WO2015007165A1 - 一种在离子阱质量分析器中进行的串级质谱分析方法 - Google Patents

一种在离子阱质量分析器中进行的串级质谱分析方法 Download PDF

Info

Publication number
WO2015007165A1
WO2015007165A1 PCT/CN2014/081622 CN2014081622W WO2015007165A1 WO 2015007165 A1 WO2015007165 A1 WO 2015007165A1 CN 2014081622 W CN2014081622 W CN 2014081622W WO 2015007165 A1 WO2015007165 A1 WO 2015007165A1
Authority
WO
WIPO (PCT)
Prior art keywords
ion
voltage
ion trap
collision
mass spectrometry
Prior art date
Application number
PCT/CN2014/081622
Other languages
English (en)
French (fr)
Inventor
徐福兴
王亮
丁传凡
Original Assignee
复旦大学
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 复旦大学 filed Critical 复旦大学
Priority to US14/905,912 priority Critical patent/US9640377B2/en
Priority to CA2955665A priority patent/CA2955665A1/en
Publication of WO2015007165A1 publication Critical patent/WO2015007165A1/zh

Links

Classifications

    • 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
    • H01J49/0081—Tandem in time, i.e. using a single spectrometer
    • 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
    • H01J49/26—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
    • H01J49/427—Ejection and selection methods
    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00—Particle spectrometers or separator tubes
    • H01J49/0027—Methods for using particle spectrometers
    • H01J49/0031—Step by step routines describing the use of the apparatus

