Miniature mass analyzers

Increased efforts are being made to develop miniature mass spectrometers, including those which are hand-portable, and to retain the performance characteristics of traditional laboratory instruments as much as possible in the miniature instruments. This review of miniature mass analyzers emphasizes analytical performance and compares the relative merits of each type of miniature mass analyzer. Miniature instruments discussed include sector, Wien filter, time-of-flight, linear quadrupole, quadrupole ion trap and Fourier transform ion cyclotron resonance mass spectrometers, as well as combinations of and variations on these major types. Special considerations that apply to small mass analyzers are noted and suggestions are made regarding the possible future development of this field. Copyright 2000 John Wiley & Sons, Ltd.     

Development of quadrupole mass spectrometers using rapid prototyping technology

In this report, we present a prototype design of a quadrupole mass filter (QMF) with hyperbolic electrodes, fabricated at the University of Liverpool using digital light processing (DLP), a low-cost and lightweight 3D rapid prototyping (RP) technique. Experimental mass spectra are shown for H₂⁺, D₂⁺, and He⁺ ions to provide proof of principle that the DLP mass filter is working as a mass analyzer in the low-mass range (1 to 10 amu). The performance of the DLP QMF has also been investigated for individual spectral peaks. Numerical simulations of the instrument were performed by coupling CPO and Liverpool QMS-2 programs to model both the ion source and mass filter, respectively, and the instrument is shown to perform as predicted by theory. DLP thus allows miniaturization of mass spectrometers at low cost, using hyperbolic (or other) geometries of mass analyzer electrodes that provide optimal ion manipulation and resolution for a given application. The potential of using RP fabrication techniques for developing miniature and microscale mass analyzers is also discussed.     

Quadrupole mass filter operation under the influence of magnetic field

This work demonstrates resolution enhancement of a quadrupole mass filter (QMF) under the influence of a static magnetic field. Generally, QMF resolution can be improved by increasing the number of rf cycles an ion experiences when passing through the mass filter. In order to improve the resolution, the dimensions of the QMF or the operating parameters need to be changed. However, geometric modifications to improve performance increase the manufacturing cost and usually the size of the instrument. By applying a magnetic field, a low‐cost, small footprint instrument with reduced power requirements can be realized. Significant improvement in QMF resolution was observed experimentally for certain magnetic field conditions, and these have been explained in terms of our theoretical model developed at the University of Liverpool. This model is capable of accurate simulation of spectra allowing the user to specify different values of mass spectrometer dimensions and applied input signals. The model predicts enhanced instrument resolution R>26 000 for a CO₂ and N₂ mixture with a 200‐mm long mass filter operating in stability zone 3 via application of an axial magnetic field. Copyright © 2013 John Wiley & Sons, Ltd.     

Comparison of ion coupling strategies for a microengineered quadrupole mass filter

The limitations of conventional machining and assembly techniques require that designs for quadrupole mass analyzers with rod diameters less than a millimeter are not merely scale versions of larger instruments. We show how silicon planar processing techniques and microelectromechanical systems (MEMS) design concepts can be used to incorporate complex features into the construction of a miniature quadrupole mass filter chip that could not easily be achieved using other microengineering approaches. Three designs for the entrance and exit to the filter consistent with the chosen materials and techniques have been evaluated. The differences between these seemingly similar structures have a significant effect on the performance. Although one of the designs results in severe attenuation of transmission with increasing mass, the other two can be scanned to m/z = 400 without any corruption of the mass spectrum. At m/z = 219, the variation in the transmission of the three designs was found to be approximately four orders of magnitude. A maximum resolution of M/DeltaM = 87 at 10% peak height has been achieved at m/z = 219 with a filter operated at 6 MHz and constructed using rods measuring (508 +/- 5) microm in diameter.     

