气相色谱矩形离子阱质谱联用仪的设计与性能

气相色谱离子阱质谱联用仪(GC-ITMS)广泛地应用于药物分析、环境分析、农药检测和食品分析、有机化学品分析、毒品分析以及医学和生物分析等领域。离子阱质谱作为色谱的检测器,决定了色质联用仪的分析性能,包括检出限、分辨率。离子阱质量分析器从传统的双曲型3D离子阱发展到2D线性离子阱,质量歧视效应得到了极大的改善,灵敏度得到了提高。矩形离子阱作为线性离子阱,结构简单,加工和装配容易,因此应用到GCMS系统中将具有非常大的优势。介绍了矩形离子阱质谱仪的设计方案、仪器整机的性能测试、质量分辨和质量歧视效应分析,与Agilent6890组成GCMS联用仪,对实际样品进行了分析。     

Development and Investigation of a Mesh-Electrode Linear Ion Trap (ME-LIT) Mass Analyzer

A mesh-electrode linear ion trap (ME-LIT) mass analyzer was developed and its performance was primarily characterized. In conventional linear ion trap mass analyzers, the trapped ions are mass-selected and then ejected in a radial direction by a slot on a trap electrode. The presence of slots can strongly affect the electric field distribution in the ion trapping region and distort the mass analysis performance. To compensate for detrimental electric field effects, the slot is usually designed and fabricated to be as small as possible, and also has very high mechanical accuracy and symmetry. A ME-LIT with several mesh electrodes was built to compensate for the effects caused by slots. Each mesh electrode was fabricated from a plate electrode with a relatively large slot and the slot was covered with a conductive mesh. Our preliminary experimental results show that the ME-LIT could considerably diminish the detrimental electric field effects caused by slots, and increase the mass resolving power and ion detection efficiency. Even with 4-mm-wide slots, a mass resolution in excess of 600 was obtained using the ME-LIT. Mass resolution could be remarkably improved using mesh electrodes in ion traps with asymmetric electrodes. The stability diagram of the ME-LIT was mapped, and highly efficient tandem mass spectrometry was demonstrated. The ME-LIT was qualified as a LIT mass analyzer. The ME-LIT can improve the mass resolution and decrease the requirements of mechanical accuracy and symmetry of slots, so it shows potential for a wide range of practical uses.

Optimization of a quadrupole ion storage trap as a source for time‐of‐flight mass spectrometry

Designs of a quadrupole ion trap (QIT) as a source for time‐of‐flight (TOF) mass spectrometry are evaluated for mass resolution, ion trapping, and laser activation of trapped ions. Comparisons are made with the standard hyperbolic electrode ion trap geometry for TOF mass analysis in both linear and reflectron modes. A parallel‐plate design for the QIT is found to give significantly improved TOF mass spectrometer performance. Effects of ion temperature, trapped ion cloud size, mass, and extraction field on mass resolution are investigated in detail by simulation of the TOF peak profiles. Mass resolution (m/Δm) values of several thousand are predicted even at room temperature with moderate extraction fields for the optimized design. The optimized design also allows larger radial ion collection size compared with the hyperbolic ion trap, without compromising the mass resolution. The proposed design of the QIT also improves the ion–laser interaction volume and photon collection efficiency for fluorescence measurements on trapped ions. Copyright © 2011 John Wiley & Sons, Ltd.     

Controlled ion fragmentation in a 2-D quadrupole ion trap for external ion accumulation in ESI FTICR mass spectrometry

Undesired fragmentation of electrospray generated ions in an rf multipole traps can be problematic in many applications. Of special interest here is ion dissociation in a 2-D quadrupole ion trap external to a Fourier transform ion cyclotron resonance mass spectrometer (FTICR MS) used in proteomic studies. In this work, we identified the experimental parameters that determine the efficiency of ion fragmentation. We have found that under the pressure conditions used in this study there is a specific combination of the radial and axial potential well depths that determines the fragmentation threshold. This combination of rf and dc fields appears to be universal for ions of different mass-to-charge ratios, molecular weights, and charge states. Such universality allows the fragmentation efficiency of the trapped ions in the course of capillary liquid chromatography (LC) separation studied to be controlled and can increase the useful duty cycle and dynamic range of a FTICR mass spectrometer equipped with an external rf only 2-D quadrupole ion trap.     

