WO2021139412A1 - 一种采样系统、质谱分析装置、采样方法和质谱分析方法 - Google Patents

一种采样系统、质谱分析装置、采样方法和质谱分析方法 Download PDF

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Publication number
WO2021139412A1
WO2021139412A1 PCT/CN2020/129555 CN2020129555W WO2021139412A1 WO 2021139412 A1 WO2021139412 A1 WO 2021139412A1 CN 2020129555 W CN2020129555 W CN 2020129555W WO 2021139412 A1 WO2021139412 A1 WO 2021139412A1
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WIPO (PCT)
Prior art keywords
sampling
flow channel
sampled
extractant
mass spectrometry
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PCT/CN2020/129555
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English (en)
French (fr)
Inventor
邓卡
罗茜
潘挺睿
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中国科学院深圳先进技术研究院
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Publication of WO2021139412A1 publication Critical patent/WO2021139412A1/zh

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    • 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
    • H01J49/0431—Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locks; Arrangements for external adjustment of electron- or ion-optical components for liquid samples
    • 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
    • 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

Definitions

  • the invention relates to the technical field of lipidomics, and more specifically, to a sampling system, a mass spectrometry analysis device, a sampling method, and a mass spectrometry analysis method.
  • sampling and analysis involve complicated operations such as freezing and sectioning, which are time-consuming and cannot be used for intraoperative or online analysis.
  • mass spectrometry analysis of the tissue surface material samples in vitro to obtain the metabolic molecular characteristics of the tumor tissue, and the freezing and cutting of the tissue in vitro will cause the cells to fold and break, resulting in the loss of some key compound information and the interference of intracellular spillage. Compound increase.
  • the technical problem to be solved by the present invention is how to improve sampling quality and sampling efficiency.
  • the present invention provides a sampling system, a mass spectrometry device, a sampling method, and a mass spectrometry method.
  • sampling system includes:
  • a sampling head the sampling head includes a sampling body, a sampling cavity, a first flow channel, a second flow channel, and a third flow channel; the sampling cavity is arranged on the first end surface of the sampling body, and the sampling cavity A sampling area is formed with the surface to be sampled; the first interface of the first flow channel, the first interface of the second flow channel, and the first interface of the third flow channel are located on the second end surface of the sampling body; The first flow channel is used to introduce the injected extractant into the sampling cavity; the second flow channel is used to introduce injected air into the sampling cavity; the third flow channel is used to introduce the sampling cavity The sampling droplets of the cavity are exported;
  • a translational positioning mechanism the translational positioning mechanism is used to drive the clamp to align with the sampled surface
  • An extractant injection mechanism communicates with the first flow channel through a first capillary path, and is used for injecting an extractant into the first flow channel;
  • a droplet transfer and transportation mechanism communicates with the second flow channel through a second capillary path, and is used to inject air into the second flow path; the droplet transfer and transportation mechanism communicates with the second flow path through the third capillary path
  • the third flow channel is in communication, and is used to lead out the sample droplets in the third flow channel;
  • a memory and a controller wherein computer-readable program codes are stored in the memory, and the controller is used to execute the computer-readable program codes to control the sampling system to realize:
  • the extractant injection mechanism injects the extractant into the first flow path
  • the droplet transfer and transportation mechanism injects air into the second flow channel at a first preset time interval, and the sampling droplets are derived from the third flow channel;
  • the translation positioning mechanism drives the clamp to move so that the sampling head is separated from the surface to be sampled.
  • the translation positioning mechanism includes a first adjustment mechanism that drives the clamp to move in a first direction; and a second adjustment mechanism that drives the clamp to move in a second direction.
  • the direction and the second direction are perpendicular to each other.
  • the translation positioning mechanism further includes a third adjustment mechanism that drives the clamp to move in a third direction, and the first direction is perpendicular to the first direction and the second direction.
  • the extractant injection mechanism is a syringe pump.
  • the droplet transfer and transportation mechanism includes a first peristaltic pump and a second peristaltic pump, wherein the first peristaltic pump communicates with the second flow channel through a second capillary tube, and the The second peristaltic pump communicates with the third flow channel through a third capillary tube.
  • the sampling body has a rectangular parallelepiped structure, one of the two opposite sides of the sampling body is provided with a tenon, and the opposite side of the other side is provided with a size matching the tenon. Mao slot.
  • the second interface of the first flow channel and the second interface of the second flow channel are located at the top of the sampling cavity.
  • the second interface of the third flow channel is close to the bottom of the sampling cavity.
  • the invention also discloses a mass spectrometry analysis device, comprising a mass spectrometer and the sampling system as described in any one of the above, and the mass spectrometer is used for performing mass spectrometry analysis on the sampled droplets.
  • the present invention also discloses a sampling method, applying the sampling system as described in any one of the above, and the sampling method includes:
  • the extractant injection mechanism injects the extractant into the first flow path
  • the droplet transfer and transportation mechanism injects air into the second flow channel at a first preset time interval, and the sampling droplets are derived from the third flow channel;
  • the translation positioning mechanism drives the clamp to move so that the sampling head is separated from the surface to be sampled.
  • the invention also discloses a mass spectrometry analysis method, including the sampling method as described above; and performing mass spectrometry analysis on the sampled droplets.
  • the controller determines the position of the surface to be sampled and controls the translation positioning mechanism to adjust the position of the clamp until the first end surface of the sampling head is in contact with the surface to be sampled.
  • the sampling surfaces are in contact;
  • the extractant injection mechanism injects the extractant into the first flow channel;
  • the droplet transfer and transport mechanism injects air into the second flow channel at a first preset time interval, and the sampling droplets are derived from the third flow channel ;
  • Interval for a second preset time the translation positioning mechanism drives the movement of the clamp so that the sampling head is separated from the surface to be sampled.
  • sampling head in the present invention directly contacts the sampled surface, automatic sampling can be realized without being separated from the body, thereby improving the sampling efficiency.
  • the droplet extraction method will not cause damage to the sampled surface.
  • the sampling cavity is close to the sampled surface, which increases the concentration of sampled droplets and reduces the possibility of loss of key compound information, thereby improving the quality of sampling.
