Compressive Mass Analysis on Quadrupole Ion Trap Systems

Conventionally, quadrupole ion trap mass spectrometers eject ions of different mass-to-charge ratio (m/z) in a sequential fashion by performing a scan of the rf trapping voltage amplitude. Due to the inherent sparsity of most mass spectra, the detector measures no signal for much of the scan time. By exploiting this sparsity property, we propose a new compressive and multiplexed mass analysis approach—multi Resonant Frequency Excitation (mRFE) ejection. This new approach divides the mass spectrum into several mass subranges and detects all the subrange spectra in parallel for increased mass analysis speed. Mathematical estimation of standard mass spectrum is demonstrated while statistical classification on the parallel measurements remains viable because of the sparse nature of the mass spectra. This method can reduce mass analysis time by a factor of 3–6 and increase system duty cycle by 2×. The combination of reduced analysis time and accurate compound classification is demonstrated in a commercial quadrupole ion trap (QIT) system.

Ion Trap Electric Field Characterization Using Slab Coupled Optical Fiber Sensors

This paper presents a method for characterizing electric field profiles of radio frequency (rf) quadrupole ion trap structures using sensors based on slab coupled optical-fiber sensor (SCOS) technology. The all-dielectric and virtually optical fiber-sized SCOS fits within the compact environment required for ion traps and is able to distinguish electric field orientation and amplitude with minimal perturbation. Measurement of the fields offers insight into the functionality of traps, which may not be obtainable solely by performing simulations. The SCOS accurately mapped the well-known field profiles within a commercially available three-dimensional quadrupole ion trap (Paul trap). The results of this test allowed the SCOS to map the more complicated fields within the coaxial ion trap with a high degree of confidence as to the accuracy of the measurement. Figure

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Resonance Activation and Collision-Induced-Dissociation of Ions Using Rectangular Wave Dipolar Potentials in a Digital Ion Trap Mass Spectrometer

Collision-induced dissociation (CID) of ions by resonance activation in a quadrupole ion trap is usually accomplished by resonance exciting the ions to higher kinetic energy, whereby the high kinetic energy ions collide with a bath gas, such as helium or argon, inside the trap and dissociate to fragments. A new ion activation method using a well-defined rectangular wave dipolar potential formed by dividing down the trapping rectangular waveform is developed and examined herein. The mass-selected parent ions are resonance excited to high kinetic energies by simply changing the frequency of the rectangular wave dipolar potential and dissociation proceeds. A relationship between the ion mass and the activation waveform frequency is also identified and described. This highly efficient (CID) procedure can be realized by simply changing the waveform frequency of the dipolar potential, which could certainly simplify tandem mass spectrometry analysis methods.

Controlled Ion Ejection from an External Trap for Extended m/z Range in FT-ICR Mass Spectrometry

An auxiliary rf waveform of the same amplitude and phase applied to all the rods of an ion accumulation multipole creates an m/z-dependent axial pseudo potential. Controlled decrease of the auxiliary rf amplitude releases ions from the accumulation multipole sequentially from high to low m/z. The slope of the auxiliary rf voltage ramp is adjusted so that ions of different m/z reach the center of the ICR cell at the same time point, which mitigates the typical time dispersion observed in external source FT-ICR and extends the observable mass range for a single data acquisition by 2- to 3-fold. For complex mixture analysis, twice the number of elemental compositions are assigned when the auxiliary rf ejection is applied compared with the standard gated trapping.

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.

