WO2022016683A1 - 一种激光离子化的固相微萃取-飞行时间质谱联用的系统 - Google Patents

一种激光离子化的固相微萃取-飞行时间质谱联用的系统 Download PDF

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WO2022016683A1
WO2022016683A1 PCT/CN2020/114178 CN2020114178W WO2022016683A1 WO 2022016683 A1 WO2022016683 A1 WO 2022016683A1 CN 2020114178 W CN2020114178 W CN 2020114178W WO 2022016683 A1 WO2022016683 A1 WO 2022016683A1
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laser
solid
time
flight mass
phase microextraction
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PCT/CN2020/114178
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French (fr)
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欧阳钢锋
徐剑桥
胡庆坤
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中山大学
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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
    • G01N27/62—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating the ionisation of gases, e.g. aerosols; by investigating electric discharges, e.g. emission of cathode
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
    • G01N1/40—Concentrating samples
    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00—Particle spectrometers or separator tubes
    • H01J49/02—Details
    • H01J49/04—Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locks; Arrangements for external adjustment of electron- or ion-optical components
    • H01J49/0459—Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locks; Arrangements for external adjustment of electron- or ion-optical components for solid samples
    • H01J49/0463—Desorption by laser or particle beam, followed by ionisation as a separate step
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
    • G01N1/40—Concentrating samples
    • G01N2001/4038—Concentrating samples electric methods, e.g. electromigration, electrophoresis, ionisation

Definitions

  • the invention relates to the field of biological analysis and detection, and more particularly, to a laser ionization solid-phase microextraction-time-of-flight mass spectrometry system.
  • Matrix-assisted laser desorption ionization is a soft ionization technique that has been widely used in the analysis and detection of biological macromolecules.
  • the working principle and process are as follows: obtain the target analyte to be measured by appropriate sample pretreatment technology, spot it and the matrix on a suitable target plate in a suitable way, after drying and crystallizing, excite with appropriate laser energy, and the matrix absorbs the laser light. energy and transfer it to the target analyte. After ionization or protonation of the target analyte, it is analyzed by an appropriate detector.
  • the interference of matrix molecules it is limited in the analysis of small molecular compounds, and the detection accuracy of small molecular compounds is not high.
  • the sample preparation techniques are usually liquid-phase extraction, solid-phase extraction, or no extraction.
  • the matrix solution needs to be prepared separately, and then the sample and matrix solution are mixed and manually dispensed, which cannot be automated.
  • the existing solid-phase microextraction probe combined with gas chromatography includes two processes, namely extraction process and desorption process; the extraction process is that the extraction fiber with adsorption coating is exposed to the sample for extraction, and the desorption process is completed by The extractor needle of the extraction process is inserted into the gasification chamber of the gas chromatography sampling device, so that the extraction fiber is exposed to the high temperature carrier gas, and the extract is continuously desorbed and entered into the subsequent gas chromatography analysis.
  • the analyte must have a relatively high temperature. Good thermal stability limits the scope of application and is not suitable for the detection of biomolecules.
  • the application number is "CN201811356564.3”, a voltage-driven solid-phase microextraction-Raman spectroscopy combined method and device for ultra-fast detection of antibiotics.
  • CN201811356564.3 a voltage-driven solid-phase microextraction-Raman spectroscopy combined method and device for ultra-fast detection of antibiotics.
  • only the extraction head of the microextraction is fixed by voltage and laser. It can quickly enrich antibiotic substances and complete in situ detection, but it cannot improve the analysis accuracy of small molecule compounds.
  • the present invention provides a laser ionization solid-phase microextraction-time-of-flight mass spectrometry method to overcome the problems of low accuracy and inability to automate small molecular compounds in the existing matrix-assisted laser desorption ionization technology in the above-mentioned prior art.
  • This system simplifies the process of sample preparation and improves the analysis accuracy of small molecule compounds.
  • a laser ionization solid-phase microextraction-time-of-flight mass spectrometry system comprising a controller, a sample pretreatment platform, and a system installed on the sample pretreatment platform.
  • the extraction head of the SPE handle is an optical fiber, one end of the optical fiber is coated with a SPE coating, and the other end is the optical coupling device is connected;
  • the laser light emitted by the laser generator is coupled through the optical coupling device;
  • the time-of-flight mass spectrometer includes a sample inlet part and an analysis part connected to the sample inlet part, the optical fiber can extend into the sample inlet;
  • the sample pretreatment platform and the time-of-flight mass spectrometer are both electrically connected to the controller.
  • the sample pre-processing platform is an existing experimental platform on which there are multiple three-axis movable robotic arms.
  • the solid-phase microextraction handle is mounted on the robotic arm.
  • the optical coupling device is a common optical instrument, mainly composed of a convex lens structure, a position adjustment base in the three-dimensional direction and an optical fiber connection interface.
  • the controller is a computer control system with an operating system that can control the experimental device; instrument.
  • the computer control system sends a signal to the sample pre-processing platform and the time-of-flight mass spectrometer, and the robotic arm controls the insertion of the extraction head of the solid-phase extraction handle.
  • the extraction head is inserted into the injection port through the mechanical arm, and the laser generator generates laser light and emits it to the photosynthetic coupling device.