  • Fig. 1 is a schematic structural diagram of a sampling system provided by an embodiment of the present invention
  • Figure 2 is a schematic structural diagram of a translational positioning mechanism provided by an embodiment of the present invention.
  • FIG. 3 is a schematic diagram of a three-dimensional structure of a sampling head provided by an embodiment of the present invention.
  • FIG. 4 is a schematic diagram of a top view structure of a sampling head provided by an embodiment of the present invention.
  • FIG. 5 is a schematic diagram of the bottom structure of a sampling head provided by an embodiment of the present invention.
  • Figure 6 is a bottom perspective structural schematic diagram of a sampling head provided by an embodiment of the present invention.
  • FIG. 7 is a schematic diagram of a three-dimensional structure of a sampling head after splicing provided by an embodiment of the present invention.
  • FIG. 8 is a schematic top view of the spliced top structure of a sampling head provided by an embodiment of the present invention.
  • FIG. 9 is a schematic flowchart of a sampling method provided by an embodiment of the present invention.
  • FIG. 10 is a schematic flowchart of a sampling method provided by an embodiment of the present invention.
  • FIG. 11 is a schematic flowchart of a mass spectrometry analysis method provided by an embodiment of the present invention.
  • 100 is the sampling head
  • 101 is the first end face
  • 102 is the second end face
  • 103 is the sampling cavity
  • 104 is the first flow channel
  • 104-1 is the first interface of the first flow channel
  • 104-2 is the first flow
  • 105 is the second runner
  • 105-1 is the first interface of the second runner
  • 105-2 is the second interface of the second runner
  • 106 is the third runner
  • 106-1 is The first interface of the third runner
  • 106-2 is the second interface of the third runner
  • 107-1 is the first tenon
  • 107-2 is the first groove
  • 108-1 is the second tenon
  • 108-2 Is the second slot
  • 200 is the clamp
  • 300 is the translation positioning mechanism
  • 301-1 is the first moving end
  • 301-2 is the first fixed end
  • 301-3 is the first drive mechanism
  • 302-1 is the second move End
  • 302-2 is the second fixed end
  • 302-3 is the second drive mechanism
  • Mass spectrometry A method in which electric and magnetic fields are used to separate the moving ions according to their mass-to-charge ratios and then detect them.
  • the mass-to-charge ratio can identify substances.
  • Mass spectrometry imaging is an imaging method based on mass spectrometry technology. This method directly scans biological samples through mass spectrometry and can simultaneously analyze the spatial distribution characteristics of hundreds of molecules on the same tissue slice or tissue chip. To put it simply, mass spectrometry imaging technology is a method of imaging using a mass spectrometer that measures the mass-to-charge ratio to analyze the standard molecular weight of biomolecules under the control of a dedicated mass spectrometry imaging software.
  • Extraction Use an extractant to extract the substance.
  • Flow path The passage of fluid (gas/liquid) in the component.
  • the core of the present invention is to provide a sampling system, mass spectrometry analysis device, sampling method and mass spectrometry analysis method to improve sampling quality and sampling efficiency.
  • the sampling system in the embodiment of the present invention includes:
  • the sampling head 100 includes a sampling body, a sampling cavity 103, a first flow channel 104, a second flow channel 105 and a third flow channel 106; the sampling cavity 13 is arranged on the first end surface 101 of the sampling body, and the sampling cavity is connected to The sampled surface forms a sampling area; the first interface 104-1 of the first flow channel, the first interface 105-1 of the second flow channel, and the first interface 106-1 of the third flow channel are located on the second end surface 102 of the sampling body;
  • the first flow channel 104 is used to introduce the injected extractant into the sampling cavity 103;
  • the second flow channel 105 is used to introduce the injected air into the sampling cavity 103;
  • the third flow channel 16 is used to sample the sampling cavity 103 Droplet export;
  • a translational positioning mechanism 300 which is used to drive the clamp 200 to align with the sampled surface
  • An extractant injection mechanism 400 communicates with the first flow channel 104 through the first capillary path, and is used to inject the extractant into the first flow channel 104;
  • the droplet transfer and transportation mechanism 500 communicates with the second flow channel 105 through the second capillary path, and is used to inject air into the second flow path 105; the droplet transfer and transportation mechanism 500 communicates with the second flow path 105 through the third capillary path.
  • the third flow channel 106 is in communication and is used to lead out the sample droplets in the third flow channel 106;
  • the memory and the controller stores computer readable program code, and the controller is used to execute the computer readable program code to control the sampling system to realize:
  • the extractant injection mechanism 400 injects the extractant into the first flow path
  • the droplet transfer and transportation mechanism 500 injects air into the second flow channel at a first preset time interval, and the sampling droplets are derived from the third flow channel;
  • the translation positioning mechanism 300 drives the clamp 200 to move at a second preset time interval so that the sampling head is separated from the surface to be sampled.
  • the controller determines the position of the sampled surface and controls the translation positioning mechanism 300 to adjust the position of the clamp 200 until the first end surface 101 of the sampling head contacts the sampled surface; the extractant injection mechanism 400 is directed to the first flow path 104 Inject the extractant; the droplet transfer transport mechanism 500 injects air into the second flow channel 105 at a first preset time interval, and the sampling droplets are derived from the third flow channel 106; at a second preset time interval, the translation positioning mechanism 300 drives the clamp
  • the 200 movement makes the sampling head separate from the surface being sampled. Since the sampling head in the present invention directly contacts the sampled surface, automatic sampling can be realized without being separated from the body, thereby improving the sampling efficiency. At the same time, the droplet extraction method will not cause damage to the sampled surface.
  • the sampling cavity is close to the sampled surface, which increases the concentration of sampled droplets and reduces the possibility of loss of key compound information, thereby improving the quality of sampling.
  • the function of the translational positioning mechanism 300 of the present invention is to realize the position adjustment of the sampling head.
  • the translational positioning mechanism 300 drives the sampling head to move in the direction of testing the surface to be sampled. Complete contact with the sampled surface.
  • the translation positioning mechanism 300 includes a first adjustment mechanism that drives the clamp 200 to move in a first direction; and a second adjustment mechanism that drives the clamp 200 to move in a second direction. Perpendicular to each other. One of the first direction and the second direction coincides with the direction in which the sampling head approaches the sampled surface.