High resolution ICP-MS — a new concept for elemental mass spectrometry

Interfering molecular species are of major concern to the analyst currently using quadrupole based ICP-MS instrumentation. The recognized advantage and convenience offered by atmospheric plasma ionisation to multielement trace analysis can be significantly deteriorated by the limited resolving power of these analyzers. The result is poor sensitivity and lack of selectivity. With respect to sensitivity and resolution significant enhancement can be achieved by using magnetic sector based high resolution analyzers instead of quadrupoles. Unfortunately, up to now, commercially available HR-ICP-MS systems have been derived from complex instruments originally designed to meet the requirements of organic mass applications. Consequently, operation and performance of those systems expose the compromise which had to be made between an atmospheric plasma atomic ion source at high potential and an analyzer technology dedicated to molecular mass spectroscopy of organic compounds. At Finnigan MAT the first purpose designed high resolution ICP-MS has now been developed, which can be operated in high and low resolution mode at enhanced sensitivity. An innovative electric and magnetic field scanning strategy (SynchroScan) results in high on-peak duty cycles. Improved magnet technology offers high speed quadrupole style survey scans covering the full elemental mass range at nominal mass resolution. By extremely rapid peak switching, for example, all barium isotopes can be monitored in less than 100 ms with more than 90% on-peak detection efficiency. Examples are shown for computer controlled high and low resolution scan modes demonstrating the analytical performance of the new instrument concept. A comparison of detection limits achieved in low and high resolution mode is given.     

Factors determining the performance of triple quadrupole, quadrupole ion trap and sector field mass spectrometer in electrospray ionization mass spectrometry. 2. Suitability for de novo sequencing

The sequence coverage by fragment ions resulting from collision-induced dissociation in a triple stage quadrupole (TSQ) and a quadrupole ion trap (QIT) mass spectrometer of 10-20-mer oligonucleotides was investigated. While (a-B) and w ion series were the most abundant on both instruments, additional ion series of sequence relevance were preferably formed in the TSQ. Thus, a total number of 83 fragment ions were used to deduce the complete sequence of a 10-mer oligonucleotide of mixed sequence from a tandem mass spectrum recorded on the TSQ. The complete sequence was also encoded in the 28 fragments that were obtained from the QIT under comparable fragmentation conditions. Spectrum complexity increased considerably at the cost of signal-to-noise ratio upon fragmentation of a 20-mer oligonucleotide in the TSQ, whereas spectrum interpretation with longer oligonucleotides was significantly more straightforward in spectra recorded on the QIT. The extent of fragmentation had to be optimized by appropriate setting of collision energy and choice of precursor ion charge state in order to obtain full sequence coverage by fragments for de novo sequencing. Moreover, full sequence information was also dependent on base sequence because of the low tendency of backbone cleavage at thymidines. Tandem mass spectrometry on the QIT yielded redundant information that was successfully utilized to deduce the complete sequence of 20-mer oligonucleotides with high confidence.     

Characterization of bioparticles using a miniature cylindrical ion trap mass spectrometer operated at rough vacuum

A miniature cylindrical ion trap mass spectrometer (CIT-MS) equipped with an inexpensive mechanical pump was constructed, and used to measure the masses of cells and microparticles generated by laser induced acoustic desorption ionization. Compared with a previous lab scale quadrupole ion trap mass spectrometer (QIT-MS), the novel miniature CIT-MS had smaller volume (the radius r(0)=5 mm), simpler ion trap fabrication and overall instrument construction, required a lower trapping voltage, and reduced the weight, power and cost of the instrument. The CIT-MS was calibrated using standard polystyrene beads of 2.982 μm diameter. The CIT-MS was used to measure the total dry weight of human red blood cells (RBCs) from a healthy female adult (2.12×10(13) Da) and a patient with anemia (1.35×10(13) Da). The coefficient of variance (CV) for the healthy individual was 21% and that for the patient was 30.4%. The CIT-MS was also applied to guinea pig RBCs and the total dry weight was determined as 1.34×10(13) Da with a CV of 37.9%. These measurements are consistent with previous QIT-MS measurements. The new miniaturized instrument has potential for applications in field-portable, biological and aerosol analysis.     