Definitions

  • the present invention belongs to the technical field of mass spectrometry, and in particular relates to a method for implementing cascade mass spectrometry in an ion trap mass analyzer. Background technique
  • mass spectrometry can achieve qualitative and quantitative analysis of compounds, and is widely used in drug analysis, environmental monitoring, national security, forensics, proteomics and other fields. It is well known that mass spectrometers can characterize and analyze the structure of compounds by tandem mass spectrometry (Tandem MS) analysis.
  • tandem MS tandem mass spectrometry
  • the analysis process of the cascade mass spectrometry is specifically as follows: the first stage is isolation, and for the ions in the sample to be analyzed, a specific mass-to-charge ratio (m/z) is selected to isolate the ions, and the isolated ions become the parent ions.
  • the second stage is Collision Induced Dissociation (CID)
  • CID Collision Induced Dissociation
  • the parent ion collides with neutral gas molecules such as helium, argon, nitrogen, etc., and the energy generated by the collision is deposited.
  • the internal energy of the parent ion increases, and the final parent ion is fragmented to obtain the fragment ion.
  • the mass of the fragment ion is analyzed to obtain the mass spectrum peak of the fragment ion, and the MS/MS analysis is completed.
  • CID is the most widely used and most thoroughly studied dissociation technology.
  • quadrupole mass spectrometers and quadrupole ion trap mass spectrometers are recognized as the most suitable devices for collision-induced dissociation.
  • the quadrupole mass spectrometer also known as the quadrupole mass filter, can only pass a certain mass of ions, so when performing tandem mass spectrometry in a quadrupole, multiple quadrupoles need to be spatially
  • the rods are connected in series, generally using a combination of three quadrupoles, that is, a triple quadrupole.
  • Triple quadrupole mass spectrometry generally has a large volume.
  • Quadrupole Ion Trap (QIT) can achieve ion isolation, dissociation, mass analysis and other steps in a well, and has unique advantages in cascade mass spectrometry.
  • the working principle of the ion trap mass analyzer is to obtain the motion state and result of ions with a certain mass-to-charge ratio in an electric field by solving the Mathieu quadratic linear differential equations.
  • the Mathieu equation is based on Newton's second law, which is based on the action of charged ions in an ion trap. It describes the trajectories and motion results of ions in a quadrupole electric field. Taking the three-dimensional ion trap as an example, by solving the Mathieu equation (Matthew equation):
  • a is a well parameter proportional to the DC voltage
  • q is a well parameter proportional to the RF voltage
  • U is the DC voltage applied to the ion trap electrode
  • V is the RF voltage applied to the ion trap electrode
  • ⁇ is the frequency of the RF voltage
  • r Is the radius of the ring
  • z Is the axial radius.
  • the ions that are ejected from the ion trap are said to be unstable, i.e., the ions are outside the stable region.
  • the stability diagram analysis when the ion trap is used for mass analysis, the ions of different mass-to-charge ratios move to the outside of the stable region under the action of the electric field with time series variation, that is, the ion detection that is ejected from the ion trap and installed outside the trap. Received and completed the quality analysis.
  • auxiliary alternating voltage also known as a dipola excitation voltage
  • the amplitude and frequency are the same, and the phases are 180 degrees out of phase.
  • the ions trapped in the ion trap have a long-term frequency ( ⁇ ) under the action of the RF voltage, and the ions of different mass-to-charge ratios have different duration frequencies.
  • the relationship between the duration frequency and the frequency of the RF voltage ( ⁇ ) is as follows:
  • ⁇ is a coefficient and is also a parameter in the ion trap stability map, which correlates the two.
  • Non-Patent Document 1 and Non-Patent Document 2 describe a method of realizing cascade mass spectrometry in which a dipole DC voltage is applied to a pair of electrodes.
  • a dipole DC voltage is applied at this time, and the ion deviates from the center of the well under the action of the DC voltage, and the movement rate is accelerated, and the RF voltage also has a certain heating on the ion. effect.
  • the internal energy of the ions is significantly increased, and eventually dissociation occurs.
  • the mass-to-charge ratio of the ions is not limited, so even if the parent ion is fragmented, the daughter ions will further dissociate under the action of dipole DC, and the resulting string will be obtained.
  • the information of the fragment peaks in the mass spectrum is more abundant.
  • the collision-induced dissociation driven by the dipole DC voltage is different from the traditional resonance excitation method. It is a non-resonant excitation method, which can obtain more abundant fragment ion information.
  • An important innovation in the dissociation method requires an additional DC power supply to provide DC voltage, a dipole DC application through circuit modification, and a dipole DC voltage with timing variation and precise control, so the hardware portion of the instrument The requirements will become more demanding and complex.
  • Non-Patent Document 1 BM Prentice, W. Xu, Z. Ouyang, SA McLuckey, DC potentials applied to an end-cap electrode of a3D ion trap for enhanced MSn functionality. International Journal of Mass Spectrometry 2011, 306, 114- 122.
  • Non-Patent Document 2 BM Prentice, SA McLuckey, Dipolar DC Collisional Activation in a "Stretched" 3-D Ion Trap: The Effect of Higher Order Fields on rf-Heating. Journal of the American Society for Mass Spectrometry 2012, 23 , 736-744 ⁇ Summary of the invention
  • the object of the present invention is to propose a cascade mass spectrometry method which can significantly simplify the experimental apparatus and experimental procedure. Law.
  • the driving voltage of the ion trap is mainly a radio frequency (RF).
  • RF radio frequency
  • the method proposed by the present invention is applicable in both modes of operation.
  • the amplitude of the square wave used to bind the ions is typically several hundred volts and is constant.
  • the resonance of the ion wave is ejected by scanning the square wave frequency.
  • the dipole-excited square wave used for ion resonance excitation is generated and controlled in the same way as the bound square wave, but its amplitude is generally less than 10 volts, and its frequency maintains a fixed proportional relationship with the bound square wave.
  • the waveforms of the bound square wave and the dipole-excited square wave used for ion ejection are symmetric waveforms, i.e., have a duty cycle of 50%.
  • U is the DC component of the rectangular square wave
  • V is the AC component of the rectangular square wave
  • ⁇ is the frequency of the rectangular wave.
  • the digital ion trap parameters are primarily values, and their expressions are as follows:
  • T RWF is a period of a digital rectangular square wave (binding voltage)
  • the value at the time of ion ejection is mainly affected by the period of the digital rectangular square wave.
  • the frequency of the resonant excitation signal In the digitized ion trap, mass analysis is performed by scanning the frequency of the square wave signal. To ensure that all ions are excited out of the ion trap at the same value, the frequency of the resonant excitation signal also The frequency of the square wave signal is scanned together.
  • the resonance excitation signal can be generated by the frequency division of the square wave signal. If the frequency division number is n, the frequency ⁇ of the resonance excitation signal is:
  • ⁇ z has the following relationship:
  • the value at the time of ion ejection can be calculated by the equations (5) and (6), which is denoted as q e j ⁇ tl . n .
  • the mass-to-charge ratio of the ions can be expressed as: Wherein T represents the period of the digitally bound voltage.
  • ⁇ ⁇ represents the period of the digitally bound voltage at which the ions are ejected from the ion trap. Substituting 1 into equation (7) shows that the mass-to-charge ratio is linear with time, that is, a linear scan of the ion mass-to-charge ratio is achieved.
  • a digital square wave or a sinusoidal voltage is used to bind ions in the ion trap, it is necessary to apply a dipole excitation voltage, that is, a pair of amplitudes and phases, as long as the ions are ejected into the ion trap by means of resonance excitation.
  • the opposite AC voltages are applied to a pair of electrodes of the ion trap, respectively, and ions are ejected from the direction in which the electrodes are located.
  • the present invention provides a tandem mass spectrometry method performed in an ion trap mass analyzer, which is divided into three stages of ion selective isolation, collision induced dissociation and mass scanning analysis, wherein:
  • the selected parent ions are isolated, and the isolated parent ions are trapped in the ion trap by collision with neutral gas molecules under the action of an electric field generated by the ion trap operating voltage;
