Theoretical collision cross-section ("CCS") in experiment design

Abstract

Methods for mass spectrometry, which include the following: Calculating an ion mobility value, collision cross-section, or interaction cross-section of a number of different analytes generated from one or more analytes of interest under one or more different analytical conditions, wherein the one or more analytical conditions comprise one or more conditions for generating the number of different analytes from the one or more analytes of interest; and Setting one or more operating parameters of a mass spectrometer in response to the calculated ion mobility values, collision cross sections or interaction cross sections to maximize or improve subsequent ion mobility separation of a number of different analyte ions, wherein the step of setting the one or more operating parameters of the mass spectrometer comprises: Selecting one or more of the one or more distinct analytical conditions based on the calculated ion mobility values, collision cross sections, or interaction cross sections to maximize or improve the subsequent ion mobility separation of the number of different analyte ions; and Setting one or more operating parameters of the mass spectrometer to generate one or more selected analytical conditions.

Description

AREA OF INVENTION

[0001] The present invention relates generally to the field of mass spectrometry and in particular to methods for mass spectrometry and mass spectrometers. BACKGROUND

[0002] Ion mobility spectrometry or separation (“IMS”) represents a powerful method for separating and identifying ions, especially in combination with liquid chromatography (“LC”) and mass spectrometry (“MS”) techniques. However, there are many cases where the IMS resolution is insufficient to separate ions that have very similar collision cross sections (“CCS”) or interaction cross sections.

[0003] The collision cross section (“CCS”) or interaction cross section measured for a particular analyte depends on the nature of the ions generated during or after the ionization process using the analyte, and also on the conditions within the measuring device, in the nature of the composition of the drift gas within an ion mobility spectrometry or separation device.

[0004] It is known to attempt to optimize the separation of ions in an ion mobility spectrometry or separation device for specific analytes. The optimal ion mobility conditions for a given analyte are determined by experimentally analyzing the same analyte under several different conditions. However, this optimization is empirical and involves a large number of time-consuming experiments. Furthermore, this unguided, experimental approach may ultimately fail to yield a satisfactory result.

[0005] Reference is made to Prabha Dwivedi, Brad Bendiak, Brian H. Clowers, Herbert H. Hill Jr., “Rapid Resolution of Carbohydrate Isomers by Electrospray Ionization Ambient Pressure Ion Mobility Spectrometry-Time-of-Flight Mass Spectrometry (ESI-APIMS-TOFMS)”. In this publication, controlling the charge carrier during ionization of positive carbohydrate ions enables the resolution of isomeric pairs through ion mobility.

[0006] Reference is also made to Rapid Commun. Mass Spectrom. 2009; 23: 3563-3569 “Use of ion mobility mass spectrometry and a collision cross-section algorithm to study an organometallic ruthenium anticancer complex and its adducts with a DNA oligonucleotide”. This publication explains an approach for calculating the theoretical cross-section for known organometallic compounds.

[0007] US Patent 2010 / 0224770A1 relates to a method for configuring an ion mobility spectrometer system, specifically for the detection of a target analyte. The proposed method includes the use of quantum chemical techniques to estimate the K0 values ​​of the target analyte and the configuration of the ion mobility spectrometer system based on a detection algorithm.

[0008] US Patent 8,296,078 B1 discloses a method for multidimensional moment analysis for characterizing signal peaks, which can be used to optimize the operation of an analysis system. Two-dimensional Péclet analysis allows the quality and signal fidelity of peaks in a two-dimensional experimental space to be analyzed and evaluated.

[0009] US Patent 2012 / 0004862A1 discloses a method for performing ion mobility spectrometry. The applied electric field has a variety of strength values ​​over time, with the individual strength values ​​generally remaining constant during a given time interval. The method further includes measuring the ion intensity and the drift time of the ionized sample as it moves through the drift zone under the applied electric field.

[0010] WO 2011 / 128 703 A1 discloses a method for identifying and / or characterizing a sample that may contain two or more isomeric or isobaric compounds, such as hydroxylated metabolites. It comprises modeling possible structures for each of two or more known isomeric or isobaric compounds, calculating a theoretical collision cross-section for each modeled structure, and averaging the calculated values ​​for each known compound to obtain a theoretical collision cross-section value.

[0011] It is desirable to provide an improved method for mass spectrometry. SUMMARY

[0012] According to the present disclosure, a method for mass spectrometry and a mass spectrometer with the features of the independent claims are proposed. The dependent claims relate to embodiments.

[0013] One embodiment relates to a mass spectrometry method in which a collision cross section or interaction cross section is theoretically calculated for each of a number of different analytes under one or more different analytical conditions. One or more operating parameters of a mass spectrometer can then be determined based on the theoretically calculated collision cross sections or interaction cross sections to maximize or improve subsequent ion mobility separation of the number of different analytes.

[0014] According to one embodiment, theoretical calculations of the collision cross sections or interaction cross sections of a number of different analytes under one or more different analytical conditions can be used to determine an optimal set of analytical conditions and / or operating parameters, thereby maximizing or improving the ion mobility separation of the number of different analytes. In this way, the mass spectrometer's ability to appropriately separate and identify the analytes from which the number of different analytes are derived can be suitably maximized or improved.

[0015] The use of theoretical calculations of the collision cross-sections or the interaction cross-sections according to one embodiment advantageously reduces the time and effort required to find the optimal set of analytical conditions and / or operating parameters compared with known empirical experimental methods, and also saves samples which in many cases can be difficult to obtain in sufficient quantity for extensive experimental optimization.

[0016] The embodiment described above represents a systematic approach for predicting the optimal experimental conditions for ionization and / or ion mobility spectrometry or separation for specific analytes.