  • the photosynthetic coupling device couples the laser light into the optical fiber and transmits it in the optical fiber.
  • the high-energy laser is transmitted to the part coated with the solid phase microextraction coating, the laser light emitted from the fiber core is absorbed by the surrounding extraction coating, and the energy is transferred to the target analyte, and the protons are ionized in the process. Transfer to or get a proton from a molecule to ionize or protonate the target molecule.
  • the analysis part of the time-of-flight mass spectrometer has a negative pressure, and the target molecule is ionized or protonated and transferred to the analysis part, thereby realizing detection and analysis.
  • the laser controller is electrically connected to the controller; the laser controller is also electrically connected to the laser generator and controls the laser wavelength of the laser generator.
  • the laser controller is electrically connected with the computer control system, and the computer control system sends out the start signal of the laser generator, and also operates the laser controller to adjust the laser wavelength of the laser generator through the computer control system, and can also receive the time-of-flight mass spectrum through the computer control system.
  • the analysis data is completed through the computer control system to complete the integrated operation of the system.
  • E the generated photon energy
  • h Planck's constant
  • c the speed of light
  • ⁇ the laser wavelength.
  • the laser controller adjusts the photon energy by adjusting the laser wavelength emitted by the laser generator.
  • the bond energy of different chemical bonds in different analytes is different, so the photon energy can be adjusted by adjusting the laser wavelength, so that the selective breaking of chemical bonds can be achieved.
  • the sample pretreatment platform is electrically connected to the time-of-flight mass spectrometer and the laser controller, respectively.
  • the sample pretreatment platform is electrically connected to the sample pretreatment platform through a signal converter.
  • the components and equipment in the system are electrically connected.
  • the standard signal sample pre-processing platform of the laser controller is different from the time-of-flight mass spectrometer. Therefore, it is necessary to use a signal converter to change the signal working mode of the laser controller to electrically connect the various components and equipment in the system. Connecting, so that all the instruments are in a linkage state. Since the running time of each instrument is different, after the computer sends a start signal at one time, if each instrument moves independently, the cooperation between instruments will be uncoordinated.
  • the specific linkage method is as follows: the computer control system opens the control software of each component, and sets the parameters according to the requirements. Set the wavelength and energy intensity of the laser controller, select the external excitation control mode, set the laser generator to the ready state, and automatically emit the laser once it receives an external electrical signal; set the working method of the sample pretreatment platform, such as the temperature of the incubator (sample temperature). (extraction temperature during pretreatment), extraction time, shaking rate, sample vial size, sample vial tray selection, three-dimensional position adjustment of robotic arm work, sample injection time, sample vial and inlet insertion depth and coating exposure depth, etc.
  • the working method of the sample pretreatment platform such as the temperature of the incubator (sample temperature). (extraction temperature during pretreatment), extraction time, shaking rate, sample vial size, sample vial tray selection, three-dimensional position adjustment of robotic arm work, sample injection time, sample vial and inlet insertion depth and coating exposure depth, etc.
  • Parameters set the working sequence of the sample preprocessing platform; set the signal duration of the signal converter, that is, the working time of the laser generator; set the charge-to-mass ratio m/z detection range of the time-of-flight mass spectrometer, the positive and negative ion working modes, and the mass spectrometer. parameters, etc.; set the working sequence of time-of-flight mass spectrometry.
  • the working sequence of the sample pre-processing platform is run, and the sample pre-processing platform starts the sample pre-processing process; the working sequence of the time-of-flight mass spectrometer is run, and the time-of-flight mass spectrometer is ready to be in the prerun state, waiting for sample injection.
  • the sample pre-processing platform starts the sample injection process; after the sample injection, the sample pre-processing platform transmits electrical signals to the time-of-flight mass spectrometer through the remote port data line, and the time-of-flight mass spectrometer starts to work; after the sample injection, the sample pre-processing platform transmits the signal through the remote port data line.
  • the converter transmits electrical signals, the signal converter transmits electrical signals to the laser controller, the laser controller controls the laser generator to generate laser light, and the laser light is transmitted to the end fiber SPE coating through the optical fiber to start the ionization process of the target analyte.
  • the coating layer and the outer coating layer are removed from one end of the optical fiber used for applying the solid phase microextraction coating.
  • the optical fiber is etched with hydrofluoric acid to remove the coating and the outer coating, so that the laser can be emitted from the side of the fiber, so that the fiber SPE coating can more easily absorb the energy of the laser and transfer the energy to the target analyte.
  • the solid-phase microextraction handle includes an outer tube, an inner tube installed in the outer tube, and a push handle connected to the inner tube; the optical fiber is installed in the inner tube, and the optical fiber is smeared and solid One end of the phase microextraction coating extends outside the inner tube; the push handle pushes the inner tube to slide inside the outer tube.
  • the function of the outer tube is that when the optical fiber needs to adsorb the target analyte and extend into the injection port, because the optical fiber is relatively fragile, it is easy to be damaged when it touches hard objects.
  • the inner tube When the outer tube enters the distance from one end, the inner tube is moved for a certain distance by pushing the push handle until the optical fiber extends out of the outer tube to realize the adsorption and desorption of the target analyte.
  • the optical fiber can be smoothly inserted into the sample bottle and the injection port, which can be directly used in different equipment, which is beneficial to the automation process of the system.