  • the collision-induced dissociation phase changes the frequency of the RF voltage signal period by changing the ions loaded on the ion trap electrode, that is, by changing the frequency of the RF voltage excited by the ions loaded on the ion trap, that is, changing the ion
  • the period of resonance excitation causes ions with a certain mass-to-charge ratio to be excited by an ion-excited RF voltage resonance of a certain period or frequency to obtain higher energy; under the action of the period, the parent ion obtains energy and is excited and excited The parent ion collides with and dissociates from the neutral molecules in the ion trap to generate fragment ions, which are cooled in the ion trap and then bound for subsequent mass analysis;
  • the magnitude of the bound voltage is constant, and the period is linearly scanned from a small to a large direction, thereby realizing a linear scan of the ion mass-to-charge ratio, and the fragment ion
  • resonance excitation occurs, and finally is ejected from the extraction hole or the extraction groove of the ion extraction electrode, and the ion detector disposed outside the ion trap detects the mass spectrometry signal of the ion.
  • the voltage amplitude and the duty ratio of the digitally bound radio frequency voltage are unchanged, the selected digitally binds the period value of the radio frequency voltage, and the initial period and the end period value are unchanged, and then a certain frequency division number is selected.
  • the period value of the RF voltage also changes with the duty ratio. As the ion resonance excites the RF voltage, the resonant motion between the ions generates collision energy.
  • the isolated parent ions are selected to be bound by the electric field generated under the digitally bound radio frequency operating voltage, and the amount of neutral cooling gas flowing into the ion trap is increased in an appropriate amount to increase Collision energy.
  • the waveform of the applied ion-excited radio frequency voltage signal is a sine wave voltage or a digital square wave voltage, or other waveform.
  • the period of the digitally bound RF voltage will be varied and adjusted according to the needs of the experiment.
  • the frequency and amplitude of the digitally bound radio frequency voltage are constant values.
  • the ratio of the ion-excited RF voltage to the digitally-bound RF voltage frequency is an arbitrary value.
  • the tandem mass spectrometry method in the present invention does not require a type of ion trap, and may be a three-dimensional ion trap, a two-dimensional linear ion, and a rectangular ion trap of various structures, which may be an ion trap array or a field adjustment. Ion traps, etc.
  • the time for changing the period of application of the dipole excitation voltage signal is not limited, and may be several milliseconds, or several hundred milliseconds, etc., and the length of time is determined by experimental requirements.
  • tandem mass spectrometry method of the present invention the method of mass spectrometry for fragment ions is adopted in a resonant excitation mode, and the mass analysis method does not affect the tandem mass spectrometry results.
  • the method of the present invention has the advantage that it can obtain the ion collision energy only by changing the period size by software control, thereby achieving dissociation, which can significantly simplify the experimental apparatus and the experimental procedure.
  • FIG. 1 is a waveform diagram of a square wave and a sine wave for driving an ion trap.
  • (a) is a waveform diagram of a symmetrical square wave
  • (b) is a waveform diagram of a symmetric sine wave.
  • Embodiment 2 is a schematic structural view of an instrument experimental platform of Embodiment 1.
  • FIG. 3 is a schematic view showing an ion-bonded square wave voltage and a dipole-excited square wave voltage applied in Embodiment 1.
  • FIG. 3 is a schematic view showing an ion-bonded square wave voltage and a dipole-excited square wave voltage applied in Embodiment 1.
  • Figure 5 is a result of the experiment of Example 1, by changing the period of the square wave voltage, generating an ion resonance collision, and realizing the mass spectrum after collision-induced dissociation, the ⁇ value is 0.3478, and the duration is 40 ms;
  • the period is 1.450 ⁇ s;
  • the period is 1 ⁇ 460 ⁇ s;
  • the period is 1 ⁇ 465 ⁇ s;
  • the period is 1 ⁇ 470 ⁇ s.
  • FIG. 6 is a schematic diagram showing an ion-trapping voltage and a dipole excitation voltage application mode when a conventional sinusoidal voltage is used to drive an ion trap and a dipole excitation voltage is also a sine wave.
  • FIG. 7 is a schematic diagram showing an ion-bonding voltage and a dipole excitation voltage applied when a linear square wave is used to drive a linear ion trap using a digital square wave voltage.
  • the technical solution uses a digital square wave voltage to drive the ion trap, and the collision-induced dissociation of the parent ion is realized by changing the period of the dipole excitation voltage. This scheme has been experimentally verified, and the specific content is as follows.
  • the ion trap in this scheme selects a rectangular ion trap for testing.
  • the instrument experimental platform is shown in Figure 2.
  • the electrospray ionization source-rectangular ion trap mass spectrometer system (ESI-RIT-MS) designed and processed by the laboratory itself.
  • the instrument consists of a three-stage differential vacuum system with a vacuum of 3 x 10 3 Pa in the third-stage vacuum chamber.
  • the ions generated by the electrospray ionization source enter the secondary vacuum chamber through the sampling cone, and are guided into a rectangular ion trap through a length of 200 mm of quadrupole ions to complete the mass analysis.
  • Helium is introduced as a cooling gas from the small holes in the back end cover electrode of the trap for ion cooling. O.
  • the digital direct synthesis (DDS) method produces a low level square wave voltage, typically a 5 volt TTL level. After the fast switching (switches) and the amplification of the MOSFET field effect transistor, the amplitude is obtained at 0-500V.
  • a continuously adjustable high voltage square wave in the p range is used as the binding voltage.
  • the dipole excitation voltage is obtained by dividing the bound voltage, that is, there is a proportional relationship between the dipole excitation voltage and the frequency of the bound voltage, the coefficient is ⁇ /2, and the ⁇ value is less than 1. That is, the periodic change of the dipole excitation voltage signal can be realized by changing the period of the tied voltage signal.
  • the square wave's period, sweep speed, symmetry and timing can be precisely controlled by software.
  • the square wave voltage applied to the rectangular ion trap is applied as shown in FIG.
  • a pair of square beam voltages of the same amplitude and opposite phases are applied to the two pairs of electrodes in the ion trap X and y directions, respectively.
  • the ions are ejected from the X direction, and the dipole excitation voltage is coupled to the square beam voltage and applied to a pair of X-direction electrodes.
  • the waveform of the dipole excitation voltage is a symmetrical waveform whose frequency is one third of the frequency of the bound square wave, that is, the ⁇ value is 2/3, and the amplitude is a certain value.
  • the frequency of the bound square wave is scanned, ions of different mass-to-charge ratios resonate at the resonance point, and are ejected from the trap and detected by the ion detector.
  • Cascade mass spectrometry is largely divided into three phases in terms of time.
  • the period of the dipole excitation voltage is changed by changing the bound voltage period.
  • the waveform of the voltage is a symmetric waveform with a duty ratio of 50% and the amplitude remains unchanged.
  • ⁇ is less than 1
  • a certain value of the dipole excitation voltage changes, the mother ion dissociates, and the fragment ions are obtained, which are bound by cooling.
  • the periodic change of the tied voltage signal is done by software.
  • the waveform of the dipole excitation voltage is a symmetric waveform, that is, the duty ratio is equal to 50%, and the ⁇ value is 2/3.
  • the fragment ions resonate under the action of the dipole excitation voltage, and finally are ejected from the extraction holes or the extraction slots of the electrodes to be detected, and the tandem mass spectrometry is completed.
  • the ion trap can be driven by a conventional sinusoidal voltage, and the dipole excitation voltage is also a sine wave.
  • the ion resonance collision energy is generated by changing the dipole excitation voltage period to achieve collision-induced dissociation of the parent ion.
  • the application of RF voltage and dipole excitation voltage is shown in Figure 6.
  • an ion trap having a hyperboloid electrode may be used, which may be a three-dimensional ion trap or a double
  • the linear ion trap of the curved electrode has the same central cross-section structure.
  • the application of the RF voltage and dipole excitation voltage is shown in Figure 7.
  • a pair of digital square wave voltages with the same amplitude and opposite phase can be applied to the double.
  • the collision-induced dissociation of the parent ions is achieved by changing the period of the dipole excitation voltage signal.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Electron Tubes For Measurement (AREA)
  • Other Investigation Or Analysis Of Materials By Electrical Means (AREA)