[0017] It is therefore understandable that an improved method for mass spectrometry is being provided.

[0018] According to one embodiment, the step of calculating an ion mobility value, collision cross-section or interaction cross-section of several different analyte ions under one or more different analytical conditions comprises calculating an ion mobility value, collision cross-section or interaction cross-section of several different analyte ions under two or more different analytical conditions.

[0019] According to one embodiment, the number of different analytes refers to the same analyte, but with different shapes, structures, states or other properties.

[0020] According to one embodiment, the number of different analytes refers to different analytes with different compositions, shapes, structures, states or other properties.

[0021] According to one embodiment, the method comprises the following: Determining, calculating, or predicting a number of different analytes that can be generated from one or more analytes of interest under one or more of the different analytical conditions, wherein the step of calculating the ion mobility value, collision cross-section, or interaction cross-section of the several different analytes under the one or more different analytical conditions includes calculating an ion mobility value, collision cross-section, or interaction cross-section for one or more of the determined, calculated, or predicted different analytes.

[0022] According to one embodiment, the step of setting one or more operating parameters of the mass spectrometer comprises the following: Selecting one or more of the different analytical conditions based on the calculated ion mobility values, collision cross sections, or interaction cross sections to maximize or improve the subsequent ion mobility separation of the number of different analyte ions, and

[0023] Setting one or more operating parameters of the mass spectrometer to generate one or more selected analytical conditions.

[0024] According to one embodiment, the method comprises separating the number of different analyte ions once or several times according to their ion mobility using the mass spectrometer.

[0025] According to one embodiment, the method comprises separating the number of different analyte ions once or several times according to the rate of change of their ion mobility with the electric field strength using the mass spectrometer.

[0026] According to one embodiment, the method comprises the following: generating the number of different analyte ions using the mass spectrometer.

[0027] According to one embodiment, the method includes mass analysis of the number of different analyte ions using the mass spectrometer.

[0028] According to one embodiment, the method comprises the following: Calculating one or more additional physicochemical or other properties of the number of different analytes under one or more different analytical conditions and

[0029] Determining one or more operating parameters of the mass spectrometer based on the calculated additional physicochemical or other properties in order to maximize or improve the subsequent ion mobility separation of the number of different analyte ions.

[0030] According to one embodiment, the one or more additional physicochemical or other properties include the peak shape, peak width, peak slope, number of peaks and / or peak kurtosis.

[0031] According to one embodiment, the method comprises the following: Determining an ion mobility value, collision cross-section or interaction cross-section difference between an ion mobility value, collision cross-section or interaction cross-section calculated under first analytical conditions and an ion mobility value, collision cross-section or interaction cross-section calculated under second different analytical conditions and

[0032] Determining one or more operating parameters of the mass spectrometer based on the determined ion mobility value, collision cross-section, or interaction cross-section difference to maximize or improve the subsequent ion mobility separation of the number of different analyte ions.

[0033] According to one embodiment, the one or more analytical conditions comprise one or more pre-ionization, ionization or post-ionization conditions for generating the number of different analyte ions and / or one or more experimental or measurement conditions for measuring the number of different analyte ions.

[0034] According to one embodiment, one or more analytical conditions are selected from the group consisting of the following: (i) the composition and / or concentration of a salt, doping agent, derivatizing agent, reagent, displacement reagent, overloading reagent or charge-reducing reagent added to a liquid sample prior to ionization, (ii) the composition and / or concentration of a neutral gas, doping gas, derivatizing agent gas, reagent gas, displacement reagent gas, overload reagent gas or charge-reducing reagent gas added to a gaseous or vapor phase sample prior to ionization, (iii) the composition and / or concentration of a neutral gas, reactive gas, doping gas, derivatizing agent, reagent gas, displacement reagent gas, overload reagent gas or charge-reducing reagent gas designed to interact or react with analyte ions according to their ion mobility after ionization and / or prior to ion separation, and (iv) the composition and / or concentration of doping ions, derivatizing ions, reagents, overcharging reagents or charge-reducing reagents designed to interact or react with analyte ions according to their ion mobility after ionization and / or before separation of the ions.

[0035] According to one embodiment, one or more analytical conditions are selected from the group consisting of: (i) a condition and / or parameter that affects the charge state of the analytes, (ii) a condition and / or parameter that affects the energy level of the analytes, (iii) a condition and / or parameter that affects the kinetic energy of the analytes, (iv) a condition and / or parameter that affects the activation energy of the analytes, and (v) a condition and / or parameter that affects the conformational shape or nature of the analytes.

[0036] According to one embodiment, one or more analytical conditions are selected from the group consisting of: (i) an ionization condition of an ion source, (ii) the type of ion source used for ionizing a sample, (iii) the voltage setting of an ion source, (iv) the ionization polarity of ions generated by an ion source, (v) the flow rate of the sample supplied to an ion source, (vi) one or more liquid chromatography conditions of a liquid chromatography system, (vii) the composition of a liquid chromatography solution or liquid chromatography solvent, and (viii) the liquid chromatography flow rate.

[0037] According to one embodiment, one or more analytical conditions are selected from the group consisting of: (i) subjecting ions to hydrogen-deuterium exchange, (ii) one or more hydrogen-deuterium exchange conditions, (iii) subjecting ions to activation, photoactivation, dissociation or photodissociation, (iv) one or more dissociation, photodissociation, activation and / or photoactivation conditions, (v) subjecting ions to heating or RF heating, (vi) one or more heating or RF heating conditions, (vii) exposing ions to electromagnetic radiation, microwave radiation or laser radiation, (viii) one or more conditions of electromagnetic radiation, microwave radiation or laser radiation, (ix) subjecting ions to fragmentation or reaction and (x) one or more fragmentation or reaction conditions.

