WO2022007424A1 - 一种新型四极杆-离子阱串联质谱离子存储系统及方法 - Google Patents

一种新型四极杆-离子阱串联质谱离子存储系统及方法 Download PDF

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WO2022007424A1
WO2022007424A1 PCT/CN2021/080045 CN2021080045W WO2022007424A1 WO 2022007424 A1 WO2022007424 A1 WO 2022007424A1 CN 2021080045 W CN2021080045 W CN 2021080045W WO 2022007424 A1 WO2022007424 A1 WO 2022007424A1
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ion
lens
quadrupole
ion guide
guide
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PCT/CN2021/080045
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French (fr)
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楚士颖
江游
方向
黄泽建
戴新华
安育廷
张谛
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中国计量科学研究院
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Publication of WO2022007424A1 publication Critical patent/WO2022007424A1/zh
Priority to US18/071,190 priority Critical patent/US20230094398A1/en

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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
    • H01J49/426—Methods for controlling ions
    • H01J49/4295—Storage methods
    • 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
    • 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
    • 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
    • H01J49/4255—Device types with particular constructional features
    • 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
    • H01J49/426—Methods for controlling ions
    • H01J49/4265—Controlling the number of trapped ions; preventing space charge effects
    • 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
    • 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
    • H01J49/067—Ion lenses, apertures, skimmers
    • 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

Definitions

  • the patent of the invention belongs to the technical field of mass spectrometry, and in particular relates to a quadrupole-ion trap tandem mass spectrometry ion storage system and method.
  • Quadrupole ion trap mass spectrometers have the advantages of full scan, high sensitivity, high resolution scan and MS n , so they are widely used in the field of analytical chemistry.
  • the quadrupole mass analyzer and the ion trap mass analyzer are applied in the same way: the same voltage is applied to the opposite electrode, and the adjacent electrode voltage is opposite.
  • a certain RF voltage and DC voltage are applied to form a quadrupole field for trapping ions.
  • the structural size of the ion trap itself limits its ion storage capacity. When too many ions are implanted, space charge effects will occur in the ion trap, resulting in mass shift and distortion of analysis results.
  • ion storage cannot be performed when the ion trap is in the ion analysis state. If the ion source produces a large number of ions, the time required to fill the ion trap may be much less than the time required for the ion trap to perform the analysis. During analysis, ions generated by the ion source are wasted, resulting in a very low duty cycle of the ion trap and reduced system sensitivity.
  • the patent of the present invention proposes a novel ion storage system and method for quadrupole-ion trap tandem mass spectrometry.
  • a novel quadrupole-ion trap tandem mass spectrometry ion storage system is provided.
  • the ion storage system sequentially includes a heated capillary, a tube lens, a Skimmer, a first ion guide, a second ion guide, a quadrupole mass analyzer, an ion trap mass analyzer, and a detector, a first lens is arranged between the first ion guide and the second ion guide, a second lens and a third lens are arranged between the second ion guide and the quadrupole mass analyzer,
  • the first and second ion guide operating modes include an ion transport mode and an ion storage mode.
  • the first ion guide and the second ion guide operation mode is the ion storage mode; when the second lens voltage is set to -20V, the first ion guide
  • the guiding and second ion guiding modes of operation are ion transport modes.
  • the first ion guide is an I-type square quadrupole, which is used for collision focusing and transmission of ions in the second stage vacuum.
  • the first ion guide is assembled by placing four flat electrodes in parallel, the electrodes are 28 mm long, and the opposite electrodes are connected together.
  • the electrodes are driven by a radio frequency voltage, and the radio frequency voltages of adjacent electrodes have opposite polarities.
  • the second ion guide is a type II square quadrupole, which is used for collision focusing and transmission of ions in the third stage vacuum.
  • the second ion guide is assembled by placing four flat plate electrodes in parallel, the electrodes are 86 mm long, and the opposite electrodes are connected together.
  • the electrodes are driven by a radio frequency voltage, and the radio frequency voltages of the adjacent electrodes have opposite polarities.
  • the ion storage system further includes a gas hole, a molecular pump, a mechanical pump, a front end cap and a back end cap.
