with cooling. Uses include analysis of large mass complexes found in biological systems, native single molecule analysis, and size and shape analysis.

A system and method of mass spectrometry is provided. Ions from an ion source are stored in a first ion storage device and in a second ion storage device. Ions are ejected from the first ion storage device to a first mass analysis device during a first ejection time period, for analysis during a first analysis time period. Ions are ejected from the second ion storage device to a second mass analysis device during a second ejection time period. The ion storage devices are connected in series such that an ion transport aperture of the first ion storage device is in communication with an ion transport aperture of the second ion storage device. The first analysis time period and the second ejection time period at least partly overlap.

There is disclosed a method for eliminating an added crosstalk signal from a measured data signal, which is generated by an image current. There is further disclosed a signal processing unit for carrying out the method. There is still further disclosed a mass spectrometer and a mass analyser comprising the signal processing unit for carrying out the method. There is yet still further disclosed a Fourier transform mass spectrometer configured to eliminate the added crosstalk signal from a measured data signal.

An electrostatic trap such as an orbitrap is disclosed, with an electrode structure. An electrostatic trapping field of the form U(r, , z) is generated to trap ions within the trap so that they undergo isochronous oscillations. The trapping field U(r, , z) is the result of a perturbation W to an ideal field U(r, , z) which, for example, is hyperlogarithmic in the case of an orbitrap. The perturbation W may be introduced in various ways, such as by distorting the geometry of the trap so that it no longer follows an equipotential of the ideal field U(r, , z), or by adding a distortion field (either electric or magnetic). The magnitude of the perturbation is such that at least some of the trapped ions have an absolute phase spread of more than zero but less than 2 radians over an ion detection period T.sub.m.

An electrostatic trap such as an orbitrap is disclosed, with an electrode structure. An electrostatic trapping field of the form U(r, ?, z) is generated to trap ions within the trap so that they undergo isochronous oscillations. The trapping field U(r, ?, z) is the result of a perturbation W to an ideal field U(r, ?, z) which, for example, is hyperlogarithmic in the case of an orbitrap. The perturbation W may be introduced in various ways, such as by distorting the geometry of the trap so that it no longer follows an equipotential of the ideal field U(r, ?, z), or by adding a distortion field (either electric or magnetic). The magnitude of the perturbation is such that at least some of the trapped ions have an absolute phase spread of more than zero but less than 2 ? radians over an ion detection period T.sub.m.

Disclosed are methods for improving compound detection and characterization. Methods for characterizing a sample are disclosed. The methods can include providing a sample to a liquid chromatography system capable of sample separation to generate sample components; analyzing sample components by multiplexed targeted selected ion monitoring (SIM) to generate an inclusion list; and performing iterative mass spectral data-dependent acquisition (DDA) from the inclusion list, to identify individual sample components thereby characterizing the sample. In one example, multiplexed targeted SIMs and iterative MS2 DDA acquisition is used to increase robust compound identification for cell culture medium analysis.

The present inventive concepts relate to determining an isotope ratio using mass spectrometry. Mass spectra of ions are obtained by generating ions, guiding the ions through a device having a mass transfer function that varies with ion current, providing at least some of the ions to a mass analyser and obtaining a mass spectrum of the ions and determining the ion current of the ions provided to the mass analyser. An isotope ratio of the ions is determined for each mass spectrum. Using the determined isotope ratio and determined ion current for each mass spectrum, a calibration relationship is determined that characterises the variation of the determined isotope ratios and the measured ion currents across the mass spectra. Then, a measured isotope ratio obtained at a determined ion current is adjusted using the calibration relationship to adjust the measured isotope ratio to an adjusted isotope ratio corresponding to a selected ion current.

A method of processing an image-charge/current signal representative of one or more ions undergoing oscillatory motion within an ion analyser apparatus, the method comprising obtaining a recording of the image-charge/current signal generated by the ion analyser apparatus in the time domain. By a signal processing unit, the method includes selecting N (where N is an integer>1) separate values (OP.sub.n, where n=1 to N; N?M) of the frequency-domain spectrum of the image-charge/current signal each from amongst a plurality of spectral peaks which include a harmonic peak associated with a target ion. By solving a system of equations:

[00001]${\mathrm{OP}}_n=\underset{m=1}{\overset{N}{.Math.}}{?}_{nm}?{\mathrm{TP}}_m,$$\mathrm{for}n=1\mathrm{to}N;$$N?M$ where ?.sub.nm are coefficients and TP.sub.m are corrected values of the spectrum, the charge of the target ion is determined based on a magnitude of a corrected value(s) (TP.sub.m) associated with that ion.

A method of tandem mass spectrometry for analysing precursor ions across a mass to charge (m/z) range of interest is provided. The method comprises analysing some of the precursor ions across the m/z range of interest in the MS1 domain using a first mass analyser of a tandem mass spectrometer operated at a first sensitivity. The method also comprises analysing some of the precursor ions across the m/z range of interest in the MS1 domain using a second mass analyser of the tandem mass spectrometer operated at a second sensitivity, wherein the second sensitivity is higher than the first sensitivity. The analysis in the MS1 domain performed by the second mass analyser is performed concurrently with the analysis performed in the MS1 domain by the first mass analyser. The method also comprises combining data from the MS1 analyses performed by the first and second mass analysers to identify and/or quantify precursor ions. The method also comprises analysing some of the precursor ions in the MS2 domain using the second mass analyser of the tandem mass spectrometer.

A method of calibrating a TOF-MS mass spectrum, to account for temperature changes, is disclosed. Ions are introduced into a Fourier Transform Mass Spectrometer and their mass to charge ratios are determined. Ions, including calibrant ions, are also introduced into a time of flight mass spectrometer and the mass to charge ratios of the calibrant ions at least are also determined. Specific peaks representative of calibrant ions are selected and matched between the TOF MS and FTMS spectra. The relative position of matched peaks in each spectrum is then used to determine a temperature correction factor for the TOF MS data, based upon the relative independence of the FTMS spectrum with respect to temperature.