Processing mass spectral data

Abstract

Mass spectrometry methods that include: Transforming time-domain mass spectral data to generate frequency-domain mass spectral data; Modifying the frequency-domain mass spectral data to generate modified frequency-domain mass spectral data by attenuating and / or removing one or more regions of the frequency-domain mass spectral data associated with peak socketing noise, which is assigned to peaks of interest in the mass spectral data, by attenuating and / or removing frequencies from the frequency-domain mass spectral data that are below a threshold frequency; and Transforming the modified frequency domain mass spectral data to generate modified time domain mass spectral data.

Description

Field of the present invention

[0001] The present invention relates generally to mass spectrometers and in particular to the processing of mass spectral data from time-of-flight mass spectrometers (“ToF mass spectrometers”). background

[0002] Mass spectral data acquired using a mass spectrometer such as a time-of-flight mass spectrometer (“ToF mass spectrometer”) may exhibit undesired peak baselining or baseline rise. This can be due, for example, to incomplete desolvation of the liquid chromatography eluent (“LC eluent”) supplied to the mass spectrometer or to collisions between ions and residual gas within the mass analyzer.

[0003] Collisions of ions with gas in the mass analyzer can cause ions to fragment and release energy, resulting in either an acceleration or a deceleration of production. If this occurs, for example, in the field-free region of a reflectron time-of-flight mass analyzer (“reflectron ToF mass analyzer”) or a linear time-of-flight mass analyzer (“linear ToF mass analyzer”), the ion peak widths are increased and unwanted peak stumps are generated in the resulting mass spectral data.The extent to which these effects occur depends on the ratio of the number of ions that experience collisions during their flight time (which is a function of their collision cross-section and background pressure) to the number of ions that do not experience collisions, as well as on the energy released during the collision process (known as the Derrick shift), which causes productions to change their velocity relative to their corresponding parent or precursor ion.

[0004] Kast et al., “Noise Filtering Techniques for Electrospray Quadrupole Time of Flight Mass Spectra”, J. Am. Soc. Mass Spectrom. 2003, 14, 766-776, discloses the removal of periodically repeating chemical background noise peaks from time-of-flight mass spectral data (“ToF mass spectral data”) by manually selecting and eliminating individual peaks in the Fourier spectrum of the mass-to-charge ratio domain data (“m / z domain data”). However, this approach does not address the problem of unwanted peak socketing effects.

[0005] It is therefore desirable to create an improved method for mass spectrometry.

[0006] US 2002 / 0024009 A1 relates to a computer-aided method for reducing the chemical background in acquired electrospray and nanospray mass spectra. US 2008 / 0270083 A1 relates to a method for processing Fourier-transform mass spectrometry data. Summary

[0007] According to the invention, a method for mass spectrometry, a device and a mass spectrometer with the features of the independent claims are provided; dependent claims relate to preferred embodiments.

[0008] According to one aspect of the invention, a mass spectrometry method is provided which includes: transforming mass spectral data to generate frequency-domain mass spectral data; modifying the frequency-domain mass spectral data to generate modified frequency-domain mass spectral data by attenuating and / or removing one or more regions of the frequency-domain mass spectral data that are associated with noise that is associated with peaks of interest in the mass spectral data; and transforming the modified frequency-domain mass spectral data to generate modified mass spectral data.

[0009] Various embodiments relate to mass spectrometry methods in which mass spectral data are transformed to obtain frequency-domain mass spectral data. In the context of this application, "frequency domain" means the space that, under the specified integral transformation or discrete version of an integral transformation, is dual to mass or mass-to-charge ratio. The frequency-domain mass spectral data are then modified by attenuating one or more regions of the transformed frequency-domain mass spectral data to obtain modified frequency-domain mass spectral data. The modified frequency-domain mass spectral data are then back-transformed to obtain modified mass spectral data.

[0010] As described in more detail below, the applicants were able to resolve the problem of peak baseline and baseline rise effects in mass spectral data, as described above.

[0011] It should be noted that, although it is common practice in some types of mass spectrometry, such as Fourier-transform ion cyclotron resonance mass spectrometry (“FTICR mass spectrometry”) or electrostatic mass spectrometry, which uses electrostatic fields with a quadrologarithmic potential distribution, to apply fast Fourier transform techniques (“FFT techniques”), this is done to convert the acquired data into the mass-to-charge ratio (m / z) domain. This is because, in these techniques, the mass-to-charge ratio of ions is related to the frequencies of the acquired data. Therefore, frequency-domain mass spectral data are not transformed to produce modified mass spectral data in these techniques.

[0012] In contrast, it is neither necessary nor typical to use such methods for time-of-flight mass spectral data (“ToF mass spectral data”) (or other mass-to-charge ratio domain or time-domain mass spectral data), since the mass-to-charge ratio can be determined directly from the acquired time-of-flight data by simply squaring the flight times. Furthermore, unlike FTICR data, there are no overlapping ions in the spectra.

[0013] In the article by Kast et al., “Noise Filtering Techniques for Electrospray Quadrupol Time of Flight Mass Spectra”, J. Am. Soc. Mass Spectrom. 2003, 14, 766-776, a method is disclosed in which periodically repeating chemical background noise peaks are removed from time-of-flight mass spectral data (“ToF mass spectral data”) by manually selecting and removing individual peaks in the Fourier spectrum of the mass-to-charge ratio domain data (“m / z domain data”).

[0014] However, it will be evident that the approach disclosed in Kast differs significantly from the methods according to various embodiments and that, in particular, the approach disclosed in Kast is not able to solve the peak socketing problem.

[0015] In particular, according to various embodiments, transformed frequency-domain mass spectral data are modified by attenuating and / or removing one or more regions of the frequency-domain mass spectral data that are associated with noise, which is assigned (i.e., localized) to peaks of interest in the mass spectral data.

[0016] Accordingly, the present disclosure is based on the finding that the techniques described herein may be effective in removing noise artifacts associated with peaks of interest, i.e., removing non-repeating peak baseline or peak tailing and baseline rise effects such as background localized at peaks in mass spectral data as described above.

[0017] In particular, the quality of mass spectral data can be improved by attenuating frequency ranges that essentially represent unwanted background noise artifacts, which are locally associated with peaks of interest and occur between peaks of interest (i.e., non-repeating baseline rises adjacent to peaks of interest). Thus, the techniques described here can be used to provide improved mass spectral data.

[0018] It will therefore be evident that different embodiments create significant improvements and enhanced methods for mass spectrometry.

[0019] The mass spectral data and / or the modified mass spectral data contain time-domain mass spectral data.

[0020] The method can further include determining mass-to-charge ratio range mass spectral data from the modified mass spectral data.