Investigation into factors affecting precision in ion trap mass spectrometry using different scan directions and axial modulation potential amplitudes

Electrospray ionization mass spectra obtained from different scan directions are observed to be dependent on the axial modulation potential amplitudes used for resonant ejection and on the positive deviation caused by higher even-multipole fields present in most commercial ion traps. The axial modulation voltage influences the dissociation of ions during resonant ejection and the observed mass shifts. The higher even-multipole fields in commercial ion traps are known to influence resonant ejection from the ion trap and can cause a loss in mass resolution for peaks in reverse scan mass spectra compared with that obtained by the forward scan. However, along with the dissociation of ions during resonant ejection causing a loss in resolution, the possibility of resolving an isotopic distribution is also shown to be influenced by the mass shifts caused by the space charge. These mass shifts differ depending on the scan direction employed. A significant loss in resolution can also result from resonant ejection using non-optimal axial modulation voltages. We also present results showing the ejection of ions at betaz = 1/2 using the reverse scan mode without the axial modulation voltage. Ion ejection at betaz = 1/2 is uncommon in commercial (stretched ion traps) with the conventional analytical scan without the use of a frequency of the axial modulation voltage corresponding to this non-linear resonance.     

Electron transfer dissociation in the hexapole collision cell of a hybrid quadrupole-hexapole Fourier transform ion cyclotron resonance mass spectrometer

Electron transfer dissociation (ETD) of proteins is demonstrated in a hybrid quadrupole-hexapole Fourier transform ion cyclotron resonance mass spectrometer (Qh-FTICRMS). Analyte ions are selected in the mass analyzing quadrupole, accumulated in the hexapole linear ion trap, reacted with fluoranthene reagent anions, and then analyzed via an FTICR mass analyzer. The hexapole trap allows for a broad fragment ion mass range and a high ion storage capacity. Using a 3 T FTICRMS, resolutions of 60 000 were achieved with mass accuracies averaging below 1.4 ppm. The high resolution, high mass accuracy ETD spectra provided by FTICR obviates the need for proton transfer reaction (PTR) charge state reduction of ETD product ions when analyzing proteins or large peptides. This is demonstrated with the ETD of ubiquitin and apomyoglobin yielding sequence coverages of 37 and 20%, respectively. We believe this represents the first reported successful combination of ETD and a FTICRMS.     

Structure and Performance of Polygonal Electrode Linear Ion Trap

The polygonal electrode linear ion trap (PeLIT) can produce quadrupolar electric field plus some higher order field, which balances the relationship between mass resolution and electrode manufacturing difficulties. The electrodes of PeLIT are relatively simple, but have a good mass resolving power. This study investigated the relationship between the electric field distribution and the ion trap structures, and the performances of PeLIT through theoretical simulation and experimental study. Research results of simulation showed that the polygonal electrode linear ion traps with different structures had different electric field distributions and mass analysis performances. The negative decapole field distorted the performances significantly. The experimental results showed that the mass resolution of reserpine ions (m/z 609) was more than 2500 using a polygonal electrode ion trap. At the same time, mass selective excitation and tandem mass spectrometry experiments were also carried.     

小型离子阱的质量校正

各种野外环境的现场检测、现场诊断、流程监控、排放物检测与控制、突发事件的处理、尤其是化学和生物武器的检测等诸多需要现场使用质谱仪的场合都对质谱仪的小型化提出了迫切的要求。小型离子阱具有较高的灵敏度,可进行MS／MS实验,可利用离子-分子反应来识别特殊的化学基团,因而是小型质谱仪的重要质量分析器。本研究对小型离子阱的工作原理作了简要介绍,并以此为依据提出了进行小型离子阱质量校正的方法,推导了相关的公式,还成功地将其应用于自制的小型矩形离子阱质谱仪进行了质量校正,并指出该方法还可用于仪器RF等电学系统性能的检验。     

Experimental evaluation of a hyperbolic ion trap for fourier transform ion cyclotron resonance mass spectrometry

The Penning ion trap, consisting of hyperbolically curved electrodes arranged as an unbroken ring electrode capped by two end electrodes whose interelectrode axis lies along the direction of an applied static magnetic field, has long been used for single-ion trapping. More recently, it has been used in “parametric” mode for ion cyclotron resonance (lCR) detection of off-axis ions. In this article, we describe and test a Penning trap whose ring electrode has been cut into four equal quadrants for conventional dipolar ICR excitation (on one pair of opposed ring quadrants) and dipolar ICR detection (on the other pair). In direct comparisons to a cubic trap, the present hyperbolic trap offers somewhat improved ICR mass spectral peak shape, higher mass resolving power, and comparable frequency shift as a function of trapping voltage. Mass measurement accuracy over a wide mass range is improved twofold and mass discrimination is somewhat worse than for a cubic trap. The relative advantages of parametric, dipolar, and quadrupole modes are briefly discussed in comparison to screened and unscreened cubic traps.     