  • a novel quadrupole-ion trap tandem mass spectrometry ion storage method is provided, and the ion storage method is based on the novel quadrupole-ion trap tandem mass spectrometry ion storage system according to any one of the preceding aspects.
  • Perform operations, the methods include Init, pre-ion, ionization, cooling, cooling1, pre-sample, sample , down (fall), zero (clear) nine timings.
  • the voltages of the second lens and the third lens are maintained at +10V and +200V respectively, and the first ion guide and the second ion guide operation mode is the ion storage mode;
  • the second lens voltage is reduced from +10V to -20V
  • the third lens voltage is reduced from +200V to -5.6V
  • the first ion guide and the second The ion guide mode of operation is the ion transport mode.
  • the quadrupole radio frequency voltage and the ion trap radio frequency voltage are raised from 0V to a certain constant value in the sequential ionization;
  • the Skimmer is used as the switch lens for ions to enter the next stage, and is set to +14V in the sequential ionization, which is turned on. state;
  • the first ion guiding voltage is kept at -2.5V, the first lens voltage is kept at -6V, and the second ion guiding voltage is kept at -6.1V during the whole mass period.
  • the present invention realizes the function of ion-guided storage by improving the timing control of the instrument.
  • the ion guide continues to store ions, increasing the duty cycle of ion storage.
  • the present invention stores more ions in the same time, and improves the sensitivity of the instrument.
  • Fig. 1 shows the structure diagram of the novel ion storage system of the quadrupole-ion trap tandem mass spectrometer according to the present invention
  • Figure 2 shows a conventional ion transmission mode timing diagram
  • Figures 3(a) and 3(b) show ion guide Q00 and Q0 structural diagrams
  • Fig. 4 shows the sequence diagram of the novel ion storage method of the quadrupole-ion trap tandem mass spectrometer according to the present invention
  • Fig. 5 shows the variation trend diagram of ion guide Q0 voltage according to an embodiment of the present invention
  • FIG. 6 shows a comparison chart of the intensity variation trend of the traditional ion transmission mode (marked by squares) and the ion-guided storage mode (marked by dots);
  • Figure 7 shows a linear diagram of an ion-guided storage mode
  • FIG. 8 shows a trend diagram of peak shift variation in the conventional ion transmission mode (marked by squares) and the ion-guided storage mode (marked by dots);
  • Fig. 9 shows the change trend diagram of the half-peak width in the conventional ion transmission mode (marked by squares) and the ion-guided storage mode (marked by dots);
  • Figure 10 shows the co-storage timing diagram of the ion guide and the ion trap
  • Figure 11 shows a total ion current chromatogram for the co-storage mode of the ion guide and ion trap
  • Fig. 12(a) shows the reserpine intensity graph for 0.05s in the conventional ion transport mode
  • Fig. 12(b) shows the reserpine intensity graph for 0.09s in the ion-guided storage mode
  • Fig. 12(c) shows the ion-guided storage mode for reserpine at 0.09s Intensity plot of reserpine in co-storage mode with ion trap.
  • FIG. 1 A novel ion storage system for quadrupole-ion trap tandem mass spectrometry according to an embodiment of the present invention is shown in FIG. 1, including: A. Heating capillary; B. Tube Lens; C. Skimmer; D. Ion guide Q00; E. I. Guide Q0; F. Quadrupole Mass Analyzer; G. Ion Trap Mass Analyzer; H. Detector; I. Gas Orifice; J. Molecular Pump; K. Mechanical Pump. Lens0, 1, and 2 are lenses 0, 1, and 2. EndCap1 is the front end cap and EndCap2 is the rear end cap.
  • the ion source ionizes the sample, passes the Tube Lens and Skimmer, and is passed to the ion guide Q00 and Q0. At this time, Q00 and Q0 are collision focusing and transmission. Through the focusing and transmission of lens 1 and lens 2, to the quadrupole mass analyzer and ion trap mass analyzer. Finally, the detector detects the ions.