  • the first adjustment mechanism includes a first moving end 301-1, a first fixed end 301-2, and a first driving mechanism 301-3.
  • the clamp 200 is set at the first moving end 301-1, and the first moving end 301- 1Slidably arranged at the first fixed end 301-2, the first moving end 301-1 can be driven by the first driving mechanism 301-3 relative to the first fixed end 301-2 to reciprocate linearly in the first direction
  • the second adjustment mechanism includes a second moving end 302-1, a second fixed end 302-2 and a second driving mechanism 302-3, wherein the first fixed end 301-2 is set at the second moving end 302-1, The second moving end 302-1 is slidably disposed on the second fixed end 302-2, and the second moving end 302-1 can be driven by the second driving mechanism 302-3 relative to the second fixed end 302-2 along the first Reciprocating linear motion in two directions.
  • the translation positioning mechanism 300 further includes a third adjustment mechanism that drives the clamp 200 to move in a third direction, and the first direction is perpendicular to the first direction and the second direction.
  • the third adjustment mechanism includes a third moving end 303-1, a third fixed end 303-2, and a third driving mechanism 303-3, wherein the third fixed end 303-2 is disposed at the third moving end 303-1 , The third moving end 303-1 is slidably arranged on the third fixed end 303-2, and the third moving end 303-1 can be driven by the third driving mechanism 303-3 relative to the third fixed end 303-2. Reciprocating linear motion in the third direction.
  • the first fixed end 301-2, the second fixed end 302-2, and the third fixed end 303-2 are matched by a screw nut to convert the rotation movement of the corresponding drive mechanism into the first moving end 301-1, The reciprocating linear movement of the second mobile end 302-1 and the third mobile end 303-1.
  • the function of the extractant injection mechanism 400 is to inject the extractant into the first flow channel, where the extractant is a syringe pump.
  • the controller controls the amount of extractant in the first flow channel by controlling the operation of the stepping motor of the syringe pump.
  • the droplet transfer and transportation mechanism 500 has two functions. The first is to inject air into the second flow channel, and the second is to transport the sample droplets derived from the third flow channel to subsequent equipment.
  • the droplet transfer and transportation mechanism 500 includes a first peristaltic pump and a second peristaltic pump, wherein the first peristaltic pump communicates with the second flow channel through the second capillary tube, and the second peristaltic pump communicates with the third flow channel through the third capillary tube.
  • the sampling body has a rectangular parallelepiped structure.
  • One of the two opposite sides of the sampling body is provided with a tenon, and the opposite side of the other side is provided with a groove with a size matching the tenon.
  • Multiple sampling heads are spliced by grooves and tenons to form an array, so that a sampling array with accurate spatial distribution structure can be obtained simply, instead of relying on translational sampling heads for repeated spatial positioning, which can help subsequent equipment to efficiently obtain material distribution space Information is especially suitable for dynamic or time-sensitive samples.
  • the sampling body is a solid structure to form the supporting body of the first flow channel 104, the second flow channel 105, the third flow channel 106, and the sampling cavity 103. It can be made of resin, plastic or glass. It is processed by printing technology. When 3D printing technology is used, UV curing 3D printing technology is especially used for processing.
  • the first port 104-1 of the first flow channel is used for the external pipeline for injecting the extractant
  • the first port 105-1 of the second flow channel is used for the external pipeline to inject the positive pressure gas source
  • the third flow channel is used for injecting the positive pressure gas source.
  • An interface 106-1 is used to connect a pipeline to form a negative pressure outlet to export sample droplets.
  • the second interface 104-2 of the first flow channel is in communication with the sampling cavity
  • the second interface 105-2 of the second flow channel is in communication with the sampling cavity
  • the second interface 106-2 of the third flow channel is in communication with the sampling cavity.
  • the cross sections of the first flow channel 104, the second flow channel 105, and the third flow channel 106 are circular, elliptical, fan-shaped, and so on.
  • the second interface 104-2 of the first flow channel and the second interface of the second flow channel 105-2 is located at the top of the sampling cavity 103. Therefore, when the extraction agent needs to be injected, the extraction agent is gradually injected downward from the top of the sampling cavity 103 through the second interface 104-2 of the first flow channel.
  • the positive pressure gas source is gradually flushed from the top of the sampling cavity 103 from the second port 105-2 of the second flow path, thereby squeezing the sampling liquid droplets in the sampling cavity 103 into the second port of the third flow path 106-2.
  • the detection rate of subsequent detection can be improved.
  • the third stream The second interface 106-2 of the channel is close to the bottom of the sampling cavity 103.
  • the sampling cavity 103 has a cylindrical structure or a hemispherical structure.
  • the sampling cavity 103 has a semi-open structure and directly contacts the sampled surface, and the second interface 106-2 of the third flow channel is closer to the sampled surface, which improves the sampling liquid.
  • the concentration of drops which can reduce the loss of key compound information.
  • the area of the sampling cavity 103 in direct contact with the surface to be sampled can reach the order of millimeters or even hundreds of microns, and the smaller the sampling area of the sampling head, the higher the spatial resolution.
  • the above-mentioned tenon and groove are arranged on a set of opposite sides, so that the sampling head can be spliced in a one-dimensional direction. Or, the above-mentioned tenon and groove are arranged on two sets of opposite sides, so as to realize two-dimensional splicing.
  • the tenon may be one or more, and for the side provided with a groove, the groove may be one or more, whether it is one or more, relatively
  • the size and position of the tenon and the groove on the side of the machine correspond to each other.
  • multiple sampling heads can be spliced together by grooves and tenons.
  • the tenon includes the first tenon 107-1 and the second tenon 108-1.
  • the socket includes the first socket 107-2 and the second socket.
  • the size of the first groove 107-2 is matched with the first tenon 107-1
  • the size of the second groove 108-2 is matched with the second tenon 108-1.
  • the two opposite sides of the four sides are a group, one of the two opposite sides of a group is provided with a tenon, and the other side is provided with a groove; the other is one of the two opposite sides A tenon is provided, and a groove is provided on the other side.
  • the first tenon 107-1 is arranged on one side of a group of two opposite sides of the sampling body, and the first groove 107-2 is arranged on the other side of the group of two opposite sides;
  • the two tenons 108-1 are arranged on one side of the other set of opposite sides of the sampling body, and the second groove 108-2 is arranged on the other side of the set of two opposite sides.