Miniaturized system of a gas chromatograph coupled with a Paul ion trap mass spectrometer

Miniature gas chromatography (GC) and miniature mass spectrometry (MS) instrumentation has been developed to identify and quantify the chemical compounds present in complex mixtures of gases. The design approach utilizes micro-GC components coupled with a Paul quadrupole ion trap (QIT) mass spectrometer. Inherent to the system are high sensitivity, good dynamic range, good QIT resolution, low GC flow-rates to minimize vacuum requirements and the need for consumables; and the use of a modular approach to adapt to volatile organic compounds dissolved in water or present in sediment. Measurements are reported on system response to gaseous species at concentrations varying over four orders of magnitude. The ability of the system to deal with complicated mixtures is demonstrated, and future improvements are discussed. The GC/QIT system described herein has a mass, volume and power that are, conservatively, one-twentieth of those of commercial off-the-shelf systems. Potential applications are to spacecraft cabin-air monitoring, robotic planetary exploration and trace-species detection for residual gas analysis and environmental monitoring.     

Field-portable, high-speed GC/TOFMS

This work is focused on developing a fast gas chromatograph, time-of-flight mass spectrometer (GC/TOFMS) for man-portable field use. The goal is to achieve a total system solution for meeting performance, size, weight, power, cost, and ruggedness requirements for a laboratory in the field. The core technology will also be adaptable to specific applications including real-time point detection for hazardous chemical releases (e.g., chemical weapons), for biological agent signature identification, and for mobile monitoring platforms (e.g., air, ship, truck). Previously we presented results of a feasibility demonstration for a 30-lb field-portable TOFMS system. In this work we present recent progress in integrating a low-power, high-speed GC and show the capability for accurately recording fast GC transients for targeted compound detection using a quadrupole ion trap, time-of-flight instrument (QitTof).     

Inductively coupled plasma mass spectrometer with axial field in a quadrupole reaction cell

A novel reaction cell for ICP-MS with an electric field provided inside the quadrupole along its axis is described. The field is implemented via a DC bias applied to additional auxiliary electrodes inserted between the rods of the quadrupole. The field reduces the settling time of the pressurized quadrupole when its mass bandpass is dynamically tuned. It also improves the transmission of analyte ions. It is shown that for the pressurized cell with the field activated, the recovery time for a change in quadrupole operating parameters is reduced to <4 ms, which allows fast tuning of the mass bandpass in concert with and at the speed of the analyzing quadrupole. When the cell is operated with ammonia, the field reduces ion-ammonia cluster formation, further enhancing the transmission of atomic ions that have a high cluster formation rate. Ni x (NH3)n+ cluster formation in a cell operated with a wide bandpass (i.e., Ni+ precursors are stable in the cell) is shown to be dependent on the axial field strength. Clusters at n = 2-4 can be suppressed by 9, 1200, and >610 times, respectively. The use of a retarding axial field for in-situ energy discrimination against cluster and polyatomic ions is shown. When the cell is pressurized with O2 for suppression of 129Xe+, the formation of 127IH2+ by reactions with gas impurities limits the detection of 129I to isotopic abundance of approximately 10(-6). In-cell energy discrimination against 127IH2+ utilizing a retarding axial field is shown to reduce the abundance of the background at m/z = 129 to ca. 3 x 10(-8) of the 127I+ signal. In-cell energy discrimination against 127IH2+ is shown to cause less I+ loss than a post-cell potential energy barrier for the same degree of 127IH2+ suppression.     