[0038] According to one embodiment, one or more analytical conditions are selected from the group consisting of: (i) a voltage applied to an ion-optical component, (ii) a path traveled by analyte ions through a section of the mass spectrometer, (iii) the transit time of analyte ions through a section of the mass spectrometer, (iv) one or more pressures inside the mass spectrometer, (v) one or more temperatures inside the mass spectrometer, (vi) the composition of a gas inside the mass spectrometer, and (vii) the strength of an electric field inside the mass spectrometer.

[0039] According to one embodiment, one or more analytical conditions are selected from the group consisting of: (i) the composition of an ion mobility separation or buffer gas, (ii) the composition of one or more additives, dopants, and / or reagents added to an ion mobility separation or buffer gas, (iii) the flow rate and / or flow direction of an ion mobility separation or buffer gas, (iv) the pressure or number density of an ion mobility separation or buffer gas, (v) the temperature within an ion mobility separation device, (vi) the strength of an electric field within an ion mobility separation device, (vii) the path length traveled by ions within an ion mobility separation device.(viii) the residence time of ions within an ion mobility separation device, (ix) the initial width of an ion pulse introduced into an ion mobility separation device, and (x) the velocity, amplitude, or repetition pattern of a traveling DC voltage wave within an ion mobility separation device.

[0040] According to one embodiment, the step of calculating the ion mobility value, the collision cross-section, or the interaction cross-section comprises the following: Calculating a three-dimensional structure of one or more different analytes and Calculating one or more of the ion mobility value, collision cross-section or interaction cross-section using the three-dimensional structure.

[0041] According to one embodiment, the step of calculating the ion mobility value, collision cross-section or interaction cross-section comprises the following: calculating the effects of electronic interactions of the number of different analyte ions with a polar or polarizable ion mobility separation or buffer gas.

[0042] According to one aspect, a mass spectrometer is provided with a control system which is set up and designed to perform the following: Calculating an ion mobility value, a collision cross-section, or an interaction cross-section of a number of different analyte ions under one or more different analytical conditions and

[0043] Setting one or more operating parameters of the mass spectrometer in response to the calculated ion mobility values, collision cross sections or interaction cross sections in order to maximize or improve subsequent ion mobility separation of a number of different analyte ions.

[0044] According to one embodiment, when two or more known target analytes or isomers are given, the structures and theoretical collision cross-section (CCS) values ​​for a range of different gas-phase ions derived from these analytes can be systematically calculated under various solution-phase and / or gas-phase conditions and / or under various ion mobility spectrometry or separation conditions. Based on these calculations, the optimal analytical conditions under which these analytes are effectively separated by ion mobility spectrometry or separation can then be predicted. This prediction can then be used to determine a subsequent ion mobility spectrometry or separation experiment, thus optimizing the experiment for each target compound.The list of different ionic forms of the target compounds and of ion mobility spectrometry or separation conditions can be limited to those available within a specific laboratory or for a specific ion source or ion mobility spectrometry or separation design.

[0045] According to one aspect, a method for ion mobility spectrometry is provided, which includes the following: (a) Identifying two or more compounds or isomeric forms of a compound or of compounds that can be separated by ion mobility, (b) Calculating theoretical structures for a variety of gas-phase ions of these compounds or gas-phase ions derived from these compounds that can be formed by changing the solution-phase or gas-phase chemistry, (c) Calculating theoretical collision cross-section or interaction cross-section values ​​for each of these ions under a variety of different ion mobility spectrometry or separation conditions, (d) using the theoretically calculated CCS values, determine the experimental gas-phase or solution-phase conditions of the instrument that are most likely to yield optimal ion mobility spectrometry or separation for that species, and then (e) Analyzing these species by ion mobility spectrometry or separation using optimal conditions.

[0046] The multitude of gas phase ions can include various charge carriers such as sodium, potassium, lithium, chlorine, bromine, fluorine, iodine, etc., as well as various adducts or derivatizing agents, different charge states, etc.

[0047] The various ion mobility spectrometry or separation conditions may include the use of different drift media such as polarizable or polar drift gases and dopants, or the introduction of energy into the ions when they are separated by ion mobility spectrometry or separation to change the gas phase structure.

[0048] Ion mobility spectrometry or separation can be coupled with mass spectrometry.