Abstract

一种在离子阱质量分析器中进行的串级质谱分析方法，属于质谱分析技术领域。该方法具体包括离子选择性隔离、碰撞诱导解离和质量扫描分析三个阶段。该碰撞诱导解离阶段是通过改变射频信号的周期大小，即通过改变加载在离子阱上的射频电压的频率，使得具有一定质荷比的母体离子被共振激发而获得能量，这些被共振激发的高能量离子与离子阱中的中性分子发生碰撞而发生解离，生成产物离子，以实现串级质谱分析。该方法仅通过软件设置改变碰撞诱导解离阶段的扫描周期即可实现碰撞诱导解离，可以显著简化串级质谱分析的实验装置和方法。

Description

一种在离子阱质量分析器中进行的串级质谱分析方法 技术领域
[0001 ] 本发明属于质谱分析技术领域，具体涉及一种在离子阱质量分析器中实现串级质 谱分析的方法。 背景技术
[0002] 质谱作为一种强大的分析技术，可以实现对化合物的定性、定量分析，广泛的应用 于药物分析、环境监测、国家安全、法医、蛋白质组学等领域。 众所周知，质谱仪可以通过 串级质谱（Tandem MS)分析对化合物的的结构进行表征和分析。 串级质谱的分析过程具 体为：第一阶段为隔离，对于待分析的样品中的离子，选定某一特定质荷比（m/z )的离子 将其隔离，被隔离的离子成为母离子（parent ion)；第二阶段为碰撞诱导解离（Col l ision Induced Dissociation，简称 CID)，母离子与中性的气体分子例如氦气、氩气、氮气等发生 碰撞，碰撞产生的能量沉积到母离子上，导致母离子自身内能增加，最终母离子发生碎裂， 得到碎片离子；第三阶段，碎片离子进行质量分析，得到碎片离子的质谱峰， MS/MS分析完 成。 如碎片离子中选定某一特定质荷比的离子隔离，将其作为母离子，继续上述过程，如此 往复下去，可以实现多级质谱分析。 CID是使用最广泛、研究最透彻的解离技术。
[0003] 在众多种类的质谱仪中，四极杆质谱仪和四极离子阱质谱仪是公认的最适合实现 碰撞诱导解离的装置。 其中，四极杆质谱仪又称为四极滤质器，仅能让某一特定质量数的 离子通过，故在四极杆中进行串级质谱分析时，需要在空间上将多个四极杆串联，一般采用 三段四极杆的组合，即三重四极杆。 三重四极杆质谱一般具有较大的体积。 四极离子阱 ( Quadrupole Ion Trap， 简称 QIT)可以在一个阱中实现离子的隔离、解离、质量分析等步 骤，在串级质谱方面具有独特的优势。
[0004] 离子阱质量分析器的工作原理是通过求解 Mathieu二次线性微分方程组，获得具 有一定质荷比的离子在电场中的运动状态和结果。 Mathieu方程根据带电离子在离子阱内 受电场的作用符合牛顿第二定律得到，它描述了离子在四极电场中的运动轨迹及运动结果 等。 以三维离子阱为例，通过解 Mathieu方程（马修方程）得到：
[0005] " 2 )。2 ' + 2 )Ω2
[0006] 式中： a是与直流电压成正比的阱参数， q是与射频电压成正比的阱参数， U为离子 阱电极上所加直流电压， V为离子阱电极上所加射频电压， Ω 为射频电压的频率， r。为环电 极半径， z。为轴向半径。通过对离子阱电极上施加电场变化，阱内的不同质荷比的离子依次 从离子阱内逸出，并被探测到。在离子阱内运动的离子被称为稳定的，即位于稳定区内。被 逐出离子阱的离子被称为不稳定的，即离子位于稳定区外。按稳定图分析，离子阱进行质量 分析时，不同质荷比的离子，在具有时序变化的电场作用下，依次运动到稳定区外，即从离 子阱中弹出并被安装在阱外的离子探测器接受到，完成质量分析。
[0007] 经过近二十多年的发展，共振激发（resonance excitation)技术已经成为离子 阱上普遍采用的离子弹出和解离的方法。 通常共振激发是通过在离子阱中用于离子弹出 的方向上的一对电极上，施加一个辅助的交流电压（AC)，也称为偶极激发电压（dipola excitation voltage)实现的，该电压具有特定的频率和幅度，且一对电极上的电压幅度、 频率相同，相位相差 180度。束缚在离子阱中的离子，在射频电压的作用下的运动具有一个 久期频率（secular frequency, ω )，不同质荷比的离子具有不同的久期频率。 久期频率与 射频电压的频率（ Ω )之间存在如下关系：
[画] a> = Io
2
[0009] β为系数，也是离子阱稳定图中的一参数，将两者相关联。当偶极激发电压的频率 与某一特定质荷比的离子的久期频率相同时，该离子发生共振，其在偶极激发电压施加的 方向上运动加剧，最终离子从电极上的小孔或狭缝中弹出，被离子探测器收集。当偶极激发 电压的频率与某一特定质荷比的离子的久期频率相偏离时，此时仍然会有共振发生，但幅 度显著降低，使得离子不足以弹出，此时离子进行的低幅度共振导致离子与阱中中性气体 分子的碰撞加剧，完成碰撞诱导解离。偶极激发电压的频率、幅度和持续的时间均会对碰撞 诱导解离的结果产生影响。 共振激发的技术虽然可以获得较高的碎裂效率，但是仍存在弊 端和不足。原因在于，只有某一固定质荷比的离子会发生共振，该离子碎裂后得到的碎片离 子的质荷比均发生变化，变大或变小，此时碎片离子的久期频率与 AC的频率不同，不会发 生共振，即不会进一步的解离，最终得到的串级质谱图中的碎片信息收到限制。
[0010] 在非专利文献 1和非专利文献 2中介绍了一种实现串级质谱的方法，即采用偶极 直流电压施加在一对电极上。当某一特定质荷比的离子被隔离后，此时偶极直流电压施加， 该离子在直流电压的作用下，偏离阱的中心，运动速率加快，同时射频电压还对该离子具有 一定的加热效应。 最终导致离子的内能显著提高，最终发生解离。 由于偶极直流电压碰撞 诱导解离不采用共振的方式，对离子的质荷比没有限定，故即使母离子碎裂，子离子仍然会 进一步在偶极直流的作用下解离，最终得到的串级质谱图中碎片峰的信息会更加丰富，偶 极直流电压驱动的碰撞诱导解离与传统的共振激发方法不同，是一种非共振激发的方法， 能够得到更丰富的碎片离子信息，是目前解离方法的一个重要创新。但是，该方法要求必须 有一个额外的直流电源用于提供直流电压，通过电路的改造实现偶极直流施加的方式，同 时偶极直流电压具有时序变化并且需要精确控制，故对仪器的硬件部分的要求必将变得更 加严苛和复杂。
[0011] 非专利文献 1： B. M. Prentice, W. Xu, Z. Ouyang, S. A. McLuckey, DC potentials applied to an end-cap electrode of a3D ion trap for enhanced MSn functionality. International Journal of Mass Spectrometry2011, 306, 114-122.