  • the push handle is connected to the robotic arm of the sample pretreatment platform.
  • the action of the push handle is operated by the robotic arm of the sample pretreatment platform, and the sample pretreatment platform automatically controls the robotic arm to drive the push handle to move through electrical signals.
  • the outer tube is connected with a sliding cylinder
  • the push handle is slidably connected with the sliding cylinder.
  • the push handle moves in the sliding cylinder, which can stabilize the movement direction of the push handle and prevent the push handle from shifting.
  • the push handle is provided with a guide groove communicating with the inner tube, and the optical fiber extends through the guide groove to the inner cavity of the inner tube.
  • the optical fiber is fixed in the inner tube through the guide groove, and the optical fiber can move together with the push handle, which also facilitates the connection of the optical fiber with the optical coupling device.
  • one end of the outer tube away from the push handle is a conical tip.
  • the pointed tip allows the outer tube to pierce the septum at the vial and inlet.
  • the beneficial effects of the present invention are: the optical fiber combined with the solid-phase micro-extraction coating can not only achieve high enrichment ability for target molecules, but also have high laser absorption ability and photoelectric conversion efficiency, so as to achieve the target molecules.
  • the solid-phase extraction coating of the optical fiber in the system has good stability during the laser ionization process, the damage rate is low, and it will not be detached by the laser excitation. There is no interference from the matrix molecules during the detection of small molecules, which significantly reduces the detection of small molecules. background interference, and improve the analysis accuracy.
  • This system simplifies the sample pretreatment process and the laser ionization process.
  • the use of the outer coating of the optical fiber can directly realize the sample pretreatment process, carry out the enrichment, separation and transfer of the target analyte, and then directly perform laser ionization. Complete automation from sample preparation to detection.
  • FIG. 1 is a schematic structural diagram of a laser ionized solid-phase microextraction-time-of-flight mass spectrometry system of the present invention
  • Figure 2 is an exploded view of the solid phase microextraction handle of the present invention.
  • FIG. 1 is an embodiment of a laser ionization solid-phase microextraction-time-of-flight mass spectrometry system, comprising a sample pretreatment platform 1 and a solid-phase microextraction handle 2 installed on the sample pretreatment platform 1 , a laser generator 3, an optical coupling device 4, a time-of-flight mass spectrometer 5, a laser controller 6 and a controller 7;
  • the sample pretreatment platform 1 is a multifunctional sample pretreatment platform, and the specific model is gerstel's MuitiPurpose Sampler MPSXT
  • laser generator 3 is Radiant tunable laser system of OPOTEK
  • time-of-flight mass spectrometer 5 is Agilent 6545-Q-TOF-LC/MS
  • laser controller 6 is Radiant tunable laser system ICE 760 of OPOTEK
  • control The device 7 is a computer control system.
  • the extraction head of the solid-phase microextraction handle 2 is an optical fiber 8, one end of the optical fiber 8 is coated with a solid-phase microextraction coating, and the other end is connected to the optical coupling device 4; the laser light emitted by the laser generator 3 passes through the optical coupling device 4. Coupling is performed; the time-of-flight mass spectrometer 5 includes a sample inlet part 501 and an analysis part 502, the optical fiber 8 can extend into the sample inlet part 501, and the outlet of the sample inlet part 501 is connected to the analysis part 502 through a capillary.
  • the laser controller 6, the sample preprocessing platform 1, and the time-of-flight mass spectrometer 5 are all electrically connected to the controller 7; the laser controller 6 is electrically connected to the laser generator 3; the sample preprocessing platform 1 is electrically connected through a signal converter 9 is electrically connected to the laser controller 6 , and the sample preprocessing platform 1 is electrically connected to the time-of-flight mass spectrometer 5 .
  • the instrument is electrically connected to the instrument, so that all instruments are in a linkage state. After setting the working parameters of each instrument, the computer control system only needs to send a start signal to the instrument, and the instrument will start according to the received linkage start signal. The running time between the instruments is coordinated, and at the same time, the whole system can run automatically, and there is no need to operate the computer control system for many times to send out signals.
  • the end of the optical fiber 8 used for applying the solid phase microextraction coating removes the coating layer and the outer coating.
  • the fiber 8 is etched with hydrofluoric acid to remove the coating and the outer coating, so that the laser can be emitted from the side of the fiber 8, so that the fiber 8 solid-phase microextraction coating can more easily absorb the energy of the laser and transfer the energy to the target analyte .
  • the controller 7 opens the control software of each instrument, and sets parameters according to requirements.
  • Set the wavelength and energy intensity of the laser controller 6, select the external excitation control mode, set the laser generator 3 to the ready state, and automatically emit laser once it receives an external electrical signal;
  • the controller 7 After the controller 7 outputs the start signal, the working sequence of the sample pre-processing platform 1 and the time-of-flight mass spectrometer 5 is started.
  • the extraction head is inserted into the injection port 501 through the robotic arm, and the sample pre-processing platform 1 transmits electrical signals to the time-of-flight mass spectrometer 5 through the remote port data line after the sample injection, and the time-of-flight mass spectrometer 5 starts to work;
  • the pre-processing platform 1 transmits electrical signals to the signal converter 9 through the remote port data line, the signal converter transmits the electrical signals to the laser controller 6, and the laser controller 6 controls the laser generator 3 to generate laser light and transmits it to the photo-combination coupling device 4.