[0021] The mass spectral data can include time-of-flight mass spectral data (“ToF mass spectral data”).

[0022] The mass spectral data can include multiple time-intensity pairs.

[0023] The mass spectral data and / or the modified mass spectral data can be transformed by: (i) a Fourier transform; (ii) a fast Fourier transform (FFT); (iii) a wavelet transform; (iv) a discrete wavelet transform; (v) a continuous wavelet transform; and / or (vi) any other integral transform or discrete version of an integral transform.

[0024] One or more regions can be selected based on the average number of collisions experienced by ions that correspond to peaks of interest in the mass spectral data.

[0025] One or more regions can be selected based on the collision cross section (“CCS”) of ions that correspond to the peaks of interest in the mass spectral data.

[0026] The mass spectral data can be transformed using a forward transformation, and the modified frequency domain mass spectral data can be transformed using an inverse transformation.

[0027] The mass spectral data can be transformed using an inverse transformation, and the modified frequency domain mass spectral data can be transformed using a forward transformation.

[0028] Modifying the frequency-domain mass spectral data may involve attenuating and / or removing frequencies from the frequency-domain mass spectral data that are above and / or below one or more threshold frequencies.

[0029] The one or more threshold frequencies may include: (i) approximately 0.5 MHz, (ii) approximately 1 MHz, (iii) approximately 1.5 MHz, (iv) approximately 2 MHz, (v) approximately 2.5 MHz, (vi) approximately 3 MHz, (vii) approximately 3.5 MHz, (viii) approximately 4 MHz, (ix) approximately 5 MHz, (x) approximately 6 MHz, (xi) approximately 7 MHz, (xii) approximately 8 MHz, (xiii) approximately 9 MHz, (xiv) approximately 10 MHz, (xv) approximately 11 MHz, (xvi) approximately 12 MHz, (xvii) approximately 13 MHz, (xviii) approximately 14 MHz, (xix) approximately 15 MHz, (xx) approximately 16 MHz, (xxi) approximately 17 MHz, (xxii) approximately 18 MHz, (xxiii) approximately 19 MHz and / or (xxiv) approximately 20 MHz.

[0030] Modifying the frequency-domain mass spectral data may involve attenuating and / or removing frequencies from the frequency-domain mass spectral data in the following range: (i) about 0-0.5 MHz, (ii) about 0.5-1 MHz, (iii) about 1-1.5 MHz, (iv) about 1.5-2 MHz, (v) about 2-2.5 MHz, (vi) about 2.5-3 MHz, (vii) about 3-3.5 MHz, (viii) about 3.5-4 MHz, (ix) about 4-5 MHz, (x) about 5-6 MHz, (xi) about 6-7 MHz, (xii) about 7-8 MHz, (xiii) about 8-9 MHz, (xiv) about 9-10 MHz, (xv) about 10-11 MHz, (xvi) about 11-12 MHz. (xvii) approximately 12-13 MHz, (xviii) approximately 13-14 MHz, (xix) approximately 14-15 MHz, (xx) approximately 15-16 MHz, (xxi) approximately 16-17 MHz, (xxii) approximately 17-18 MHz, (xxiii) approximately 18-19 MHz, (xxiv) approximately 19-20 MHz and / or (xxv) > 20 MHz.

[0031] Modifying the frequency-domain mass spectral data can involve attenuating and / or removing one or more regions of the frequency-domain mass spectral data using one or more step, window, apodization, or tapering functions.

[0032] The one or more windowing, apodization, or tapering functions may include a function that comprises: a maximum frequency and a minimum frequency; wherein the function is relatively high below the maximum frequency and above the minimum frequency; and wherein the function is relatively low above the maximum frequency and below the minimum frequency.

[0033] The function can be non-zero below the maximum frequency and above the minimum frequency; and the function can be approximately zero above the maximum frequency and below the minimum frequency.

[0034] The function may include an apodization or tapering function that smoothly tapers to approximately zero at the maximum frequency and / or the minimum frequency.

[0035] The one or more stage, apodization, or tapering functions may contain a function that includes: a maximum frequency; where the function is relatively high below the maximum frequency; and where the function is relatively low above the maximum frequency.

[0036] The function can be non-zero below the maximum frequency; and The function can be approximately zero above the maximum frequency.

[0037] The function may include an apodization or tapering function that smoothly drops to zero at the maximum frequency.

[0038] The one or more stage, apodization, or tapering functions may contain a function that includes: a minimum frequency; where the function is relatively high above the minimum frequency; and where the function is relatively low below the minimum frequency.

[0039] The function can be non-zero above the minimum frequency; and The function can be approximately zero below the minimum frequency.

[0040] The function may include an apodization or tapering function that smoothly drops to approximately zero at the minimum frequency.

[0041] The minimum and / or maximum frequency may include: (i) approximately 0 MHz; (ii) approximately 0.5 MHz; (iii) approximately 1 MHz; (iv) approximately 1.5 MHz; (v) approximately 2 MHz; (vi) approximately 2.5 MHz; (vii) approximately 3 MHz; (viii) approximately 3.5 MHz; (ix) approximately 4 MHz; (x) approximately 5 MHz; (xi) approximately 6 MHz; (xii) approximately 7 MHz; (xiii) approximately 8 MHz; (xiv) approximately 9 MHz; (xv) approximately 10 MHz; (xvi) approximately 11 MHz; (xvii) approximately 12 MHz; (xviii) approximately 13 MHz; (xix) approximately 14 MHz; (xx) approximately 15 MHz; (xxi) approximately 16 MHz; (xxii) approximately 17 MHz; (xxiii) approximately 18 MHz; (xxiv) approximately 19 MHz; and / or (xxv) approximately 20 MHz.

[0042] The frequency-domain mass spectral data can be modified in a predefined manner that does not depend on the mass spectral data and / or the frequency-domain mass spectral data.

[0043] The process can be carried out automatically without user interaction.

[0044] The procedure may also include acquiring mass spectral data using a mass spectrometer.

[0045] The steps of transforming the mass spectral data, modifying the frequency domain mass spectral data, and transforming the modified frequency domain mass spectral data can be performed in real time simultaneously with the step of acquiring the mass spectral data.

[0046] According to another aspect of the invention, a device is created which contains: a device designed and adapted to transform mass spectral data in order to generate frequency-domain mass spectral data; a device designed and adapted to modify frequency-domain mass spectral data to produce modified frequency-domain mass spectral data by attenuating and / or removing one or more regions of the frequency-domain mass spectral data that are associated with noise that is associated with peaks of interest in the mass spectral data; and a facility designed and adapted to transform the modified frequency domain mass spectral data in order to generate modified mass spectral data.