[0012] 非 专 利 文 献 2 :B. M. Prentice, S. A. McLuckey, Dipolar DC Collisional Activation in a "Stretched "3-D Ion Trap： The Effect of Higher Order Fields on rf-Heating. Journal of the American Society for Mass Spectrometry2012, 23, 736-744· 发明内容
[0013] 本发明的目的是提出一种可以显著简化实验装置和实验流程的串级质谱分析方 法。
[0014] 离子阱的驱动电压主要是射频电压（radio frequency，简称 RF)。 目前，驱动离子 阱的射频电压可以有两种类型，一种是传统的正弦波驱动，另一种是数字方波驱动。本发明 提出的方法在两种工作模式下均适用。
[0015] 下文以数字方波为例进行说明。 在数字方波驱动的离子阱中，用于束缚离子的方 波的幅值一般为几百伏，且为一定值。 离子阱工作时，通过方波频率的扫描，实现离子的共 振弹出。用于离子共振激发的偶极激发方波同束缚方波一样，均由相同的方式产生和控制， 但是其幅值较低一般在 10伏以内，其频率与束缚方波保持一固定的比例关系。束缚方波和 用于离子弹出的偶极激发方波的波形均为对称波形，即具有 50%的占空比。
[0016] 使用与马修方程中类似的参数（a，q)来描述离子在数字化方波离子阱中的稳定情 况。 当一个质量为 m、电荷为 e的离子在纯四极场中运动时，参数（a， q)可表示为：
Figure imgf000005_0001
[0018] 其中， r。是离子阱的场半径， U是矩形方波的直流分量， V是矩形方波的交流分量， Ω是矩形波的频率。本发明实验过程中矩形方波的占空比均为 50% (方波），且不含直流分 量，因此 U=0， V等于方波高电平和低电平的差值的一半（半峰值）。 数字离子阱参数主要 是 值，其表达式如下：
2
[0020] 其中 TRWF为数字矩形方波 (束缚电压）的周期，离子弹出时的 值主要受到数字矩 形方波的周期的影响。 当束缚方波电压幅值 V固定不变时，改变方波的周期可实现不同 值。
[0021 ] 在数字化离子阱中，质量分析是通过对方波信号的频率进行扫描而实现的，为保 证所有的离子都在同一个 值上被共振激发出离子阱外，共振激发信号的频率也随着方波 信号的频率一起扫描。 共振激发信号可由方波信号的分频产生，若分频数为 n，则共振激发 信号的频率 ω 为：
Figure imgf000005_0002
[0023] 离子的共振频率（secular frequency) ω s与数字束缚电压信号频率 Ω之间的关 系可以用参数 3 2来表示：
[0024] ω s= β ζ Ω /2 (4)
[0025] 当数字束缚电压信号为方波时， β z与 存在下述关系：
[0026] β, (5)
Figure imgf000005_0003
[0027] 当外加的共振激发信号的频率和离子的共振频率相等时，离子发生共振激发现象 而被逐出离子阱外，根据式（ 3 )和（ 4 )可得：
Figure imgf000005_0004
[0029] 当分频数 η确定时，便可通过式（5 )和（6 )计算得到离子弹出时的 值，记作 qej∞tl。n。 此时，离子的质荷比可表示为： [0031 ] 其中 T表示数字束缚电压的周期。
[0032] 可以看出，当幅度 V保持不变时，对数字束缚电压的频率进行线性扫描并不是对 质荷比的线性扫描。为实现对质荷比的线性扫描，可实施如下的周期扫描方式：设数字束缚 电压的初始周期为 Tstart，持续 Ν个周期数后，将周期增大一个固定的步长 Tstep，此时数字束 缚电压的周期变为 Tstart+Tstep。 然后再持续 N个周期数，依此类推。 则对于扫描过程中的任 意一步 i，有：
[0033] H t+iTstep (8)
[0034] t^ ^ m) + Ί]Ν / 2： (7;^Γ / 2 + T J + Iltim / 2) (9)
[0035] 其中 表示第 i步时经过的时间，以第 i步的中间时刻（即第 i步持续 N/2个周 期数时）为准。 通过式（8)和（9)联立可以消去变量 i，得到：
[0036] ： ζ = 2 + (2: ; / Ν (10)
[0037] Τχ代表离子被逐出离子阱时刻所对应的数字束缚电压的周期。把 1 代入到式（7) 中就可以看出，质荷比与时间 成线性关系，即实现了对离子质荷比的线性扫描。
[0038] 无论是数字方波还是正弦波电压用于离子阱中束缚离子，只要采用通过共振激发 的方式将离子弹出离子阱时，均需要施加一个偶极激发电压，即一对幅度相同、相位完全相 反的交流电压分别施加到离子阱的一对电极上，离子从该电极所在的方向弹出。
[0039] 鉴于以上理论基础，本发明提供一种在离子阱质量分析器中进行的串级质谱分析 方法，依次分为离子选择隔离、碰撞诱导解离和质量扫描分析三阶段，其中：
[0040] 所述离子选择隔离阶段，被选择的母离子被隔离，被隔离的母离子在离子阱工作 电压产生的电场作用下，通过与中性气体分子的碰撞冷却被束缚在离子阱中；
[0041 ] 所述碰撞诱导解离阶段，通过改变加载在离子阱电极上的离子激发射频电压信号 周期的大小，即通过改变加载在离子阱上的离子激发射频电压的频率，也即改变了离子共 振激发的周期，使得具有一定质荷比的离子被具有某一周期或频率的离子激发射频电压共 振激发而获得较高的能量；在周期的作用下，母离子获得能量和被激发， 被激发的母体离 子通过与离子阱中的中性分子发生碰撞并解离，产生碎片离子，碎片离子在离子阱中经过 冷却后被束缚，以进行后续的质量分析；
[0042] 所述质量扫描分析阶段，当离子经碰撞诱导解离过程后， 束缚电压幅值不变，周 期从小往大的方向进行线性扫描，从而实现对离子质荷比的线性扫描，碎片离子在偶极激 发电压的作用下，发生共振激发，最终从离子引出电极的引出孔或引出槽中被逐出，被设置 在离子阱外的离子探测器检测获得离子的质谱信号。
[0043] 所述碰撞诱导解离阶段具体内容进一步描述如下：
[0044] 在此阶段中，数字束缚射频电压的电压幅度和占空比不变，选定数字束缚射频电 压的周期值，且初始周期与终止周期值不变，再选定某个分频数 η，即选定离子激发射频电 压与数字束缚射频电压两者之间频率关系 β值（η= β /2)，由于 β值的关系，离子共振激发 射频电压的周期值也随着改变且占空比不变，随着离子共振激发射频电压的变化，离子之 间实现共振运动产生碰撞能量。
