阶梯电极离子阱质量分析器的结构与性能

本研究从理论上优化了一种新型结构的线型离子阱质量分析器-阶梯电极离子阱质量分析器,它是由2对阶梯电极与1对端盖电极组成。与传统平板电极矩形离子阱长阶梯电极离子阱相比,具有调节电场分布的优点,同时在几何结构设计上更接近于双曲面电极结构,但比双曲面电极更容易加工。通过改变阶梯电极结构的高度、宽度、场半径比例等几何参数,实现了对离子阱内部电场分布的优化,从而实现离子阱性能的优化。理论模拟研究结果表明,根据几何结构和电场分布优化获得的阶梯电极离子阱质量分析器(X0×Y0=9 mm×5 mm),可以在225 Da/ s 扫速下获得10150的质量分辨率。阶梯电极离子阱结构简单,分辨能力明显高于矩形离子阱。初步的实验结果表明,阶梯电极离子阱具有较好的串级质谱分析性能。     

印刷线路板分压离子阱的离子单向出射性能研究

印刷线路板(Printed-Circuit-Board,PCB)分压离子阱是一种新型质量分析器,其突出优点在于内部电场可通过调节射频分压比进行优化.本实验在PCB分压离子阱离子出射方向的两组离散电极上配置了非对称的射频分压,以引入奇次阶场成分,使得射频电场的场中心(即离子运动中心)发生偏移,从而实现离子单向出射.通过数值计算软件SIMION和AXSIM分析了射频分压比差值与其内部电场分布的关系,并模拟离子运动轨迹,得到离子出射情况和模拟质谱峰.模拟结果表明,当两组离散电极的射频分压比差值为20％时,在合适的AC频率条件下,对于m/z=609 Th的离子,PCB分压离子阱的离子单向出射率可达90％以上,且质量分辨率大于2500.本研究可使PCB分压离子阱在基本不损失质量分辨率和使用单检测器模式下,大幅提高离子检测效率,因而在小型化质谱仪应用中具有显著优势.     

半圆弧面线性离子阱性能优化的模拟研究

半圆弧面线性离子阱具有电极结构简单、便于加工和安装精度高等优点。为进一步提升半圆弧面线性离子阱的分析性能,本研究在实验室原有半圆弧面线性离子阱的基础上提出了一种四面开槽的半圆弧面线性离子阱,并对其电极半径与场半径之比r/r0以及离子出射方向上电极的“拉伸”距离进行了优化。模拟结果表明：当r/r0=5：5,离子出射方向上的电极向外“拉伸”0.8~1.2 mm时,离子阱的性能有较大提升,尤其是“拉伸”距离为0.9 mm时所得质量分辨率最高,当扫描速率为409 Da/s时, m/z=609 Da的离子质量分辨率可达到6264( M/△M, FWHM)。作为对比,本研究同时对双曲面线性离子阱的性能进行了仿真优化,结果表明,经过优化后的半圆弧面线性离子阱的性能可与双曲面线性离子阱相媲美。     

新型三角形电极圆环离子阱的理论模拟研究

圆环离子阱由于其离子储存能力明显优于相同体积下的三维离子阱,近年来被认为是离子阱小型化发展的另一个重要方向。为进一步优化圆环形离子阱的质谱性能,特别是质量分辨能力,本研究提出了一种由三角形电极构建的新型圆环离子阱,它由两个完全等同的、截面为三角形的圆环电极及两个大小不等的圆筒型电极所组成,离子通过共振激发方式弹出。通过理论模拟和对电极结构的优化,获得了具有非对称性的三角形电极结构,通过改善圆环结构,优化电场分布,提高了离子引出效率和离子阱的质量分辨能力,其中一种最优化结构的圆环离子阱对m/z 609离子的质量分辨率达到1486。     