  • the ion trap mass analyzer In traditional ion transmission mode, only the ion trap mass analyzer can store ions, the ion trap cannot store ions while in-trap ion analysis is performed, which results in a duty cycle (the amount of analyte ions being sampled relative to the total cycle time) percentage of time) is very low.
  • the timing diagram is shown in Figure 2: the quadrupole RF voltage and the ion trap RF voltage increase from 0V to a constant value during ionization (ionization) ion capture, and then decrease in the next sequence.
  • Lens2 is -5.7V in ionization (ionization) ion capture, and +200V in other timings.
  • the Skimmer acts as a switch lens for ions entering the next stage, which is turned on (+14V) during ionization (ionization) ion capture, and turned off after the ions enter the next stage. After the Skimmer is turned off (-150V), the ion trap only operates inside the trap and cannot store ions.
  • Q00 has been -3V
  • Lnes0 has been -4.8V
  • Q0 has been -4.4V
  • Lnes1 has been -6V.
  • the mass spectrometry control scheme of the present invention before the ions are introduced into the mass analyzer (quadrupole, ion trap), the ion guide is operated to store the ions generated by the electrospray.
  • Q00 type I square quadrupole, shown in Fig. 3(a)
  • Q00 is used for collisional focusing and transport of ions in the second stage vacuum. It is assembled by placing four flat electrodes in parallel, the electrodes are 28mm long, and the opposite electrodes are connected together. The electrodes are driven by radio frequency voltages, and the radio frequency voltages of adjacent electrodes have opposite polarities.
  • Q0 type II square quadrupole, shown in Fig. 3(b)
  • Q0 is used for collisional focusing and transport of ions in the third stage vacuum. It is also assembled by placing four flat electrodes in parallel, the electrodes are 86mm long, and the opposite electrodes are connected together. The electrodes are driven by a radio frequency voltage, and the radio frequency voltages of the adjacent electrodes have opposite polarities.
  • Lens1 is used as a switch when the ion guide is used to store ions.
  • the ion guide When Lens1 is set to +10V, the ion guide will store ions.
  • the ion guide When Lens1 is set to -20V, the ion guide is traditional Ion transport mode.
  • FIG. 4 The time sequence of the mass spectrometry control scheme according to the embodiment of the present invention is shown in FIG. 4 :
  • the quadrupole radio frequency voltage and the ion trap radio frequency voltage are raised from 0V to a constant value in the ionization (ionization) section; the Skimmer is used as the switch lens for ions to enter the next stage, and the timing is set to +14V, which is in the open state. ; Lens1 and Lens2 keep +10V and +200V in the first three sequences Init, pre-ion and ionization, preventing the ions generated by electrospray from entering the mass analyzer and storing them in the ion guide Q0; Throughout the quality cycle, Q00 has been -2.5V, Lens0 has been -6V, and Q0 has been -6.1V.
  • Lens1 is reduced from +10V to -20V
  • Lens2 is reduced from +200V to -5.6V, so that ions are introduced from the guide Q0 to the quadrupole and finally to the ion trap.
  • the mass-to-height ratio scan range m/z 550 to 650, and the Q0 voltage of the ion-guided storage mode was optimized.
  • the relationship between the Q0 voltage and the signal intensity is shown in Figure 5.
  • the optimal value for Q0 storage is -6.1V.
  • the strength of the new ion-guided storage mode in the nonlinear region is lower than that of the traditional ion transport mode, which is caused by the difference in the mechanical structure of the components (Q0 and ion trap) themselves.
  • the storage capacity of the ion trap is greater than the Q0 storage capacity.
  • the ion-guided Q0 has been in the storage ion mode, and the storage capacity increases linearly to about 52% in the figure.
  • the storage capacity of Q0 has reached saturation.
  • About 20% of the signal enhancement comes from Q00 storage.
  • the proportions are basically the same.
  • Q0 and Q00 are completely saturated, and ions begin to overflow from them. With the increase of the number of overflowing ions, the number of effectively detected particles decreases, and thus the intensity decreases, and the dot marking curve has been showing a downward trend.