[0049] According to one embodiment, the mass spectrometer may further include the following: (a) an ion source selected from the group consisting of: (i) an electrospray ionization (“ESI”) ion source, (ii) an atmospheric pressure photoionization (“APPI”) ion source, (iii) an atmospheric pressure chemical ionization (“APCI”) ion source, (iv) a matrix-assisted laser desorption ionization (“MALDI”) ion source, (v) a laser desorption ionization (“LDI”) ion source, (vi) an atmospheric pressure ionization (“API”) ion source, (vii) a desorption ionization on silicon (“DIOS”) ion source, (viii) an electron impact (“EI”) ion source, (ix) a chemical ionization (“Cl”) ion source, (x) a field ionization (“Fl”) ion source, (xi) a (xii) field desorption (“FD”) ion source, (xii) an inductively coupled plasma (“ICP”) ion source, (xiii) a fast atom bombardment (“FAB”) ion source, (xiv) a liquid secondary ion mass spectrometry (“LSIMS”) ion source,(xv) a desorption electrospray ionization (“DESI”) ion source, (xvi) a radioactive nickel-63 ion source, (xvii) an atmospheric pressure matrix-assisted laser desorption ionization ion source, (xviii) a thermospray ion source, (xix) an atmospheric sampling glow discharge ionization (“ASGDI”) ion source, (xx) a glow discharge (“GD”) ion source, (xxi) an impactor ion source, (xxii) a direct analysis in real time (“DART”) ion source, (xxii) a laser spray ionization (“LSI”) ion source, (xxiv) a sonic spray ionization (“SSI”) ion source, (xxv) a matrix-assisted Intake ionization (“MAII”) ion source, (xxvi) a solvent-assisted intake ionization (“SAII”) ion source, (xxvii) a desorption electrospray ionization (“DESI”) ion source and (xxviii) a laser ablation electrospray ionization (“LAESI”) ion source and / or, (b) one or more continuous or pulsed ion sources and / or (c) one or more ion guides and / or (d) one or more ion mobility separation devices and / or one or more field asymmetric ion mobility spectrometer devices and / or (e) one or more ion traps or one or more ion containment areas and / or (f) one or more collision, fragmentation or reaction cells selected from the group consisting of: (i) a collision-induced dissociation (“CID”) fragmentation device, (ii) a surface-induced dissociation (“SID”) fragmentation device, (iii) an electron transfer dissociation (“ETD”) fragmentation device, (iv) an electron capture dissociation (“ECD”) fragmentation device, (v) an electron impact or collision dissociation fragmentation device, (vi) a photo-induced dissociation (“PID”) fragmentation device, (vii) a laser-induced dissociation fragmentation device, (viii) an infrared radiation-induced dissociation device, (ix) a 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) an 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 ("EID") fragmentation device and / or, (g) a mass analyzer selected from the group consisting of: (i) a quadrupole mass analyzer, (ii) a two-dimensional or linear quadrupole mass analyzer, (iii) a Paul or three-dimensional 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 (“ICR”) mass analyzer, (viii) a Fourier transform ion cyclotron resonance (“FTICR”) mass analyzer, (ix) an electrostatic mass analyzer configured 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 and / or, (h) one or more energy analyzers or electrostatic energy analyzers and / or (i) one or more ion detectors and / or (j) one or more mass filters selected from the group consisting of: (i) a quadrupole mass filter, (ii) a two-dimensional or linear quadrupole ion trap, (iii) a Paul or three-dimensional 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 and / or (k) a device or ion gate for pulsing ions and / or (l) a device for converting a substantially continuous ion beam into a pulsed ion beam.

[0050] The mass spectrometer may also have one of the following features: (i) a C-trap and a mass analyzer comprising 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 transferred to the C-trap and then injected into the mass analyzer, and wherein in a second operating mode ions are transferred to the C-trap and then transferred to a collision cell or electron transfer dissociation device where at least some ions are fragmented into fragment ions, and wherein the fragment ions are then transferred to the C-trap before being injected into the mass analyzer, and / or (ii) a ring-stack ion guide with multiple electrodes, each having an opening through which ions are allowed to pass during use, wherein the distance between the electrodes increases along 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 which is smaller than the first diameter, and wherein opposite phases of an alternating or RF voltage are applied to successive electrodes during use.

[0051] According to one embodiment, the mass spectrometer may further comprise a device that is set up and designed to supply an alternating or RF voltage to the electrodes. The AC or RF voltage can have an amplitude selected from the following group: (i) < 50 V peak-to-peak, (ii) 50–100 V peak-to-peak, (iii) 100–150 V peak-to-peak, (iv) 150–200 V peak-to-peak, (v) 200–250 V peak-to-peak, (vi) 250–300 V peak-to-peak, (vii) 300–350 V peak-to-peak, (viii) 350–400 V peak-to-peak, (ix) 400–450 V peak-to-peak, (x) 450–500 V peak-to-peak, and (xi) > 500 V Peak to peak.

[0052] The alternating or RF voltage can have a frequency selected from the following group: (i) < 100 kHz, (ii) 100 - 200 kHz, (iii) 200 - 300 kHz, (iv) 300 - 400 kHz, (v) 400 - 500 kHz, (vi) 0.5 - 1.0 MHz, (vii) 1.0 - 1.5 MHz, (viii) 1.5 - 2.0 MHz, (ix) 2.0 - 2.5 MHz, (x) 2.5 - 3.0 MHz, (xi) 3.0 - 3.5 MHz, (xii) 3.5 - 4.0 MHz, (xiii) 4.0 - 4.5 MHz, (xiv) 4.5 - 5.0 MHz, (xv) 5.0 - 5.5 MHz, (xvi) 5.5 - 6.0 MHz, (xvii) 6.0 - 6.5 MHz, (xviii) 6.5 - 7.0 MHz, (xix) 7.0 - 7.5 MHz, (xx) 7.5 - 8.0 MHz, (xxi) 8.0 - 8.5 MHz, (xxii) 8.5 - 9.0 MHz, (xxiii) 9.0 - 9.5 MHz, (xxiv) 9.5 - 10.0 MHz and (xxv) > 10.0 MHz.

[0053] The mass spectrometer may also include a chromatography or other separation device upstream of an ion source. According to one embodiment, the chromatography separation device comprises a liquid chromatography or gas chromatography device. According to another embodiment, the separation device may comprise: (i) a capillary electrophoresis (“CE”) separation device, (ii) a capillary electrochromatography (“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.

[0054] The mass spectrometer may include a chromatography detector.

[0055] The chromatography detector may comprise a destructive chromatography detector, preferably selected from the group consisting of: (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”).

[0056] Additionally or alternatively, the chromatography detector may comprise a non-destructive chromatography detector, preferably selected from the group consisting of: (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 flow detector (“radio flow detector”) and (ix) a chiral detector (“chiral detector”).

[0057] The ion guidance can be maintained at a pressure selected from the group consisting of the following: (i) < 0.0001 mbar, (ii) 0.0001 - 0.001 mbar, (iii) 0.001 - 0.01 mbar, (iv) 0.01 - 0.1 mbar, (v) 0.1 - 1 mbar, (vi) 1 - 10 mbar, (vii) 10 - 100 mbar, (viii) 100 - 1000 mbar and (ix) > 1000 mbar.