稳定图的测定与矩形离子阱质谱性能分析

从理论上讲, 离子阱质谱仪的性能是由阱内电场分布决定的,而电场分布又是由组成离子阱的电极几何结构和离子阱工作电压决定的. 对于矩形离子阱, 即使不考虑其几何结构的偏差, 其阱内的电场分布一般也很复杂. 在矩形离子阱内, 除四极电场外, 还包含多种成分的其他各种高阶场, 它们直接影响离子在阱内的运动轨迹和离子阱质谱的性能. 由于各种电场成分对离子阱内离子运动的影响非常复杂, 还很难从数学上给出精确的解析解, 使得目前从理论上还无法预测高阶场成分对质谱性能的影响. 本工作通过测定不同几何结构的矩形离子阱的稳定图, 从实验上比较了不同场半径, 即不同电场分布条件下的离子阱质谱性能的差别. 实验中, 通过改变离子阱的几何比例结构, 详细测定了不同结构的矩形离子阱的稳定图特征, 并与实验测得的质谱分析结果进行比较. 同时, 我们还详细介绍了矩形离子阱质谱的稳定图的测定方法, 并根据得到的不同情况下的稳定图结构分析了离子阱的质谱性能. 研究结果表明： 可以通过比较试验得到的稳定图结构来判断其离子阱质谱仪的性能如质量分辨能力等. 此外, 实验结果还发现： 对于y方向拉伸结构的矩形离子阱, 其实验绘制得到的是不完整的稳定图. 但根据稳定图边界的特点, 通过采用四极直流电压调制的方法, 可以对y方向拉伸结构的矩形离子阱的性能进行改善, 极大地提高了阱的质量分辨能力.     

栅网电极离子阱质量分析器的结构与性能

报道了一种结构非常简单的新型线型离子阱质量分析器,它由4块"栅网电极"电极与2块端盖电极合围而成的一个近似于长方体的离子存储和分析空间。"栅网电极"的结构为:首先在矩形电极上加工一个"口"字型的通孔,然后再用导电的栅网覆盖住"口"字表面构成。这4块含有栅网的电极合围成一个四面对称的长方体空间,它们与二个端盖电极组成一个完整的离子阱。用栅网电极构成离子阱质量分析器具有以下优势:(1)结构非常简单。它可以极大地减小离子阱质量分析器对组成离子阱电极的机械加工精度要求,如电极对称性,离子引出孔的线性度与大小,以及对离子阱组装精度的要求,使离子阱质谱的生产工艺和使用维护更加简化;(2)由于传统离子引出电极上的离子引出槽被省去,使得离子阱电极的对称性提高,这有可能改善离子阱内部的电场分布,提高离子阱质量分析器的质谱性能;(3)由于离子引出电极的大部分为栅网,它可以成倍提高离子引出效率,提高质谱仪的分析灵敏度。初步的实验结果表明,用本工作给出的用栅网电极组成的离子阱质量分析器,当栅网宽度为4 mm时,在较低的离子共振激发电压下,即可将离子从阱中弹出,并可以获得高于400的质量分辨率和300 Thomson以上的质量扫描范围。     

离子阱阵列的理论模拟研究

采用电脑模拟的方法对一种新型的离子阱质量分析器——离子阱阵列进行了电极结构的优化.该离子阱质量分析器为一种多通道质量分析器,可以同时对不同的离子进行储存和质量分析.本实验主要研究了该离子阱质量分析器的性能和电极结构之间的关系.通过对离子运动轨迹的计算分析,可以得到模拟的离子质谱峰.通过对模拟离子质谱峰的分析,可以区分出使得离子阱性能较优的电极结构.在对模拟质谱峰的分析中,峰形和离子弹出效率都作为性能指标被考虑.有部分模拟的数据与实验结果进行了对比.     

用数字离子阱进行快速质量分析

利用数字离子阱技术进行样品的快速质量分析.在样品离子被引入离子阱的过程中,同时扫描数字射频工作电压的频率和离子共振偶极电压的频率,使得离子在进入离子阱质量分析器后,立即被相应的共振偶极电压所共振激发而逐出离子阱,并被离子探测器测量到.本方法相较于传统离子阱分析过程省去了离子引入、离子冷却和离子清空3个阶段,减少了约3/4的实验分析时间.通过对扫描速度、离子门电压参数的优化,数字束缚射频频率从1000～ 400 kHz线性扫描,扫描速度为2385 Th/s,离子门电压为9V,对利血平(m/z 609),精氨酸(m/z 174)等样品的进行测试,离子信号强度达到最优.结果表明,利用本方法可以获得与离子阱质量分析传统方法相同的质谱结果.     

四极离子阱数字式共振激发控制技术的研发与应用

共振激发控制技术是提高四极离子阱分辨率、灵敏度,实现其多级质谱分析的关键技术。针对质谱仪小型化趋势,提出基于现场可编程门阵列(filed-programmable gate array,FPGA)软件实现直接数字合成器(direct digital synthesizer,DDS)信号幅度调制的方法,开发出数字式共振激发控制技术,研制出结构更简单的共振激发控制系统。在对性能要求较高的电喷雾离子源-矩形离子阱质谱仪中,应用这套系统实现了单质荷比选择离子、三级质谱分析和600~2000 Thomson质荷比范围的全扫描等功能。相比使用模拟技术实现幅度调制的控制单元,数字式共振激发控制单元的功耗只有其10%,系统性能也满足四极离子阱的需求。     