Multipurpose Dissociation Cell for Enhanced ETD of Intact Protein Species

We describe and characterize an improved implementation of ETD on a modified hybrid linear ion trap-Orbitrap instrument. Instead of performing ETD in the mass-analyzing quadrupole linear ion trap (A-QLT), the instrument collision cell was modified to enable ETD. We partitioned the collision cell into a multi-section rf ion storage and transfer device to enable injection and simultaneous separate storage of precursor and reagent ions. Application of a secondary (axial) confinement voltage to the cell end lens electrodes enables charge-sign independent trapping for ion–ion reactions. The approximately 2-fold higher quadrupole field frequency of this cell relative to that of the A-QLT enables higher reagent ion densities and correspondingly faster ETD reactions, and, with the collision cell’s longer axial dimensions, larger populations of precursor ions may be reacted. The higher ion capacity of the collision cell permits the accumulation and reaction of multiple full loads of precursor ions from the A-QLT followed by FT Orbitrap m/z analysis of the ETD product ions. This extends the intra-scan dynamic range by increasing the maximum number of product ions in a single MS/MS event. For analyses of large peptide/small protein precursor cations, this reduces or eliminates the need for spectral averaging to achieve acceptable ETD product ion signal-to-noise levels. Using larger ion populations, we demonstrate improvements in protein sequence coverage and aggregate protein identifications in LC-MS/MS analysis of intact protein species as compared to the standard ETD implementation.

Extending the Dynamic Range of the Ion Trap by Differential Mobility Filtration

A miniature, planar, differential ion mobility spectrometer (DMS) was interfaced to an LCQ classic ion trap to conduct selective ion filtration prior to mass analysis in order to extend the dynamic range of the trap. Space charge effects are known to limit the functional ion storage capacity of ion trap mass analyzers and this, in turn, can affect the quality of the mass spectral data generated. This problem is further exacerbated in the analysis of mixtures where the indiscriminate introduction of matrix ions results in premature trap saturation with non-targeted species, thereby reducing the number of parent ions that may be used to conduct MS/MS experiments for quantitation or other diagnostic studies. We show that conducting differential mobility-based separations prior to mass analysis allows the isolation of targeted analytes from electrosprayed mixtures preventing the indiscriminate introduction of matrix ions and premature trap saturation with analytically unrelated species. Coupling these two analytical techniques is shown to enhance the detection of a targeted drug metabolite from a biological matrix. In its capacity as a selective ion filter, the DMS can improve the analytical performance of analyzers such as quadrupole (3D or linear) and ion cyclotron resonance (FT-ICR) ion traps that depend on ion accumulation.

The Effective Temperature of Ions Stored in a Linear Quadrupole Ion Trap Mass Spectrometer

The extent of internal energy deposition into ions upon storage, radial ejection, and detection using a linear quadrupole ion trap mass spectrometer is investigated as a function of ion size (m/z 59 to 810) using seven ion-molecule thermometer reactions that have well characterized reaction entropies and enthalpies. The average effective temperatures of the reactants and products of the ion-molecule reactions, which were obtained from ion-molecule equilibrium measurements, range from 295 to 350 K and do not depend significantly on the number of trapped ions, m/z value, ion trap q _z value, reaction enthalpy/entropy, or the number of vibrational degrees of freedom for the seven reactions investigated. The average of the effective temperature values obtained for all seven thermometer reactions is 318?±?23 K, which indicates that linear quadrupole ion trap mass spectrometers can be used to study the structure(s) and reactivity of ions at near ambient temperature.

Characterization of a DAPI-RIT-DAPI System for Gas-Phase Ion/Molecule and Ion/Ion Reactions

The discontinuous atmospheric pressure interface (DAPI) has been developed as a facile means for efficiently introducing ions generated at atmospheric pressure to an ion trap in vacuum [e.g., a rectilinear ion trap (RIT)] for mass analysis. Introduction of multiple beams of ions or neutral species through two DAPIs into a single RIT has been previously demonstrated. In this study, a home-built instrument with a DAPI-RIT-DAPI configuration has been characterized for the study of gas-phase ion/molecule and ion/ion reactions. The reaction species, including ions or neutrals, can be introduced from both ends of the RIT through the two DAPIs without complicated ion optics or differential pumping stages. The primary reactant ions were isolated prior to reaction and the product ions were mass analyzed after controlled reaction time period. Ion/molecule reactions involving peptide radical ions and proton-transfer ion/ion reactions have been carried out using this instrument. The gas dynamic effect due to the DAPI operation on internal energy deposition and the reactivity of peptide radical ions has been characterized. The DAPI-RIT-DAPI system also has a unique feature for allowing the ion reactions to be carried out at significantly elevated pressures (in 10^–1 Torr range), which has been found to be helpful to speed up the reactions. The viability and flexibility of the DAPI-RIT-DAPI system for the study of gas-phase ion reactions have been demonstrated.

