WO2016141733A1 - 一种线性离子阱中激发离子的方法 - Google Patents

一种线性离子阱中激发离子的方法 Download PDF

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WO2016141733A1
WO2016141733A1 PCT/CN2015/095259 CN2015095259W WO2016141733A1 WO 2016141733 A1 WO2016141733 A1 WO 2016141733A1 CN 2015095259 W CN2015095259 W CN 2015095259W WO 2016141733 A1 WO2016141733 A1 WO 2016141733A1
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ion trap
ion
ions
kinetic energy
linear ion
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党乾坤
谢小东
徐福兴
陈银娟
丁传凡
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Fudan University
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    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00—Particle spectrometers or separator tubes
    • H01J49/26—Mass spectrometers or separator tubes
    • H01J49/34—Dynamic spectrometers
    • H01J49/42—Stability-of-path spectrometers, e.g. monopole, quadrupole, multipole, farvitrons
    • H01J49/4205—Device types
    • H01J49/422—Two-dimensional RF ion traps
    • H01J49/4225—Multipole linear ion traps, e.g. quadrupoles, hexapoles
    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00—Particle spectrometers or separator tubes
    • H01J49/004—Combinations of spectrometers, tandem spectrometers, e.g. MS/MS, MSn
    • H01J49/0045—Combinations of spectrometers, tandem spectrometers, e.g. MS/MS, MSn characterised by the fragmentation or other specific reaction
    • H01J49/0063—Combinations of spectrometers, tandem spectrometers, e.g. MS/MS, MSn characterised by the fragmentation or other specific reaction by applying a resonant excitation voltage
    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00—Particle spectrometers or separator tubes
    • H01J49/02—Details
    • H01J49/10—Ion sources; Ion guns
    • H01J49/16—Ion sources; Ion guns using surface ionisation, e.g. field-, thermionic- or photo-emission
    • H01J49/165—Electrospray ionisation
    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00—Particle spectrometers or separator tubes
    • H01J49/26—Mass spectrometers or separator tubes
    • H01J49/34—Dynamic spectrometers
    • H01J49/42—Stability-of-path spectrometers, e.g. monopole, quadrupole, multipole, farvitrons
    • H01J49/4205—Device types
    • H01J49/422—Two-dimensional RF ion traps
    • H01J49/423—Two-dimensional RF ion traps with radial ejection
    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00—Particle spectrometers or separator tubes
    • H01J49/02—Details
    • H01J49/06—Electron- or ion-optical arrangements
    • H01J49/062—Ion guides
    • H01J49/063—Multipole ion guides, e.g. quadrupoles, hexapoles

Definitions

  • the invention belongs to the technical field of mass analysis instruments, and in particular relates to a method for exciting ions in a linear ion trap.
  • Mass spectrometers have been widely used in biology, food safety, the pharmaceutical industry, environmental monitoring and homeland security. It has excellent ability to characterize and quantify chemicals.
  • Cascade mass spectrometry is the core means of analyzing the structure of a compound and determining the type of compound.
  • cascade mass spectrometry methods such as infrared multiphoton dissociation, electron transfer dissociation, electron capture dissociation, proton transfer dissociation and collision induced dissociation.
  • collision-induced dissociation is the most widely used because it is easy to implement and the product is easy to predict.
  • a linear ion trap is an important mass spectrometer that can store both ions and masses of ions. It can be used as a mass analyzer alone or in series with other mass analyzers such as time-of-flight, quadrupoles, etc. for more complex functions. As a mass analyzer, it has the advantages of simple structure, small size, low vacuum operation, and cascade mass spectrometry in a single well. When connected in series with other mass analyses, it can be used to select ions, accumulate ions to increase sensitivity, and perform molecular ion reactions.
  • the collision-induced dissociation process in an ion trap is generally divided into the following steps: First, the parent ion is isolated, and the ions of interest are selected by means of an inverse Fourier transform waveform or a forward-reverse scan or a stable image vertex isolation. Second, the collision-induced dissociation phase generally increases the amplitude of the ion vibration by applying an auxiliary AC voltage (ie, AC) that matches the ion duration frequency, and approaches the edge of the electrode, thereby absorbing more from the RF (ie, RF) field. Multi-energy, kinetic energy increases, and in the process of collision with neutral gas molecules, kinetic energy is continuously converted into internal energy to achieve dissociation.