[0045] 本发明中，在所述碰撞诱导解离阶段，选择隔离的母离子被在数字束缚射频工作 电压下产生的电场作用下束缚，适量增加通入离子阱内的中性冷却气体，增加碰撞能量。
[0046] 本发明中，在所述碰撞诱导解离阶段，施加离子激发射频电压信号波形是正弦波 电压或者数字方波电压，或者其它波形。
[0047] 本发明中，在所述碰撞诱导解离阶段，数字束缚射频电压的周期大小， 将根据实 验需要加以改变和调节。
[0048] 本发明中，在所述碰撞诱导解离阶段，数字束缚射频电压的频率和幅度为定值。
[0049] 本发明中，在所述碰撞诱导解离阶段，离子激发射频电压与数字束缚射频电压频 率比值为任意值。
[0050] 本发明中的串级质谱分析方法对离子阱的种类没有要求，可以是三维离子阱、二 维线形离子和各种结构的矩形离子阱， 可以是离子阱阵列，也可以是场调节离子阱等。
[0051 ] 本发明中的串级质谱分析方法，改变偶极激发电压信号周期施加的时间不受限 制，可以是几毫秒，也可以是几百毫秒等， 其时间长短由实验需要决定。
[0052] 本发明中的串级质谱分析方法，实现碎片离子的质量分析的方式采用共振激发的 方式，质量分析方式不会对串级质谱分析结果产生影响。
[0053] 本发明方法的优点在于， 它仅通过软件的控制改变周期大小即得到离子碰撞能 量， 从而实现解离，可以显著简化实验装置和实验流程。 附图说明
[0054] 图 1用于驱动离子阱的方波和正弦波的波形示意图。 其中， ( a)为对称方波的波 形示意图，（b )为对称正弦波的波形示意图。
[0055] 图 2为实施例 1的仪器实验平台结构示意图。
[0056] 图中标号：1-离子源；2-导引杆；3-检测器；4-离子阱；5机械泵；6-涡能泵；
7-冷却气。
[0057] 图 3为实施例 1中采用的离子束缚方波电压和偶极激发方波电压施加方式示意 图。
[0058] 图 4为实施例 1的实验结果，对母离子的选择性隔离的质谱图，样品采用利血平 (m/z=609)。
[0059] 图 5为实施例 1的实验结果，通过改变方波电压的周期，产生离子共振碰撞，实现 碰撞诱导解离后的质谱图， β 值为 0. 3478，持续时间为 40ms； (a)周期为 1. 450 μ s； (b)周 期为 1· 460 μ s； (c)周期为 1· 465 μ s； (d)周期为 1· 470 μ s。
[0060] 图 6为采用传统的正弦波电压驱动离子阱，偶极激发电压也采用正弦波时的离子 束缚电压和偶极激发电压施加方式示意图。
[0061 ] 图 7为采用数字方波电压驱动线形离子阱，偶极激发电压采用数字方波时的离子 束缚电压和偶极激发电压施加方式示意图。 具体实施方式 [0062] 实施例 1
[0063] 本技术方案采用数字方波电压驱动离子阱，通过改变偶极激发电压的周期实现母 离子的碰撞诱导解离，此方案已进行了实验验证，具体内容如下。
[0064] 该方案中的离子阱选择矩形离子阱进行测试。 仪器实验平台如图 2所示，本实验 室自行设计和加工的电喷雾电离源 -矩形离子阱质谱仪器系统（ESI-RIT-MS)。仪器由三级 差分真空系统构成，离子阱所在第三级真空腔内真空度可达到 3 X 10 3Pa。 电喷雾电离源产 生的离子通过取样锥孔进入二级真空腔，经过一段长度为 200毫米的四极离子导引进入矩 形离子阱中，完成质量分析。 氦气作为冷却气从阱的后端盖电极上的小孔中引入用于离子 冷却。试剂：利血平（Reserpine，m/z=175，上海阿拉丁试剂有限公司），配制成 5 X 10 5M的溶 液，溶剂采用甲醇：水 =50 ： 50，其中含有 0. 05%的醋酸。
[0065] 数字直接合成（DDS)的方法产生低电平的方波电压，一般为 5V的 TTL电平。 经过 快速开关（switches )和 M0SFET场效应管的放大后，得到幅度在 0_500V。 p范围内连续可调 的高压方波用作束缚电压。 偶极激发电压通过束缚电压的分频得到，即偶极激发电压与束 缚电压的频率之间存在一比例关系，系数为 β /2， β值小于 1。即偶极激发电压信号的周期 改变可以通过改变束缚电压信号的周期而实现。方波的周期、扫速、对称性和时序可以通过 软件精确控制。 矩形离子阱上的方波电压的施加方式如图 3所示。 一对幅度相同、相位完 全相反的方波束缚电压分别施加到离子阱 X和 y方向的两对电极上。 离子从 X方向弹出， 偶极激发电压与方波束缚电压耦合后施加到一对 X方向电极上。
[0066] 通过进行常规的质量扫描的方法，可以得到一张样品离子的完整谱图。 此时偶极 激发电压的波形为对称波形，其频率为束缚方波的频率的三分之一，即 β 值为 2/3，幅度为 一定值。随着束缚方波的频率扫描，不同质荷比的离子依次到达共振点发生共振，从阱中弹 出被离子探测器检测。 串级质谱分析从时间上主要分为三个阶段。
[0067] 串级质谱分析第一阶段，将利血平离子隔离，并通过冷却将其束缚在阱中，此时偶 极激发电压不施加。 此时在该阶段后直接进行质量扫描，得到的是只有一个 609质谱峰的 谱图，如图 4所示。
[0068] 串级质谱分析第二阶段，通过改变束缚电压周期从而改变偶极激发电压的周期， 同时，该电压的波形为对称波形，占空比为 50%，幅度保持不变。 β值为小于 1的某个值，在 偶极激发电压周期变化的作用下，母离子发生解离，得到碎片离子，经过冷却后被束缚。 束 缚电压信号的周期改变通过软件完成。
[0069] 串级质谱分析第三阶段，偶极激发电压的波形为对称波形，即占空比等于 50%， β 值为 2/3。 碎片离子在偶极激发电压的作用下，发生共振，最终从电极的引出孔或引出槽中 弹出被检测，完成串级质谱分析。
[0070] 初步的实验结果表明，在串级质谱分析的第二阶段，即碰撞诱导解离阶段， β 值固 定在 0. 3478，束缚电压信号周期分别为 1. 450 μ s、 1. 460 μ s、 1. 465 μ s、 1. 470 μ s时，母离 子利血平离子发生了不同程度的碎裂，如图 5 (a) -5 (d)所示。
[0071 ] 本发明中，还可采用传统的正弦波电压驱动离子阱，偶极激发电压也采用正弦波， 通过改变偶极激发电压周期产生离子共振碰撞能量，实现母离子的碰撞诱导解离。 射频电 压和偶极激发电压的施加如图 6所示。
[0072] 本发明中，采用具有双曲面电极的离子阱，可以是三维离离子阱也可以是采用双 曲面电极的线形离子阱，两者的中心截面结构相同，射频电压和偶极激发电压的施加如图 7所示，还可将一对幅度相同、相位完成相反的数字方波电压分别施加到双曲面离子阱的 X 方向和 y方向的两对电极上，通过改变偶极激发电压信号周期，实现母离子的碰撞诱导解 离。

