WO2019228157A1 - 一种lc/ms和ms自动切换高通量连续进样装置 - Google Patents

一种lc/ms和ms自动切换高通量连续进样装置 Download PDF

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WO2019228157A1
WO2019228157A1 PCT/CN2019/085922 CN2019085922W WO2019228157A1 WO 2019228157 A1 WO2019228157 A1 WO 2019228157A1 CN 2019085922 W CN2019085922 W CN 2019085922W WO 2019228157 A1 WO2019228157 A1 WO 2019228157A1
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column
inlet
outlet
sample
switching valve
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张云
孙爱君
马宣
徐辉龙
胡云峰
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中国科学院南海海洋研究所
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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/04—Preparation or injection of sample to be analysed
    • G01N30/24—Automatic injection systems

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  • the invention relates to a LC / MS and MS automatic switching high-throughput continuous sampling device for a liquid chromatography-mass spectrometer.
  • Liquid chromatography-mass spectrometry is an important tool for the qualitative and quantitative analysis of organic substances by combining liquid chromatography and mass spectrometry. It not only reflects the high separation performance of liquid chromatography, but also the powerful discrimination capacity of mass spectrometry. For a wide range of applications.
  • the introduction method of the mass spectrometry system samples can be divided into two types according to the complexity of the samples: one is LC / MS mode, that is, biological samples with complex components, which are automatically The sampler sucks the sample through the chromatographic column and separates the complicated biological sample into the mass spectrometer for separate detection.
  • the other is the MS mode, which means that the biological sample with a single composition is manually injected (without going through a liquid chromatograph).
  • the manual direct injection method has the following disadvantages: 1 manually injecting the sample into the mass spectrometer inlet with a syringe, the operation is tedious, and the acquisition software cannot be taken into account at the same time, and 2 people are required to cooperate at the same time; 2 the solvent needs to be used to clean the spray needle and pipeline , Methanol, acetonitrile and other solvents are volatile, which is not good for the health of the operator; 3 The time required to complete a sample test is about 3 to 5 minutes, which takes a long time; 4 The spray needle and the connecting pipeline are often blocked, causing wear and tear of accessories and increasing costs; 5 Manual injection requires a relatively large amount of sample and large sample loss. At the same time, it is easy to cause instrument contamination and affect the performance of the instrument.
  • the present invention provides an LC / MS and MS automatic switching high-throughput continuous sampling device.
  • the purpose of continuous automatic sampling is achieved by using an automatic sampler in a liquid chromatograph.
  • the liquid chromatography-mass spectrometer includes liquid chromatography and mass spectrometry system
  • liquid chromatography includes automatic sampling Column, Column Thermostat 1 and Column Thermostat 2, Column Thermostat 1 is equipped with a chromatographic column.
  • the LC / MS and MS automatic switching high-throughput continuous sampling device includes a column switching valve and a three-way valve. The valve has an inlet and multiple outlets. The inlet of the column switching valve is connected to the autosampler of the liquid chromatograph. One outlet of the column switching valve is connected to the column oven of the liquid chromatograph.
  • the inlet of the heated runner is connected, the outlet of the heated runner of column one is connected to the inlet of the column, the outlet of the column is connected to the inlet of the three-way valve, and the other outlet of the column switching valve is connected to the liquid chromatograph.
  • the heating channel inlet of the second column oven is connected, the outlet of the heating channel of the second oven is connected to the inlet of the three-way valve, the sample outlet of the three-way valve is connected to the inlet of the mass spectrometer system, and the column is switched.
  • the valve is electrically connected to the control system of the LC / MS.
  • a DAD detector is also provided on the pipeline between the three-way valve sample inlet and the sample inlet of the mass spectrometry system.
  • the column switching valve includes a 6-position 2-way column switching valve, a 10-position 2-way column switching valve, or a 10-position 4-way column switching valve.
  • a column switching valve and a three-way valve are installed in the column thermostat module of the liquid chromatograph, and the operation control software of the LC / MS instrument is re-upgraded and configured at the same time, so that the operation control software realizes the automatic column switching valve. Switch between two LC / MS and MS injection modes, and then set up the LC / MS and MS automatic sampling procedures to achieve the purpose of high-throughput continuous injection.
  • the invention eliminates the tedious operation of manual direct injection or frequent replacement of chromatographic columns and two-way procedures, so that the time required for a single-component sample to be detected by a liquid chromatography-mass spectrometer is only 1 to 2 minutes.
  • the sampler can detect 30 to 50 samples with high throughput in one hour, and can realize the detection under the same acquisition instruction in LC / MS mode and MS mode, which greatly improves the work efficiency of operators and the utilization rate of mass spectrometers. .
  • FIG. 1 is a schematic structural diagram of the sample injection device of the present invention switched to the LC / MS mode, and at this time, the 1> 2 path of the column switching valve is connected;
  • FIG. 2 is a schematic structural diagram of the sampling device of the present invention switched to the MS mode, and at this time, the 1> 6 path of the column switching valve is communicated.
  • an LC / MS and MS automatic switching high-throughput continuous sampling device of this embodiment includes a column switching valve 1 and a tee installed on a column oven module of a liquid chromatograph.
  • Valve 2 is an existing instrument, including liquid chromatography and mass spectrometry system, where the liquid chromatography includes autosampler 3, column thermostat 1 and column thermostat 2 5 and column thermostat 1 4 Column 7 is provided.
  • the column switching valve 1 is an Agilent 6-position 2-port column switching valve, of which 1 port is the injection port, 2-6 ports are the sample port, and the injection port (1 port) of the column switching valve 1 It is connected to the autosampler 3 of the liquid chromatograph through a pipeline.
  • One sample outlet (2 ports) of the column switching valve 1 is connected to the heating runner inlet of the column thermostat 1-4 of the liquid chromatograph through a pipeline.
  • the outlet of the heated runner of column oven 4 is connected to the inlet of chromatographic column 7 through a pipeline, the outlet of column 7 is connected to the inlet of three-way valve 2 through a pipeline, and the other outlet of column switching valve 1 ( (6 port) is connected to the inlet of the heating runner of column 2 of the liquid chromatograph through the pipeline, and the outlet of the heating runner of the second oven of column 5 is connected to the inlet 2 of the three-way valve 2 through the pipeline.
  • the sample outlet of the through valve 2 is connected to the sample inlet of the mass spectrometer system 6 through a pipeline.
  • a DAD detector is further provided between the sample outlet of the three-way valve 2 and the sample port of the mass spectrometer system 6, It should be noted that the DAD detector is not a standard configuration of the LC / MS instrument. It can be selected as required. At the same time, the column switching valve 1 is electrically connected to the LC / MS instrument's control system.
  • the LC / MS and MS automatic switching high-throughput continuous sampling devices of the present invention are mainly divided into the following points:

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Abstract

一种LC/MS和MS自动切换高通量连续进样装置，包括柱切换阀（1）和三通阀（2），柱切换阀（1）进样口与液相色谱仪的自动进样器（3）相连，柱切换阀（1）的一个出样口与液相色谱仪（3）的柱温箱一（4）的加热流道进口相连，柱温箱一（4）的加热流道出口与色谱柱（7）进口相连，色谱柱（7）出口与三通阀（2）的进样口一相连，柱切换阀（1）的另一个出样口与液相色谱仪的柱温箱二（5）的加热流道进口相连，柱温箱二（5）的加热流道出口与三通阀（2）的进样口二相连，三通阀（2）出样口与质谱系统（6）进样口相连，柱切换阀（1）与液质联用仪控制系统电连接。省去了手动直接进样的繁琐操作或者频繁替换色谱柱和两通的程序，实现LC/MS模式和MS模式在同一个采集指令下完成检测，大大提高了操作人员工作效率和质谱仪器使用率。

Description

一种LC/MS和MS自动切换高通量连续进样装置 技术领域
本发明涉及一种用于液质联用仪的LC/MS和MS自动切换高通量连续进样装置。
背景技术
液质联用仪是将液相色谱和质谱结合起来的对有机物进行定性定量分析的重要工具，既体现了液相色谱的高分离性能，又体现了质谱强大的鉴别能力，在分析检测方面得到了广泛的应用。
以布鲁克公司的液质联用仪为例，质谱系统样品的导入方式根据样品的复杂程度分为两种：一种是LC/MS模式，即成分复杂的生物样品，通过液相色谱仪利用自动进样器吸取样品经过色谱柱分离后将复杂的生物样品导入到质谱中进行分别检测；另一种是MS模式，即成分单一的生物样品，以手动进样的方式(不经过液相色谱仪)直接通过质谱的进样口将单化合物样品注入质谱中进行检测，或者通过将液相色谱仪中的色谱柱替换成两通，然后利用液相色谱仪的自动进样器不经过色谱柱将单一样品导入质谱中进行检测，由于质谱仪器操作人员每天需要检测很多成分单一的生物样品，而MS模式的两种进样方式各存在以下缺陷：
1)手动直接进样方式存在以下弊端：①手动用注射器在质谱进样口注入样品，操作繁琐，不能同时兼顾操作采集软件，需要2个人员同时配合；②需要手动用溶剂清洗喷雾针及管线，甲醇、乙腈等溶剂易挥发，对操作人员的身体健康不利；③完成一个样品检测的时间大概3～5min，费时较长；④喷雾针及连接管线经常堵塞，造成配件损耗，花费增多；⑤手动注入需要样品量比较大，样品损耗大，同时容易造成仪器污染，影响仪器的性能。
2)替换两通自动进样方式存在以下弊端：①需要频繁将色谱柱与两通替换，操作比较繁琐；②容易拧不紧管线接口，造成漏液；③由于替换频繁，管线接口容易拧坏，造成配件损耗；④检测样品时容易忘记将色谱柱和两通替换，造成检测出错；⑤LC/MS和MS样品不能同时检测，需分别设置采样程序。
发明内容
针对以上问题，本发明提供一种LC/MS和MS自动切换高通量连续进样装置，利用液相色谱仪中的自动进样器达到连续自动进样的目的。
为实现上述目的，本发明的技术方案是：
一种LC/MS和MS自动切换高通量连续进样装置，用于液质联用仪，所述的液质联用仪包括液相色谱仪和质谱系统，液相色谱仪包括自动进样器、柱温箱一和柱温箱二，柱温箱一中设有色谱柱，所述的LC/MS和MS自动切换高通量连续进样装置包括柱切换阀和三通阀，柱切换阀具有一个进样口和多个出样口，柱切换阀的进样口与液相色谱仪的自动进样器相连，柱切换阀的一个出样口与液相色谱仪的柱温箱一的加热流道进口相连，柱温箱一的加热流道出口与色谱柱进口相连，色谱柱出口与三通阀的进样口一相连，柱切换阀的另一个出样口与液相色谱仪的柱温箱二的加热流道进口相连，柱温箱二的加热流道出口与三通阀的进样口二相连，三通阀的出样口与质谱系统的进样口相连，柱切换阀与液质联用仪的控制系统电连接。