[0047] The mass spectral data and / or the modified mass spectral data include time-domain mass spectral data.

[0048] The device can be designed and adapted to determine mass-to-charge ratio range mass spectral data from the modified mass spectral data.

[0049] The mass spectral data can include time-of-flight mass spectral data (“ToF mass spectral data”).

[0050] The mass spectral data can include multiple time-intensity pairs.

[0051] The device can be designed and adapted to transform the mass spectral data and / or the modified mass spectral data by means of: (i) a Fourier transform; (ii) a fast Fourier transform (FFT); (iii) a wavelet transform; (iv) a discrete wavelet transform; (v) a continuous wavelet transform; and / or (vi) any other integral transform or discrete version of an integral transform.

[0052] The device can be designed to select one or more areas based on the average number of collisions experienced by ions that correspond to peaks of interest in the mass spectral data.

[0053] The device can be designed to select one or more regions based on the collision cross section (“CCS”) of ions that correspond to the peaks of interest in the mass spectral data.

[0054] The device can be designed and adapted to transform the mass spectral data using a forward transformation and to transform the modified frequency domain mass spectral data using a reverse transformation.

[0055] The device can be designed and adapted to transform the mass spectral data using a back-transformation and to transform the modified frequency domain mass spectral data using a forward-transformation.

[0056] The device can be designed and adapted to modify the frequency-domain mass spectral data by attenuating and / or removing frequencies from the frequency-domain mass spectral data that are above and / or below one or more threshold frequencies.

[0057] The one or more threshold frequencies may include: (i) approximately 0.5 MHz, (ii) approximately 1 MHz, (iii) approximately 1.5 MHz, (iv) approximately 2 MHz, (v) approximately 2.5 MHz, (vi) approximately 3 MHz, (vii) approximately 3.5 MHz, (viii) approximately 4 MHz, (ix) approximately 5 MHz, (x) approximately 6 MHz, (xi) approximately 7 MHz, (xii) approximately 8 MHz, (xiii) approximately 9 MHz, (xiv) approximately 10 MHz, (xv) approximately 11 MHz, (xvi) approximately 12 MHz, (xvii) approximately 13 MHz, (xviii) approximately 14 MHz, (xix) approximately 15 MHz, (xx) approximately 16 MHz, (xxi) approximately 17 MHz, (xxii) approximately 18 MHz, (xxiii) approximately 19 MHz and / or (xxiv) approximately 20 MHz.

[0058] The device can be designed and adapted to modify the frequency-domain mass spectral data by attenuating and / or removing frequencies from the frequency-domain mass spectral data in the following range: (i) about 0-0.5 MHz, (ii) about 0.5-1 MHz, (iii) about 1-1.5 MHz, (iv) about 1.5-2 MHz, (v) about 2-2.5 MHz, (vi) about 2.5-3 MHz, (vii) about 3-3.5 MHz, (viii) about 3.5-4 MHz, (ix) about 4-5 MHz, (x) about 5-6 MHz, (xi) about 6-7 MHz, (xii) about 7-8 MHz, (xiii) about 8-9 MHz, (xiv) about 9-10 MHz, (xv) about 10-11 MHz, (xvi) about 11-12 MHz, (xvii) approximately 12-13 MHz, (xviii) approximately 13-14 MHz, (xix) approximately 14-15 MHz, (xx) approximately 15-16 MHz, (xxi) approximately 16-17 MHz, (xxii) approximately 17-18 MHz, (xxiii) approximately 18-19 MHz, (xxiv) approximately 19-20 MHz and / or (xxv) > 20 MHz.

[0059] The device can be designed and adapted to modify the frequency domain mass spectral data by attenuating and / or removing one or more regions of the frequency domain mass spectral data using one or more step, window, apodization or tapering functions.

[0060] The one or more windowing, apodization, or tapering functions may contain a function that includes: a maximum frequency and a minimum frequency; where the function is relatively high below the maximum frequency and above the minimum frequency; and where the function is relatively low above the maximum frequency and below the minimum frequency.

[0061] The function can be non-zero below the maximum frequency and above the minimum frequency; and the function can be approximately zero above the maximum frequency and below the minimum frequency.

[0062] The function may include an apodization or tapering function that smoothly tapers to approximately zero at the maximum frequency and / or the minimum frequency.

[0063] The one or more stage, apodization, or tapering functions may contain a function that includes: a maximum frequency; where the function is relatively high below the maximum frequency; and where the function is relatively low above the maximum frequency.

[0064] The function can be non-zero below the maximum frequency; and The function can be approximately zero above the maximum frequency.

[0065] The function may include an apodization or tapering function that smoothly drops to zero at the maximum frequency.

[0066] The one or more stage, apodization, or tapering functions may contain a function that includes: a minimum frequency; where the function is relatively high above the minimum frequency; and where the function is relatively low below the minimum frequency.

[0067] The function can be non-zero above the minimum frequency; and The function can be approximately zero below the minimum frequency.

[0068] The function may include an apodization or tapering function that smoothly drops to approximately zero at the minimum frequency.

[0069] The minimum and / or maximum frequency may include: (i) approximately 0 MHz; (ii) approximately 0.5 MHz; (iii) approximately 1 MHz; (iv) approximately 1.5 MHz; (v) approximately 2 MHz; (vi) approximately 2.5 MHz; (vii) approximately 3 MHz; (viii) approximately 3.5 MHz; (ix) approximately 4 MHz; (x) approximately 5 MHz; (xi) approximately 6 MHz; (xii) approximately 7 MHz; (xiii) approximately 8 MHz; (xiv) approximately 9 MHz; (xv) approximately 10 MHz; (xvi) approximately 11 MHz; (xvii) approximately 12 MHz; (xviii) approximately 13 MHz; (xix) approximately 14 MHz; (xx) approximately 15 MHz; (xxi) approximately 16 MHz; (xxii) approximately 17 MHz; (xxiii) approximately 18 MHz; (xxiv) approximately 19 MHz; and / or (xxv) approximately 20 MHz.

[0070] The device can be designed and adapted to modify the frequency-domain mass spectral data in a predefined manner that does not depend on the mass spectral data and / or the frequency-domain mass spectral data.

[0071] The device can be designed and adapted to automatically transform the mass spectral data without user interaction to generate the frequency domain mass spectral data, to modify the frequency domain mass spectral data to generate the modified frequency domain mass spectral data, and to transform the modified frequency domain mass spectral data to generate the modified mass spectral data.

[0072] According to another aspect of the invention, a mass spectrometer containing the device described above is created.

[0073] The mass spectrometer can be designed and adapted to acquire mass spectral data.