  • the optical coupling device 4 couples the laser light into the optical fiber 8 and transmits it in the optical fiber 8 .
  • the high-energy laser is transmitted to the part coated with the solid phase microextraction coating, the laser light emitted from the 8 core of the fiber is absorbed by the surrounding extraction coating, and the energy is transferred to the target analyte.
  • a proton is transferred to or from a molecule, thereby achieving ionization or protonation of the target molecule.
  • the analysis part 502 of the time-of-flight mass spectrometer 5 has negative pressure, and the target molecules are ionized or protonated and then transmitted to the analysis part 502 , and the analysis part 502 finally transmits the analysis results to the controller 7 to realize automatic detection.
  • the beneficial effects of this embodiment when the system is used in the laboratory, the special solid-phase microextraction coating outside the optical fiber 8 can not only achieve high enrichment ability for target molecules, but also high laser absorption ability and photoelectric conversion efficiency, Thus, the laser ionization process of the target molecule is realized.
  • the solid-phase extraction coating of the optical fiber in the system has good stability during the laser ionization process, the damage rate is low, and it will not be detached by the laser excitation. There is no interference from the matrix molecules during the detection of small molecules, which significantly reduces the detection of small molecules. background interference, and improve the analysis accuracy.
  • This system simplifies the process of sample pretreatment and laser ionization.
  • the use of optical fiber 8 outer coating can directly realize the sample pretreatment process, carry out the enrichment, separation and transfer of target analytes, and then directly carry out laser ionization, It can realize all the automation from sample preparation to detection process.
  • Embodiment 2 another embodiment of a laser ionization solid-phase microextraction-time-of-flight mass spectrometry 5 combined system is different from Embodiment 1 in that the solid-phase extraction handle is further limited.
  • the solid phase microextraction handle 2 includes an outer tube 201, an inner tube 202 installed in the outer tube 201, and a push handle 203 connected to the inner tube 202; the optical fiber 8 is installed in the inner tube 202, and the optical fiber 8 is coated with a solid phase microextraction coating One end extends to the outside of the inner tube 202 ; the push handle 203 pushes the inner tube 202 to slide inside the outer tube 201 .
  • the function of the outer tube 201 is that when the optical fiber 8 needs to adsorb the target analyte and extend into the sample inlet part 501, since the optical fiber 8 is relatively fragile and easily damaged when it touches hard objects, the outer tube 201 can be used to pierce the sample bottle and the inlet.
  • the septum of the sample port 501 when the outer tube 201 enters one end of the distance, drives the inner tube 202 to move a certain distance by pushing the push handle 203 until the optical fiber 8 extends out of the outer tube 201, so as to realize the adsorption and absorption of the target analyte. desorption.
  • the optical fiber 8 can be smoothly inserted into the sample bottle and the sample inlet part 501, and can be directly used in different equipment, which is beneficial to the automation process of the system.
  • the push handle 203 is connected to the robotic arm of the sample preprocessing platform 1 .
  • the action of the push handle 203 is operated by the robotic arm of the sample pretreatment platform 1 , and the sample pretreatment platform 1 automatically controls the robotic arm to drive the push handle 203 to move through an electrical signal.
  • the outer tube 201 is connected with a sliding cylinder 204
  • the push handle 203 is located in the sliding cylinder 204 and is slidably connected with the sliding cylinder 204 .
  • the pushing handle 203 moves in the sliding cylinder 204 , which can stabilize the moving direction of the pushing handle 203 and prevent the pushing handle 203 from shifting.
  • the push handle 203 is provided with a guide groove 205 that communicates with the inner tube 202, and the optical fiber 8 extends through the guide groove 205 to the lumen of the inner tube 202.
  • the optical fiber 8 is fixed in the inner tube 202 via the guide groove 205 , and the optical fiber 8 can move together with the push handle 203 , which also facilitates the connection of the optical fiber 8 with the optical coupling device 4 .
  • the end of the outer tube 201 away from the push handle 203 is a tapered prong 206 .
  • the prongs 206 may facilitate the outer tube 201 to pierce the septum of the sample vial and inlet portion 501 .