  • auxiliary AC voltage ie, AC
  • the ions In the collision-induced dissociation phase, the ions must have sufficient kinetic energy to collide with the gas to dissociate.
  • the maximum kinetic energy that the ion can reach is determined by its q value.
  • the relationship of q in the linear ion trap is as follows:
  • q is a relationship proportional to the amplitude of the RF RF voltage, where V is the zero-peak of the RF RF signal, m and e are the mass and charge of the ion, r 0 is the field radius, and ⁇ is the RF voltage signal The frequency of the circle.
  • the value of q must be suitable. If it is too small, the ions will not get enough kinetic energy to achieve dissociation; if it is too large, more fragment ions will not be detected due to the low mass cutoff effect.
  • the low mass cutoff effect means that for ions with a q value greater than 0.908, outside the stable region of the ion trap, the motion is in an unstable state and cannot be stored. Under normal circumstances, the q value is chosen to be between 0.2 and 0.4. Under the condition of ensuring sufficient dissociation, the smaller the q value, the better.
  • Non-Patent Document 1 reports that the initial energy of the ion is increased by heating the buffer gas, and the q-worth method is lowered.
  • ion collision dissociation can be divided into two processes: ion excitation and ion dissociation, which can make ion excitation proceed at a higher q value, and then rapidly reduce the q value, so that ion dissociation occurs at a lower q value.
  • a non-patent document 2 reports a pulse q-value dissociation method (PQD).
  • the conventional collision-induced dissociation method in a linear ion trap applies an auxiliary excitation signal only to a pair of electrodes of the well, because the two directions in the ideal quadrupole field do not affect each other, mainly causing the ions to be excited in the x or y direction. . If the ions can be excited simultaneously in both directions, the average kinetic energy and the maximum kinetic energy of the ions are improved compared to the one-way excitation, so that the q value can be lowered.
  • Non-Patent Document 1 Racine A.H., Payne A.H., Remes P.M., Glish G.L. Thermally assisted collision-induced dissociation in a quadrupole ion trap mass spectrometer. Anal. Chem. 78, 4609-4614 (2006)
  • Non-Patent Document 2 Schwartz, J.C., Syka, J.E.P., Quarmby, S.T. Proceedings of the 53rd ASMS Conference on Mass Spectrometry and Allied Topics; San Antonio, TX, June 5-9 (2005).
  • the present invention provides a method of exciting ions in a linear ion trap by exciting ions in the linear ion trap simultaneously in the x and y directions, thereby increasing the average kinetic energy and maximum kinetic energy of the ions.
  • the specific implementation is on the pair of electrodes x and y. Applying an auxiliary AC voltage in a dipole manner, that is, the phases of the alternating signals applied to the opposite pair of electrodes are 180 degrees out of phase; or, respectively, applying an auxiliary alternating current in a unipolar manner on the pair of electrodes x and y Voltage, ie an alternating signal is applied only on a single electrode.
  • the traditional ion excitation mode mainly causes the ions to increase in amplitude in a single coordinate direction.
  • the ion amplitude has the following relationship with the average kinetic energy:
  • ⁇ is the RF circular frequency
  • ri is the maximum ion motion radius.
  • the kinetic energy of ions is mainly determined by the first term. It can be seen that the kinetic energy is proportional to the square of the radius of motion.
  • the depth of the potential well of the ion motion is as follows:
  • D is the well depth in the x or y direction in a single direction
  • ⁇ is the angle between the line connecting the ion point and the origin and the x axis (less than 90 degrees).
  • the x and y directions move simultaneously, and the ions are at a higher kinetic energy for a longer period of time. Because the unidirectional excitation kinetic energy changes approximately sinusoidal with time, in a period, some time short kinetic energy is near the lowest value, and at the same time, even if the x-direction kinetic energy is at the lowest value, the y-direction kinetic energy can be in comparison. High value, which increases the average kinetic energy.