数字离子阱质谱仪低质量截止值的改进方法

本研究在实验室自制的线形数字离子阱质量分析器上,通过改变数码电源的频率扫描方式,在CID过程中,通过扫描数字束缚方波电源的频率和数字激发方波的频率实现母体解离。例如对于利血平母体离子,当将离子数字束缚方波频率从500 kHz扫描到560 kHz,可以测量到低质荷比的碎片离子,成功实现了串级质谱分析的低质量碎片离子的分析。通过与利血平三重四极质谱串级质谱分析实验结果的比较,发现可以在数字离子阱质谱仪上获得与三重四极质谱相同的串级质谱测量结果。结果表明,本方法可以用于低质量离子的测量,克服了传统离子阱质谱进行串级质谱分析的一个主要难点,显著提高数字离子阱质谱的性能。     

Mass‐selective axial ejection from a linear ion trap with a direct current extraction field

We have developed a new mass‐selective axial ejection method from a linear ion trap (LIT). In this method, a set consisting of a trap wire lens and an extraction wire lens positioned orthogonally to each other was placed between quadrupole rods. The trap wire lens confines the ions inside the trap, and the extraction wire axially extracts ions from the trap. Ions introduced into the LIT are trapped between the inlet lens and the trap wire lens. In addition to the wire lenses, a set of excitation lenses, which are aligned orthogonally to the trap wire lens, are inserted between rods. The ions are resonantly excited in the direction perpendicular to the trap wire lens by applying a supplemental alternating current (AC) to the excitation lenses. Excited ions with a large motion pass over the trap wire lens, while unexcited ions remain trapped inside. Ions that have passed over the trap wire lens are then extracted by the extraction wire lens. The characteristics of the mass‐selective ejection with a direct current (DC) extraction field were investigated by both simulation and experiment. A mass resolving power of m/Δm = 1300 was achieved at a scan rate of 500 Th/s. The dependence of the ejection efficiency on trap wire lens bias was measured, and an ejection efficiency of 20% at a scan rate of 500 Th/s was achieved by optimizing the DC bias on the trap wire lens. Copyright © 2009 John Wiley & Sons, Ltd.     

Novel linear ion trap mass analyzer composed of four planar electrodes

A novel linear ion trap mass analyzer was developed using just four elongated planar electrodes, mounted in parallel, and employing an RF potential for ion trapping in the radial and axial directions. Mass analysis was achieved using the mass-selective instability scan with ion ejection in the radial direction. The performance of this new device was characterized in comparison with the 6-electrode rectilinear ion trap (RIT) from which it is derived. The 4-electrode trap gives optimum performance in an asymmetric geometry, just like the original optimized 6-electrode RIT. The strong RF fringing fields at the ends of the RF rods account for axial ion trapping without use of extra electrodes or an axial DC voltage. Field calculations and simulations have been carried out to study the trapping potential inside RITs with various configurations. Demonstrated capabilities include analysis of externally injected ions with mass resolution in excess of 1000 and a mass/charge range of 650 Th as well as tandem mass spectrometry capabilities. The geometric simplicity and performance characteristics of the 4-electrode RIT make it particularly attractive in the development of next generation miniaturized mass spectrometers.     

Dual buffer gases for ion manipulation in a miniature ion trap mass spectrometer with a discontinuous atmospheric pressure interface

The discontinuous atmospheric pressure interface (DAPI) has been developed to allow a direct transfer of ions from atmosphere into an ion trap mass spectrometer with minimum pumping capability. Air is introduced into the trap with ions and used as a buffer gas for the ion trap operation. In this study, a method of introducing helium as a second buffer gas was developed for a miniature mass spectrometer using a dual DAPI configuration. The buffer gas effects on the performance of a linear ion trap (LIT) with hyperbolic electrodes were characterized for ion isolation, fragmentation and a mass-selective instability scan. Significant improvement was obtained with helium for resolutions of mass analysis and ion isolation, while moderate advantage was gained with air for collision-induced dissociation. The buffer gas can be switched between air and helium for different steps within a single scan, which allows further optimization of the instrument performance for tandem mass spectrometry.     