Signal suppression in electrospray ionization Fourier transform mass spectrometry of multi-component samples

The high resolution, mass range and sensitivity of Fourier transform mass spectrometry (FTMS) suggest that it could be a valuable tool for the quantitative analysis of biomolecules. To determine the applicability of electrospray ionization combined with FTMS to the quantitation of biomolecules in multi-component samples, mixtures of varying compositions and concentrations of cytochrome c, angiotensin II, insulin and chicken egg white lysozyme were examined. The instrument used has an electrospray source with a hexapole trap to accumulate ions for injection into an ion cyclotron resonance mass analyzer. Linear responses for single component samples of angiotensin II and insulin were in the range 0.031-3 microM and those of both cytochrome c and lysozyme were between 0.031 and 1 microM. In examining various mixtures of the proteins with angiotensin II, it was found that the presence of the large molecules suppresses the signal of the smaller molecules. This is suggested to be a result of ion-ion interactions producing selective ion loss from either the hexapole trap or the ion cyclotron resonance mass analyzer trap. More massive, more highly charged ions can collisionally transfer large amounts of translational energy to smaller, less highly charged ions, ejecting the smaller ions from the trap. Mass discrimination effects resulting from the trapping voltage were also examined. It was found that relative signal intensities of ions of different masses depend on trapping voltage for externally produced ions. The effect is most significant for spectra including masses that differ by 30% or more. This suggests that for quantitation all samples and standards be run at a constant trapping potential.     

How far can ion trap miniaturization go? Parameter scaling and space‐charge limits for very small cylindrical ion traps

A broad effort is underway to make radiofrequency (RF) ion trap mass spectrometers small enough for portable chemical analysis. A variety of trap geometries and fabrication approaches are under development from several research groups. A common issue is the reduced trapping capacity in smaller traps, with the associated reduction in sensitivity. This article explores the key variables that scale with trap size including RF voltage, frequency, electrical capacitance, power and pseudopotential well depth. High‐field electric breakdown constrains the maximum RF voltages used in smaller ion traps. Simulations show the effects of space charge and the limits of trapping capacity as a function of trap dimensions for cylindrical ion traps down to the micrometer level. RF amplitudes that scale as the1/3, 1/2 and 2/3 power of trap radius, r₀, were studied. At a fixed level of performance, the number of analyzable ions scales as r₀ⁿ, with n ranging from 1.55 to 1.75 depending on the choice of voltage scaling. The implications for miniaturized ion trap mass spectrometry are discussed. Copyright © 2014 John Wiley & Sons, Ltd.     

Electrospray ionization—Fourier transform ion cyclotron resonance mass spectrometry at 11.5 tesla: Instrument design and initial results

Initial results obtained using a new electrospray ionization (ESI) Fourier transform ion cyclotron resonance (FTICR) mass spectrometer operated at a magnetic field 11.5 tesla are presented. The new instrument utilized an electrostatic ion guide between the ESI source and FTICR trap that provided up to 5% overall transmission efficiency for light ions and up to 30% efficiency for heavier biomolecules. The higher magnetic field in combination with an enlarged FTICR ion trap made it possible to substantially improve resolving power and operate in a more robust fashion for large biopolymers compared to lower field instruments. Mass resolution up to 10⁶ has been achieved for intermediate size biopolymers such as bovine ubiquitin (8.6 kDa) and bovine cytochrome c (12.4 kDa) without the use of frequency drift correction methods. A mass resolution of 370,000 has been demonstrated for isotopically resolved molecular ions of bovine serum albumin (66.5 kDa). Comparative measurements were made with the same spectrometer using a lower field 3.5-tesla magnet allowing the performance gains to be more readily quantified. Further improvements in pumping capacity of the vacuum system and efficiency of ion transmission from the source are expected to lead to further substantial sensitivity gains.     