  • the invention realizes the simultaneous excitation of ions in two directions, and can also apply an auxiliary AC voltage in a unipolar manner on the pair of electrodes x and y, that is, an alternating signal is applied only on a single electrode.
  • the auxiliary AC signal applied may be an AC signal having a single frequency, such as a sine wave, a moment Shape wave, triangle wave.
  • the applied auxiliary AC signal may be an AC signal including a plurality of frequency superpositions, such as a noise signal, an inverse Fourier transformed signal.
  • the two alternating current signals applied to the x and y electrodes may be of the same type, such as being sinusoidal.
  • the amplitudes can be different, the frequencies can be different, and the phase difference can vary from 0 to 360 degrees, but not 90 degrees.
  • the two alternating current signals applied to the x and y electrodes may be completely different in type, such as a sine wave on the x electrode and a sine wave containing a plurality of frequencies on the y electrode.
  • the stage of applying an alternating current signal to the x and y electrodes simultaneously is a stage in which ions are dissociated.
  • the linear ion trap includes a quadrupole used as an ion trap, including a hyperbolic linear ion trap, including a rectangular ion trap, including a triangular ion trap, including other linear traps of various shapes or configurations.
  • the invention has the advantages that the ions can be excited to move in both the x and y coordinate directions, and the ions obtain higher kinetic energy than the excitation in only one direction, and more kinetic energy is converted into the inner collision process. Yes, so that dissociation is more likely to occur. Further, the required q value can be lowered, more fragment ions are observed, and the low mass cutoff problem is improved. At the same time, when the same one-way excitation conditions are the same, the dissociation rate can be accelerated, the dissociation time can be shortened, and the fragmentation efficiency and collision-induced dissociation efficiency can be improved.
  • Figure 1 A diagram of an auxiliary voltage signal applied in a dipole mode using a quadrupole as a model of a linear ion trap.
  • FIG. 2 is a schematic diagram of an implementation circuit of a specific embodiment 1 of the present invention, in which a triangular electrode ion trap is used as a linear ion trap.
  • Fig. 3a is a simulation diagram of the ion trajectory of a conventional one-way excitation of ions of 10 mass-to-charge ratios 556 in Example 1 for Example 1.
  • Fig. 3b is a simulation diagram of ion motion trajectory under the bidirectional excitation of the present invention within 20 ms for the ions of 10 mass-to-charge ratios 556 for Example 1.
  • Fig. 4a is a simulation diagram showing the trajectory of ion x-direction motion of ions of mass-to-charge ratio 556 under conventional one-way excitation with time.
  • Fig. 4b is a simulation diagram showing the change of the trajectory of the ion y direction of the ions of the mass-to-charge ratio 556 under the bidirectional excitation of the present invention as a function of time.
  • Example 1 is the ion mass to charge ratio of ions 556 in the traditional way the kinetic energy E r excitation radial time varying analog FIG.
  • FIG. 5b Example 1 is a mass to charge ratio of the ion kinetic energy E r 556 radial time varying analog FIG bidirectional excitation ion under the present invention.
  • Figure 6 is a schematic view showing the structure of the instrument platform of the first embodiment.
  • Figure 7a For Example 1, the ratio of the fragment ion a4/b4 of the enkephalin sample to the q value in the case of the conventional one-way excitation (1 representative) and the two-way excitation of the present invention (2 represents) Figure.
  • Fig. 7b is a graph showing the fragmentation efficiency of an enkephalin sample as a function of q in the case of the conventional one-way excitation and the two-way excitation of the present invention.
  • Figure 8a is a tandem mass spectrum of an enkephalin sample for Example 1, with an excitation amplitude of 200 mV and an excitation time of 20 ms, obtaining the same energy deposition (fragment ion a4/b4 is 3), under one-way excitation.
  • Figure 8b Cascade mass spectrum of an enkephalin sample for Example 1, with an excitation amplitude of 200 mV and an excitation time of 20 ms, obtaining the same energy deposition (fragment ion a4/b4 is 3), and bidirectional excitation.
  • Fig. 1 is a schematic view showing the structure of an auxiliary excitation voltage signal applied in a dipole manner as one of the embodiments of the present invention.
  • the quadrupole is used as a model for a linear ion trap, but the invention is applicable to all linear ion traps.