[0074] The device can be designed and adapted to simultaneously acquire the mass spectral data in real time, transform the mass spectral data, modify the frequency domain mass spectral data, and transform the modified frequency domain mass spectral data.

[0075] According to another aspect, a procedure is disclosed which includes: Providing time-of-flight data (in one embodiment, time-intensity pairs) to a fast Fourier transform processor (“FFT processor”) for generating frequency domain data; Digital manipulation of frequency ranges from frequency domain data to improve spectral quality by removing chemical or electrical noise; and Reconstructing the time-of-flight data from the manipulated frequency range using an inverse FFT algorithm.

[0076] The spectrometer may contain an ion source selected from the following group: (i) an electrospray ion source (“ESI” ion source); (ii) an atmospheric pressure photoionization ion source (“APPI ion source”), (iii) an atmospheric pressure chemical ionization ion source (“APCI ion source”), (iv) a matrix-assisted laser desorption ionization ion source (“MALDI ion source”), (v) a laser desorption ionization ion source (“LDI ion source”), (vi) an atmospheric pressure ionization ion source (“API ion source”), (vii) a desorption / ionization-on-silicon ion source (“DIOS ion source”), (viii) an electron impact ion source (“EI ion source”), (ix) a chemical ionization ion source (“CI ion source”), (x) a field ionization ion source (“FI ion source”), (xi) a field desorption ion source (“FD ion source”), (xii) a Inductively coupled plasma ion source (“ICP ion source”),(xiii) a fast atom bombardment ion source (“FAB ion source”), (xiv) a liquid secondary ion mass spectrometry ion source (“LSIMS ion source”), (xv) a desorption electrospray ionization ion source (“DESI ion source”), (xvi) a radioactive nickel-63 ion source, (xvii) a matrix-assisted atmospheric pressure laser desorption ionization ion source, (xviii) a thermospray ion source, (xix) an atmospheric sampling glow discharge ionization ion source (“ASGDI ion source”), (xx) a glow discharge ion source (“GD ion source”), (xxi) an impactor ion source, (xxii) a direct analysis in real time ion source (DART ion source), (xxii) a laser spray ionization ion source (LSI ion source), (xxiv) a sonic spray ionization ion source (SSI ion source), (xxv) a matrix-assisted inlet ionization ion source (MAII ion source),(xxvi) a solvent-assisted inlet ionization source (“SAII ion source”), (xxvii) a desorption electrospray ionization ion source (“DESI ion source”), (xxviii) a laser ablation electrospray ionization ion source (“LAESI ion source”) and (xxix) a surface-assisted laser desorption ionization ion source (“SALDI ion source”).

[0077] The spectrometer can contain one or more continuous or pulsed ion sources.

[0078] The spectrometer can contain one or more ion guides.

[0079] The spectrometer may include one or more ion mobility separation devices and / or one or more field asymmetric ion mobility spectrometer devices.

[0080] The spectrometer can contain one or more ion traps or one or more ion confinement regions.

[0081] The spectrometer may contain one or more impact, fragmentation, or reaction cells selected from the following group: (i) an impact-induced dissociation fragmentation device (“CID fragmentation device”), (ii) a surface-induced dissociation fragmentation device (“SID fragmentation device”), (iii) an electron transfer dissociation fragmentation device (“ETD fragmentation device”), (iv) an electron capture dissociation fragmentation device (“ECD fragmentation device”), (v) an electron impact or collision dissociation fragmentation device, (vi) a photo-induced dissociation fragmentation device (“PID fragmentation device”), (vii) a laser-induced dissociation fragmentation device, (viii) an infrared radiation-induced dissociation device. (ix) an ultraviolet radiation-induced dissociation device,(x) a nozzle-skimmer interface fragmentation device, (xi) an in-source fragmentation device, (xii) an in-source impact-induced dissociation fragmentation device, (xiii) a thermal or temperature source fragmentation device, (xiv) an electric field-induced fragmentation device, (xv) a magnetic field-induced fragmentation device, (xvi) an enzyme digestion or enzyme degradation fragmentation device, (xvii) an ion-ion reaction fragmentation device, (xviii) an ion-molecule reaction fragmentation device, (xix) an ion-atom reaction fragmentation device, (xx) an ion-metastable ion reaction fragmentation device, (xxi) an ion-metastable molecule reaction fragmentation device, (xxii) a Ion-metastable atom reaction fragmentation device, (xxiii) an ion-ion reaction device for reacting ions to form adducts or productions,(xxiv) an ion-molecule reaction device for reacting ions to form adducts or productions, (xxv) an ion-atom reaction device for reacting ions to form adducts or productions, (xxvi) an ion-metastable ion reaction device for reacting ions to form adducts or productions, (xxvii) an ion-metastable molecule reaction device for reacting ions to form adducts or productions, (xxviii) an ion-metastable atom reaction device for reacting ions to form adducts or productions, and (xxix) an electron ionization dissociation fragmentation device (“EID fragmentation device”).

[0082] The ion-molecule reaction device can be designed to perform ozonolysis for the localization of olefinic (double) bonds in lipids.

[0083] The spectrometer may include a mass analyzer selected from the following group: (i) a quadrupole mass analyzer, (ii) a 2D or linear quadrupole mass analyzer, (iii) a Paul or 3D quadrupole mass analyzer, (iv) a Penning trap mass analyzer, (v) an ion trap mass analyzer, (vi) a magnetic sector mass analyzer, (vii) an ion cyclotron resonance mass analyzer (“ICR mass analyzer”), (viii) a Fourier transform ion cyclotron resonance mass analyzer (“FTICR mass analyzer”), (ix) an electrostatic mass analyzer designed to generate an electrostatic field with a quadrologarithmic potential distribution, (x) an electrostatic Fourier transform mass analyzer, (xi) a Fourier transform mass analyzer, (xii) a time-of-flight mass analyzer, (xiii) an orthogonal acceleration time-of-flight mass analyzer and (xiv) a linear acceleration time-of-flight mass analyzer.

[0084] The spectrometer can contain one or more energy analyzers or electrostatic energy analyzers.

[0085] The spectrometer can contain one or more ion detectors.

[0086] The spectrometer may contain one or more mass filters selected from the following group: (i) a quadrupole mass filter, (ii) a 2D or linear quadrupole ion trap, (iii) a Paul or 3D quadrupole ion trap, (iv) a Penning ion trap, (v) an ion trap, (vi) a magnetic sector mass filter, (vii) a time-of-flight mass filter, and (viii) a Wien filter.

[0087] The spectrometer may include a device or ion gate for pulsed ions; and / or a device for converting an essentially continuous ion beam into a pulsed ion beam.