  • the peak shift (Fig. 8) and resolution (Fig. 9) of the traditional ion trap storage mode and the new ion-guided Q0 storage mode were compared, because the intensity of the traditional mode was greater than that of the new ion-guided storage mode. , therefore, the peak shift and resolution of the conventional mode are larger.
  • quadrupole RF voltage and ion trap RF voltage are raised from 0V to a constant value in the ionization (ionization) section; Skimmer is all set to + in the entire sequence 5.5V; Lens1 is reduced from +10V to -20V in the ionization sequence, and Lens2 is reduced from +200V to -20V in the ionization sequence, so that the stored ions enter the ion trap.
  • Q00 has been -2.5V
  • Lens0 has been -4.1V
  • Q0 has been -6V.
  • Lens1 is raised from -20V to +10V
  • Lens2 is raised from -5.7V to +200V, so that ions can be stored in the ion guide middle.
  • the peak intensity of the traditional ion transmission mode at 0.05s is 0.9645V as shown in Figure 12(a), and the peak intensity of the ion-guided storage mode at 0.09s is shown as 1.475V as shown in Figure 12(b).
  • the sum of the two is 2.4395V.
  • the co-storage mode of ion guide and ion trap was created: set the ion guide storage in other segments except the inozation segment, the time sum is 0.09s, and the time of the inozation segment (traditional mode ion trap storage) is set to 0.05s , the peak intensity of 2.254V is shown in Figure 12(c), which is similar to 2.4395V. This proves that the co-storage function of ion guide and ion trap is realized.
  • the invention relates to a novel ion storage technology of quadrupole-ion trap tandem mass spectrometry.
  • the present invention uses two ion guide systems Q00 and Q0 for ion storage, and is combined with the traditional ion trap storage mode, the duty cycle reaches 100%, and the storage capacity of the mass spectrometer is increased. The sensitivity of the instrument is improved and the detection limit of the instrument is reduced.