  • the RF RF power supply outputs two RF RF signals of opposite phases, and the two signals are respectively coupled to an auxiliary AC signal AC through a coupling coil, and then respectively applied to a pair of opposite electrodes.
  • the RF RF signals are identical, and the auxiliary excitation signals AC are 180 degrees out of phase. This is the way the dipole is applied. If the auxiliary AC signal AC is applied only to one of each pair of electrodes, it is a unipolar application mode.
  • the invention can be practiced in both ways.
  • the coupled auxiliary AC signal AC can be various types of single frequency AC signals, such as sine wave signals, triangular wave signals, square wave signals, etc., or can be a plurality of frequency superimposed AC signals, such as noise signals, anti-Fourier Transform signals, etc.
  • the two auxiliary AC signals AC1 and AC2 coupled to the two pairs of electrodes may be the same type of AC signals, such as sinusoidal signals, or different types of AC signals, such as AC1 is a sine wave and AC2 is a square wave. .
  • AC1 and AC2 may be identical, including the same amplitude, frequency, and phase, or may have different amplitude, frequency, and phase, or may be three. There are two differences, but also three They are all different. For a single-frequency square wave signal, the duty ratios of the two signals may be the same or different.
  • FIG. 1 a schematic diagram of voltage signal application is shown in FIG.
  • the ion trap of this scheme selects the linear ion trap of the triangular electrode and applies the same auxiliary sinusoidal AC signal AC to the two pairs of electrodes of the ion trap in a dipole manner.
  • the auxiliary AC signal AC outputted by the measurement and control system is first divided into two paths, one is directly coupled to the RF RF signal and applied to the pair of electrodes, and the other is coupled to the other pair of electrodes through the controllable signal switch and then coupled to the RF RF signal.
  • the signal switch can control whether the auxiliary AC signal is output and not output in different timing stages.
  • the cascade mass spectrometry includes three important stages, ion isolation, ion collision induced dissociation phase, ion scanning phase, opening the switch only in the ion collision induced dissociation phase, outputting the auxiliary AC signal, and switching off the other phases.
  • the switch In the case of the traditional excitation dissociation method, the switch is always off and there is no auxiliary AC signal output.
  • 3 to 5 are the results of theoretical simulation of the embodiment in the first embodiment.
  • Figure 3 shows the bidirectional excitation of the invention and the conventional one-way excitation.
  • the excitation signal frequency is adjusted to the optimal value, that is, the ion kinetic energy is the largest, the other conditions are completely the same, and the displacement of the ions in the X and Y directions is shifted.
  • a comparison chart of changes over time It can be seen that the solution of the invention allows ions to be simultaneously excited in both directions.
  • Figure 4 further shows a simulation of the motion trajectory of ions in the xy plane.
  • Figure 5 shows the relationship between the single bidirectional ion kinetic energy of ions over time.
  • the maximum kinetic energy of bidirectional excitation is 32 eV, while the unidirectional is 25 eV. This method increases the ion kinetic energy by nearly 30%.
  • the electrospray ion source-delta electrode ion trap mass spectrometer system designed and processed by the laboratory itself has the structure shown in Fig. 6.
  • the instrument consists of a three-stage differential vacuum system with a vacuum of up to 10 -5 Torr in the vacuum chamber, and helium as a cooling gas with a gas pressure of 8 ⁇ 10 -5 Torr.
  • the ions generated by the electrospray ion source pass through the small holes of the sampling plate, and the sampling cone holes enter the second-stage vacuum chamber, and enter the triangular electrode ion trap mass analyzer under the transmission of the 200 mm long quadrupole ion guiding rod.
  • the enkephalin sample is a standard sample for studying ion dissociation of electrospray ionization mass spectrometry.
  • the ratio of fragment ions a4 and b4 can reflect the internal energy of ion deposition. The larger the ratio, the larger the internal energy of deposition.
  • the experimental conditions in Figures 7 and 8 are as follows. Bottom: The dissociation time is 20ms, the excitation signal amplitude is 200mV, and the excitation frequency is optimized to maximize the fragmentation efficiency or the ratio of a4 to b4.