Increased Fragmentation Efficiency of Ions in a Low Pressure Linear Ion Trap with an Added dc Octopole Field

In-trap fragmentation of ions in a hybrid linear ion trap triple quadrupole mass spectrometer occurs at pressures about 5e-5 torr. At these low pressures, efficient fragmentation of heavy ions (such as the singly charged homogenously substituted triazatriphosphorine of mass 2721.89 Da) can take a long time because of the relatively low collision frequency with the background gas and the high internal energy content required to produce fragmentation. Increasing the amplitude used for dipolar excitation leads to loss of the ion upon the quadrupole rods. In the work presented here, the addition of a dc octopolar field to a linear ion trap is described. The dc octopolar field was created by the addition of four auxiliary electrodes situated between the quadrupole rods at a distance of 10 mm from the axis. The inclusion of the dc octopolar field was shown to cause the ions’ frequency of motion to shift out of phase with the excitation signal at high radial amplitudes. This resulted in beat-like trajectories with periods of excitation and de-excitation as the ions’ frequency of motion shifted in and out of phase with the excitation signal. This led to a reduction in the loss of ions on the quadrupole rods during the excitation process. The result is an increased fragmentation efficiency relative to the fragmentation efficiency obtained when using an LIT constructed of round rods only. The inclusion of the dc octopolar field allowed the ion to be fragmented more efficiently in a relatively short excitation period.     

Quadrupole mass filters with octopole fields

The performance of quadrupole mass filters with added octopole fields in the range 2.0-4.0% has been investigated. The added fields are much greater than those normally added to conventional rod sets by mechanical tolerances or construction errors. Quadrupole rod sets with added octopole fields were constructed with round rods by making one pair of rods greater in diameter than the other pair. For positive ions, resolution at half height of only about 200 is possible if the negative direct current (dc) output of the quadrupole power supply is connected to the smaller rods. If the positive dc output of the quadrupole power supply is connected to the smaller rods, the resolution improves dramatically; a resolution at half height of 5800 has been observed with a rod set with 2.6% added octopole field. For negative ions the best resolution is obtained with the polarity of the dc reversed, i.e. with the negative dc applied to the smaller rods. These findings are unexpected in view of the literature that argues that to obtain high mass resolution with quadrupole mass filters, higher order multipoles must be kept as small as possible. Numerical simulations of peak shapes agree qualitatively with experiments. Simulation of the boundaries of the first stability region for positive ions shows that when the positive dc is applied to the smaller rods, the addition of a 2.0% octopole field causes the boundaries to shift slightly but the boundaries are well defined, and the tip of the stability region remains sharp. When the positive dc is applied to the larger rods, the boundaries of the stability region move out and become diffuse. For instruments that require a rod set that can be used both as a linear trap and a mass filter, these rod sets may offer improved trap performance while still being capable of providing conventional mass analysis.     

A segmented radiofrequency-only quadrupole collision cell for measurements of ion collision cross section on a triple quadrupole mass spectrometer

The gas collision cell of a triple quadrupole mass spectrometer has been modified to consist of ten short quadrupole rod segments that allow an axial field to be applied to the cell in order to make measurements of ion mobility. The radiofrequency (rf)-quadrupole field provides effective radial confinement that greatly reduces diffusional losses at low pressure. The mobilities of mass-selected ions from an ionspray source have been measured at a pressure of 8 × 10^?3 torr at electric fields of 0. 1 to 3 V/cm, and used to calculate the collision cross sections of the ions. The measured cross sections compare well with those measured by other techniques.     

Evaluation of small mass spectrometer systems for permanent gas analysis

This work is aimed at understanding the aspects of designing a miniature mass spectrometer (MS) system. Several types of small MS systems are evaluated and discussed, including linear quadrupole, quadrupole ion trap, time of flight, and sector. Analysis of hydrogen, helium, oxygen, and argon in a nitrogen background with the concentrations of the components of interest ranging from 0 to 5000 parts per million (ppm). The performance of each system in terms of accuracy, precision, limits of detection, response time, recovery time, scan rate, size, and weight is assessed. The relative accuracies of the systems varied from <1% to approximately 40% with an average below 10%. Relative precisions varied from 1% to 20%, with an average below 5%. The detection limits had a large distribution, ranging from 0.2 to 170 ppm. The systems had a diverse response time ranging from 4 to 210 s, as did the recovery time with a 6-to-210-s distribution. Most instruments had scan times near 1 s; however, one instrument exceeded 13 s. System weights varied from 9 to 52 kg and sizes ranged from 15 x 10(3) cm3 to 110 x 10(3) cm3. A performance scale is set up to rank each system, and an overall performance score is given to each system.     