Implementation of Precursor and Neutral Loss Scans on a Miniature Ion Trap Mass Spectrometer and Performance Comparison to a Benchtop Linear Ion Trap

Implementation of orthogonal double resonance precursor and neutral loss scans on the Mini 12 miniature rectilinear ion trap mass spectrometer is described, and performance is compared to that of a commercial Thermo linear trap quadropole (LTQ) linear ion trap. The ac frequency scan version of the technique at constant rf voltage is used here because it is operationally much simpler to implement. Remarkably, the Mini 12 shows up to two orders of magnitude higher sensitivity compared to that of the LTQ. Resolution on the LTQ is better than unit at scan speeds of ~?400 Th/s, whereas peak widths on the Mini 12, on average, range from 0.5 to 2.0 Th full width at half maximum and depend heavily on the precursor ion Mathieu q parameter as well as the pump down time that precedes the mass scan. Both sensitivity and resolution are maximized under higher pressure conditions (short pump down time) on the Mini 12. The effective mass range of the product ion ejection waveform was found to be 5.8 Th on the Mini 12 in the precursor ion scan mode vs. that of 3.9 Th on the LTQ. In the neutral loss scan mode, the product ion selectivity was between 8 and 11 Th on the Mini 12 and between 7 and 8 Th on the LTQ. The effects of nonlinear resonance lines on the Mini 12 were also explored.

Open image in new window

Graphical Abstract ?

     

Mass selective ejection by axial resonant excitation from a linear ion trap

We describe a new mass selective ejection method from a linear ion trap, which we call axial resonant excitation (AREX). A set of vane lenses are inserted between each quadrupole rod to produce electrostatic potential that is approximately harmonic along the central axis of the quadrupole field. After ions with specific m/z are resonantly oscillated in the axial direction, the ions are mass selectively ejected in the axial direction. At a high scan rate of 11 Th/ms, AREX achieved a high ejection efficiency of more than 60%, which is more than three times higher than a conventional mass selective axial ejection method from a linear trap using fringing field.     

Miniature toroidal radio frequency ion trap mass analyzer

A miniature ion trap mass analyzer is reported. The described analyzer is a 1/5-scale version of a previously reported toroidal radio frequency (rf) ion trap mass analyzer. The toroidal ion trap operates with maximum rf trapping voltages about 1 kVp-p or less; however despite the reduced dimensions, it retains roughly the same ion trapping capacity as conventional 3D quadrupole ion traps. The curved geometry provides for a compact mass analyzer. Unit-mass resolved mass spectra for n-butylbenzene, xenon, and naphthalene are reported and preliminary sensitivity data are shown for naphthalene. The expected linear mass scale with rf amplitude scan is obtained when scanned using a conventional mass-selective instability scan mode combined with resonance ejection.     

在线固相萃取-超高效液相色谱-线性离子阱串联质谱法直接测定水中10种藻类毒素

建立了全自动在线固相萃取-超高效液相色谱-线性离子阱串联质谱法直接测定水中10种藻类毒素的方法.利用程序实现多次进样,通过在线固相萃取对藻类毒素进行富集,然后切换六通阀,将富集的目标物冲洗至分析柱进行分离后,进入线性离子阱质谱检测.10种藻类毒素在相应的浓度范围内线性关系良好,相关系数均大于0.99,检出限在0.0015~0.0050μg/L之间,3个浓度水平(0.02、0.10和1.00μg/L)的加标回收率为83.7%~98.5%.结果表明,在线固相萃取极大简化了前处理过程,线性离子阱串联质谱法提高了痕量藻类毒素测定的灵敏度,增强子离子扫描(EPI)谱库的建立为藻类毒素的确证提供保障.本方法适用于水体中多种藻类毒素的快速确证和定量测定.     

Use of a quadrupole linear ion trap mass spectrometer in metabolite identification and bioanalysis

A new type of quadrupole linear ion trap mass spectrometer, Q TRAP trade mark LC/MS/MS system (Q TRAP trade mark ), was evaluated for its performance in two studies: firstly, the in vitro metabolism of gemfibrozil in human liver microsomes, and, secondly, the quantification of propranolol in rat plasma. With the built-in information-dependent-acquisition (IDA) software, the instrument utilizes full scan MS in the ion trap mode and/or constant neutral loss scans as survey scans to trigger product ion scan (MS(2)) and MS(3) experiments to obtain structural information of drug metabolites 'on-the-fly'. Using this approach, five metabolites of gemfibrozil were detected in a single injection. This instrument combines some of the unique features of a triple quadrupole mass spectrometer, such as constant neutral loss scan, precursor ion scan and multiple reaction monitoring (MRM), together with the capability of a three-dimensional ion trap. Therefore, it becomes a powerful instrument for metabolite identification. The fast duty cycle in the ion trap mode allows the use of full product ion scan for quantification. For the quantification of propranolol, both MRM mode and full product ion scan in the ion trap mode were employed. Similar sensitivity, reproducibility and linearity values were established using these two approaches. The use of the product ion scan mode for quantification provided a convenient tool in selecting transitions for improving selectivity during the method development stage.