[0088] The spectrometer can include a C-trap and a mass analyzer with an outer tubular electrode and a coaxial inner spindle-shaped electrode forming an electrostatic field with a quadrologarithmic potential distribution, wherein in a first operating mode ions are allowed to pass through to the C-trap and then injected into the mass analyzer, and wherein in a second operating mode ions are allowed to pass through to the C-trap and then to a collision cell or electron transfer dissociation device, wherein at least some ions are fragmented into fragment ions, and wherein the fragment ions are then allowed to pass through to the C-trap before being injected into the mass analyzer.

[0089] The spectrometer can include a ring-stacked ion guide comprising several electrodes, each having an opening through which ions pass during use, wherein the distance between the electrodes increases along the length of the ion path, and wherein the openings in the electrodes in an upstream section of the ion guide have a first diameter, and wherein the openings in the electrodes in a downstream section of the ion guide have a second diameter that is smaller than the first diameter, and wherein opposite phases of an alternating or RF voltage are applied to successive electrodes during use.

[0090] According to one embodiment, the mass spectrometer further includes a device designed and adapted to supply an alternating or RF voltage to the electrodes. The AC or RF voltage preferably has an amplitude selected from the following group: (i) < about 50 V peak-to-peak, (ii) about 50-100 V peak-to-peak, (iii) about 100-150 V peak-to-peak, (iv) about 150-200 V peak-to-peak, (v) about 200-250 V peak-to-peak, (vi) about 250-300 V peak-to-peak, (vii) about 300-350 V peak-to-peak, (viii) about 350-400 V peak-to-peak, (ix) about 400-450 V peak-to-peak, (x) about 450-500 V peak-to-peak, and (xi) > about 500 V Peak-to-peak.

[0091] The alternating or RF voltage can have a frequency selected from the following group: (i) < about 100 kHz, (ii) about 100-200 kHz, (iii) about 200-300 kHz, (iv) about 300-400 kHz, (v) about 400-500 kHz, (vi) about 0.5-1.0 MHz, (vii) about 1.0-1.5 MHz, (viii) about 1.5-2.0 MHz, (ix) about 2.0-2.5 MHz, (x) about 2.5-3.0 MHz, (xi) about 3.0-3.5 MHz, (xii) about 3.5-4.0 MHz, (xiii) about 4.0-4.5 MHz, (xiv) about 4.5-5.0 MHz, (xv) about 5.0-5.5 MHz, (xvi) approximately 5.5-6.0 MHz, (xvii) approximately 6.0-6.5 MHz, (xviii) approximately 6.5-7.0 MHz, (xix) approximately 7.0-7.5 MHz, (xx) approximately 7.5-8.0 MHz, (xxi) approximately 8.0-8.5 MHz, (xxii) approximately 8.5-9.0 MHz, (xxiii) approximately 9.0-9.5 MHz, (xxiv) approximately 9.5-10.0 MHz and (xxv) > approximately 10.0 MHz.

[0092] The spectrometer may also include a chromatography or other separation device upstream of an ion source. According to one embodiment, the chromatography separation device may include a liquid chromatography or gas chromatography device. Alternatively, the separation device may include: (i) a capillary electrophoresis separation device (“CE separation device”), (ii) a capillary electrochromatography separation device (“CEC separation device”), (iii) a separation device with a substantially rigid ceramic-based multilayer microfluidic substrate (“ceramic tile”), or (iv) a supercritical fluid chromatography separation device.

[0093] The ion guidance can be maintained at a pressure selected from the following group: (i) < about 0.0001 mbar, (ii) about 0.0001-0.001 mbar, (iii) about 0.001-0.01 mbar, (iv) about 0.01-0.1 mbar, (v) about 0.1-1 mbar, (vi) about 1-10 mbar, (vii) about 10-100 mbar, (viii) about 100-1000 mbar and (ix) > about 1000 mbar.

[0094] Analyte ions can be subjected to electron transfer dissociation fragmentation (ETD fragmentation) in an ETD fragmentation device. Analyte ions can be induced to interact with ETD reagents within an ion guide or fragmentation device.

[0095] Alternatively, to effect electron transfer dissociation, either: (a) analyte ions are fragmented or caused to dissociate and form product or fragment ions after interacting with reagent ions, and / or (b) electrons are transferred from one or more reagent anions or negatively charged ions to one or more multiply charged analyte cations or positively charged ions, whereupon at least some of the multiply charged analyte cations or positively charged ions are caused to dissociate and form product or fragment ions, and / or (c) analyte ions are fragmented or caused to dissociate and form product or fragment ions after interacting with neutral reagent gas molecules or atoms or a non-ionic reagent gas.and / or (d) transfer electrons from one or more neutral nonionic or uncharged starting gases or vapors to one or more multiply charged analyte cations or positively charged ions, whereupon at least some of the multiply charged analyte cations or positively charged ions are caused to dissociate and form product or fragment ions, and / or (e) transfer electrons from one or more neutral nonionic or uncharged superbase reagent gases or vapors to one or more multiply charged analyte cations or positively charged ions, whereupon at least some of the multiply charged analyte cations or positively charged ions are caused to dissociate and form product or fragment ions, and / or (f) transfer electrons from one or more neutral,(a) transfer electrons from one or more non-ionic or uncharged alkali metal gases or vapors to one or more multiply charged analyte cations or positively charged ions, whereupon at least some of the multiply charged analyte cations or positively charged ions are caused to dissociate and form product or fragment ions, and / or (b) transfer electrons from one or more neutral, non-ionic or uncharged gases, vapors or atoms to one or more multiply charged analyte cations or positively charged ions, whereupon at least some of the multiply charged analyte cations or positively charged ions are caused to dissociate and form product or fragment ions, wherein the one or more neutral, non-ionic or uncharged gases, vapors or atoms are selected from the following group: (i) sodium vapor or atoms, (ii) lithium vapor or atoms, (iii) potassium vapor or atoms, (iv) rubidium vapor or atoms,(v) Cesium vapor or atoms, (vi) Francium vapor or atoms, (vii) C60 vapor or atoms and (viii) Magnesium vapor or atoms.

[0096] The multiply charged analyte cations or positively charged ions can contain peptides, polypeptides, proteins or biomolecules.

[0097] Alternatively, to effect electron transfer dissociation: (a) the reagent anions or negatively charged ions are derived from a polyaromatic hydrocarbon or a substituted polyaromatic hydrocarbon and / or (b) the reagent anions or negatively charged ions are derived from the following group: (i) anthracene, (ii) 9,10-diphenylanthracene, (iii) naphthalene, (iv) fluorine, (v) phenanthrene, (vi) pyrene, (vii) fluoranthene, (viii) chrysene, (ix) triphenylene, (x) perylene, (xi) acridine, (xii) 2,2'-dipyridyl, (xiii) 2,2'-biquinoline, (xiv) 9-anthracenecarbonitrile, (xv) dibenzothiophene, (xvi) 1,10'-phenanthroline, (xvii) 9'-Anthracene carbonitrile and (xviii) anthraquinone and / or (c) contain the reagents or negatively charged ions azobenzene anions or azobenzene radical anions.