  • Figure 7a reflects that the parent ion enkephalin q is in the range of 0.23 to 0.42.
  • the ion bidirectional excitation of the present invention is higher than the conventional one-way excitation of a4 and b4, that is, the internal energy of deposition is more, and the larger q is. The effect is more obvious.
  • Figure 7b reflects that at lower q values, the bidirectionally excited fragmentation efficiency of the present invention is higher.

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Abstract

一种在线性离子阱中激发离子的方法，属于质量分析仪器的技术领域。在线性离子阱中，在离子碰撞诱导解离阶段，在其径向X和Y方向同时施加辅助激发信号，提高离子两个方向的动能，进一步与中心气体碰撞而发生解离，将动能转换为内能，以实现串级质谱分析。离子X方向和Y方向的动能都得到增强，较传统的离子主要在一个方向激发的解离方式，有更多动能转换为内能，从而可以提高解离效率，缩短反应时间，改善离子阱中低质量截止效应。

Description

一种线性离子阱中激发离子的方法 技术领域
本发明属于质量分析仪器技术领域，具体涉及一种在线性离子阱中激发离子的方法。
背景技术
质谱仪已被广泛应用于生物学，食品安全，制药工业，环境监测和国土安全等领域。它具有优异的对化学物质进行定性和定量的能力。串级质谱是分析化合物结构和确定化合物种类的核心手段。在质谱中，有一系列的串级质谱方法，如红外多光子解离，电子转移解离，电子捕获解离，质子转移解离和碰撞诱导解离等。其中碰撞诱导解离由于容易实施，且产物容易预测等优势，应用最为广泛。
线性离子阱是一种重要的质谱装置，既可以存储离子，也可以对离子进行质量分析。它可以单独作为质量分析器，也可以与其它质量分析器，如飞行时间，四极杆等串联使用，实现更为复杂的功能。作为质量分析器，它具有结构简单，体积小，可在较低真空度下工作，单一阱中即可实现串级质谱功能等优势。与其它质量分析串联时，可用来选择离子，累积离子提高灵敏度，进行分子离子反应等。
离子阱中碰撞诱导解离过程一般分为以下几步：第一，隔离母离子，通过反傅里叶变换波形或者正反扫描或者稳定图顶点隔离等手段将感兴趣的离子选择出来。第二，碰撞诱导解离阶段，一般通过施加一与离子久期频率匹配的辅助交流电压(即AC)，使离子振动幅度增大，而接近电极边缘，从而从射频(即RF)场吸收更多能量，动能增大，在与中性气体分子碰撞过程中，不断将动能转换为内能，实现解离。
在碰撞诱导解离阶段，离子必须有足够的动能才能与气体碰撞解离，离子所能达到的最大动能由其q值决定，线性离子阱中q的关系式如下：
Figure PCTCN2015095259-appb-000001
其中，q是与射频RF电压幅值成正比的关系式，其中V是射频RF电压信号的零峰值，m和e分别是离子的质量和电荷数，r0是场半径，Ω是射频电压信号的圆频率。
离子在阱中的运动，可以看做是在一个势阱中运动，其动能不能超过势阱的深度。 由于在理想四极场中，离子在x和y方向的运动互不影响，因此只需每个方向的动能不超过势阱的深度即可。对于q<0.4，阱深的近似表达式为：
Figure PCTCN2015095259-appb-000002
实现碰撞诱导解离，q的取值必须适合，如果太小，离子将得不到足够的动能，不能实现解离；如果太大，由于低质量截止效应，更多的碎片离子检测不到。低质量截止效应是指对于q值大于0.908的离子，处于离子阱稳定图区域之外，运动处于不稳定状态，不能被存储。一般情况下q值选取在0.2至0.4之间，在保证解离充分情况下，q值越小越好。