进一步地，所述三通阀出样口与质谱系统进样口之间的管路上还设有DAD检测器
进一步的，所述的柱切换阀包括6位2通柱切换阀、10位2通柱切换阀或10位4通柱切换阀。
本发明通过在液相色谱仪的柱温箱模块加装一个柱切换阀和一个三通阀，同时对液质联用仪的操作控制软件进行重新升级配置，使得操作控制软件实现柱切换阀自动切换LC/MS和MS两种进样模式，再通过设置LC/MS和MS两种模式的自动进样程序，实现高通量连续进样的目的。
与现有技术相比，本发明的有益效果在于：
本发明省去了手动直接进样的繁琐操作或者频繁替换色谱柱和两通的程序，使得液质联用仪器检测一个单一成分样品的时间只需要1～2min，同时通过液相色谱仪的自动进样器一小时可以高通量检测样品数达30～50个，而且可以实现LC/MS模式和MS模式在同一个采集指令下完成检测，大大提高了操作人员工作效率和质谱仪器的使用率。
附图说明
图1为本发明进样装置切换至LC/MS模式的结构示意图，此时柱切换阀的1>2通路连通；
图2为本发明进样装置切换至MS模式的结构示意图，此时柱切换阀的1>6通路连通。
具体实施方式
为使本发明的上述目的、特征和优点能够更加明显易懂，下面结合附图和具体实施方式对本发明作进一步详细的说明。
如图1和图2所示，本实施例的一种LC/MS和MS自动切换高通量连续进样装置，包 括安装在液相色谱仪柱温箱模块上的柱切换阀1和三通阀2。液质联用仪为现有仪器，包括液相色谱仪和质谱系统，其中，液相色谱仪包括自动进样器3、柱温箱一4和柱温箱二5，柱温箱一4中设有色谱柱7。
本实施例中，柱切换阀1采用安捷伦公司的6位2通柱切换阀，其中1口为进样口，2-6口为出样口，柱切换阀1的进样口(1口)通过管路与液相色谱仪的自动进样器3相连，柱切换阀1的一个出样口(2口)通过管路与液相色谱仪的柱温箱一4的加热流道进口相连，柱温箱一4的加热流道出口通过管路与色谱柱7进口相连，色谱柱7出口通过管路与三通阀2的进样口一相连，柱切换阀1的另一个出样口(6口)通过管路与液相色谱仪的柱温箱二5的加热流道进口相连，柱温箱二5的加热流道出口通过管路与三通阀2的进样口二相连，三通阀2的出样口通过管路与质谱系统6的进样口相连，本实施例中，三通阀2的出样口与质谱系统6的进样口之间还设有DAD检测器，需要说明的是，DAD检测器并不是液质联用仪的标准配置，根据需要进行选配，同时，柱切换阀1与液质联用仪的控制系统电连接。
本发明的LC/MS和MS自动切换高通量连续进样装置，其具体的运行方式主要分为以下几点：
1)连接好所需的管线和通路，使得当6位2通柱切换阀连接1>2通路时系统为LC/MS模式，当6位2通柱切换阀连接1>6通路时系统为MS模式；
2)对液质联用仪控制系统的操作软件进行更新，激活能驱动6位2通柱切换阀的功能模块(为产品自带)，使得控制系统可以实现一键控制LC/MS和MS模式的自动切换；
3)在操作软件中分别设置好LC/MS和MS两种模式下液相色谱采集的方法和质谱采集的方法，其中，在MS模式下液相色谱采集方法由于不经过色谱柱和不需要DAD检测器，所以液相色谱采集时间设置在1-2min，DAD检测器选择不打开，流速和溶剂比例可以根据需求设定，同时在MS模式下柱切换阀连接的方式设置为1>6，在LC/MS模式柱切换阀连接的方式设置为1>2；
4)在操作软件中编辑液质联用仪的样品表(sample list)，设置好需要采集LC/MS和MS样品的信息和方法，使LC/MS和MS模式实现自动切换并在同一个采集指令(sample list)下完成检测。
上列详细说明是针对本发明可行实施例的具体说明，该实施例并非用以限制本发明的专利范围，凡未脱离本发明所为的等效实施或变更，均应包含于本案的专利范围中。