Twelve Million Resolving Power on 4.7 T Fourier Transform Ion Cyclotron Resonance Instrument with Dynamically Harmonized Cell—Observation of Fine Structure in Peptide Mass Spectra

Resolving power of about 12,000 000 at m/z 675 has been achieved on low field homogeneity 4.7 T magnet using a dynamically harmonized Fourier transform ion cyclotron resonance (FT ICR) cell. Mass spectra of the fine structure of the isotopic distribution of a peptide were obtained and strong discrimination of small intensity peaks was observed in case of resonance excitation of the ions of the whole isotopic cluster to the same cyclotron radius. The absence of some peaks from the mass spectra of the fine structure was explained basing on results of computer simulations showing strong ion cloud interactions, which cause the coalescence of peaks with m/z close to that of the highest magnitude peak. The way to prevent peak discrimination is to excite ion clouds of different m/z to different cyclotron radii, which was demonstrated and investigated both experimentally and by computer simulations.

Selective and Nonselective Cleavages in Positive and Negative CID of the Fragments Generated from In-Source Decay of Intact Proteins in MALDI-MS

Selective and nonselective cleavages in ion trap low-energy collision-induced dissociation (CID) experiments of the fragments generated from in-source decay (ISD) with matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS) of intact proteins are described in both positive and negative ion modes. The MALDI-ISD spectra of the proteins demonstrate common, discontinuous, abundant c- and z′-ions originating from cleavage at the N–Cα bond of Xxx-Asp/Asn and Gly-Xxx residues in both positive- and negative-ion modes. The positive ion CID of the c- and z′-ions resulted in product ions originating from selective cleavage at Asp-Xxx, Glu-Xxx and Cys-Xxx residues. Nonselective cleavage product ions rationalized by the mechanism of a “mobile proton” are also observed in positive ion CID spectra. Negative ion CID of the ISD fragments results in complex product ions accompanied by the loss of neutrals from b-, c-, and y-ions. The most characteristic feature of negative ion CID is selective cleavage of the peptide bonds of acidic residues, Xxx-Asp/Glu/Cys. A definite influence of α-helix on the CID product ions was not obtained. However, the results from positive ion and negative ion CID of the MALDI-ISD fragments that may have long α-helical domains suggest that acidic residues in helix-free regions tend to degrade more than those in helical regions.

Rapid screening of active ingredients in drugs by mass spectrometry with low-temperature plasma probe

A high-throughput method for rapid screening of active ingredients in drugs has been developed with mass spectrometry coupled to a low-temperature plasma (LTP) probe ion source. Without sample preparation or pretreatment, the active ingredients of 11 types of commercial pharmaceuticals, including hormones, antipyretic analgesics, cardiovascular, digestant, neuro-psychotherapeutic, diuretic, antithyroid, sulfa anti-inflammatory, antiparastic, sedative-hypnotics, and antibacterial, were directly desorbed/ionized and detected by a linear ion trap mass spectrometry (MS). The structures of these ingredients were elucidated by tandem MS. The analysis of 18 methyltestosterone tablets could be accomplished within 1.9 min, which allows fast detection with a speed of approximate 600 samples within 1 h. This work demonstrated that LTP probe ion source combined with MS is a high-throughput method for screening of pharmaceuticals and potentially applied to on-line quality control in pharmaceutical industry.