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Abstract

一种激光离子化的固相微萃取-飞行时间质谱联用的系统，包括控制器（7）、样品前处理平台（1）、固相微萃取手柄（2）、激光发生器（3）、光学耦合装置（4）和飞行时间质谱（5）；固相微萃取手柄（2）的萃取头为光纤（8），光纤（8）的一端涂抹有固相微萃取涂层，另一端与光学耦合装置（4）连接；飞行时间质谱（5）包括进样口部（501）和分析部（502），光纤（8）可伸入进样口部（501）。样品前处理平台（1）和飞行时间质谱（5）与控制器（7）电连接。光纤（8）结合固相微萃取涂层，不仅能够实现对目标分子的高富集能力，还具有高激光吸收能力及光电转化效率，从而实现对目标分子的激光离子化过程。且光纤（8）的固相萃取涂层在激光离子化过程中稳定性较好，损伤率低，自身不会被激光激发脱离，显著降低小分子检测时的背景干扰。

Description

一种激光离子化的固相微萃取-飞行时间质谱联用的系统 技术领域
本发明涉及生物分析检测领域，更具体地，涉及一种激光离子化的固相微萃取-飞行时间质谱联用的系统。
背景技术
基质辅助激光解吸离子化技术(MALDI)是一种软电离技术，在生物大分子的分析检测方面得到了广泛应用。其工作原理为和流程为：通过适当样品前处理技术获得待测目标分析物，将其与基质以合适方式点在适用的靶板上，待干燥结晶后，以适当激光能量激发，基质吸收激光能量并转移给目标分析物。目标分析物离子化或质子化后，通过适当检测器进行分析。但受制于基质分子的干扰，其在小分子化合物的分析方面受到限制，小分子化合物的检测准确率不高。
对于基质辅助激光解吸，其样品前处理技术通常为液相萃取，固相萃取，或者不萃取。需要另外配置基质溶液，然后将样品和基质溶液混合后人工点板，无法进行自动化。而现有固相微萃取探针结合气相色谱时，包括两个流程，分别为萃取过程和解吸过程；萃取过程为具有吸附涂层的萃取纤维暴露在样品中进行萃取，解吸过程是将以完成萃取过程的萃取器针头插入气相色谱进样装置的气化室内，使萃取纤维暴露在高温载气中，并使萃取物不断地被解吸下来，进入后序的气相色谱分析，分析物必须具有较好的热稳定性，限制应用范围，不适用于生物分子的检测。
申请号为“CN201811356564.3”的一种电压驱动固相微萃取-拉曼光谱联用超快速检测抗生素类物质的方法及装置，该方案中也只是通过电压以及激光令固定微萃取的萃取头可以快速的富集抗生素类物质和完成原位检测，却也无法提高小分子化合物分析准确率。
发明内容
本发明为克服上述现有技术中现有的基质辅助激光解吸离子化技术中，小分子化合物准确率低和无法自动化进行的问题，提供一种激光离子化的固相微 萃取-飞行时间质谱联用的系统，简化样品前处理的过程同时提高小分子化合物的分析准确率。
为解决上述技术问题，本发明采用的技术方案是：一种激光离子化的固相微萃取-飞行时间质谱联用的系统，包括控制器、样品前处理平台、安装于所述样品前处理平台上的固相微萃取手柄、激光发生器、光学耦合装置和飞行时间质谱；所述固相微萃取手柄的萃取头为光纤，所述光纤的一端涂抹有固相微萃取涂层，另一端与所述光学耦合装置连接；所述激光发生器发出的激光经过所述光学耦合装置进行耦合；所述飞行时间质谱包括进样口部和与所述进样口部连接的分析部，所述光纤可伸入所述进样口部；所述样品前处理平台和所述飞行时间质谱均与所述控制器电连接。
样品前处理平台为现有的实验平台，其上有多个可三轴移动的机械臂。固相微萃取手柄安装在机械臂上。光学耦合装置为光学的常用仪器，主要由凸透镜结构、三维方向上的位置调节基座和光纤连接接口组成，控制器为计算机控制系统，具有可控制实验器件的操作系统；飞行时间质谱也是现有的仪器。在上述的技术方案中，控制器设置好样品前处理平台和飞行时间质谱的工作参数后，计算机控制系统向样品前处理平台和飞行时间质谱发出信号，机械臂控制固相萃取手柄的萃取头插入取样瓶上，通过光纤上的固相萃取涂层吸附样品瓶中一定量的目标分析物。通过机械臂将萃取头插入至进样口部内，激光发生器产生激光，并发射至光合耦合装置上，光合耦合装置将激光耦合到光纤中，并在光纤中进行传输。当高能量的激光传输至涂抹有固相微萃取涂层部分，从光纤纤芯射出的激光被涂敷在周围的萃取涂层吸收，并将能量转移给目标分析物，在电离过程中将质子转移到分子或从分子得到质子，从而实现目标分子离子化或质子化。而飞行时间质谱的分析部具有负压，目标分子离子化或质子化后传输到分析部上，从而实现检测分析。
优选的，还包括激光控制器；所述激光控制器与所述控制器电连接；所述激光控制器还与所述激光发生器电连接并控制所述激光发生器的激光波长。激光控制器与计算机控制系统电连接，通过计算机控制系统发出激光发生器的启动信号，也通过计算机控制系统来操作激光控制器调节激光发生器的激光波长，还可以通过计算机控制系统接收飞行时间质谱的分析数据，通过计算机控制系统完成系统的一体化操作。