[0058] According to one embodiment, analyte ions can be subjected to electron transfer dissociation (“ETD”) fragmentation in an electron transfer dissociation fragmentation device. The analyte ions can be caused to interact with ETD reagents within an ion guide or fragmentation device.

[0059] According to one embodiment, 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) electrons are transferred from one or more neutral non-ionic 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) electrons are transferred from one or more neutral non-ionic 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) electrons are transferred from one or more neutral,(a) electrons are transferred 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 (g) electrons are transferred 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 group consisting of: (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) C, 60 -vapor or atoms and (viii) magnesium vapor or atoms.

[0060] The multiply charged analyte cations or positively charged ions can include peptides, polypeptides, proteins, or biomolecules.

[0061] According to one embodiment, 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 group consisting of: (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.

[0062] According to one embodiment, the electron transfer dissociation fragmentation process can include the interaction of analyte ions with reagents, wherein the reagents include dicyanobenzene, 4-nitrotoluene or azulene. BRIEF DESCRIPTION OF THE DRAWING

[0063] Various embodiments are now described only as examples and with reference to the accompanying drawing. It shows: Fig. 1. A flowchart according to one embodiment. DETAILED DESCRIPTION

[0064] One embodiment relates to a method wherein a collision cross-section or an interaction cross-section of several different analytes can be theoretically calculated under one or more different analytical conditions under one, two or more different pre-ionization, ionization and / or post-ionization conditions to generate the number of different analytes and / or one or more experimental conditions or measurement conditions to measure the number of different analytes, and then one or more of the one or more different analytical conditions can be selected on the basis of the calculated collision cross-sections or interaction cross-sections to maximize or improve a subsequent ion mobility separation of the number of different analytes using a mass spectrometer.One or more operating parameters of the mass spectrometer can be set based on the calculated collision cross sections or interaction cross sections to generate one or more selected analytical conditions in order to maximize or improve the subsequent ion mobility separation of the number of different analyte ions using the mass spectrometer.

[0065] The embodiment may include: determining or predicting a number of different analytes that can be generated from one or more analytes of interest under one or more of the different analytical conditions, for example under one, two or more different pre-ionization, ionization and / or post-ionization conditions; calculating the collision cross-section or interaction cross-section for each of the determined or predicted different analytes; and then selecting one or more of the different analytical conditions.

[0066] Additionally or alternatively, the embodiment may include: calculating a collision cross-section or interaction cross-section for a number of different analytes under one, two or more different experimental or measurement conditions and subsequently selecting one or more of the one or more different experimental or measurement conditions to maximize or improve the subsequent ion mobility separation of the number of different analytes.

[0067] According to one embodiment, one or more additional physicochemical or other properties of the number of different analytes, such as the ion mobility peak shape, ion mobility peak width, ion mobility peak slope, number of ion mobility peaks, and / or ion mobility peak kurtosis, can be calculated under one or more different analytical conditions and used to determine one or more operating parameters of the mass spectrometer in order to maximize or improve the subsequent ion mobility separation of the number of different analytes. For example, it may be the case that different ions, such as protomer ions, can be separated under certain conditions, such as in CO2, but not under other conditions, such as in He or N2, for example, into two or more peaks.

[0068] According to one embodiment, a collision cross-section or interaction cross-section difference between a collision cross-section or interaction cross-section calculated under first analytical conditions and a collision cross-section or interaction cross-section calculated under second different analytical conditions can be determined and used to select the analytical conditions and to determine one or more operating parameters of the mass spectrometer.

[0069] According to various embodiments, the separation of species or isomers can be improved or modified by selecting the charge state, charge carrier, or derivatizing agent. Alternatively or additionally, the selection of ion mobility spectrometry or separation drift media can be used to influence the separation by ion mobility spectrometry or separation. According to one embodiment, a polarizable drift gas or drift medium containing, for example, neutral gas-phase elements with a permanent dipole moment can be used to selectively modify the separation of different analytes or isomers of an analyte. The interaction of polarizable or polar neutral elements with ions depends on the electronic structure of the ions (local or bulk dipole moments), which can be highly specific for a given structure.

[0070] According to one embodiment, given a known compound identity, three-dimensional gas-phase structures for ions formed from that compound can be calculated. Molecular mechanics and quantum chemistry modeling approaches can be used to achieve this. Commercially available software, such as Gaussian (www.gaussian.com), can be used to perform such calculations.

[0071] These structures allow for the calculation of theoretical collision cross sections using software such as MobCal from Indiana University. See AA Shvartsburg and MF Jarrold, “An Exact Hard Spheres Scattering Model for the Mobilities of Polyatomic Ions”, Chem. Phys. Lett. 1996, 261, 86–91.

[0072] Within these calculations, the effect of the apparent collision cross section (“CCS”) of long-range electronic interactions between ions and polar or polarizable molecules in the ion mobility spectrometry or separation drift medium (buffer gas) can be taken into account, for example to calculate an interaction cross section.

[0073] Fig. Figure 1 shows a flowchart of one embodiment.

[0074] In step 1, target analytes are identified. For example, for a particular analysis, it may be known that two compounds with ions exhibiting identical or very similar mass-to-charge ratios may be present. These may be stereo or positional isomers, or the compounds may have entirely different elemental compositions or structures. Additionally or alternatively, they may be conformers of the same compound. Mass spectrometry alone may not be able to separate these species, either because they have the same mass-to-charge ratio or because the mass resolution of the analyzer used is insufficient.