Quadrupole Mass Filter: Design and Performance for Operation in Stability Zone 3

The predicted performance of a quadrupole mass filter (QMF) operating in Mathieu stability zone 3 is described in detail using computer simulations. The investigation considers the factors that limit the ultimate maximum resolution (R_max) and percentage transmission (%Tx), which can be obtained for a given QMF for a particular scan line of operation. The performance curve (i.e., the resolution (R) versus number (N) of radio frequency (rf) cycles experienced by the ions in the mass filter) has been modeled for the upper and lower tip of stability zone 3. The saturation behavior of the performance curve observed in practice for zone 3 is explained. Furthermore, new design equations are presented by examining the intersection of the scan line with stability zone 3. Resolution versus transmission characteristics of stability zones 1 and 3 are compared and the dependence of performance for zones 1 and 3 is related to particular instrument operating parameters.

Vacuum Ultraviolet Action Spectroscopy of Polysaccharides

We studied the optical properties of gas-phase polysaccharides (maltose, maltotetraose, and maltohexaose) ions by action spectroscopy using the coupling between a quadrupole ion trap and a vacuum ultraviolet (VUV) beamline at the SOLEIL synchrotron radiation facility (France) in the 7 to 18 eV range. The spectra provide unique benchmarks for evaluation of theoretical data on electronic transitions of model carbohydrates in the VUV range. The effects of the nature of the charge held by polysaccharide ions on the relaxation processes were also explored. Finally the effect of isomerization of polysaccharides (with melezitose and raffinose) on their photofragmentation with VUV photons is presented.

Study of Nonlinear Resonance Effect in Paul Trap

In this article, we investigated the nonlinear resonance effect in the Paul trap with a superimposed hexapole field, which was assumed as a perturbation to the quadrupole field. On the basis of the Poincare-Lighthill-Kuo (PLK) perturbation method, ion motional equation, known as nonlinear Mathieu equation (NME) was expressed as the addition of approximation equations in terms of perturbation order. We discussed the frequency characteristics of ion axial-radial (z-r) coupled motion in the nonlinear field, derived the expressions of ion trajectories and nonlinear resonance conditions, and found that the mechanism of nonlinear resonance is similar to the normal resonance. The frequency spectrum of ion motion in nonlinear field includes not only the natural frequency series but also nonlinear introduced frequency series, which provide the driving force for the nonlinear resonance. The nonlinear field and the nonlinear effects are inevitable in practical ion trap experiments. Our method provides better understanding of these nonlinear effects and would be helpful for the instrumentation for ion trap mass spectrometers.      

Mapping the Stability Diagram of a Quadrupole Mass Spectrometer with a Static Transverse Magnetic Field Applied

Previous experimental and theoretical work identified that the application of a static magnetic (B) field can improve the resolution of a quadrupole mass spectrometer (QMS) and this simple method of performance enhancement offers advantages for field deployment. Presented here are further data showing the effect of the transverse magnetic field upon the QMS performance. For the first time, the asymmetry in QMS operation with B _x and B _y is considered and explained in terms of operation in the fourth quadrant of the stability diagram. The results may be explained by considering the additional Lorentz force (v x B) experienced by the ion trajectories in each case. Using our numerical approach, we model not only the individual ion trajectories for a transverse B field applied in x and y but also the mass spectra and the effect of the magnetic field upon the stability diagram. Our theoretical findings, confirmed by experiment, show an improvement in resolution and ion transmission by application of magnetic field for certain operating conditions.