  • the first groove 107-2 and the first tenon 107-1 are positioned opposite each other. Specifically, it can be understood as: on a set of two opposite sides, the connecting surface of the first groove 107-2 and the first tenon 107-1 is opposite to each other.
  • the other group of the sampling body is parallel to the two sides. This arrangement can ensure that the first tenon 107-1 of the current sampling head can be spliced with the first groove 107-2 at the corresponding position of the adjacent sampling head. All sampling heads are the same size.
  • the center line of the first groove 107-2 and the center line of the first tenon 107-1 are coplanar with the center line of the sampling body. This arrangement can ensure that the sampling head can be centered during the splicing process on the side where the first tenon 107-1 and the first groove 107-2 are arranged.
  • the second groove 108-2 and the second tenon 108-1 are positioned opposite each other, which can be specifically understood as: on a set of two opposite sides, the connecting surface of the second groove 108-2 and the second tenon 108-1 is opposite to that of the second tenon 108-1.
  • the other group of the sampling body is parallel to the two sides.
  • Such a setting can ensure that the second tenon 108-1 of the current sampling head can be spliced with the second groove 108-2 at the corresponding position of the adjacent sampling head. All sampling heads are the same size.
  • the center line of the second groove 108-2 and the center line of the second tenon 108-1 are coplanar with the center line of the sampling body. This arrangement can ensure that the sampling head can be centered during the splicing process on the side surface where the second tenon 108-1 and the second groove 108-2 are provided.
  • the invention also discloses a mass spectrometry analysis device, which includes the above-mentioned sampling system. Since the above-mentioned sampling system has the above beneficial effects, the mass spectrometry analysis device including the sampling system also has corresponding effects, which will not be repeated here.
  • the present invention also discloses a sampling method, applying any one of the above sampling systems, the sampling method includes:
  • Step S1 Determine the position of the sampled surface and control the translation positioning mechanism to adjust the position of the clamp until the first end surface of the sampling head is in contact with the sampled surface;
  • Step S2 The extraction agent injection mechanism injects the extraction agent into the first flow path
  • Step S3 The droplet transfer and transportation mechanism injects air into the second flow channel at intervals of a first preset time, and the sampling droplets are derived from the third flow channel;
  • Step S4 at a second preset time interval, the translation positioning mechanism drives the fixture to move so that the sampling head is separated from the surface to be sampled
  • the present invention also discloses a mass spectrometry analysis method, which applies any one of the above sampling systems, and the mass spectrometry analysis method includes:
  • Step S1 Determine the position of the sampled surface and control the translation positioning mechanism to adjust the position of the clamp until the first end surface of the sampling head is in contact with the sampled surface;
  • Step S2 The extraction agent injection mechanism injects the extraction agent into the first flow path
  • Step S3 The droplet transfer and transportation mechanism injects air into the second flow channel at intervals of a first preset time, and the sampling droplets are derived from the third flow channel;
  • Step S4 The translation positioning mechanism drives the clamp to move at a second preset time interval so that the sampling head is separated from the surface to be sampled;
  • Step S5 Perform mass spectrometry analysis on the sample droplets.
  • the sampling head in the present invention directly contacts the sampled surface, automatic sampling can be realized without being separated from the body, thereby improving the sampling efficiency.
  • the droplet extraction method will not cause damage to the sampled surface.
  • the sampling cavity is close to the sampled surface, which increases the concentration of sampled droplets and reduces the possibility of loss of key compound information, thereby improving the quality of sampling.
  • the results of mass spectrometry analysis are not only related to the substance information carried by the sampled droplets, but also related to the correspondence between the substance information and the spatial distribution. Therefore, with the mass spectrometry analysis method of the present invention, the translational positioning mechanism moves in multiple directions, and the sampling heads can form an array containing positioning information, thereby improving the spatial distribution efficiency.
  • connection should be understood in a broad sense.
  • it can be a fixed connection, a detachable connection, or an integral connection; it can be a mechanical connection, It can also be an electrical connection; it can be directly connected, or indirectly connected through an intermediate medium, and it can be the internal communication between two components.
  • connection should be understood in a broad sense.
  • it can be a fixed connection, a detachable connection, or an integral connection; it can be a mechanical connection, It can also be an electrical connection; it can be directly connected, or indirectly connected through an intermediate medium, and it can be the internal communication between two components.