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Abstract

本发明公开了一种新型四极杆-离子阱串联质谱离子存储系统及方法，属于质谱技术领域。该系统顺次包括加热毛细管、镜筒透镜、取样锥、第一离子导引、第二离子导引、四极杆质量分析器、离子阱质量分析器和检测器，所述第一离子导引和第二离子导引之间设有第一透镜，所述第二离子导引和四极杆质量分析器之间设有第二透镜和第三透镜，其中，所述第一离子导引和第二离子导引运行模式包括离子传输模式和离子存储模式。与传统时序控制方法相比，在相同的时间内，本发明存储了更多的离子，提高了仪器的灵敏度。

Description

一种新型四极杆-离子阱串联质谱离子存储系统及方法 技术领域
本发明专利属于质谱技术领域，具体涉及一种四极杆-离子阱串联质谱离子存储系统及方法。
背景技术
四极离子阱质谱仪具有全扫描、高灵敏度、高分辨率扫描和MS n的优点，因此广泛应用于分析化学领域。
四极杆质量分析器和离子阱质量分析器的电压施加方式相同：相对电极施加相同电压，相邻电极电压相反。对于离子阱质量分析器，施加一定的射频电压和直流电压形成四极场用于囚禁离子。然而，离子阱本身的结构尺寸限制了其离子存储能力。当注入离子过多时，离子阱便会出现空间电荷效应，导致质量偏移，分析结果失真等问题。
此外，当离子阱处于离子分析状态时不能进行离子存储。如果离子源产生的离子数量很大，则填充离子阱所需的时间可能远远小于离子阱进行分析所需的时间。在分析期间，会浪费离子源产生的离子，从而导致离子阱的占空比非常低，并导致系统灵敏度降低。
发明内容
基于以上问题，本发明专利提出了一种四极杆-离子阱串联质谱的新型离子存储系统及方法。
根据本发明的第一方面，提供一种新型四极杆-离子阱串联质谱离子存储系统。
所述离子存储系统顺次包括加热毛细管、镜筒透镜(tube lens)、取样锥(Skimmer)、第一离子导引、第二离子导引、四极杆质量分析器、离子阱质量分析器和检测器，所述第一离子导引和第二离子导引之间设有第一透镜，所述第二离子导引和四极杆质量分析器之间设有第二透镜和第三透镜，
其中，所述第一离子导引和第二离子导引运行模式包括离子传输模式和离子存储模式。
进一步的，当所述第二透镜电压设置为+10V时，第一离子导引和第二离子 导引运行模式为离子存储模式；当所述第二透镜电压设置为-20V时，第一离子导引和第二离子导引运行模式为离子传输模式。
进一步的，所述第一离子导引为I型方四极杆，用于第二级真空中离子的碰撞聚焦和传输。
进一步的，所述第一离子导引由四片平板电极平行放置组装，电极长28mm，相对电极连接在一起，电极使用射频电压驱动，相邻电极的射频电压极性相反。
进一步的，所述第二离子导引为II型方四极杆，用于第三级真空中离子的碰撞聚焦和传输。
进一步的，所述第二离子导引由四片平板电极平行放置组装，电极长86mm，相对电极连接在一起，电极使用射频电压驱动，相邻电极的射频电压极性相反。
进一步的，所述离子存储系统还包括气体孔、分子泵、机械泵、前端盖和后端盖。
根据本发明的第二方面，提供一种新型四极杆-离子阱串联质谱离子存储方法，所述离子存储方法基于前述任一方面所述的新型四极杆-离子阱串联质谱的离子存储系统进行操作，所述方法包括Init(初始化)、pre-ion(预离子化)、ionization(离子化)、cooling(冷却)、cooling1(冷却1)、pre-sample(预采样)、sample(采样)、down(下降)、zero(清零)九个时序。
其中，在时序Init、pre-ion和ionization中，第二透镜和第三透镜的电压分别保持+10V和+200V，第一离子导引和第二离子导引运行模式为离子存储模式；
在时序cooling、cooling1、pre-sample、sample、down、zero中，第二透镜电压由+10V降为-20V，第三透镜电压由+200V降为-5.6V，第一离子导引和第二离子导引运行模式为离子传输模式。
进一步的，四极杆射频电压、离子阱射频电压在时序ionization中，由0V升高到某一恒定值；Skimmer作为离子进入下一级的开关透镜，在时序ionization中设置为+14V，处于打开状态；在整个质量周期内，第一离子导引电压保持为-2.5V，第一透镜电压保持为-6V，第二离子导引电压保持为-6.1V。