Claims (3)

  1. 一种LC/MS和MS自动切换高通量连续进样装置，用于液质联用仪，所述的液质联用仪包括液相色谱仪和质谱系统，液相色谱仪包括自动进样器、柱温箱一和柱温箱二，柱温箱一中设有色谱柱，其特征在于：所述的LC/MS和MS自动切换高通量连续进样装置包括柱切换阀和三通阀，柱切换阀具有一个进样口和多个出样口，柱切换阀的进样口与液相色谱仪的自动进样器相连，柱切换阀的一个出样口与液相色谱仪的柱温箱一的加热流道进口相连，柱温箱一的加热流道出口与色谱柱进口相连，色谱柱出口与三通阀的进样口一相连，柱切换阀的另一个出样口与液相色谱仪的柱温箱二的加热流道进口相连，柱温箱二的加热流道出口与三通阀的进样口二相连，三通阀的出样口与质谱系统的进样口相连，柱切换阀与液质联用仪的控制系统电连接。
  2. 根据权利要求1所述的一种LC/MS和MS自动切换高通量连续进样装置，其特征在于：所述三通阀出样口与质谱系统进样口之间的管路上还设有DAD检测器。
  3. 根据权利要求1所述的一种LC/MS和MS自动切换高通量连续进样装置，其特征在于：所述的柱切换阀包括6位2通柱切换阀、10位2通柱切换阀或10位4通柱切换阀。
PCT/CN2019/085922 2019-01-14 2019-05-08 一种lc/ms和ms自动切换高通量连续进样装置 WO2019228157A1 (zh)

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