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Abstract

一种采样系统、质谱分析装置、采样方法和质谱分析方法，使用所述的采样系统，控制器确定被采样表面的位置控制平移定位机构（300）调整夹具（200）的位置直至采样头（100）的第一端面与被采样表面相接触；萃取剂注入机构（400）向第一流道（104）注入萃取剂；间隔第一预设时间液滴转移运输机构（500）向第二流道（105）注入空气，并由第三流道（106）导出采样液滴；间隔第二预设时间平移定位机构（300）带动夹具（200）运动使得采样头（100）脱离被采样表面。由于所述的采样头（100）直接与被采样表面接触，无需离体就能够实现自动采样从而提高了采样效率。同时，采用液滴萃取的方式，不会对被采样表面造成创伤，采样空腔（103）贴近被采样表面，提高了采样液滴浓度，减少关键化合物信息丢失的可能，从而提高了采样质量。

Description

一种采样系统、质谱分析装置、采样方法和质谱分析方法 技术领域
本发明涉及脂质组学技术领域，更具体地说，涉及一种采样系统、质谱分析装置、采样方法和质谱分析方法。
 背景技术
随着质谱技术的发展，脂质组学在肿瘤生物标志物的识别、疾病诊断、药物靶点及先导化合物的发现和药物作用机制研究等方面已展现出广泛的应用前景。
传统的离体组织冷冻切片式的分析方式，采样与分析由于涉及到冷冻、切片等操作操作复杂，耗时长，无法用于术中或在线分析。且通过切片等离体的组织表面物质样本进行质谱分析以得到肿瘤组织的代谢分子特性，而离体的组织冰冻和切割会造成细胞折叠和破碎，使得部分关键化合物信息丢失和细胞内溢出的干扰化合物增多。
因此，如何提高采样质量和采样效率，是目前本领域技术人员亟待解决的问题。
 技术问题
有鉴于此，本发明所要解决的技术问题是如何提高采样质量和采样效率，为此，本发明提供了一种采样系统、质谱分析装置、采样方法和质谱分析方法。
 技术解决方案
为实现上述目的，本发明提供如下技术方案：
一种采样系统，所述采样系统包括：
采样头，所述采样头包括采样本体、采样空腔、第一流道、第二流道和第三流道；所述采样空腔设置在所述采样本体的第一端面，所述采样空腔与被采样表面形成采样区域；所述第一流道的第一接口、所述第二流道的第一接口和所述第三流道的第一接口位于所述采样本体的第二端面；所述第一流道用于将注入的萃取剂引入至所述采样空腔中；第二流道用于将注入空气引入至所述采样空腔；所述第三流道用于将所述采样空腔的采样液滴导出；
夹持采样头的夹具；
平移定位机构，所述平移定位机构用于带动所述夹具与所述被采样表面对齐；
萃取剂注入机构，所述萃取剂注入机构通过第一毛细管路与所述第一流道连通，用于向所述第一流道内注入萃取剂；
液滴转移运输机构，所述液滴转移运输机构通过第二毛细管路与所述第二流道连通，用于向第二流道内注入空气；所述液滴转移运输机构通过第三毛细管路与所述第三流道连通，用于将所述第三流道内的采样液滴导出；
存储器和控制器，所述存储器内存储有计算机可读程序代码，所述控制器用以执行所述计算机可读程序代码以控制采样系统实现：
确定被采样表面的位置控制所述平移定位机构调整所述夹具的位置直至所述采样头的第一端面与所述被采样表面相接触；
所述萃取剂注入机构向第一流道注入萃取剂；
间隔第一预设时间所述液滴转移运输机构向第二流道注入空气，并由第三流道导出采样液滴；
间隔第二预设时间所述平移定位机构带动所述夹具运动使得所述采样头脱离被采样表面。
在本发明其中一个实施例中，所述平移定位机构包括带动所述夹具在第一方向移动的第一调整机构；和带动所述夹具在第二方向移动的第二调整机构，所述第一方向和所述第二方向相互垂直。
在本发明其中一个实施例中，所述平移定位机构还包括带动所述夹具在第三方向移动的第三调整机构，所述第一方向与所述第一方向和所述第二方向均垂直。
在本发明其中一个实施例中，所述萃取剂注入机构为注射泵。
在本发明其中一个实施例中，所述液滴转移运输机构包括第一蠕动泵和第二蠕动泵，其中，所述第一蠕动泵通过第二毛细管与所述第二流道连通，所述第二蠕动泵通过第三毛细管与所述第三流道连通。
在本发明其中一个实施例中，所述采样本体呈长方体结构，所述采样本体相对的两个侧面中的一个侧面设置有榫头，另外一个侧面相对的位置设置有尺寸与所述榫头相配合的卯槽。
在本发明其中一个实施例中，所述第一流道的第二接口和所述第二流道的第二接口位于所述采样空腔的顶部。
在本发明其中一个实施例中，所述第三流道的第二接口靠近所述采样空腔的底部。
本发明还公开了一种质谱分析装置，包括质谱分析仪和如上述中任一项所述的采样系统，所述质谱分析仪用于对采样液滴进行质谱分析。
本发明还公开了一种采样方法，应用如上述中任一项所述的采样系统，该采样方法包括：
确定被采样表面的位置控制所述平移定位机构调整所述夹具的位置直至所述采样头的第一端面与所述被采样表面相接触；
所述萃取剂注入机构向第一流道注入萃取剂；
间隔第一预设时间所述液滴转移运输机构向第二流道注入空气，并由第三流道导出采样液滴；
间隔第二预设时间所述平移定位机构带动所述夹具运动使得所述采样头脱离被采样表面。
本发明还公开了一种质谱分析方法，包括如上述所述的采样方法；和对采样液滴进行质谱分析。
 有益效果
从上述的技术方案可以看出，使用本发明中的采样系统，控制器确定被采样表面的位置控制所述平移定位机构调整所述夹具的位置直至所述采样头的第一端面与所述被采样表面相接触；所述萃取剂注入机构向第一流道注入萃取剂；间隔第一预设时间所述液滴转移运输机构向第二流道注入空气，并由第三流道导出采样液滴；间隔第二预设时间所述平移定位机构带动所述夹具运动使得所述采样头脱离被采样表面。由于本发明中的采样头直接与被采样表面接触，无需离体就能够实现自动采样从而提高了采样效率。同时，采用液滴萃取的方式，不会对被采样表面造成创伤，采样空腔贴近被采样表面，提高了采样液滴浓度，减少关键化合物信息丢失的可能，从而提高了采样质量。
 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获得其他的附图。
图1为本发明实施例所提供的一种采样系统的结构示意图；
图2为本发明实施例所提供的一种平移定位机构的结构示意图