解决低质量截止的方法主要有两种。第一就是尽可能的降低q值，如非专利文献1报道了通过加热缓冲气体，使离子初始内能增加，而降低q值得方法。第二，离子碰撞解离又可分为离子激发和离子解离两个过程，可使离子激发在较高q值进行，然后迅速降低q值，从而使离子解离在较低q值发生，如非专利文献2报道了脉冲q值解离方法(PQD)。
目前，线性离子阱中的传统碰撞诱导解离方法，仅在阱的一对电极上施加辅助激发信号，因为理想四极场中两个方向运动互不影响，主要引起离子在x或者y方向激发。如果能使离子在两个方向上同时激发，相较单向激发，离子的平均动能和最大动能都得到提高，从而可以降低q值。
非专利文献1：Racine A.H.,Payne A.H.,Remes P.M.,Glish G.L.Thermally assisted collision-induced dissociation in a quadrupole ion trap mass spectrometer.Anal.Chem.78,4609-4614(2006)
非专利文献2：Schwartz,J.C.,Syka,J.E.P.,Quarmby,S.T.Proceedings of the 53rdASMS Conference on Mass Spectrometry and Allied Topics；San Antonio,TX,June5–9(2005)。
发明内容
本发明的目的在于提供一种能够提高离子的平均动能和最大动能的在线性离子阱中激发离子的方法。
本发明提供在线性离子阱中激发离子的方法，是使线性离子阱中离子同时在x和y方向激发，从而提高离子平均动能和最大动能。具体实现方式，是在x和y两对电极上 以偶极的方式分别施加一辅助交流电压，即相对的一对电极上所施加的交流信号的相位相差180度；或者，在x和y两对电极上以单极的方式分别施加一辅助交流电压，即仅在单个电极上施加交流信号。
线性离子阱中，传统离子激发方式主要引起离子在单一坐标方向上幅度增大。在纯四极场中，离子幅度与平均动能有如下关系：
Figure PCTCN2015095259-appb-000003
其中，m是离子质量,Ω是射频圆频率，ri是最大离子运动半径,
Figure PCTCN2015095259-appb-000004
最可几离子热速度,
Figure PCTCN2015095259-appb-000005
和
Figure PCTCN2015095259-appb-000006
仅与射频场有关的项。离子动能主要由第一项决定，可见动能与运动半径的平方是正比关系。又
Figure PCTCN2015095259-appb-000007
故当两个方向幅度都增大时，离子会不再沿着x＝0或y＝0运动，而是xy平面与坐标轴有一定夹角的运动，半径会更大而增加离子的平均动能。
另外，在xy平面，离子运动的势阱深度关系式如下：
Dxy＝D(1+tan2θ)
Figure PCTCN2015095259-appb-000008
其中D是在单一方向x或y方向的势阱深度，Φ为离子位置与原点的连线与x轴的夹角(小于90度)。
可见，沿着一定夹角运动，势阱更深，所能达到的动能也更大。
此外x和y方向运动同时激发，离子处于较高动能的时间更长。因为单一方向激发动能随时间变化近似呈现正弦波的变化，所以在一个周期内，有部分时间短动能位于最低值附近，而同时激发时，即使x方向动能处于最低值，y方向动能可以处于较高值，从而提高平均动能。
本发明实现离子两个方向同时激发的方式，也可在x和y两对电极上以单极的方式分别施加一辅助交流电压，即仅在单个电极上施加交流信号。
本发明中，所施加的辅助交流信号可以是具有单一频率的交流信号，如正弦波，矩 形波，三角波。
本发明中，所施加的辅助交流信号可以是包含多种频率叠加的交流信号，如噪声信号，反傅里叶变换的信号。
本发明中，x和y电极上所施加的两个交流信号，可以类型完全相同，如都是正弦波。对于相同类型的信号，其幅度可以不同，其频率可以不同，其相位差可以从0到360度变化，但不包括90度。