[0075] Additionally or alternatively, a group of known target compounds can be selected for a specific analysis. For example, target pesticides, peptides, lipids, or carbohydrates can be chosen.

[0076] In any case, the purpose of an embodiment is to determine the experimental conditions in such a way that the ion mobility spectrometry or separation of two or more of these target compounds or of two or more ions of a compound can be optimized.

[0077] According to the preferred embodiment, the optimization of the ion mobility spectrometry or separation can improve the subsequent identification and quantification of isobaric or nominally isobaric compounds and reduce interferences in the ion mobility spectrometry or separation spectra, thereby enabling a more accurate calculation of cross-sections and peak areas.

[0078] In step 2, a range of possible analysis conditions can be selected.

[0079] Depending on the facilities within a given laboratory and the flexibility of the design of the ion mobility device, the ion source, and / or the inlet to the ion source, a range of different conditions can be investigated and used. The following list of preferred conditions is not exhaustive. Various solution and gas-phase chemistries can be used to modify the nature of the gas-phase ions generated from the analytes.

[0080] According to embodiments employing electrospray ionization, adding a salt solution to the analyte flow prior to ionization allows for the control of the charge carrier present on the analyte ion and / or the generation of known adducts. For example, according to embodiments employing a positive-ion electrospray, the addition of formic acid results in the predominance of protonated ions [M+nH] n+are formed, where n is the number of charges. The addition of sodium chloride (NaCl) leads to the predominance of sodiated ions [M+nNa] a+ be formed.

[0081] In general, adducts of the form [M+nY] n+ formed by adding a suitable soluble ionic salt, where Y = Na, K, Li, H, NH3 etc.

[0082] According to embodiments that use a negative ion mode, adducts can be formed in a similar manner. For example, adducts can be formed by adding soluble salts to generate [M+X], where X = F, Cl, Br, I, NO3, etc. With a negative ion, [M-nH] -n can be produced by adding, for example, ammonium hydroxide.

[0083] Many further embodiments for different solution-phase chemistries are being considered. According to some embodiments, more complex or larger derivatizing agents can be investigated and used based on knowledge of the chemical reactivity of the analytes.

[0084] For example, according to embodiments using gas chromatography (“GC”)-MS, acylation, silylation, alkylation, and / or esterification can be employed, using common derivatization methods and commercially available derivatization reagents. According to embodiments using liquid chromatography (“LC”)-MS, Schiff base forming reagents, primary and secondary amines, and / or chromopores can be used for fluorometric detection, also using commonly available reagents. According to these embodiments, derivatization can be performed offline prior to separation.

[0085] According to some embodiments, the derivatization of the ionized analyte can be carried out either prior to ion mobility spectrometry or separation and / or within the ion mobility spectrometry or separation apparatus in the gas phase. This can be achieved, for example, by adding reactive neutral and / or charged species to an RF-constrained reaction cell, for example at a pressure below atmospheric pressure.

[0086] According to one embodiment, an overcharging and / or a charge reduction can be used additionally or alternatively to predictably change the nature of the ions formed from the analyte.

[0087] According to one embodiment, the charge state of an ion can be manipulated either in the solution phase prior to ionization and / or in the gas phase, for example by so-called overcharging and / or charge reduction techniques. For example, in embodiments using electrospray ionization (“ESI”), the addition of mNBA (“m-nitrobenzyl alcohol”), tetramethylenesulfone (“sulfolane”), and / or dimethyl sulfoxide (“DMSO”) can lead to an increase in the intensity of higher charged ions.

[0088] According to one embodiment, a reduction in the charge of analytes ions can be achieved, for example, by using an atmospheric pressure or sub-atmospheric pressure neutralization chamber, wherein a corona discharge and / or ultraviolet ("UV") radiation and / or another energy source is used to generate reagents that can be caused to interact with the analytes ions, resulting in a reduction of the analytes' charge state. According to other embodiments, base compounds, such as triethylammonium bicarbonate and / or imidazole, can be added to solution prior to ionization, and / or base molecules can be introduced into the gas phase, for example, at atmospheric pressure or at a pressure below atmosphere, to interact with the analytes ions.

[0089] According to embodiments in which different ionization techniques, such as atmospheric pressure chemical ionization (“APCI”) or sub-atmospheric pressure chemical ionization, matrix-assisted laser desorption ionization (“MALDI”), etc., are used, other reagents and / or methods for manipulating the chemical nature of the analyte ions may be used.

[0090] In all these embodiments, the nature of the ions generated from the analyte is predictable. According to one embodiment, a single analyte can be manipulated to generate several different types of gas-phase ions, depending on the available solution-phase and / or gas-phase chemistry.

[0091] According to one embodiment, a number of different alternative experiments can be considered, leading to a number of different forms of the same analyte ion. The expected or predicted analyte ion species can then be theoretically modeled, and the theoretical ion mobility spectrometry or separation behavior can be investigated to determine, prior to experiments, optimal results. Various IMS drift gas compositions

[0092] The choice of drift medium for ion mobility spectrometry or separation can dramatically influence the separation. According to one embodiment, a polarizable drift gas, buffer gas, or drift medium containing neutral gas-phase elements, for example, with a permanent dipole moment, can be used to selectively modify the separation of different analyte ions or isomers of an analyte. In another embodiment, a selection of different drift gas compositions can be made, and the predicted effect on analyte ion mobility can be investigated by theoretical collision cross-section (CCS) calculations. Depending on the electronic structure of the analyte ions, ion mobility spectrometry or separation may be superior in one drift gas compared to another. Various pre-IMS or intra-IMS activation energies

[0093] According to one embodiment, the activation of an ion can, for example, be used to increase the internal temperature by an arbitrary or known amount in order to cause unfolding and / or a transition between conformational states. According to various embodiments, laser and / or other energy sources can be used to excite ions before and / or during ion mobility spectrometry or separation.