图3为本发明实施例所提供的一种采样头的立体结构示意图；
图4为本发明实施例所提供的一种采样头的俯视结构示意图；
图5为本发明实施例所提供的一种采样头的仰视结构示意图；
图6为本发明实施例所提供的一种采样头的仰视透视结构示意图；
图7为本发明实施例所提供的一种采样头拼接后的立体结构示意图；
图8为本发明实施例所提供的一种采样头拼接后的俯视结构示意图；
图9为本发明实施例所提供的一种采样方法的流程示意图；
图10为本发明实施例所提供的一种采样方法的流程示意图；
图11为本发明实施例所提供的一种质谱分析方法的流程示意图。
图中，100为采样头、101为第一端面、102为第二端面、103为采样空腔、104为第一流道、104-1为第一流道的第一接口、104-2为第一流道的第二接口、105为第二流道、105-1为第二流道的第一接口、105-2为第二流道的第二接口、106为第三流道、106-1为第三流道的第一接口、106-2为第三流道的第二接口、107-1为第一榫头、107-2为第一卯槽、108-1为第二榫头、108-2为第二卯槽、200为夹具、300为平移定位机构、301-1为第一移动端、301-2为第一固定端、301-3为第一驱动机构、302-1为第二移动端、302-2为第二固定端、302-3为第二驱动机构、303-1为第三移动端、303-2为第三固定端、303-3为第三驱动机构、400为萃取剂注入机构、500为液滴转移运输机构。
 本发明的实施方式
术语解释：
质谱分析：用电场和磁场将运动的离子按它们的质荷比分离后进行检测的方法，可以通过质荷比辨识物质。
质谱成像技术：质谱成像是以质谱技术为基础的成像方法，该方法通过质谱直接扫描生物样品成像，可以在同一张组织切片或组织芯片上同时分析数百种分子的空间分布特征。简单而言，质谱成像技术就是借助于质谱的方法，再配套上专门的质谱成像软件控制下，使用一台通过测定质荷比来分析生物分子的标准分子量的质谱仪来成像的方法。
萃取：使用萃取剂提取物质。
表面采样：从被采样表面提取物质样本。
在体：不采用离体切片方式，直接在被采样表面操作。
流道：流体（气/液）在元件内的通路。
本发明的核心在于提供一种采样系统、质谱分析装置、采样方法和质谱分析方法，以提高采样质量和采样效率。
此外，下面所示的实施例不对权利要求所记载的发明内容起任何限定作用。另外，下面实施例所表示的构成的全部内容不限于作为权利要求所记载的发明的解决方案所必需的。
为此，请参阅图1至图8，本发明实施例中的采样系统，包括：
采样头100，采样头包括采样本体、采样空腔103、第一流道104、第二流道105和第三流道106；采样空腔13设置在采样本体的第一端面101，采样空腔与被采样表面形成采样区域；第一流道的第一接口104-1、第二流道的第一接口105-1和第三流道的第一接口106-1位于采样本体的第二端面102；第一流道104用于将注入的萃取剂引入至采样空腔103中；第二流道105用于将注入空气引入至采样空腔103；第三流道16用于将采样空腔103的采样液滴导出；
夹持采样头的夹具200；
平移定位机构300，平移定位机构300用于带动夹具200与被采样表面对齐；
萃取剂注入机构400，萃取剂注入机构400通过第一毛细管路与第一流道104连通，用于向第一流道104内注入萃取剂；
液滴转移运输机构500，液滴转移运输机构500通过第二毛细管路与第二流道105连通，用于向第二流道105内注入空气；液滴转移运输机构500通过第三毛细管路与第三流道106连通，用于将第三流道106内的采样液滴导出；
存储器和控制器，存储器内存储有计算机可读程序代码，控制器用以执行计算机可读程序代码以控制采样系统实现：
确定被采样表面的位置控制平移定位机构300调整夹具200的位置直至采样头的第一端面与被采样表面相接触；
萃取剂注入机构400向第一流道注入萃取剂；
间隔第一预设时间液滴转移运输机构500向第二流道注入空气，并由第三流道导出采样液滴；
间隔第二预设时间平移定位机构300带动夹具200运动使得采样头脱离被采样表面。
使用本发明中的采样系统，控制器确定被采样表面的位置控制平移定位机构300调整夹具200的位置直至采样头的第一端面101与被采样表面相接触；萃取剂注入机构400向第一流道104注入萃取剂；间隔第一预设时间液滴转移运输机构500向第二流道105注入空气，并由第三流道106导出采样液滴；间隔第二预设时间平移定位机构300带动夹具200运动使得采样头脱离被采样表面。由于本发明中的采样头直接与被采样表面接触，无需离体就能够实现自动采样从而提高了采样效率。同时，采用液滴萃取的方式，不会对被采样表面造成创伤，采样空腔贴近被采样表面，提高了采样液滴浓度，减少关键化合物信息丢失的可能，从而提高了采样质量。
请参阅图2本发明的平移定位机构300的作用是，实现采样头的位置调整，当采样头与被采样表面对齐时，平移定位机构300带动采样头向考经被采样表面的方向移动，直至与被采样表面完全接触。在本发明其中一个实施例中，平移定位机构300包括带动夹具200在第一方向移动的第一调整机构；和带动夹具200在第二方向移动的第二调整机构，第一方向和第二方向相互垂直。第一方向和第二方向二者中的其中一个方向与采样头靠近被采样表面的方向重合。第一调整机构包括第一移动端301-1、第一固定端301-2和第一驱动机构301-3，其中，夹具200设置在的第一移动端301-1，第一移动端301-1可滑动的设置在第一固定端301-2，第一移动端301-1能够在第一驱动机构301-3的驱动下相对于第一固定端301-2沿第一方向进行往复直线运动；第二调整机构包括第二移动端302-1、第二固定端302-2和第二驱动机构302-3，其中，第一固定端301-2设置在的第二移动端302-1，第二移动端302-1可滑动的设置在第二固定端302-2，第二移动端302-1能够在第二驱动机构302-3的驱动下相对于第二固定端302-2沿第二方向进行往复直线运动。
为了提高平移定位机构300的调节范围，平移定位机构300还包括带动夹具200在第三方向移动的第三调整机构，第一方向与第一方向和第二方向均垂直。其中，第三调整机构包括第三移动端303-1、第三固定端303-2和第三驱动机构303-3，其中，第三固定端303-2设置在的第三移动端303-1，第三移动端303-1可滑动的设置在第三固定端303-2，第三移动端303-1能够在第三驱动机构303-3的驱动下相对于第三固定端303-2沿第三方向进行往复直线运动。