本发明中，x和y电极上所施加的两个交流信号，可以类型完全不相同，如x电极上是正弦波，y电极上是包含多个频率的正弦波。
本发明中，同时在x和y电极上施加交流信号的阶段，为离子发生解离的阶段。
本发明中，线性离子阱包括作为离子阱使用的四极杆，包括双曲面线性离子阱，包括矩形离子阱，包括三角离子阱，包括其它各种形状或结构的线性离子阱。
本发明的优点在于可以使离子在x和y两个坐标方向运动都的到激发，而相较仅在一个方向激发，离子获得更高的动能，与气体碰撞过程中有更多动能转换为内能，从而更加容易发生解离。进一步可以降低所需的q值，观察到更多的碎片离子，改善低质量截止问题。同时，与现有单向激发条件相同时，可以加快解离速率，缩短解离时间，提高碎裂效率和碰撞诱导解离效率。
附图说明
图1：以四极杆作为线性离子阱的模型，本发明以偶极方式实施的辅助电压信号施加图。
图2：本发明具体实施例1的实施电路示意图，其中三角电极离子阱作为线性离子阱。
图3a：为实施例1，10个质荷比556的离子在20ms内传统单向激发下的离子运动轨迹模拟图。
图3b:为实施例1，10个质荷比556的离子在20ms内本发明的双向激发下的离子运动轨迹模拟图。
图4a:为实施例1，质荷比556的离子在传统单向激发下的离子x方向运动轨迹随时间变化模拟图。
图4b:为实施例1，质荷比556的离子在本发明的双向激发下的离子y方向运动轨迹随时间变化模拟图。
图5a:为实施例1，质荷比556的离子在传统单向激发下的离子径向动能Er随时间 变化模拟图。
图5b:为实施例1，质荷比556的离子在本发明的双向激发下的离子径向动能Er随时间变化模拟图。
图6:为实施例1的仪器平台结构示意图。
图7a：为实施例1,在传统单向激发(1代表)和本发明的双向激发(2代表)两种情况下，脑啡肽样品的碎片离子a4/b4的比值随q值的变化关系图。
图7b：为实施例1，在传统单向激发和本发明的双向激发两种情况下，脑啡肽样品的碎裂效率随q值的变化关系图。
图8a:为实施例1，在激发幅度为200mV，激发时间为20ms，获得相同能量沉积(碎片离子a4/b4为3)，单向激发下，脑啡肽样品的串级质谱图。
图8b:为实施例1，在激发幅度为200mV，激发时间为20ms，获得相同能量沉积(碎片离子a4/b4为3)，双向激发下，脑啡肽样品的串级质谱图。
具体实施方式
下面结合附图和实施例对本发明作进一步详细说明，以更好的了解本发明。
本技术方案通过在线性离子阱x和y两个方向施加辅助激发信号，使离子阱中的离子在两个方向运动都得到激发，从而与传统的单方向激发方式对比在相同条件下离子获得更高的动能，进一步激发的离子与气体分子碰撞而沉积更多的内能。图1为该发明实施方案之一，以偶极方式施加辅助激发电压信号的结构示意图。图中四级杆作为线性离子阱的模型，但该发明适用于所有线性离子阱。射频RF电源输出两路相位相反的射频RF信号，两路信号分别通过耦合线圈耦合一个辅助交流信号AC，然后分别施加到一对相对的电极上。在每对电极的两个电极上，射频RF信号完全相同，辅助激发信号AC相位相差180度。此即为偶极施加方式。如果仅在每对电极中的一个电极上施加辅助交流信号AC，则为单极施加方式。两种方式都可实施本发明。耦合的辅助交流信号AC可以是各种类型的单一频率的交流信号，如正弦波信号，三角波信号，方波信号等，也可以是多种频率叠加的交流信号，如噪音信号，反傅里叶变换信号等。耦合到两对电极上的两路辅助交流信号AC1和AC2，可以是相同类型的交流信号，如都是正弦波信号，也可以是不同类型的交流信号，如AC1是正弦波，AC2是方波。其中，如果是单一频率的相同类型的交流信号，如单一正弦波信号，AC1和AC2可以完全相同，包括幅度、频率、相位皆相同，也可以幅度、频率和相位三者有一不同，也可以三者有两不同，也可以三 者皆不同。如是单一频率的方波信号，两路信号的占空比可以相同也可以不同。