本发明的有益效果：本发明通过改进仪器的时序控制，实现了离子导引存储功能。当离子阱处于离子分析状态时(此时离子阱无法存储)，离子导引持续进 行离子存储，提高了离子存储的占空比。与传统时序控制方法相比，在相同的时间内，本发明存储了更多的离子，提高了仪器的灵敏度。
附图说明
为了更清楚地说明本发明实施例或现有技术中的技术方案，下面将对实施例或现有技术描述中所需要使用的附图作简单地介绍，显而易见地，下面描述中的附图仅仅是本发明的一些实施例，对于本领域普通技术人员来讲，在不付出创造性劳动的前提下，还可以根据这些附图示出的结构获得其他的附图。
图1示出根据本发明的四极杆-离子阱串联质谱的新型离子存储系统结构图；
图2示出传统离子传输模式时序图；
图3(a)和图3(b)示出离子导引Q00和Q0结构图；
图4示出根据本发明的四极杆-离子阱串联质谱的新型离子存储方法时序图；
图5示出根据本发明实施例的离子导引Q0电压变化趋势图；
图6示出传统离子传输模式(方块标记)与离子导引存储模式(圆点标记)强度变化趋势对比图；
图7示出离子导引存储模式线性图；
图8示出传统离子传输模式(方块标记)与离子导引存储模式(圆点标记)峰偏移变化趋势图；
图9示出传统离子传输模式(方块标记)与离子导引存储模式(圆点标记)半峰宽变化趋势图；
图10示出离子导引与离子阱共同存储时序图；
图11示出离子导引与离子阱共同存储模式的总离子流色谱图；
图12(a)示出传统离子传输模式0.05s的利血平强度图，图12(b)示出离子导引存储模式0.09s的利血平强度图,图12(c)示出离子导引与离子阱共同存储模式的利血平强度图。
具体实施方式
这里将详细地对示例性实施例进行说明，其示例表示在附图中。下面的描述涉及附图时，除非另有表示，不同附图中的相同数字表示相同或相似的要素。以下示例性实施例中所描述的实施方式并不代表与本公开相一致的所有实施方式。 相反，它们仅是与如所附权利要求书中所详述的、本公开的一些方面相一致的装置和方法的例子。
本公开的说明书和权利要求书中的术语“第一”、“第二”等是用于区别类似的对象而不必用于描述特定的顺序或先后次序。应该理解这样使用的数据在适当情况下可以互换，以便这里描述的本公开的实施例例如能够以除了在这里图示或描述的那些以外的顺序实施。
此外，术语“包括”和“具有”以及他们的任何变形，意图在于覆盖不排他的包含，例如，包含了一系列步骤或单元的过程、方法、系统、产品或设备不必限于清楚地列出的那些步骤或单元，而是可包括没有清楚地列出的或对于这些过程、方法、产品或设备固有的其它步骤或单元。
多个，包括两个或者两个以上。
和/或，应当理解，对于本公开中使用的术语“和/或”，其仅仅是一种描述关联对象的关联关系，表示可以存在三种关系。例如，A和/或B，可以表示：单独存在A，同时存在A和B，单独存在B这三种情况。
根据本发明实施例的四极杆-离子阱串联质谱的新型离子存储系统如图1所示，包括：A.加热毛细管；B.Tube Lens；C.Skimmer；D.离子导引Q00；E.离子导引Q0；F.四极杆质量分析器；G.离子阱质量分析器；H.检测器；I.气体孔；J.分子泵；K.机械泵。Lens0、1、2为透镜0、1、2。EndCap1为前端盖，EndCap2为后端盖。
下面对传统离子传输模式和本发明质谱控制方案进行比对：
传统离子传输模式：离子源将样品离子化，通过Tube Lens、Skimmer，传入到离子导引Q00和Q0，此时Q00和Q0是碰撞聚焦和传输作用，通过透镜1和透镜2的聚焦传输，传到四极杆质量分析器和离子阱质量分析器。最后，检测器对离子进行检测。
在传统离子传输模式中，只有离子阱质量分析器能够存储离子，离子阱在进行阱内离子分析的同时无法存储离子，这就导致占空比(相对于总循环时间，分析物离子被采样的时间的百分比)非常低。时序图如图2示：四极杆射频电压、离子阱射频电压在ionization(离子化)离子捕获时，由0V升高到某一值恒定，随后在下一时序降低。Lens2在ionization(离子化)离子捕获时为-5.7V，其他 时序都为+200V。Skimmer作为离子进入下一级的开关透镜，在ionization(离子化)离子捕获时打开(+14V)，离子进入下一级后关闭。Skimmer关闭(-150V)后，离子阱只进行阱内操作，无法存储离子。在整个循环过程中，Q00一直为-3V，Lnes0一直为-4.8V，Q0一直为-4.4V，Lnes1一直为-6V。