根据E＝hc/λ，E为产生的光子能量，h为普朗克常量，c为光速，λ为激光波长，激光控制器通过调节激光发生器发出的激光波长，进而调节光子能量。而不同分析物中的不同化学键的键能不同，因此通过调节激光波长即可调节光子能量，从而可以实现化学键的选择性断裂。
优选的，所述样品前处理平台分别和所述飞行时间质谱和所述激光控制器电连接。所述样品前处理平台通过信号转换器与所述样品前处理平台电连接。将系统中的各部件设备进行电连接，激光控制器的制式信号样品前处理平台和飞行时间质谱不同，因此需要使用信号转换器改变激光控制器的信号工作模式将系统中的各部件设备进行电连接，从而使得所有仪器处于联动状态，由于每个仪器的运行时间都不一样，计算机一次性发出启动信号后，如果每个仪器都单独运动的话，仪器与仪器之间的协作就会发生不协调，因此需要先后向仪器发出启动信号，但这样要多次操作计算机控制系统，难以实现实验过程的全自动化。而将仪器联动后，通过计算机控制系统设置好各仪器的工作参数后，仪器接收到启动信号后，后启动的仪器只有再接收联动的启动信号后，仪器才会会启动，使得计算机控制系统能够发出启动信号后，系统每个仪器就能够按先后顺序自动化运行。
具体的联动方式为：计算机控制系统打开各组成部分控制软件，并根据需求设置好参数。设置激光控制器的波长及能量强度，并选择外部激发控制方式，设置激光发生器为准备状态，一旦接收外部电信号就可以自动发射激光；设置样品前处理平台的工作方法，如孵化器温度(样品前处理过程中的萃取温度)、萃取时间、震荡速率、样品瓶规格、样品瓶托盘选择、机械臂工作的三维位置调节、进样时间、样品瓶及进样口插入深度及涂层暴露深度等参数；设置好样品前处理平台的工作序列；设置好信号转换器的信号时长，即激光发生器的工作时间；设置好飞行时间质谱的荷质比m/z检测范围、正负离子工作模式、质谱参数等；设置好飞行时间质谱的工作序列。
计算机控制系统发生启动信号后，运行样品前处理平台的工作序列，样品前处理平台开始进行样品前处理过程；运行飞行时间质谱的工作序列，飞行时间质谱ready后为prerun状态，等待进样。样品前处理平台开始进行进样过程；进样后样品前处理平台通过remote端口数据线向飞行时间质谱传输电信号，飞行时间质谱开始工作；进样后样品前处理平台通过remote端口数据线向信号转 换器传输电信号，信号转换器向激光控制器传输电信号，激光控制器控制激光发生器产生激光，激光经光纤传输至末端光纤固相微萃取涂层，开始目标分析物离子化进程。
优选的，所述光纤用于涂抹固相微萃取涂层的一端去除涂覆层和外包层。光纤通过使用氢氟酸蚀刻的方式去除涂覆层和外包层，使激光能够从光纤侧面射出，使得光纤固相微萃取涂层更容易吸收激光的能量并且将能量转移给目标分析物。
优选的，所述固相微萃取手柄包括外管、安装于所述外管内的内管和与所述内管连接的推动柄；所述光纤安装于所述内管，且所述光纤涂抹固相微萃取涂层的一端延伸至所述内管外；所述推动柄推动所述内管在所述外管内滑动。外管的作用是当光纤需要吸附目标分析物和伸入进样口部的时候，由于光纤较为脆弱，触碰硬物容易损坏，可以先通过外管刺穿样品瓶和进样口部的隔垫，当外管进入一端距离后，在通过推动推动柄带动内管运动一段距离，直至光纤伸入外管之外，实现对目标分析物的吸附和脱附。通过固相微萃取手柄的结构，能够顺利将光纤伸入样品瓶和进样口部，能够在不同设备中直接使用，利于系统的自动化进程。
优选的，所述推动柄与所述样品前处理平台的机械臂连接。推动柄的动作通过样品前处理平台的机械臂操作，样品前处理平台通过电信号自动控制机械臂带动推动柄运动。
优选的，所述外管连接有滑动筒，所述推动柄与所述滑动筒滑动连接。推动柄在滑动筒内运动，能够稳定推动柄的运动方向，避免推动柄偏移。
优选的，所述推动柄设置有连通至所述内管的引导槽，所述光纤穿过所述引导槽延伸至所述内管的内腔。光纤经由引导槽固定在内管中，光纤能够跟随推动柄一起运动，也便于光纤与光学耦合装置连接。
优选的，所述外管远离所述推动柄的一端为锥形的尖头。尖头可以利于外管刺穿样品瓶和进样口部的隔垫。
与现有技术相比，本发明的有益效果是：光纤结合固相微萃取涂层，不仅能够实现对目标分子的高富集能力，还具有高激光吸收能力及光电转化效率，从而实现对目标分子的激光离子化过程。系统中光纤的固相萃取涂层在激光离子化过程中稳定性较好，损伤率低，自身不会被激光激发脱离，小分子的检测 的时候没有了基质分子的干扰，显著降低小分子检测时的背景干扰，提高分析准确率。
本系统简化了样品前处理过程和激光离子化的过程，使用光纤外涂层可以直接实现样品前处理过程，进行对目标分析物的富集、分离和转移，然后可以直接进行激光离子化，能够实现从样品前处理到检测过程的全部自动化操作。
附图说明
图1是本发明的一种激光离子化的固相微萃取-飞行时间质谱联用的系统的结构示意图；
图2是本发明本发明的固相微萃取手柄的爆炸图。
具体实施方式
附图仅用于示例性说明，不能理解为对本专利的限制；为了更好说明本实施例，附图某些部件会有省略、放大或缩小，并不代表实际产品的尺寸；对于本领域技术人员来说，附图中某些公知结构及其说明可能省略是可以理解的。附图中描述位置关系仅用于示例性说明，不能理解为对本专利的限制。