[0094] To Fig. Returning to point 1, it should be noted that in step 3 theoretical collision cross-section CCS values ​​for the analytes can be calculated under the different experimental conditions or combinations of the different experimental conditions proposed in step 2.

[0095] In step 4, a theoretical ion mobility or two-dimensional ion mobility mass / charge ratio drift-time spectrum can be generated based on the calculated collision cross section CCS, mass / charge ratio and charge state of the analyte and optionally the known operating parameters of the ion mobility spectrometry or separation system, which are to be used for each of the proposed experimental conditions for which theoretical collision cross section CCS values ​​were calculated.

[0096] The operating parameters of the ion mobility spectrometry or separation device may include the pressure or number density of the ion mobility spectrometry or separation drift gas, the temperature, the electrostatic field, the path length of the ion mobility spectrometry or separation cell, and / or the initial width of the ion pulse introduced into the ion mobility spectrometry or separation device, etc. For embodiments employing a rolling-wave ion mobility spectrometry or separation, the wave amplitude velocity and the wave repetition pattern may also be considered and used.

[0097] According to one embodiment, the operating parameters can include the path length traveled by ions within an ion mobility separation device and / or the residence time of ions within an ion mobility separation device. The path length traveled by ions within an ion mobility separation device and / or the residence time of ions within an ion mobility separation device can be minimized while still ensuring sufficient resolution of the different ions. This advantageously minimizes the time and / or path length required for a given experiment.

[0098] In step 5, the conditions for optimal separation of the analytes can be determined, for example, based on the investigation of the theoretical ion mobility spectrometry or separation data calculated in step 4.

[0099] Finally, in step 6, the analysis can be carried out using the analyte under the optimal experimental conditions for generating experimental data determined during the previous steps.

[0100] According to one embodiment, the approach of the embodiment described above can be used to predict the best conditions for tandem IMS-IMS experiments. According to this embodiment, the collision cross-section (CCS) and therefore the ion mobility spectrometry or separation drift time for the analyte ions passing through two sequential ion mobility spectrometry or separation devices, optionally with different separation conditions, can be calculated. This information can be used to develop the optimal combination of IMS-IMS separation conditions for an analyte mixture.

[0101] According to one embodiment, optimal conditions for production and / or precursor ions can be theoretically determined, considered and used.

[0102] The method or workflow according to one embodiment can be applied to differential ion mobility or field asymmetric ion mobility spectrometry (FAIMS), optionally using a suitable mathematical model that relates the ion mobility spectrometry or separation to the gas phase structure and the drift medium.

[0103] It should be noted that, according to one embodiment, the experimental ion mobility spectrometry or separation conditions can be guided by theoretical calculation of the analyte ion mobility, for example, under various solution and gas-phase conditions, in order to enable the development of an optimized ion mobility spectrometry or separation experiment based on these theoretical calculations. This reduces the experimental time required to find the optimal conditions for different target analytes and saves samples that can be difficult to obtain in sufficient quantities for extensive experimental optimization.

[0104] Although the present invention has been described with reference to preferred embodiments, those skilled in the art should understand that various changes to the form and details can be made without deviating from the scope of protection of the invention as set out in the attached claims.