Claims

WO 2015/007165 权 利 要 求 书 PCT/CN2014/081622
1. 一种在离子阱质量分析器中进行的串级质谱分析方法，其特征在于：依次分为离子 选择隔离、碰撞诱导解离和质量扫描分析三个阶段；其中：
在所述离子选择隔离阶段，被选择的母离子被隔离，被隔离的母离子在离子阱工作电 压产生的电场作用下，通过与中性气体分子的碰撞冷却被束缚在离子阱中；
在所述碰撞诱导解离阶段，改变加载在离子阱电极上的离子激发射频电压信号周期的 大小，从而改变了离子共振激发射频电压的周期，使得具有一定质荷比的离子被具有某一 周期或频率的离子激发射频电压共振激发而获得较高的能量；被共振激发的离子与离子 阱中的中性分子发生碰撞并发生解离产生碎片离子，碎片离子在离子阱中经过冷却后被束 缚，以进行后续的质量分析；
在所述质量扫描分析阶段，离子阱中的离子在离子阱电极上加载的偶极激发电压的作 用下，发生共振激发，最终从离子引出电极的引出孔或引出槽中被逐出，并被设置在离子阱 外的离子探测器检测而获得离子的质谱信号。
2.根据权利要求 1所述的串级质谱分析方法，其特征在于：在所述碰撞诱导解离阶段， 保持数字束缚射频电压的电压幅度和占空比不变，选定数字束缚射频电压的周期值，且初 始周期与终止周期值不变；再选定某个分频数 n，即选定离子激发射频电压与数字束缚射 频电压两者之间频率关系 值， η= ψ /2；由于 值的关系，离子共振激发射频电压的周期 值也随着改变且占空比不变，随着离子共振激发射频电压的变化，离子之间实现共振运动 产生碰撞能量。
3. 根据权利要求 1所述的串级质谱分析方法，其特征在于：在所述质量扫描分析阶段 对离子质荷比进行线性扫描。
4.根据权利要求 1所述的串级质谱分析方法，其特征在于：在所述碰撞诱导解离阶段， 所施加的离子激发射频电压信号波形是数字方波或者正弦波。
5. 根据权利要求 2所述的串级质谱分析方法，其特征在于：在所述碰撞诱导解离阶段 中，增加通入离子阱内的中性冷却气体。
6.根据权利要求 2所述的串级质谱分析方法，其特征在于：所述碰撞诱导解离阶段，数 字束缚射频电压的频率和幅度为定值。
7.根据权利要求 2所述的串级质谱分析方法，其特征在于：在所述碰撞诱导解离阶段， 离子激发射频电压与数字子束缚射频电压频率比值为任意值。
8. 根据权利要求 1所述的串级质谱分析方法，其特征在于：所述离子阱为三维离子阱， 或者二维线形离子阱。
9.根据权利要求 1所述的串级质谱分析方法，其特征在于：所述离子阱为离子阱阵列， 或者为场调节离子阱。
PCT/CN2014/081622 2013-07-18 2014-07-04 一种在离子阱质量分析器中进行的串级质谱分析方法 WO2015007165A1 (zh)

Priority Applications (2)

Application Number Priority Date Filing Date Title
US14/905,912 US9640377B2 (en) 2013-07-18 2014-07-04 Method for tandem mass spectrometry analysis in ion trap mass analyzer
CA2955665A CA2955665A1 (en) 2013-07-18 2014-07-04 Method for tandem mass spectrometry analysis in ion trap mass analyzer

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN201310303472.XA CN103413751B (zh) 2013-07-18 2013-07-18 一种在离子阱质量分析器中进行的串级质谱分析方法
CN201310303472.X 2013-07-18

Publications (1)

Publication Number Publication Date
WO2015007165A1 true WO2015007165A1 (zh) 2015-01-22

Family

ID=49606751

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2014/081622 WO2015007165A1 (zh) 2013-07-18 2014-07-04 一种在离子阱质量分析器中进行的串级质谱分析方法

Country Status (4)

Country Link
US (1) US9640377B2 (zh)
CN (1) CN103413751B (zh)
CA (1) CA2955665A1 (zh)
WO (1) WO2015007165A1 (zh)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2740604C1 (ru) * 2020-07-14 2021-01-15 Федеральное государственное бюджетное образовательное учреждение высшего образования "Рязанский государственный радиотехнический университет имени В.Ф. Уткина" Способ масс-анализа ионов в квадрупольных полях с возбуждением колебаний на границы устойчивости
RU2749549C1 (ru) * 2020-07-14 2021-06-15 Федеральное государственное бюджетное образовательное учреждение высшего образования "Рязанский государственный радиотехнический университет имени В.Ф. Уткина" Устройство масс-анализа ионов с квадрупольными полями с возбуждением колебаний на границе устойчивости
CN113628951A (zh) * 2021-06-25 2021-11-09 西安空间无线电技术研究所 一种混合离子体系的双射频囚禁与势场匹配方法

Families Citing this family (24)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103413751B (zh) 2013-07-18 2016-08-10 复旦大学 一种在离子阱质量分析器中进行的串级质谱分析方法
CN103730325A (zh) * 2013-12-27 2014-04-16 昆山禾信质谱技术有限公司 一种在线快速分析挥发性有机物的装置和方法
CN104916520B (zh) * 2014-03-10 2018-06-22 芜湖谱实源仪器有限公司 一种改进离子阱质谱仪低质量截止值的方法
CN104362070A (zh) * 2014-11-14 2015-02-18 复旦大学 离子阱质量分析器中直流电压驱动的串级质谱分析方法
JP2016226088A (ja) * 2015-05-27 2016-12-28 エスアイアイ・セミコンダクタ株式会社 給電システム
CN106601581B (zh) * 2015-10-14 2018-05-11 北京理工大学 降低线性离子阱中空间电荷效应的系统和方法
US11348778B2 (en) * 2015-11-02 2022-05-31 Purdue Research Foundation Precursor and neutral loss scan in an ion trap
CN105355537B (zh) * 2015-11-13 2020-08-14 复旦大学 离子阱低质量数截止值串级质谱分析方法
CN105632867B (zh) * 2015-12-30 2020-07-07 复旦大学 一种提高栅网离子阱性能的方法
WO2017149603A1 (ja) * 2016-02-29 2017-09-08 株式会社島津製作所 質量分析装置
CN105655224B (zh) * 2016-03-09 2018-02-09 清华大学 一种小型化的二级真空矩型离子阱质谱仪及其检测方法
CN110291614B (zh) * 2016-12-22 2021-10-29 中国计量科学研究院 基于四极杆线性离子阱串联质谱仪器的离子分离检测方法
EP3373324A1 (en) * 2017-03-10 2018-09-12 Thermo Finnigan LLC Methods and systems for quantitative mass analysis
US10347477B2 (en) * 2017-03-24 2019-07-09 Thermo Finnigan Llc Methods and systems for quantitative mass analysis
CN108593754A (zh) * 2018-04-24 2018-09-28 清华大学 一种痕量物质串级质谱分析方法
CN109686646A (zh) * 2018-12-14 2019-04-26 上海裕达实业有限公司 质谱串级分析方法及其存储介质
CN109860013B (zh) * 2019-01-24 2021-07-23 复旦大学 一种基于数字离子阱的双向激发解离方法
CN115380209B (zh) * 2020-02-06 2024-01-05 上海宸安生物科技有限公司 用于为离子操纵装置产生共振激发的设备和方法
CN112071737B (zh) * 2020-03-20 2024-04-16 昆山聂尔精密仪器有限公司 一种离子激发和离子选择信号的生成方法和装置
CN112362718B (zh) * 2020-10-12 2024-07-02 深圳市卓睿通信技术有限公司 一种拓宽质谱仪检测质量范围的方法及装置
CN112233963B (zh) * 2020-10-29 2023-12-05 上海裕达实业有限公司 高碰撞能量交变电压离子解离装置及质谱分析方法
CN113161219B (zh) * 2020-12-30 2024-02-02 杭州谱育科技发展有限公司 无需色谱分离的质谱分析系统及方法
CN114005725A (zh) * 2021-11-02 2022-02-01 北京衡昇仪器有限公司 双90度偏转三重四极杆等离子质谱仪
CN114628220B (zh) * 2022-01-27 2024-08-09 清华大学 真空离子富集方法