下面通过具体实施例，并结合附图，对本发明的技术方案作进一步的具体描述：
实施例1
如图1所示为一种激光离子化的固相微萃取-飞行时间质谱联用的系统的实施例，包括样品前处理平台1、安装于样品前处理平台1上的固相微萃取手柄2、激光发生器3、光学耦合装置4、飞行时间质谱5、激光控制器6和控制器7；在本实施例中，样品前处理平台1是多功能样品前处理平台，具体的型号是gerstel的MuitiPurpose Sampler MPSXT，激光发生器3的型号是OPOTEK的Radiant tunable laser system，飞行时间质谱5是安捷伦的6545-Q-TOF-LC/MS，激光控制器6是OPOTEK的Radiant tunable laser system ICE 760，控制器7是计算机控制系统。
具体的，固相微萃取手柄2的萃取头为光纤8，光纤8的一端涂抹有固相微萃取涂层，另一端与光学耦合装置4连接；激光发生器3发出的激光经过光学耦合装置4进行耦合；飞行时间质谱5包括进样口部501和分析部502，光纤8可伸入进样口部501，进样口部501的出口通过毛细管与分析部502连接。
在本实施例中，激光控制器6、样品前处理平台1、飞行时间质谱5均与控 制器7电连接；激光控制器6与激光发生器3电连接；样品前处理平台1通过信号转换器9与激光控制器6电连接，样品前处理平台1与飞行时间质谱5电连接。将仪器与仪器进行电连连接，从而使得所有仪器处于联动状态，设置好各仪器的工作参数后，计算机控制系统只需要向仪器发出一次启动信号后，仪器根据收到联动的启动信号才启动，协调了仪器与仪器之间的运行时间，同时，令整个系统可以自动运行，不需要多次操作计算机控制系统发出信号。
其中，光纤8用于涂抹固相微萃取涂层的一端去除涂覆层和外包层。光纤8通过使用氢氟酸蚀刻的方式去除涂覆层和外包层，使激光能够从光纤8侧面射出，使得光纤8固相微萃取涂层更容易吸收激光的能量并且将能量转移给目标分析物。
本实施例的工作原理或工作流程：控制器7打开各仪器的控制软件，并根据需求设置好参数。设置激光控制器6的波长及能量强度，并选择外部激发控制方式，设置激光发生器3为准备状态，一旦接收外部电信号就可以自动发射激光；设置样品前处理平台1的工作方法，如孵化器温度(样品前处理过程中的萃取温度)、萃取时间、震荡速率、样品瓶规格、样品瓶托盘选择、机械臂工作的三维位置调节、进样时间、样品瓶及进样口插入深度及涂层暴露深度等参数；设置好样品前处理平台1的工作序列；设置好信号转换器9的信号时长，即激光发生器3的工作时间；设置好飞行时间质谱5的荷质比m/z检测范围、正负离子工作模式、质谱参数等；设置好飞行时间质谱5的工作序列。
控制器7输出启动信号后，开始运行样品前处理平台1和飞行时间质谱5的工作序列，机械臂控制固相萃取手柄的萃取头插入取样瓶上，通过光纤8上的固相萃取涂层吸附样品瓶中一定量的目标分析物。通过机械臂将萃取头插入至进样口部501内，同时进样后样品前处理平台1通过remote端口数据线向飞行时间质谱5传输电信号，飞行时间质谱5开始工作；进样后的样品前处理平台1通过remote端口数据线向信号转换器9传输电信号，信号转换器向激光控制器6传输电信号，激光控制器6控制激光发生器3产生激光，并发射至光合耦合装置4上，光合耦合装置4将激光耦合到光纤8中，并在光纤8中进行传输。当高能量的激光传输至涂抹有固相微萃取涂层部分，从光纤8纤芯射出的激光被涂敷在周围的萃取涂层吸收，并将能量转移给目标分析物，在电离过程中将质子转移到分子或从分子得到质子，从而实现目标分子离子化或质子化。 而飞行时间质谱5的分析部502具有负压，目标分子离子化或质子化后传输到分析部502上，分析部502最终将分析结果传输至控制器7上，从而实现自动化检测。
本实施例的有益效果：本系统在实验室使用的时候，光纤8外特制固相微萃取涂层，不仅能够实现对目标分子的高富集能力，还具有高激光吸收能力及光电转化效率，从而实现对目标分子的激光离子化过程。系统中光纤的固相萃取涂层在激光离子化过程中稳定性较好，损伤率低，自身不会被激光激发脱离，小分子的检测的时候没有了基质分子的干扰，显著降低小分子检测时的背景干扰，提高分析准确率。本系统简化了样品前处理过程和激光离子化的过程，使用光纤8外涂层可以直接实现样品前处理过程，进行对目标分析物的富集、分离和转移，然后可以直接进行激光离子化，能够实现从样品前处理到检测过程的全部自动化操作。
实施例2
如图2所示为一种激光离子化的固相微萃取-飞行时间质谱5联用的系统的另一实施例，与实施例1的区别在于，对固相萃取手柄进一步的限定。