[0098] The process of electron transfer dissociation fragmentation can involve the interaction of analyte ions with reagents, where the reagents include dicyanobenzene, 4-nitrotoluene, or azulene.

[0099] A chromatography detector may be provided, wherein the chromatography detector contains: either a destructive chromatography detector selected from the following group: (i) a flame ionization detector (“FID”), (ii) an aerosol-based detector or a nanoquantity analyte detector (“NQAD”), (iii) a flame photometry detector (“FPD”), (iv) an atomic emission detector (“AED”), (v) a nitrogen phosphorus detector (“NPD”) and (vi) an evaporative light scattering detector (“ELSD”) or a non-destructive chromatography detector, optionally selected from the following group: (i) a fixed or variable wavelength UV detector, (ii) a thermal conductivity detector (“TCD”), (iii) a fluorescence detector, (iv) an electron capture detector (“ECD”), (v) a conductivity monitoring device, (vi) a photoionization detector (“PID”), (vii) a refractive index detector (“RID”), (viii) a radio current detector and (ix) a chiral detector.

[0100] The spectrometer can be operated in various modes, including a mass spectrometry mode (“MS mode”); a tandem mass spectrometry mode (“MS / MS mode”); a mode in which starting or precursor ions are alternatively fragmented or converted to produce fragments or productions, and are not fragmented or converted, or fragmented or converted to a lesser extent; a multiple reaction monitoring mode (“MRM mode”); a data-dependent analysis mode (“DDA mode”); a data-independent analysis mode (“DIA mode”); a quantification mode; or an ion mobility spectrometry mode (“IMS mode”). Brief description of the drawings

[0101] Various embodiments of the present invention are now described by way of example only with reference to the accompanying drawings, wherein: Fig. 1 shows a time-of-flight mass spectrometer (“ToF mass spectrometer”) which can be operated according to one embodiment; Fig. 2 a computer program according to one embodiment in which raw data are transformed to generate frequency domain data, and the frequency domain data are modified and transformed to generate reconstructed data; Fig. 3. Raw time-of-flight mass spectral data and time-of-flight mass spectral data processed according to one embodiment are shown; Fig. 4 shows a superimposed representation of raw time-of-flight mass spectral data and time-of-flight mass spectral data that have been processed according to an embodiment; Fig. 5. Raw time-of-flight mass spectral data and time-of-flight mass spectral data processed according to one embodiment; and Fig. Six raw time-of-flight mass spectral data and time-of-flight mass spectral data processed according to one embodiment are shown. Detailed description

[0102] Various embodiments will now be described. Fig. Figure 1 shows a mass spectrometer according to an embodiment comprising one or more upstream stages 1, an acceleration region 2, a field-free region or drift region 3, an ion detector 4 arranged at the exit region of the field-free region or drift region 3, and a control system 5.

[0103] Ions formed in one or more upstream stages 1 of the mass spectrometer are designed to enter the acceleration region 2, where they are driven by an acceleration pulse applied to an accelerating electrode in the field-free region or drift region 3. The ions are accelerated to a velocity determined by the energy imparted by the acceleration pulse and the mass or mass-to-charge ratio of the ions. Ions with a relatively low mass-to-charge ratio achieve a relatively high velocity and reach the ion detector 4 before ions with a relatively high mass-to-charge ratio.

[0104] Thus, after a time determined by their velocity and the distance traveled, ions reach the ion detector 4, which makes it possible to determine the mass or mass-to-charge ratio of the ions. Each ion or group of ions arriving at the detector 4 is scanned by the detector 4, and the control system 5 determines a value indicating the time-of-flight and / or the mass-to-charge ratio (“m / z”) of the ion or group of ions. The data for multiple ions can be collected and combined to generate a time-of-flight spectrum (“ToF spectrum”) and / or a mass spectrum.

[0105] According to various embodiments, the detector 4 generates a pulse for each ion or group of ions arriving at the detector 4. This pulse can then be digitized by the control system 5 and converted into a time-intensity pair, i.e., a data value containing a time-of-flight value along with an intensity value. In these embodiments, several such time-intensity pairs can be collected and combined, e.g., histogramged, to generate the time-of-flight spectrum (“ToF spectrum”) and / or a mass spectrum.

[0106] Thus, in various embodiments, time-domain and / or mass-to-charge ratio-domain mass spectrometry data are acquired using a mass spectrometer. If time-domain mass spectrometry data are acquired, they can optionally be converted into mass-to-charge ratio-domain mass spectrometry data.

[0107] In various embodiments, the acquired mass spectral data are subjected to digital signal filtering techniques such as fast Fourier transform digital signal filtering techniques (“FFT digital signal filtering techniques”) (e.g. using control system 5) to improve the quality of the mass spectral data.

[0108] In particular, and as discussed above, according to the various embodiments, the acquired mass spectral data are transformed to obtain frequency-domain mass spectral data (to obtain transformed mass spectral data). For the purposes of this application, "frequency domain" means the space that is dual to mass or mass-to-charge ratio under the specified integral transformation or discrete version of an integral transformation. The frequency-domain mass spectral data (the transformed mass spectral data) are then modified by attenuating one or more regions of the frequency-domain mass spectral data (the transformed mass spectral data) (e.g., by...).using one or more step, window, apodization or tapering functions) to obtain modified frequency-domain mass spectral data (to obtain modified transformed mass spectral data), and then the modified frequency-domain mass spectral data (the modified transformed mass spectral data) are transformed to obtain modified mass spectral data.

[0109] According to various embodiments, the mass spectral data are processed in a manner that removes localized baseline aberrations, which are typically associated with and adjacent to peaks of interest, for example by applying a fast Fourier transform (“FFT”) and apodization. These techniques are particularly advantageous in the analysis of intact monoclonal antibodies (“MABs”).

[0110] The procedure can include: providing time-of-flight data (e.g., time-intensity pairs) to a fast Fourier transform processor (“FFT processor”) to generate frequency domain data; digitally manipulating ranges of frequencies from the frequency domain data to improve spectral quality by removing chemical or electrical noise; and reconstructing the time-of-flight data from the manipulated frequency domain using an inverse fast Fourier transform algorithm (“inverse FFT algorithm”). Thus, one or more frequency ranges from the frequency domain mass spectral data can be attenuated or removed using one or more step, window, apodization, or tapering functions. The output data contains a spectrum of improved quality.