具体实施例1，电压信号施加示意图如图2。该方案的离子阱选择三角形电极的线性离子阱，以偶极方式施加同一辅助正弦波交流信号AC至离子阱的两对电极。测控系统输出的辅助交流信号AC，先分成两路，一路直接与射频RF信号耦合施加到一对电极上，另一路通过可控制的信号开关再与射频RF信号耦合施加到另一对电极。该信号开关可以控制该路辅助交流信号在不同时序阶段内输出与不输出。实际实验过程中，串级质谱包括三个重要阶段，离子隔离，离子碰撞诱导解离阶段，离子扫描阶段，仅在离子碰撞诱导解离阶段打开开关，输出辅助交流信号，其它阶段开关关闭。如果是传统的激发解离方法，则开关始终关闭，无辅助交流信号输出。
图3-图5是对该实施例1中实施方案进行理论模拟的结果。具体模拟条件为质荷比为556的离子的q＝0.25，激发信号幅度为100mV，碰撞气为氦气，气压为0.08mTorr，温度为300K。
图3显示的是该发明的双向激发与传统的单向激发两种情况下，激发信号频率分别调节至最优值，即离子动能最大，其他条件完全相同，离子在X和Y方向偏离的位移随时间变化关系对比图。可见该发明的方案可以使离子在两个方向同时得到明显的激发。
图4进一步显示离子在xy平面的运动轨迹模拟图，传统的单向激发离子主要沿着y＝0直线运动，而本发明双向激发离子沿着x＝y直线运动，偏离坐标轴一定角度，使离子运动的幅度更大，而获得更高的动能。
图5显示的是离子的单双向离子动能随时间变化关系图，双向激发的最大动能为32eV，而单向为25eV，该方法提高离子动能将近30％。
图6-图8是对是实施例1中的实验方案进行实验验证的结果。
本实验室自行设计和加工的电喷雾离子源-三角形电极离子阱质谱仪器系统，其结构如图6所示。仪器由三级差分真空系统构成，离子阱所在真空腔内真空度可达10-5Torr，氦气作为冷却气，气压维持在8×10-5Torr。电喷雾离子源产生的离子通过采样板小孔，取样锥孔进入第二级真空腔，在长200mm的四极离子导引杆传输作用下，进入三角形电极离子阱质量分析器。试剂：亮氨酸脑啡肽(Leucine encephalin，m/z 556,吉尔生化上海有限公司)，溶剂采用甲醇：水＝50:50，其中含有0.5％的醋酸。
脑啡肽样品是研究电喷雾质谱的离子解离的标准样品，其碎片离子a4和b4的比例能反应离子沉积内能的多少，该比例越大，沉积的内能越大。图7和8中的实验条件如 下：解离时间为20ms，激发信号幅度为200mV，激发频率通过优化使其碎裂效率最大或a4与b4的比值最大。
图7a反映母离子脑啡肽q在0.23至0.42范围内，本发明的离子双向激发较传统单向激发的a4与b4的比值更高，即沉积的内能更多，而且q越大这种效应越明显。
图7b反映在较低的q值，本发明的双向激发的碎裂效率更高。
在相同离子内能沉积情况下，由a4与b4的比值反映，皆为3，图8a为传统单向激发的质谱图，q为0.33，图8b为本发明双向激发的质谱图，q为0.43，可见该方法能观察到更多碎片离子。

Claims (6)

  1. 一种在线性离子阱中激发离子的方法，其特征在于：离子发生解离阶段，在x和y两对电极上以偶极的方式分别施加一辅助交流电压，或者，在x和y两对电极上以单极的方式分别施加一辅助交流电压，使离子在径向X和Y方向同时激发。
  2. 根据权利要求1所述的在线性离子阱中激发离子的方法，其特征在于所施加的辅助交流信号是具有单一频率的交流信号。
  3. 根据权利要求1所述的在线性离子阱中激发离子的方法，其特征在于所施加的辅助交流信号是包含多种频率叠加的交流信号。
  4. 根据权利要求1或2或3所述的在线性离子阱中激发离子的方法，其特征在于x和y电极上所施加的两个交流信号，类型完全相同，其幅度相同或不同，其频率相同或不同，其相位差从0到360度变化，但不包括90度。
  5. 根据权利要求1或2或3所述的在线性离子阱中激发离子的方法，其特征在于x和y电极上所施加的两个交流信号，类型完全不相同。
  6. 根据权利要求1或2所述的在线性离子阱中激发离子的方法，其特征在于所述线性离子阱包括作为离子阱使用的四极杆、双曲面线性离子阱、矩形离子阱或三角离子阱。
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