上述第一固定端301-2、第二固定端302-2和第三固定端303-2上通过丝杠螺母进行配合，将对应的驱动机构的旋转运动转换为第一移动端301-1、第二移动端302-1和第三移动端303-1的往复直线运动。
萃取剂注入机构400的作用是向第一流道中注入萃取剂，其中，该萃取剂为注射泵。控制器通过控制注射泵的步进电机的运行控制第一流道中萃取剂的量。
而液滴转移运输机构500有两个作用，第一向第二流道注入空气，第二，将第三流道导出的采样液滴输送到后续设备。液滴转移运输机构500包括第一蠕动泵和第二蠕动泵，其中，第一蠕动泵通过第二毛细管与第二流道连通，第二蠕动泵通过第三毛细管与第三流道连通。
为了提高采样的精度，本发明中，采样本体呈长方体结构，采样本体相对的两个侧面中的一个侧面设置有榫头，另外一个侧面相对的位置设置有尺寸与榫头相配合的卯槽。多个采样头通过卯槽和榫头拼接后成为阵列，如此可以简单地获得具有准确空间分布结构的采样阵列，而不必依赖平移采样头反复进行空间定位，可以帮助后续设备高效地获得物质分布的空间信息，对于具有动态或时间敏感的样本尤为适用。
本发明中采样本体为实体结构以形成第一流道104、第二流道105、第三流道106和采样空腔103的支撑主体，其可以为树脂、塑料或者玻璃材质，通过注塑工艺、3D打印技术加工而成，当采用3D打印技术时，特别采用紫外光固化3D打印技术进行加工。
第一流道的第一接口104-1用于外接管路用于进行注入萃取剂，第二流道的第一接口105-1用于外接管路注入正压气源，第三流道的第一接口106-1用于外接管路形成负压出口导出采样液滴。第一流道的第二接口104-2与采样腔体连通，第二流道的第二接口105-2与采样腔体连通，第三流道的第二接口106-2与采样腔体连通。第一流道104、第二流道105、第三流道106的横截面为圆形、椭圆形、扇形等等结构。
其中，由于第一流道104和第二流道105分别注入萃取剂和空气，为了方便施压以及充满采样空腔103，第一流道的第二接口104-2和第二流道的第二接口105-2位于采样空腔103的顶部。因此，当需要注入萃取剂时，通过第一流道的第二接口104-2自采样空腔103的顶部逐渐向下注入萃取剂，当萃取剂充满且萃取剂与被采集表面的代谢物充分接触后，由第二流道的第二接口105-2自采样空腔103的顶部逐渐冲入正压气源，从而挤压采样空腔103中的采样液滴进入第三流道的第二接口106-2。为了使得高浓度的采样液滴首先进入第三流道的第二接口106-2中，提高采样液滴的浓度，从而能够提高后续检测的检测检出率，本发明实施例中，第三流道的第二接口106-2靠近采样空腔103的底部。
采样空腔103为圆柱结构或半球形结构，采样空腔103为半开口结构直接与被采样表面直接接触，且第三流道的第二接口106-2更加靠近被采集表面，提高了采样液滴的浓度，从而能够减少关键化合物信息丢失。且采样空腔103与被采样表面直接接触的面积能够达到毫米级甚至百微米级，而采样头采样的面积越小空间分辨率越高。
上述榫头和卯槽设置在一组相对的侧面上，从而使得采样头一维方向上进行拼接。或者，上述榫头和卯槽设置在两组相对的侧面上，从而实现二维方向的拼接。
本发明其中一个实施例中，针对设置有榫头的侧面，该榫头可以为一个或者多个，针对设置有卯槽的侧面，该卯槽可以为一个或者多个，不管是一个还是多个，相对的侧面的榫头和卯槽其尺寸以及位置均相对应。如此设置，多个采样头能够通过卯槽和榫头拼接在一起。当榫头的数量为两个时，榫头包括第一榫头107-1和第二榫头108-1，当卯槽的数量为两个时，卯槽包括第一卯槽107-2和第二卯槽108-2，第一卯槽107-2尺寸与第一榫头107-1相配合，第二卯槽108-2尺寸与第二榫头108-1相配合。
四个侧面中两两相对的侧面为一组，一组相对的两个侧面中的一个侧面设置有一个榫头，另外一个侧面设置有一个卯槽；另外一组相对的两个侧面中的一个侧面设置有一个榫头，另外一个侧面设置有一个卯槽。
具体的，第一榫头107-1设置在采样本体一组相对的两个侧面中的一个侧面上，第一卯槽107-2设置在该组相对的两个侧面中的另一个侧面上；第二榫头108-1设置在采样本体另一组相对的两个侧面中的一个侧面，第二卯槽108-2设置在该组相对的两个侧面中的另一个侧面上。
第一卯槽107-2和第一榫头107-1位置相对，具体可以理解为：在一组相对的两个侧面上，第一卯槽107-2和第一榫头107-1的连接面与采样本体的另外一组相对个两个侧面平行。如此设置能够保证当前采样头的第一榫头107-1能够与相邻的采样头对应位置的第一卯槽107-2相拼接。所有的采样头的尺寸均相同。优选的，第一卯槽107-2的中心线、第一榫头107-1的中心线与采样本体的中心线共面。如此设置能够保证在设置有第一榫头107-1和第一卯槽107-2的侧面上，采样头在拼接过程中能够对中。
第二卯槽108-2和第二榫头108-1位置相对，具体可以理解为：在一组相对的两个侧面上，第二卯槽108-2和第二榫头108-1的连接面与采样本体的另外一组相对个两个侧面平行。如此设置能够保证当前采样头的第二榫头108-1能够与相邻的采样头对应位置的第二卯槽108-2相拼接。所有的采样头的尺寸均相同。优选的，第二卯槽108-2的中心线、第二榫头108-1的中心线与采样本体的中心线共面。如此设置能够保证在设置有第二榫头108-1和第二卯槽108-2的侧面上，采样头在拼接过程中能够对中。
本发明还公开了一种质谱分析装置，包括上述的采样系统。由于上述采样系统具有以上有益效果，包括该采样系统的质谱分析装置也具有相应的效果，此处不再赘述。
请参阅图9和图10，本发明还公开了一种采样方法，应用上述中任一项的采样系统，该采样方法包括：
步骤S1：确定被采样表面的位置控制所述平移定位机构调整所述夹具的位置直至所述采样头的第一端面与所述被采样表面相接触；
步骤S2：所述萃取剂注入机构向第一流道注入萃取剂；
步骤S3：间隔第一预设时间所述液滴转移运输机构向第二流道注入空气，并由第三流道导出采样液滴；