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101320016A (zh) * 2008-01-29 2008-12-10 复旦大学 一种用多个离子阱进行串级质谱分析的方法
US20100084552A1 (en) * 2008-10-06 2010-04-08 Shimadzu Corporation Quadrupole mass spectrometer
CN102169791A (zh) * 2010-02-05 2011-08-31 岛津分析技术研发（上海）有限公司 一种串级质谱分析装置及质谱分析方法
CN102937622A (zh) * 2012-11-20 2013-02-20 复旦大学 一种在离子阱中进行的串级质谱分析方法
CN103413751A (zh) * 2013-07-18 2013-11-27 复旦大学 一种在离子阱质量分析器中进行的串级质谱分析方法

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8610056B2 (en) * 1994-02-28 2013-12-17 Perkinelmer Health Sciences Inc. Multipole ion guide ion trap mass spectrometry with MS/MSn analysis
JP4228201B2 (ja) * 2003-05-22 2009-02-25 トヨタ自動車株式会社 燃料電池の出力特性推定装置
US7582864B2 (en) * 2005-12-22 2009-09-01 Leco Corporation Linear ion trap with an imbalanced radio frequency field
GB0612503D0 (en) * 2006-06-23 2006-08-02 Micromass Ltd Mass spectrometer
US8309914B2 (en) * 2008-01-31 2012-11-13 Dh Technologies Development Pte. Ltd. Method of operating a linear ion trap to provide low pressure short time high amplitude excitation with pulsed pressure
US8178835B2 (en) * 2009-05-07 2012-05-15 Thermo Finnigan Llc Prolonged ion resonance collision induced dissociation in a quadrupole ion trap
CN102751162A (zh) * 2010-12-31 2012-10-24 聚光科技(杭州)股份有限公司 一种提高离子阱碰撞诱导解离性能的方法及装置

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101320016A (zh) * 2008-01-29 2008-12-10 复旦大学 一种用多个离子阱进行串级质谱分析的方法
US20100084552A1 (en) * 2008-10-06 2010-04-08 Shimadzu Corporation Quadrupole mass spectrometer
CN102169791A (zh) * 2010-02-05 2011-08-31 岛津分析技术研发（上海）有限公司 一种串级质谱分析装置及质谱分析方法
CN102937622A (zh) * 2012-11-20 2013-02-20 复旦大学 一种在离子阱中进行的串级质谱分析方法
CN103413751A (zh) * 2013-07-18 2013-11-27 复旦大学 一种在离子阱质量分析器中进行的串级质谱分析方法

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2740604C1 (ru) * 2020-07-14 2021-01-15 Федеральное государственное бюджетное образовательное учреждение высшего образования "Рязанский государственный радиотехнический университет имени В.Ф. Уткина" Способ масс-анализа ионов в квадрупольных полях с возбуждением колебаний на границы устойчивости
RU2749549C1 (ru) * 2020-07-14 2021-06-15 Федеральное государственное бюджетное образовательное учреждение высшего образования "Рязанский государственный радиотехнический университет имени В.Ф. Уткина" Устройство масс-анализа ионов с квадрупольными полями с возбуждением колебаний на границе устойчивости
CN113628951A (zh) * 2021-06-25 2021-11-09 西安空间无线电技术研究所 一种混合离子体系的双射频囚禁与势场匹配方法

Also Published As

Publication number Publication date
US20160365231A1 (en) 2016-12-15
CA2955665A1 (en) 2015-01-22
CN103413751A (zh) 2013-11-27
US9640377B2 (en) 2017-05-02
CN103413751B (zh) 2016-08-10

Similar Documents

Publication Publication Date Title
WO2015007165A1 (zh) 一种在离子阱质量分析器中进行的串级质谱分析方法
US8097844B2 (en) Mass-analysis method and mass-analysis apparatus
Ding et al. A digital ion trap mass spectrometer coupled with atmospheric pressure ion sources
US7692142B2 (en) Differential-pressure dual ion trap mass analyzer and methods of use thereof
US7528370B2 (en) High-Q pulsed fragmentation in ion traps
CN102937622B (zh) 一种在离子阱中进行的串级质谱分析方法
US6949743B1 (en) High-Q pulsed fragmentation in ion traps
JP2003249190A (ja) 電荷調整方法とその装置、および質量分析装置
US20130001415A1 (en) Frequency scan linear ion trap mass spectrometry
JP2012521002A (ja) タンデム質量分析計において複数の前駆体イオンを処理する方法
GB2541795A (en) Method and apparatus for mass spectrometry of macromolecular complexes
US20230178350A1 (en) Rapid identification and sequence analysis of intact proteins in complex mixtures
US20190013194A1 (en) Ion excitation method in linear ion trap
WO2011007528A1 (ja) 質量分析計及び質量分析方法
CN105355537B (zh) 离子阱低质量数截止值串级质谱分析方法
EP0746873B1 (en) Quadrupole trap ion isolation method
US20160358766A1 (en) Reducing overfragmentation in ultraviolet photodissociation
CN104362070A (zh) 离子阱质量分析器中直流电压驱动的串级质谱分析方法
Payne et al. Tandem mass spectrometry in quadrupole ion trap and ion cyclotron resonance mass spectrometers
JP2016507151A (ja) 自動排出イオントラップを用いた質量分析器における、気相反応の改善された効率および精密制御
CA2481299A1 (en) Fragmentation of ions by resonant excitation in a low pressure ion trap
US7888634B2 (en) Method of operating a linear ion trap to provide low pressure short time high amplitude excitation
JP4506260B2 (ja) イオン蓄積装置におけるイオン選別の方法
CN109860013B (zh) 一种基于数字离子阱的双向激发解离方法
CN113964014A (zh) 基于线性离子阱质谱仪的离子碎裂装置及方法

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 14826798

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 14826798

Country of ref document: EP

Kind code of ref document: A1

WWE Wipo information: entry into national phase

Ref document number: 14905912

Country of ref document: US

ENP Entry into the national phase

Ref document number: 2955665

Country of ref document: CA