Claims

[1] Methods of mass spectrometry which include: Calculating an ion mobility value, collision cross-section, or interaction cross-section of a number of different analytes generated from one or more analytes of interest under one or more different analytical conditions, wherein the one or more analytical conditions comprise one or more conditions for generating the number of different analytes from the one or more analytes of interest; and Setting one or more operating parameters of a mass spectrometer in response to the calculated ion mobility values, collision cross sections or interaction cross sections to maximize or improve subsequent ion mobility separation of a number of different analyte ions, wherein the step of setting the one or more operating parameters of the mass spectrometer comprises: Selecting one or more of the one or more distinct analytical conditions based on the calculated ion mobility values, collision cross sections, or interaction cross sections to maximize or improve the subsequent ion mobility separation of the number of different analyte ions; and Setting one or more operating parameters of the mass spectrometer to generate one or more selected analytical conditions. [2] Method according to claim 1, wherein the number of different analytes refers to the same analyte, but with different forms, structures, or states. [3] Method according to claim 1, wherein the number of different analytes refers to different analytes with different compositions, shapes, structures, or states. [4] A method according to any of the preceding claims, further comprising: Determining, calculating, or predicting a number of different analytes that can be generated from one or more analytes of interest under one or more of the conditions for generating the number of different analytes from one or more analytes of interest, wherein the step of calculating the ion mobility value, collision cross section or interaction cross section of the several different analytes under the one or several different analytical conditions includes calculating an ion mobility value, collision cross section or interaction cross section for one or more of the determined, calculated or predicted different analytes. [5] Method according to any of the preceding claims, further comprising: single or multiple separation of the number of different analyte ions according to their ion mobility using the mass spectrometer. [6] Method according to any of the preceding claims, which further comprises: single or multiple separation of the number of different analyte ions according to the rate of change of their ion mobility with the electric field strength using the mass spectrometer. [7] Method according to any of the preceding claims, further comprising: generating the number of different analyte ions using the mass spectrometer. [8] The method of claim 7, which further comprises: Mass analysis of the number of different analyte ions using a mass spectrometer. [9] A method according to any of the preceding claims, further comprising: Calculating one or more additional physicochemical properties of the number of different analytes under one or more different analytical conditions and Determining one or more operating parameters of the mass spectrometer based on the calculated additional physicochemical properties in order to maximize or improve the subsequent ion mobility separation of the number of different analyte ions. [10] Method according to claim 9, wherein one or more additional physicochemical properties include the peak shape, peak width, peak slope, number of peaks and / or peak kurtosis. [11] A method according to any of the preceding claims, wherein the method comprises: Determining an ion mobility value, collision cross-section or interaction cross-section difference between an ion mobility value, collision cross-section or interaction cross-section calculated under first analytical conditions and an ion mobility value, collision cross-section or interaction cross-section calculated under second different analytical conditions and Determining one or more operating parameters of the mass spectrometer based on the determined ion mobility value, collision cross-section, or interaction cross-section difference to maximize or improve the subsequent ion mobility separation of the number of different analyte ions. [12] A method according to any of the preceding claims, wherein one or more analytical conditions are selected from the group consisting of: (i) the composition and / or concentration of a salt, doping agent, derivatizing agent, reagent, displacement reagent, overloading reagent or charge-reducing reagent added to a liquid sample containing the analytes of interest prior to ionization of the analytes of interest, (ii) the composition and / or concentration of a neutral gas, doping gas, derivatizing gas, reagent gas, displacement reagent gas, overload reagent gas or charge-reducing reagent gas added to a gaseous or vapor-phase sample containing the analytes of interest prior to ionization, (iii) the composition and / or concentration of a neutral gas, reactive gas, doping gas, derivatizing agent, reagent gas, displacement reagent gas, overload reagent gas or charge-reducing reagent gas designed to interact or react with ions generated from the analytes of interest by ionization to produce the number of different analyte ions, and / or prior to the separation of the number of different analyte ions according to their ion mobility, and (iv) the composition and / or concentration of doping ions, derivatizing ions, reagents, overcharging reagents or charge-reducing reagents designed to interact or react with ions produced by ionization of the analytes of interest to generate the number of different analyte ions and / or prior to the separation of the number of different analyte ions according to their ion mobility. [13] Method according to any of the preceding claims, wherein the one or more analytical conditions are selected from the group consisting of: (i) a condition and / or parameter that affects the charge state of the analytes, (ii) a condition and / or parameter that affects the energy level of the analytes, (iii) a condition and / or parameter that affects the kinetic energy of the analytes, (iv) a condition and / or parameter that affects the activation energy of the analytes, and (v) a condition and / or parameter that affects the conformational shape or nature of the analytes. [14] Method according to any one of the preceding claims, wherein the one or more analytical conditions are selected from the group consisting of: (i) an ionization condition of an ion source, (ii) the type of ion source used for the ionization of a sample containing the analytes of interest, (iii) the voltage setting of an ion source, (iv) the ionization polarity of ions generated by an ion source, (v) the flow rate of the sample supplied to an ion source, (vi) one or more liquid chromatography conditions of a liquid chromatography system upstream of the mass spectrometer, (vii) the composition of a liquid chromatography solution or liquid chromatography solvent of a liquid chromatography system upstream of the mass spectrometer, and (viii) the liquid chromatography flow rate of a liquid chromatography system upstream of the mass spectrometer. [15] A method according to any one of the preceding claims, wherein the one or more analytical conditions are selected from the group consisting of: (i) the condition that the number of different analytes are subjected to hydrogen-deuterium exchange, (ii) one or more hydrogen-deuterium exchange conditions, (iii) the condition that the number of different analytes are subjected to activation, photoactivation, dissociation or photodissociation, (iv) one or more dissociation, photodissociation, activation and / or photoactivation conditions, (v) the condition that the number of different analytes are subjected to heating or RF heating, (vi) one or more heating or RF heating conditions, (vii) the condition that the number of different analytes are exposed to electromagnetic radiation, microwave radiation or laser radiation,(viii) one or more conditions of electromagnetic radiation, microwave radiation or laser radiation, (ix) the condition that the number of different analytes are subject to fragmentation or reaction and (x) one or more fragmentation or reaction conditions. [16] Method according to any one of the preceding claims, wherein the one or more analytical conditions are selected from the group consisting of: (i) a voltage applied to an ion-optical component, (ii) a path traveled by analyte ions through a section of the mass spectrometer, (iii) the transit time of analyte ions through a section of the mass spectrometer, (iv) one or more pressures inside the mass spectrometer, (v) one or more temperatures inside the mass spectrometer, (vi) the composition of a gas inside the mass spectrometer and (vii) the strength of an electric field inside the mass spectrometer. [17] Method according to any of the preceding claims, wherein the step of calculating the ion mobility value, the impact cross-section or the interaction cross-section comprises: Calculating a three-dimensional structure of one or more different analytes and Calculating one or more of the ion mobility value, collision cross-section or interaction cross-section using the three-dimensional structure. [18] Method according to any of the preceding claims, wherein the step of calculating the ion mobility value, the collision cross-section or the interaction cross-section comprises: calculating the effects of electronic interactions of the number of different analytes with a polar or polarizable ion mobility separation or buffer gas. [19] Mass spectrometers with a control system that is set up and designed to perform the following: (i) Calculating an ion mobility value, a collision cross section, or an interaction cross section of a number of different analytes generated from one or more analytes of interest under one or more different analytical conditions, wherein the one or more analytical conditions comprise one or more conditions for generating the number of different analytes from the one or more analytes of interest; and (ii) Determining one or more operating parameters of the mass spectrometer in response to the calculated ion mobility values, collision cross sections or interaction cross sections in order to maximize or improve subsequent ion mobility separation of a number of different analyte ions, wherein the step of determining the one or more operating parameters of the mass spectrometer comprises: Selecting one or more of the one or more distinct analytical conditions based on the calculated ion mobility values, collision cross sections, or interaction cross sections to maximize or improve the subsequent ion mobility separation of the number of different analyte ions; and Setting one or more operating parameters of the mass spectrometer to generate one or more selected analytical conditions.

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