步骤S4：间隔第二预设时间所述平移定位机构带动所述夹具运动使得所述采样头脱离被采样表面
请参阅图11，本发明还公开了一种质谱分析方法，应用上述中任一项的采样系统，该质谱分析方法包括：
步骤S1：确定被采样表面的位置控制所述平移定位机构调整所述夹具的位置直至所述采样头的第一端面与所述被采样表面相接触；
步骤S2：所述萃取剂注入机构向第一流道注入萃取剂；
步骤S3：间隔第一预设时间所述液滴转移运输机构向第二流道注入空气，并由第三流道导出采样液滴；
步骤S4：间隔第二预设时间所述平移定位机构带动所述夹具运动使得所述采样头脱离被采样表面；
步骤S5：对采样液滴进行质谱分析。
采用本发明中的质谱分析方法，由于采用上述采样方法，不仅实现了
由于本发明中的采样头直接与被采样表面接触，无需离体就能够实现自动采样从而提高了采样效率。同时，采用液滴萃取的方式，不会对被采样表面造成创伤，采样空腔贴近被采样表面，提高了采样液滴浓度，减少关键化合物信息丢失的可能，从而提高了采样质量。而质谱分析的结果，不仅与采样液滴的携带的物质信息相关，而且与该物质信息与空间分布对应关系相关。因此，采用本发明中的质谱分析方法，平移定位机构的在多个方向进行移动，且采样头能够组成陈列，包含定位信息，从而提高了空间分布效率。
在本申请的描述中，需要说明的是，术语“中心”、“上”、“下”、“左”、“右”、“竖直”、“水平”、“内”、“外”等指示的方位或位置关系为基于附图所示的方位或位置关系，仅是为了便于描述本申请和简化描述，而不是指示或暗示所指的装置或元件必须具有特定的方位、以特定的方位构造和操作，因此不能理解为对本申请的限制。此外，术语“第一”、“第二”、“第三”仅用于描述目的，而不能理解为指示或暗示相对重要性。
除非另有明确的规定和限定，术语“安装”、“相连”、“连接”应做广义理解，例如，可以是固定连接，也可以是可拆卸连接，或一体地连接；可以是机械连接，也可以是电连接；可以是直接相连，也可以通过中间媒介间接相连，可以是两个元件内部的连通。对于本领域的普通技术人员而言，可以具体情况理解上述术语在本申请中的具体含义。
对所公开的实施例的上述说明，使本领域专业技术人员能够实现或使用本发明。对这些实施例的多种修改对本领域的专业技术人员来说将是显而易见的，本文中所定义的一般原理可以在不脱离本发明的精神或范围的情况下，在其它实施例中实现。因此，本发明将不会被限制于本文所示的这些实施例，而是要符合与本文所公开的原理和新颖特点相一致的最宽的范围。

Claims (11)

  1. 一种采样系统，其特征在于，所述采样系统包括：
    采样头，所述采样头包括采样本体、采样空腔、第一流道、第二流道和第三流道；所述采样空腔设置在所述采样本体的第一端面，所述采样空腔与被采样表面形成采样区域；所述第一流道的第一接口、所述第二流道的第一接口和所述第三流道的第一接口位于所述采样本体的第二端面；所述第一流道用于将注入的萃取剂引入至所述采样空腔中；第二流道用于将注入空气引入至所述采样空腔；所述第三流道用于将所述采样空腔的采样液滴导出；
    夹持采样头的夹具；
    平移定位机构，所述平移定位机构用于带动所述夹具与所述被采样表面对齐；
    萃取剂注入机构，所述萃取剂注入机构通过第一毛细管路与所述第一流道连通，用于向所述第一流道内注入萃取剂；
    液滴转移运输机构，所述液滴转移运输机构通过第二毛细管路与所述第二流道连通，用于向第二流道内注入空气；所述液滴转移运输机构通过第三毛细管路与所述第三流道连通，用于将所述第三流道内的采样液滴导出；
    存储器和控制器，所述存储器内存储有计算机可读程序代码，所述控制器用以执行所述计算机可读程序代码以控制采样系统实现：
    确定被采样表面的位置控制所述平移定位机构调整所述夹具的位置直至所述采样头的第一端面与所述被采样表面相接触；
    所述萃取剂注入机构向第一流道注入萃取剂；
    间隔第一预设时间所述液滴转移运输机构向第二流道注入空气，并由第三流道导出采样液滴；
    间隔第二预设时间所述平移定位机构带动所述夹具运动使得所述采样头脱离被采样表面。
  2. 如权利要求1所述的采样系统，其特征在于，所述平移定位机构包括带动所述夹具在第一方向移动的第一调整机构；和带动所述夹具在第二方向移动的第二调整机构，所述第一方向和所述第二方向相互垂直。
  3. 如权利要求2所述的采样系统，其特征在于，所述平移定位机构还包括带动所述夹具在第三方向移动的第三调整机构，所述第一方向与所述第一方向和所述第二方向均垂直。
  4. 如权利要求1所述的采样系统，其特征在于，所述萃取剂注入机构为注射泵。
  5. 如权利要求1所述的采样系统，其特征在于，所述液滴转移运输机构包括第一蠕动泵和第二蠕动泵，其中，所述第一蠕动泵通过第二毛细管与所述第二流道连通，所述第二蠕动泵通过第三毛细管与所述第三流道连通。
  6. 如权利要求1所述的采样系统，其特征在于，所述采样本体呈长方体结构，所述采样本体相对的两个侧面中的一个侧面设置有榫头，另外一个侧面相对的位置设置有尺寸与所述榫头相配合的卯槽。
  7. 如权利要求1所述的采样系统，其特征在于，所述第一流道的第二接口和所述第二流道的第二接口位于所述采样空腔的顶部。
  8. 如权利要求1所述的采样系统，其特征在于，所述第三流道的第二接口靠近所述采样空腔的底部。
  9. 一种质谱分析装置，其特征在于，包括质谱分析仪和如权利要求1至8中任一项所述的采样系统，所述质谱分析仪用于对采样液滴进行质谱分析。
  10. 一种采样方法，其特征在于，应用如权利要求1至8中任一项所述的采样系统，该采样方法包括：
    确定被采样表面的位置控制所述平移定位机构调整所述夹具的位置直至所述采样头的第一端面与所述被采样表面相接触；
    所述萃取剂注入机构向第一流道注入萃取剂；
    间隔第一预设时间所述液滴转移运输机构向第二流道注入空气，并由第三流道导出采样液滴；
    间隔第二预设时间所述平移定位机构带动所述夹具运动使得所述采样头脱离被采样表面。
  11. 一种质谱分析方法，其特征在于，包括如权利要求10所述的采样方法；和对采样液滴进行质谱分析。
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