本发明质谱控制方案：在离子引入质量分析器(四极杆、离子阱)之前，对离子导引进行操作，以存储电喷雾产生的离子。
Q00(I型方四极杆，如图3(a)所示)用于第二级真空中离子的碰撞聚焦和传输。它由四片平板电极平行放置组装，电极长28mm，相对电极连接在一起，电极使用射频电压驱动，相邻电极的射频电压极性相反。
Q0(II型方四极杆，如图3(b)所示)用于第三级真空中离子的碰撞聚焦和传输。它也由四片平板电极平行放置组装，电极长86mm，相对电极连接在一起，电极使用射频电压驱动，相邻电极的射频电压极性相反。
根据本发明实施例的质谱控制方案将Lens1当做离子导引存储离子时的开关，当Lens1设置为+10V时，离子导引便会存储离子，当Lens1设置为-20V时，离子导引为传统离子传输模式。
根据本发明实施例的质谱控制方案时序如图4所示：
四极杆射频电压、离子阱射频电压在ionization(离子化)段，由0V升高到某一恒定值；Skimmer作为离子进入下一级的开关透镜，在此时序设置为+14V，处于打开状态；Lens1和Lens2在前三个时序Init、pre-ion和ionization中，一直保持+10V和+200V，阻止了电喷雾产生的离子进入到质量分析器，使其存储到离子导引Q0中；在整个质量周期内，Q00一直为-2.5V，Lens0一直为-6V，Q0一直为-6.1V。
在后六个时序(cooling、cooling1、pre-sample、sample、down、zero)中，Lens1由+10V降为-20V，Lens2由+200V降为-5.6V，这样离子便从导引Q0中引入到四极杆，最终进入到离子阱。
实施例1
离子导引存储
使用利血平样品，质何比扫描范围m/z 550到650，将离子导引存储模式的Q0电压进行优化，Q0电压与信号强度之间的关系如图5所示。得到Q0存储的最优值 为-6.1V。
使用利血平样品，质何比扫描范围m/z 550到650，将传统离子传输模式与离子导引存储模式进行对比，得到了存储时间与信号强度之间的关系，实验结果如图6所示。
从传统离子传输模式和离子导引存储模式二者信号强度变化趋势可以看出：随着存储时间的增大，二者信号强度先增强，达到饱和后，强度均趋于稳定。对于离子导引存储模式：在0.03s-0.22s时间内，强度呈线性增加如图7，R 2＝0.9923；0.22s-0.55s时间内，呈非线性增加；0.55s以后，达到饱和，强度几乎不变。从图6中可以看出，离子导引Q0实现了存储功能，并且达到了与传统离子阱存储模式相同的强度变化趋势。
而整体来看，新型离子导引存储模式在非线性区间的强度低于传统离子传输模式，这是部件(Q0与离子阱)本身的机械结构差异导致的。
从机械结构设计方面来分析，离子阱的存储容量要大于Q0存储容量。图6中圆点标记曲线，0.22s之前，离子导引Q0一直处于存储离子模式，存储容量线性增加到约图中52％，0.22s-0.55s时间内，Q0存储容量已经达到饱和，此时约20％的信号增强来源于Q00的存储。结合Q00，Q0，离子阱三者机械设计算出的内部体积，比例基本一致。0.6s之后，此时Q0和Q00已经完全饱和，离子开始从两者中溢出，随着溢出离子数量的增多导致有效检测的粒子数量减少，从而强度降低，圆点标记曲线一直呈下降趋势。
在0.03s-0.22s时间段内计算R 2，R 2＝0.9923。
不同存储时间下，对比了传统离子阱存储模式与新型离子导引Q0存储模式的峰偏移情况(图8)和分辨率情况(图9)，由于传统模式的强度大于新型离子导引存储模式，因此，传统模式的峰偏移和分辨率较大。
实例2
离子导引与离子阱共同存储
离子导引与离子阱共同存储时序如图10：四极杆射频电压、离子阱射频电压在ionization(离子化)段，由0V升高到某一恒定值；Skimmer在整个时序中全部设置为+5.5V；Lens1在ionization时序中分别为由+10V降为-20V，Lens2在ionization时序中由+200V降为-20V，使存储的离子进入到离子阱中。在整个 质量周期内，Q00一直为-2.5V，Lens0一直为-4.1V，Q0一直为-6V。在后六个时序(cooling、cooling1、pre-sample、sample、down、zero)中，Lens1由-20V升为+10V，Lens2由-5.7V升为+200V，这样离子便能存储到离子导引中。