Comparison of Three Plasma Sources for Ambient Desorption/Ionization Mass Spectrometry

Plasma-based desorption/ionization sources are an important ionization technique for ambient surface analysis mass spectrometry. In this paper, we compare and contrast three competing plasma based desorption/ionization sources: a radio-frequency (rf) plasma needle, a dielectric barrier plasma jet, and a low-temperature plasma probe. The ambient composition of the three sources and their effectiveness at analyzing a range of pharmaceuticals and polymers were assessed. Results show that the background mass spectrum of each source was dominated by air species, with the rf needle producing a richer ion spectrum consisting mainly of ionized water clusters. It was also seen that each source produced different ion fragments of the analytes under investigation: this is thought to be due to different substrate heating, different ion transport mechanisms, and different electric field orientations. The rf needle was found to fragment the analytes least and as a result it was able to detect larger polymer ions than the other sources. Figure

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A combined linear ion trap for mass spectrometry

We propose a novel ion cyclotron resonance ion trap capable of confining ions even at high pressure. The trap consists of three capacitively coupled axial sections, each composed of four circular cross-section rods parallel to the magnetic field axis. Ion confinement along the magnetic field direction is provided by applying the same static voltage to each set of “endcap” rods. As for a two-dimensional quadrupole mass filter, a sufficiently high rf frequency (several MHz) leads to an “effective” electrostatic “pseudopotential” well with a minimum on the trap central axis. Ions are confined radially by the combination of an applied axial static magnetic field and a radially inward-directed electric field resulting from differential rf voltages applied to each set of four rods. Ion confinement properties are revealed from a Paul traplike “stability diagram,” whereas ion trajectories are analyzed in terms of Penning-type ion cyclotron rotation, magnetron rotation, and axial oscillation motional modes. Ion cyclotron frequency increases with the strength of the rf trapping field. Ion magnetron motion becomes stable if the rf voltage is high enough. Therefore, ion trajectories can be stable even in the presence of ion-neutral collisions. Adding an ac potential to a Penning trap should dramatically increase the upper mass detection limit.     

Fluorescence Imaging for Visualization of the Ion Cloud in a Quadrupole Ion Trap Mass Spectrometer

Laser-induced fluorescence is used to visualize populations of gaseous ions stored in a quadrupole ion trap (QIT) mass spectrometer. Presented images include the first fluorescence image of molecular ions collected under conditions typically used in mass spectrometry experiments. Under these “normal” mass spectrometry conditions, the radial (r) and axial (z) full-width at half maxima (FWHM) of the detected ion cloud are 615 and 214 μm, respectively, corresponding to ~6 % of r ₀ and ~3 % of z ₀ for the QIT used. The effects on the shape and size of the ion cloud caused by varying the pressure of helium bath gas, the number of trapped ions, and the Mathieu parameter q _z are visualized and discussed. When a “tickle voltage” is applied to the exit end-cap electrode, as is done in collisionally activated dissociation, a significant elongation in the axial, but not the radial, dimension of the ion cloud is apparent. Finally, using spectroscopically distinguishable fluorophores of two different m/z values, images are presented that illustrate stratification of the ion cloud; ions of lower m/z (higher q _z ) are located in the center of the trapping region, effectively excluding higher m/z (lower q _z ) ions, which form a surrounding layer. Fluorescence images such as those presented here provide a useful reference for better understanding the collective behavior of ions in radio frequency (rf) trapping devices and how phenomena such as collisions and space-charge affect ion distribution.

Can the Effective Potential of a Linear Quadrupole be Extended to Values of the Mathieu Parameter q Up to 0.90?

The motion of ions in a linear quadrupole is usually described by solutions to the Mathieu equation. A simplifying approximation to this theory that is widely used for low values of the Mathieu parameters a and q describes ion motion in an effective potential. In this work, we have calculated the effective potential for any q from displacements of calculated ion trajectories caused by a dipole DC electric field. It is assumed that the dipole DC electric field at the center of the displaced trajectory is countered by an “effective” electric field. For all q values, the effective electric field is found to increase linearly with the distance from the center of the quadrupole. The trapping forces probed in this way increase continuously with q up to the first stability region boundary at q=0.908. The well depth (D) at any q can be described by $ D=q\frac{V_{rf}}{c} $ , where c=3.955±0.005, very similar to the standard effective potential model with c=4.000.