[0111] It will be understood that these techniques acknowledge that processing time-of-flight mass spectral data (“ToF mass spectral data”) via apodization of the transformed frequency domain data by removing peak tailing and by background subtraction localized to peaks offers advantages in improving data quality. In particular, the propagation of peak socketing or baseline rise, e.g., due to incomplete desolvation or collisions with residual gas in the time-of-flight mass analyzer (“ToF mass analyzer”), can be reduced or removed, for example, by attenuating ranges of frequencies that are essentially unwanted background noise artifacts locally associated with and occurring between peaks of interest (non-repeating baseline rise adjacent to peaks of interest).

[0112] Thus, one or more step, window, apodization, or tapering functions can be designed to attenuate and / or remove one or more regions of the frequency-domain mass spectral data associated with non-repeating noise artifacts, which may be associated with peaks of interest. The frequencies of the frequency-domain mass spectral data to be attenuated and / or removed can be predefined, i.e., independent of the acquired mass spectral data. For example, frequencies of the frequency-domain mass spectral data above and / or below one or more predefined cutoff frequencies can be attenuated and / or removed.

[0113] Fig. 2 represents a data processing program for fast Fourier transform (“FFT”) according to various embodiments.

[0114] By performing a fast Fourier transform (FFT) on raw time-of-flight mass spectral data (i.e., non-mass-to-charge ratio range data, or m / z range data) and removing frequencies up to approximately 2 MHz (i.e., using a step function or a hat function), and then reconstructing the time-of-flight mass spectral data using an inverse fast Fourier transform (FFT), it becomes apparent that unwanted signal between the glycosylated peaks is attenuated, and the spectral quality is improved. This is because, for each peak of interest, the output spectrum begins to overshoot on either side of the peak of interest when the frequencies are attenuated.

[0115] Fig. 3 and Fig. Figure 4 shows example spectra in which there is clear evidence of the removal of the baseline artifact peaks that are located below the glycosylated monoclonal antibody peaks.

[0116] A further improvement in the data processing procedure can be achieved by using shaped frequency filter masks (i.e., apodization functions, i.e., functions that smoothly decay to zero at their minimum and / or maximum values) to reduce the overshoot effect caused by the use of a step or hat function. This can resolve the problem that occurs in the Fig. In example 3, the data fall below zero, which can obscure smaller non-artifact peaks that occur in the valleys. Further tuning of the apodization function can reduce the "overshoot effect," so that any smaller peaks occurring adjacent to larger peaks can still be observed. Fig. Figure 5 shows a spectrum comparing the raw data with data processed using an apodization function.

[0117] Although the above embodiments have been described with regard to performing a fast Fourier transform (“FFT”) in the forward direction, applying an apodization function, and then applying an inverse fast Fourier transform (“FFT”), it would also be possible to use other transformation methods, such as discrete or continuous wavelet transformation methods. Thus, according to various embodiments, the mass spectral data and / or the modified mass spectral data can be transformed by: (i) a Fourier transform; (ii) a fast Fourier transform (FFT); (iii) a wavelet transform; (iv) a discrete wavelet transform; (v) a continuous wavelet transform; and / or (vi) any other integral transform or discrete version of an integral transform.

[0118] Similarly, the mass spectral data can be transformed using a forward transformation and the modified frequency-domain mass spectral data can be transformed using an inverse transformation, or alternatively, the mass spectral data can be transformed using an inverse transformation and the modified frequency-domain mass spectral data can be transformed using a forward transformation.

[0119] The techniques described here can be performed "on-the-fly" during data acquisition (in real time), for example, where processing takes place in customized firmware / hardware or one or more digital signal processors ("DSPs"). Thus, the techniques can be performed automatically without user interaction.

[0120] Although the above embodiments have been described in relation to the removal of low-frequency noise, it would also be possible to remove or attenuate high-frequency noise and its harmonics.

[0121] According to one embodiment, methods for fast Fourier transform (FFT) or other transformations can be used to remove frequencies and harmonics of electronic noise in the time domain of mass spectral data.

[0122] Fig. Figure 6 shows example spectra where noise peaks are removed from an electrical recording using fast Fourier transform (“FFT”) techniques.

[0123] The techniques described here can also be applied to data acquired using other types of time-of-flight mass spectrometers (“ToF mass spectrometers”), and more generally to data acquired using other types of mass spectrometers that, for example, produce time-domain and / or mass-to-charge ratio domain mass spectral data.

[0124] It is understood that, according to various embodiments, the algorithm removes the instrumental aberration associated with each mass spectral peak, with the aberration appearing as a base around each ion peak and tending to cause broadening and loss of resolution.

[0125] Various designs work by attenuating only a relatively small fraction of the low-frequency components of the frequency domain data.

[0126] Various embodiments are not limited to mass-to-charge ratio scale spectral data (“m / z-scale spectral data”), but can equally be applied to time-domain time-of-flight scale spectral data (“time-domain TOF-scale spectral data”). Ultimately, these various embodiments search for low-frequency fluctuations in the signal, which are typically associated with aberrations in analyte signals resulting from collisions with residual gas.

[0127] According to various embodiments, peak baseline artifacts are reduced by attenuating a low-frequency range of the frequency-domain mass spectral data.

[0128] According to various other embodiments, the area in which the frequency domain data are attenuated and / or removed is selected on the basis of the average number of collisions that the detected ions have experienced, e.g. on the basis of the collision cross section (“CCS”) of the detected ions.

[0129] Peak aberrations (e.g., peak socketing), which are corrected by various designs, can originate from collisions of ions with residual gas in the time-of-flight mass analyzer (TOF mass analyzer). These collisions can lead to variations in the ion velocities. The degree of aberration can depend on the probability of the analyte ion colliding with residual gas molecules and the way in which the time-of-flight system (TOF system) handles changes in energy during flight.

[0130] The probability that an analyte ion collides with a gas molecule depends on the collision cross-section of the analyte ion with respect to the background gas, the partial pressure on the time-of-flight path (“TOF path”), and the path length traveled by the analyte ion in the residual gas within the time-of-flight path (“TOF path”).

[0131] Consider, for example, a monoclonal antibody (“mAb”) that is analyzed with the following parameters: Molecular weight = 147 kDa; Charges = 50; Kinetic energy (“KE”) = 10000 eV per charge; TOF path length = 2 m; Impact cross-sectional area (“CCS”) = 7000 angstroms 2 ; and Pressure = 5 × 10 -7 mB.

[0132] It can be calculated that the mean free path is approximately 1.2 m, so it can be estimated that an ion experiences an average of 1.7 collisions on its journey through the TOF mass analyzer.