观察离子导引与离子阱共同存储模式下强度如图11所示，可以看到第一个点的值，多次均约为0.9V，与直接进样0.05s时接近，远小于后面的值，这符合我们的设置，第一点因为离子导引还未存储，所以较小，后面离子导引开始存储所以强度较大。
传统离子传输模式0.05s时峰强为0.9645V如图12(a)，离子导引存储模式0.09s时峰强为1.475V如图12(b)，两者相加为2.4395V。之后，创建了离子导引与离子阱共同存储模式：将离子导引存储设置在除inozation段的其他段中，时间总和为0.09s，设置inozation段(传统模式离子阱存储)的时间为0.05s，得到峰强2.254V如图12(c)，与2.4395V较为相近。由此证明：实现了离子导引与离子阱共同存储功能。
本发明涉及一种四极杆-离子阱串联质谱的新型离子存储技术。与传统质谱仪控制方法不同，本发明将两个离子导引系统Q00、Q0用于离子存储，并与传统离子阱存储模式相结合，占空比达到100％，增大了质谱的存储容量，提高了仪器灵敏度，降低了仪器检测限。
上面结合附图对本发明的实施例进行了描述，但是本发明并不局限于上述的具体实施方式，上述的具体实施方式仅仅是示意性的，而不是限制性的，本领域的普通技术人员在本发明的启示下，在不脱离本发明宗旨和权利要求所保护的范围情况下，还可做出很多形式，这些均属于本发明的保护之内。

Claims (9)

  1. 一种新型四极杆-离子阱串联质谱离子存储系统，其特征在于，所述离子存储系统顺次包括加热毛细管、镜筒透镜、取样锥、第一离子导引、第二离子导引、四极杆质量分析器、离子阱质量分析器和检测器，所述第一离子导引和第二离子导引之间设有第一透镜，所述第二离子导引和四极杆质量分析器之间设有第二透镜和第三透镜，
    其中，所述第一离子导引和第二离子导引运行模式包括离子传输模式和离子存储模式。
  2. 根据权利要求1所述的新型四极杆-离子阱串联质谱离子存储系统，其特征在于，当所述第二透镜电压设置为+10V时，第一离子导引和第二离子导引运行模式为离子存储模式；当所述第二透镜电压设置为-20V时，第一离子导引和第二离子导引运行模式为离子传输模式。
  3. 根据权利要求1所述的新型四极杆-离子阱串联质谱离子存储系统，其特征在于，所述第一离子导引为I型方四极杆，用于第二级真空中离子的碰撞聚焦和传输。
  4. 根据权利要求3所述的新型四极杆-离子阱串联质谱离子存储系统，其特征在于，所述第一离子导引由四片平板电极平行放置组装，电极长28mm，相对电极连接在一起，电极使用射频电压驱动，相邻电极的射频电压极性相反。
  5. 根据权利要求1所述的新型四极杆-离子阱串联质谱离子存储系统，其特征在于，所述第二离子导引为II型方四极杆，用于第三级真空中离子的碰撞聚焦和传输。
  6. 根据权利要求5所述的新型四极杆-离子阱串联质谱离子存储系统，其特征在于，所述第二离子导引由四片平板电极平行放置组装，电极长86mm，相对电极连接在一起，电极使用射频电压驱动，相邻电极的射频电压极性相反。
  7. 根据权利要求1所述的新型四极杆-离子阱串联质谱离子存储系统，其特征在于，所述离子存储系统还包括气体孔、分子泵、机械泵、前端盖和后端盖。
  8. 一种新型四极杆-离子阱串联质谱离子存储方法，其特征在于，所述离子存储方法基于前述任一方面所述的新型四极杆-离子阱串联质谱的离子存储系统进行操作，所述方法包括：初始化、预离子化、离子化、冷却、冷却1、预采样、采样、下降、清零九个时序；
    其中，在时序初始化、预离子化和离子化中，第二透镜和第三透镜的电压分别保持+10V和+200V，第一离子导引和第二离子导引运行模式为离子存储模式；
    在时序冷却、冷却1、预采样、采样、下降、清零中，第二透镜电压由+10V降为-20V，第三透镜电压由+200V降为-5.6V，第一离子导引和第二离子导引运行模式为离子传输模式。
  9. 根据权利要求1所述的新型四极杆-离子阱串联质谱离子存储方法，其特征在于，四极杆射频电压、离子阱射频电压在时序离子化中，由0V升高到某一恒定值；取样锥作为离子进入下一级的开关透镜，在时序离子化中设置为+14V，处于打开状态；在整个质量周期内，第一离子导引电压保持为-2.5V，第一透镜电压保持为-6V，第二离子导引电压保持为-6.1V。
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