固相微萃取手柄2包括外管201、安装于外管201内的内管202和与内管202连接的推动柄203；光纤8安装于内管202，且光纤8涂抹固相微萃取涂层的一端延伸至内管202外；推动柄203推动内管202在外管201内滑动。外管201的作用是当光纤8需要吸附目标分析物和伸入进样口部501的时候，由于光纤8较为脆弱，触碰硬物容易损坏，可以先通过外管201刺穿样品瓶和进样口部501的隔垫，当外管201进入一端距离后，在通过推动推动柄203带动内管202运动一段距离，直至光纤8伸入外管201之外，实现对目标分析物的吸附和脱附。通过固相微萃取手柄2的结构，能够顺利将光纤8伸入样品瓶和进样口部501，能够在不同设备中直接使用，利于系统的自动化进程。
其中，推动柄203与样品前处理平台1的机械臂连接。推动柄203的动作通过样品前处理平台1的机械臂操作，样品前处理平台1通过电信号自动控制机械臂带动推动柄203运动。
具体的，外管201连接有滑动筒204，推动柄203位于滑动筒204内并与滑动筒204滑动连接。推动柄203在滑动筒204内运动，能够稳定推动柄203的运动方向，避免推动柄203偏移。推动柄203设置有连通至内管202的引导 槽205，光纤8穿过引导槽205延伸至内管202的内腔。光纤8经由引导槽205固定在内管202中，光纤8能够跟随推动柄203一起运动，也便于光纤8与光学耦合装置4连接。
为了便于外管201穿过隔垫，外管201远离推动柄203的一端为锥形的尖头206。尖头206可以利于外管201刺穿样品瓶和进样口部501的隔垫。
本实施例与实施例1的其余特征和工作原理一致。
显然，本发明的上述实施例仅仅是为清楚地说明本发明所作的举例，而并非是对本发明的实施方式的限定。对于所属领域的普通技术人员来说，在上述说明的基础上还可以做出其它不同形式的变化或变动。这里无需也无法对所有的实施方式予以穷举。凡在本发明的精神和原则之内所作的任何修改、等同替换和改进等，均应包含在本发明权利要求的保护范围之内。

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  1. 一种激光离子化的固相微萃取-飞行时间质谱联用的系统，包括控制器(7)、样品前处理平台(1)和安装于所述样品前处理平台(1)上的固相微萃取手柄(2)，其特征在于，还包括激光发生器(3)、光学耦合装置(4)和飞行时间质谱(5)；所述固相微萃取手柄(2)的萃取头为光纤(8)，所述光纤(8)的一端涂抹有固相微萃取涂层，另一端与所述光学耦合装置(4)连接；所述激光发生器(3)发出的激光经过所述光学耦合装置(4)进行耦合；所述飞行时间质谱(5)包括进样口部(501)和与所述进样口部连接的分析部(502)，所述光纤(8)可伸入所述进样口部(501)；所述样品前处理平台(1)和所述飞行时间质谱(5)均与所述控制器(7)电连接。
  2. 根据权利要求1所述的一种激光离子化的固相微萃取-飞行时间质谱联用的系统，其特征在于，还包括与所述控制器(7)电连接的激光控制器(6)；所述激光控制器(6)还与所述激光发生器(3)电连接并控制所述激光发生器(3)的激光波长。
  3. 根据权利要求2所述的一种激光离子化的固相微萃取-飞行时间质谱联用的系统，其特征在于，所述样品前处理平台(1)分别与所述激光控制器(6)和所述飞行时间质谱(5)电连接。
  4. 根据权利要求3所述的一种激光离子化的固相微萃取-飞行时间质谱联用的系统，其特征在于，所述样品前处理平台(1)通过信号转换器(9)与所述激光控制器(6)电连接。
  5. 根据权利要求1-4任一所述的一种激光离子化的固相微萃取-飞行时间质谱联用的系统，其特征在于，所述光纤用于涂抹固相微萃取涂层的一端去除涂覆层和外包层。
  6. 根据权利要求5所述的一种激光离子化的固相微萃取-飞行时间质谱联用的系统，其特征在于，所述固相微萃取手柄(2)包括外管(201)、安装于所述外管(201)内的内管(202)和与所述内管(202)连接的推动柄(203)；所述光纤(8)安装于所述内管(202)，且所述光纤(8)涂抹固相微萃取涂层的一端延伸至所述内管(202)外；所述推动柄(203)推动所述内管(202)在所述外管(201)内滑动。
  7. 根据权利要求6所述的一种激光离子化的固相微萃取-飞行时间质谱联用的系统，其特征在于，所述推动柄(203)与所述样品前处理平台(1)的机械臂连接。
  8. 根据权利要求7所述的一种激光离子化的固相微萃取-飞行时间质谱联用的系统，其特征在于，所述外管(201)连接有滑动筒(204)，所述推动柄(203)与所述滑动筒(204)滑动连接。
  9. 根据权利要求8所述的一种激光离子化的固相微萃取-飞行时间质谱联用的系统，其特征在于，所述推动柄(203)设置有连通至所述内管(202)的引导槽(205)，所述光纤(8)穿过所述引导槽(205)延伸至所述内管(202)的内腔。
  10. 根据权利要求6所述的一种激光离子化的固相微萃取-飞行时间质谱联用的系统，其特征在于，所述外管(201)远离所述推动柄(203)的一端为锥形的尖头(206)。
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