Experimental Characterization of Secular Frequency Scanning in Ion Trap Mass Spectrometers

Secular frequency scanning is implemented and characterized using both a benchtop linear ion trap and a miniature rectilinear ion trap mass spectrometer. Separation of tetraalkylammonium ions and those from a mass calibration mixture and from a pesticide mixture is demonstrated with peak widths approaching unit resolution for optimized conditions using the benchtop ion trap. The effects on the spectra of ion trap operating parameters, including waveform amplitude, scan direction, scan rate, and pressure are explored, and peaks at black holes corresponding to nonlinear (higher-order field) resonance points are investigated. Reverse frequency sweeps (increasing mass) on the Mini 12 are shown to result in significantly higher ion ejection efficiency and superior resolution than forward frequency sweeps that decrement mass. This result is accounted for by the asymmetry in ion energy absorption profiles as a function of AC frequency and the shift in ion secular frequency at higher amplitudes in the trap due to higher order fields. We also found that use of higher AC amplitudes in forward frequency sweeps biases ions toward ejection at points of higher order parametric resonance, despite using only dipolar excitation. Higher AC amplitudes also increase peak width and decrease sensitivity in both forward and reverse frequency sweeps. Higher sensitivity and resolution were obtained at higher trap pressures in the secular frequency scan, in contrast to conventional resonance ejection scans, which showed the opposite trend in resolution on the Mini 12. Mass range is shown to be naturally extended in secular frequency scanning when ejecting ions by sweeping the AC waveform through low frequencies, a method which is similar, but arguably superior, to the more usual method of mass range extension using low q resonance ejection.

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Toward high pressure miniature protein mass spectrometer: Theory and initial results

Current miniature mass spectrometers mainly focus on the analyses of organic and small biological molecules. In this study, we explored the possibility of developing high resolution miniature ion trap mass spectrometers for whole protein analysis. Theoretical derivation, GPU assisted ion trajectory simulation, and initial experiments on home‐developed “brick” mass spectrometer were carried out. Results show that ion‐neutral collisions have smaller damping effect on large protein ions, and a higher buffer gas pressure should be applied during ion trap operations for protein ions. As a result, higher pressure ion trap operation not only benefits instrument miniaturization, but also improves mass resolution of protein ions. Dynamic mass scan rate and generation of low charge state protein ions are also found to be helpful in terms of improving mass resolutions. Theory and conclusions found in this work are also applicable in the development of benchtop mass spectrometers.     

Atmospheric pressure matrix-assisted laser desorption/ionisation ion trap mass spectrometry of synthetic polymers: a comparison with vacuum matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry

Atmospheric pressure matrix-assisted laser desorption/ionisation quadrupole ion trap (AP-MALDI/QIT) mass spectrometry has been investigated for the analysis of polyethylene glycol (PEG 1500) and a hyperbranched polymer (polyglycidol) in the presence of alkali-metal salts. Mass spectra of PEG 1500 obtained at atmospheric pressure showed dimetallated matrix/analyte adducts, in addition to the expected alkali-metal/PEG ions, for all matrix/alkali-metal salt combinations. The relative intensities of the desorbed ions were dependent on the matrix, the alkali-metal salt added to aid cationisation and the ion trap interface conditions [capillary temperature, in-source collisionally-induced dissociation (CID)]. These data indicate that the adducts are rapidly stabilised by collisional cooling enabling them to be transferred into the ion trap. Experiments using identical sample preparation conditions were carried out on a vacuum MALDI time-of-flight (ToF) mass spectrometer. In all cases, vacuum MALDI-ToF spectra showed only alkali-metal/PEG ions and no matrix/analyte adducts. The tandem mass spectrometry (MS/MS) capability of the ion trap has been demonstrated for a lithiated polyglycol yielding a rich fragment-ion spectrum. Analysis of the hyperbranched polymer polyglycidol by AP-MALDI/QIT reveals the characteristic ion series for these polymers as also observed under vacuum MALDI-ToF conditions.     

A high-resolution scanning microprobe matrix-assisted laser desorption/ionization ion source for imaging analysis on an ion trap/Fourier transform ion cyclotron resonance mass spectrometer

A new scanning microprobe matrix-assisted laser desorption/ionization (SMALDI) ion source for high spatial resolution has been developed for linear ion trap and Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS). The source is fully compatible with commercial ion trap flanges (such as the LTQ series, Thermo Fisher Scientific). The source is designed for atmospheric pressure (AP) operation but is also suitable for mid-pressure operation. The AP mode is especially useful for investigating volatile compounds. The source can be interchanged with other ion sources within a minute when operated in the AP mode. Combining high-lateral resolution MALDI imaging with high mass resolution and high mass accuracy mass spectrometry, available in the FT-ICR mode, provides a new quality of analytical information, e.g. from biological samples. First results obtained with the new ion source demonstrate a maximum lateral resolution of 0.6 by 0.5 microm. Depending on the limit of detection of the chosen mass analyzer, however, the size of the focus had to be enlarged to a diameter of up to 8 microm in the FT-ICR mode, in order to create enough ions for detection. Mass spectra acquired for analytical imaging were obtained from single laser pulses per pixel in all the experiments. This mode allows us to investigate biological thin sections with desorption focus diameters in the micrometer range, known to cause complete evaporation of material under the laser focus with a very limited number of laser pulses. As a first example, peptide samples deposited in microstructures were investigated with the new setup. A high quality and validity of the acquired images were obtained in the ion trap mode due to the low limit of detection. High mass resolution and accuracy but poorer image quality were obtained in the ICR mode due to the lower detection sensitivity of the ICR detector.     