Modelling mass analyzer performance with fields determined using the boundary element method

Computer modelling is widely used in the design of mass analysers to evaluate proposed designs and determine the effects of manufacturing imperfections. For quadrupole mass filters and ion traps, the models require accurate values of the electric field throughout the regions of the analyser in which ions travel. Most published results using models to predict mass analyser behaviour use electric fields computed with finite element (FE) or finite difference (FD) method. However, the boundary element method (BEM) is capable of achieving the same, or higher, accuracy with both computation times and memory requirements that are at least an order of magnitude less than those required by FE and FD methods. In this paper, electric field evaluation is performed using the BEM formulated in a manner described by previous workers; modifications to their method are described, which lead to higher accuracy field values. Simultaneous equation solution techniques are incorporated, which avoid solutions that are physically not realistic. The performance of linear quadrupole mass spectrometers with hyperbolic, circular and planar section electrodes has been determined using fields computed using these methods and compared with previous results obtained by alternative field computation techniques and with experiment. Behaviour of an ion trap mass spectrometer with circular symmetry has also been investigated. The results demonstrate that in each case using the BEM to determine the fields produces the observed behaviour. Copyright © 2010 John Wiley & Sons, Ltd.     

Potentiometric determination of mefenamic acid in pharmaceutical formulation by membrane sensor based on ion-pair with basic dye

The characteristics,performance and application of membrane sensors based on ion-pair Brilliant Green mefenamate are described.The sensor’s response to the mefenamate ion has the sensitivity of （86.0±2.0） mV/pC over the range of 9×10^-5-1×10^-2moI/Land the detection limit of 4.5×10^-5mol/L at pH 8.5-12.The sensor is easily assembled at a relatively low cost and has fast response time（5-10 s）.The proposed sensor displayed good selectivity for mefenamate ion in the presence of different substances.It was used to determine mefenamic acid in pharmaceuticals.     

基于高效液相色谱-三重四极杆质谱技术测定荔枝和香蕉中的草铵膦及3种代谢物

采用高效液相色谱-三重四极杆质谱技术，建立了荔枝和香蕉中草铵膦及3种代谢物的检测分析方法。样品加水超声提取，离心沉淀后进样分析，分析物经Extend-C18色谱柱分离，以0.1%氨水-甲醇（9：1，v/v）作为流动相等度洗脱，在电喷雾负离子扫描、多反应监测模式下，外标法定量分析，同时探讨了前处理和仪器分析条件对草铵膦及代谢物的影响效果。结果表明，草铵膦及3种代谢物在1~1000 μg/L范围内，峰面积与质量浓度的线性关系良好；当添加浓度水平在50、100、1000 μg/kg时，草铵膦及代谢物在荔枝和香蕉中的平均回收率为82.9%~98.6%，相对标准偏差（RSD）为2.6%~6.3%，检出限（LOD）为5~10 μg/kg。本方法简化了样品前处理步骤，具有良好的可靠性和灵敏度，适于荔枝和香蕉中草铵膦及其代谢物的快速分析。     

Simultaneous determination of 10 first-generation histamine h1 receptor blockers in feeds by ultra-high-performance liquid chromatography triple quadrupole ion trap hybrid mass spectrometer

A method for simultaneous determination of 10 first-generation histamine H1 receptor blockers in feeds by ultra-high-performance liquid chromatography triple quadrupole mass spectrometry combined with solid phase extraction. Instrument conditions, extraction solvents, and purification methods have been optimized. Under the optimum conditions, these analytes were separated effectively at 6 min. These feeds have been extracted by acid acetonitrile and purified by mixed cation exchange solid-phase extraction. The performance of this method meets the requirements of veterinary residue detection in feeds in China. It is appropriate for the confirmatory monitoring and quantitative analysis of 105 feed samples, five kinds of histamine H1 receptor blockers have been detected in 10 samples.