[0133] The applicants have recognized that the degree of signal broadening (the size of the peak baseline) is a function of the average number of collisions experienced by each ion species.

[0134] Since the collision cross section (“CCS”) of the analyte peaks is known or can alternatively be measured using an ion mobility separation device or otherwise estimated (e.g. for unknown ions), and since all other parameters are also known, the mean free path and the approximate number of collisions experienced for each peak can be calculated.

[0135] According to various embodiments, for any or all peaks of interest in the mass spectral data, correction to the frequency domain data can be applied as needed (or not) and / or to varying degrees, e.g., depending on the number of collisions that the ions contributing to the peak have undergone. This can further improve the quality of the mass spectral data.

[0136] According to various such embodiments, for peaks where the collision cross-section (“CCS”) is unknown, the collision cross-section (“CCS”) can be determined based on the mass-to-charge ratio (“m / z”) measured from the spectrum, using CCS ≈ k*mass 2 / 3 approach.

[0137] Accordingly, the frequency domain mass spectral data are selectively modified depending on the estimated extent of peak broadening (peak socketing), i.e., depending on the estimated number of collisions or the collision cross section (“CCS”) of ions that contribute, for example, to mass spectroscopic peaks of interest in the mass spectral data.

[0138] The one or more regions of frequency-domain mass spectrometry data to be attenuated and / or removed can be selected based on the estimated extent of peak broadening (peak socketing), for example, for each mass spectroscopic peak of interest. Alternatively, the one or more regions of frequency-domain mass spectrometry data to be attenuated and / or removed can be selected based on the estimated number of collisions experienced by ions contributing to one or more, or each, of the mass spectroscopic peaks present in the mass spectrometry data.

[0139] In particular, one or more regions of frequency-domain mass spectral data to be attenuated and / or removed can be selected based on the collision cross section (“CCS”) of ions contributing to one or more or each of the mass spectroscopic peaks that appear in the mass spectral data.

[0140] In these embodiments, the collision cross section (“CCS”) of ions contributing to a given mass spectroscopic peak may be known (e.g., if the mass spectroscopic peak corresponds to a known ion species) and / or alternatively be determined (e.g., by means of a mobility separation device) and / or estimated (e.g., based on the mass-to-charge ratio of the mass spectroscopic peak).

[0141] As experts will recognize, numerous implementations offer improved data quality and create an alternative method to background subtraction.

Claims

[1] Methods of mass spectrometry, which include: Transforming time-domain mass spectral data to generate frequency-domain mass spectral data; Modifying the frequency-domain mass spectral data to generate modified frequency-domain mass spectral data by attenuating and / or removing one or more regions of the frequency-domain mass spectral data associated with peak socketing noise, which is associated with peaks of interest in the mass spectral data, by attenuating and / or removing frequencies from the frequency-domain mass spectral data that are below a threshold frequency; and Transforming the modified frequency domain mass spectral data to generate modified time domain mass spectral data. [2] Method according to claim 1, further comprising determining mass-to-charge ratio domain mass spectral data from the modified time domain mass spectral data. [3] Method according to any of the preceding claims, wherein the time-domain mass spectral data comprise time-of-flight mass spectral data. [4] Method according to any of the preceding claims, wherein the time-domain mass spectral data and / or the modified time-domain mass spectral data are transformed by: (i) a Fourier transform; (ii) a fast Fourier transform (FFT); (iii) a wavelet transformation; (iv) a discrete wavelet transformation; (v) a continuous wavelet transformation; and / or (vi) any other integral transformation or discrete version of an integral transformation. [5] Method according to claim 3, wherein one or more regions are selected on the basis of the average number of collisions experienced by ions, corresponding to peaks of interest in the time-domain mass spectral data. [6] Method according to claim 3, wherein one or more regions are selected on the basis of the collision cross section (“CCS”) of ions that correspond to peaks of interest in the time domain mass spectral data. [7] Method according to any of the preceding claims, wherein the modification of the frequency domain mass spectral data comprises attenuating and / or removing one or more regions of the frequency domain mass spectral data using one or more step or window functions. [8] Method according to claim 7, wherein the one or more window functions comprise a function comprising: a maximum frequency and a minimum frequency; where the function is relatively high below the maximum frequency and above the minimum frequency; and where the function is relatively low above the maximum frequency and below the minimum frequency. [9] The method of claim 7, wherein the one or more stage functions include a function comprising: a minimum frequency; where the function is relatively high above the minimum frequency; and where the function is relatively low below the minimum frequency. [10] Method according to claim 8 or 9, wherein the function falls smoothly to zero at the maximum frequency and / or at the minimum frequency. [11] Method according to any one of claims 8-10, wherein the minimum and / or maximum frequency comprises: (i) about 0.5 MHz; (ii) about 1 MHz; (iii) about 1.5 MHz; (iv) about 2 MHz; (v) about 2.5 MHz; (vi) about 3 MHz; (vii) about 3.5 MHz; (viii) about 4 MHz; (ix) about 5 MHz; (x) about 6 MHz; (xi) about 7 MHz; (xii) about 8 MHz; (xiii) about 9 MHz; (xiv) about 10 MHz; (xv) about 11 MHz; (xvi) about 12 MHz; (xvii) about 13 MHz; (xiii) about 14 MHz; (xix) about 15 MHz; (xx) about 16 MHz; (xxi) about 17 MHz; (xxii) approximately 18 MHz; (xxiii) approximately 19 MHz; and / or (xxiv) approximately 20 MHz. [12] Method according to any of the preceding claims, wherein the frequency domain mass spectral data are modified in a predefined manner which does not depend on the time domain mass spectral data and / or the frequency domain mass spectral data. [13] Method according to any of the preceding claims, wherein the method is carried out automatically without user interaction. [14] A method according to any of the preceding claims, further comprising acquiring the time-domain mass spectral data using a mass spectrometer; wherein the steps of transforming the time-domain mass spectral data, modifying the frequency-domain mass spectral data and transforming the modified frequency-domain mass spectral data are performed simultaneously with the step of acquiring the time-domain mass spectral data. [15] Device containing: a device designed and adapted to transform time-domain mass spectral data to generate frequency-domain mass spectral data; a device designed and adapted to modify frequency-domain mass spectral data to generate modified frequency-domain mass spectral data by attenuating and / or removing one or more regions of the frequency-domain mass spectral data associated with peak socketing noise associated with peaks of interest in the mass spectral data, by attenuating and / or removing frequencies from the frequency-domain mass spectral data that are below a threshold frequency, and a facility designed and adapted to transform the modified frequency domain mass spectral data to generate modified time domain mass spectral data. [16] Mass spectrometer comprising the device according to claim 15.

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