Ion trajectory simulation for electrode configurations with arbitrary geometries

A multi-particle ion trajectory simulation program ITSIM 6.0 is described, which is capable of ion trajectory simulations for electrode configurations with arbitrary geometries. The electrode structures are input from a 3D drawing program AutoCAD and the electric field is calculated using a 3D field solver COMSOL. The program CreatePot acts as interface between the field solver and ITSIM 6.0. It converts the calculated electric field into a field array file readable by ITSIM 6.0 and ion trajectories are calculated by solving Newton's equation using Runge-Kutta integration methods. The accuracy of the field calculation is discussed for the ideal quadrupole ion trap in terms of applied mesh density. Electric fields of several different types of devices with 3D geometry are simulated, including ion transport through an ion optical system as a function of pressure. Ion spatial distributions, including the storage of positively charged ions only and simultaneous storage of positively/negatively charged ions in commercial linear ion traps with various geometries, are investigated using different trapping modes. Inelastic collisions and collision induced dissociation modeled using RRKM theory are studied, with emphasis on the fragmentation of n-butylbenzene inside an ideal quadrupole ion trap. The mass spectrum of 1,3-dichlorobenzene is simulated for the rectilinear ion trap device and good agreement is observed between the simulated and the experimental mass spectra. Collisional cooling using helium at different pressures is found to affect mass resolution in the rectilinear ion trap.     

Characterization of bis-carboxyethyl germanium sesquioxide and its complexes with amino acids using electrospray QqTOF mass spectrometry

This work deals with the application of electrospray ionization mass spectrometry (ESI-MS) with QqTOF analyzer for the characterization of Ge-132 complexes with different amino acids in aqueous solution with the emphasis on the determination of elemental composition. ESI mass spectra provide complementary structural information in both polarity modes. Some reaction products were suggested based on the interpretation of high resolution mass spectra. Moreover, the experimental isotopic distributions of ions were compared with theoretical calculated isotopic clusters. The superposition of many ion overlays was observed due to the wide isotopic distributions of studied polyisotopic complexes. The high resolution QqTOF analyzer enabled the discrimination of these ion signals differing at least by 0.12 mass units. The occurrence of overlaid signals from ions with smaller mass difference was successfully recognized based on the shift of isotopic distribution, and their elemental composition was verified using mass accuracies of non-overlaid isotopes at the borders of the isotopic cluster. Mass spectra obtained with ion trap and single quadrupole analyzers support QqTOF data.     

Spherical FAIMS: comparison of curved electrode geometries

High-field asymmetric waveform ion mobility spectrometry (FAIMS) can operate at atmospheric pressure to separate gas-phase ions on the basis of a difference in the mobility of an ion at high fields relative to its mobility at low field strengths. Several novel cell geometries have been proposed in addition to the commercially available planar and cylindrical designs. Nevertheless, there is still much to explore about three-dimensional (3-D) curved cell geometries (spherical and hemispherical) and comparison to two-dimensional (2-D) curved geometries (cylindrical). The geometry of a FAIMS cell is one of the essential features affecting the transmission, resolution, and resolving power of FAIMS. Electric fields in a spherical design allow advantages such as virtual potential wells that can induce atmospheric-pressure near-trapping conditions and help reduce ion losses. Curvature of electrodes enables the ions to remain focused near the gap median, which help to improve sensitivity and ion trapping at higher pressures. Here we detail the design and characterization of a novel FAIMS cell having spherical electrode geometry and compare it to hemispherical and cylindrical cells. These FAIMS cells were interfaced with a quadrupole ion trap mass spectrometer in this study. Several structural classes of common explosives were employed to evaluate the separation power of these geometries. FAIMS spectra were generated by scanning the compensation voltage (CV) while operating the mass spectrometer in total ion mode. The identification of ions was accomplished through mass spectra acquired at fixed values of CVs. The performance of FAIMS using cylindrical, hemispherical, and spherical cells was compared and trends identified. For all trials, the best transmission was obtained by the spherical FAIMS cell while hemispherical FAIMS provided the best resolution and resolving power.