Sampler, sampling module and method for sampling biological tissue surface

Abstract

The invention discloses a sampler, a sampling module and a biological tissue surface sampling method. The sampler comprises a multi-channel micro-droplet generating assembly, a connecting assembly and a pressure sensing assembly. The multi-channel micro-droplet generation assembly comprises a sampling pen point, a liquid channel, a gas channel and a recovery channel, the liquid channel, the gas channel and the recovery channel are formed in the sampling pen, and micro-droplets are generated on the contact interface of the sampling end by regulating and controlling the pressure, the flow speed and the time sequence of gas / liquid media and used for making contact with tissue. Biological component information on the surface of the tissue is intercepted by the micro-droplets through dissolution and diffusion, so that the volume of the micro-droplets formed at each sampling point is not influenced by a sampling process and a mechanical structure, the to-be-detected tissue is not damaged, rapid on-line nondestructive extraction of the metabolite on the surface of the tissue can be realized, and the detection accuracy is improved. And high time-space resolution extraction of metabolites can be realized. The sampler and the sampling module can also be used for sampling on the surface of non-biological tissue.

Description

Technical Field

[0001] The invention relates to the technical field of sampling devices, and in particular to a sampler, a sampling module and a sampling method. Background Art

[0002] A sampler is needed for in-depth analysis of biological components on the surface of an object, especially on the surface of a tissue. However, current samplers not only have low sampling volume accuracy, but also low sampling concentration accuracy.

[0003] It can be seen that whether it is possible to provide an improved sampler based on the deficiencies in the prior art has become a technical problem that needs to be urgently solved by those skilled in the art. Summary of the invention

[0004] The technical problem to be solved by the present invention is to overcome the defects in the prior art and provide a sampler, a sampling module and a sampling method.

[0005] The present invention solves the above technical problems through the following technical solutions:

[0006] A sampler, comprising:

[0007] A multi-channel micro-droplet generation component comprises a sampling pen tip, wherein one end of the sampling pen tip in the length direction is a sampling end, and the other end is a connecting end. A liquid channel, a gas channel and a recovery channel are provided in the sampling pen tip, the outlet of the gas channel is connected to the liquid channel, and the outlet of the liquid channel and the inlet of the recovery channel intersect at the sampling end.

[0008] Preferably, it also includes:

[0009] A clamp, detachably mounted on the sampling pen tip;

[0010] A connecting sleeve, one end of which is detachably connected to the clamp;

[0011] A pen holder, detachably connected to the other end of the connecting sleeve;

[0012] Pipeline joints;

[0013] A liquid conduit is disposed in the pen barrel and communicated with the liquid channel through the pipe joint;

[0014] A gas conduit is disposed in the pen barrel and communicated with the gas channel through the pipe joint;

[0015] The recovery conduit is arranged in the pen barrel and communicated with the recovery channel through the pipe joint.

[0016] Preferably, it also includes:

[0017] A disc, one end of which is arranged at the connection end of the sampling pen tip and is provided with a through hole for the liquid conduit, the gas conduit and the recovery conduit to pass through;

[0018] A push rod is mounted on the other end of the disc;

[0019] The pressure sensor is arranged in the pen barrel and contacts the push rod.

[0020] Preferably, it also includes:

[0021] A pressure sensing assembly is installed at the connecting end, and the pressure sensing assembly includes an upper braking structure, a lower braking structure, an elastic member and a pressure sensor;

[0022] The upper brake structure comprises a first cross bar, a first vertical bar and a second cross bar connected in sequence;

[0023] The lower brake structure comprises a third crossbar, a second vertical bar and a fourth crossbar connected in sequence;

[0024] The elastic member connects the lower end of the first cross bar and the upper end of the third cross bar;

[0025] The lower end of the third crossbar and the upper end of the second crossbar are arranged opposite to each other and keep a gap;

[0026] The pressure sensor is disposed at the lower end of the third crossbar and is used to detect the distance between the second crossbar and the third crossbar.

[0027] Preferably, it also includes:

[0028] A connecting component is used to connect the sampling pen head and the pressure sensing component.

[0029] Preferably, the gas channel is located between the liquid channel and the recovery channel.

[0030] Preferably, the liquid channel comprises a first upper section and a first lower section;

[0031] The gas channel includes a second upper section and a second lower section;

[0032] The recovery channel includes a third upper section and a third lower section;

[0033] The first upper section, the second upper section and the third upper section are arranged in parallel along the length direction of the sampling pen tip;

[0034] The lower end of the first lower section and the lower end of the third lower section are close to each other and intersect;

[0035] The lower end of the second lower section is communicated with the first lower section.

[0036] Preferably, the diameter of the sampling end is smaller than the diameter of the connecting end.

[0037] A sampling module, comprising the above-mentioned sampler, further comprising:

[0038] A microfluidic gas-liquid control unit, which generates a continuous pure water flow required by the sampler and an air flow required for cutting sample droplets;

[0039] A connecting conduit is connected to connect the sampler and the microfluidic gas-liquid control unit.

[0040] A method for sampling the surface of biological tissue, using the above-mentioned sampling module, the sampling method comprises the following steps:

[0041] Preparation steps: pass the metabolite dilution solution into the liquid channel and stop when the liquid level reaches the intersection;

[0042] Sampling steps: the sampling end of the sampling pen is brought into contact with the surface of the tissue to be sampled, the metabolite diluent continues to be introduced into the liquid channel, and the gas is introduced into the gas channel at the same time, and by controlling the flow rate ratio of the diluent / gas, quantitative segmentation of trace droplets is achieved at the intersection of the lower ends of the liquid channel and the gas channel; after the droplets are segmented, the liquid channel is kept stable, and the gas is continued to be introduced into the gas channel, and the segmented droplets are pushed to the sampling end where the lower end of the liquid channel contacts the tissue surface, thereby allowing metabolites on the tissue surface to dissolve and diffuse into the droplets; during the dissolution and diffusion process, the gas channel and the liquid channel remain stationary to ensure that the contact process between the droplets and the tissue surface is stationary and stable, and the substances are fully dissolved and diffused into the droplets;

[0043] Collection steps: After the dissolution and diffusion are completed, continue to introduce gas into the gas channel, keep the liquid level in the liquid channel stable, and the sampling droplets enter the recovery channel from the lower end of the recovery channel under the action of gas pressure.

[0044] On the basis of being in accordance with the common sense in the art, the above-mentioned preferred conditions can be arbitrarily combined to obtain the preferred embodiments of the present invention.

[0045] The positive and progressive effect of the present invention is that the sampler of the present invention includes a multi-channel micro-droplet generation component, a connection component, and a pressure sensing component. The multi-channel micro-droplet generation component includes a sampling pen head and a liquid channel, a gas channel, and a recovery channel opened inside the sampling pen. By adjusting the pressure and flow rate of the gas / liquid medium and the timing, micro-droplets are generated at the contact interface of the sampling end for contacting the tissue. The biological component information on the surface of the tissue is intercepted by the micro-droplets through dissolution and diffusion, ensuring that the volume of the micro-droplets formed at each sampling point is not affected by the sampling process and the mechanical structure, and will not cause damage to the tissue to be detected, and can realize rapid online non-destructive extraction of metabolites on the tissue surface, and can also realize high temporal and spatial resolution extraction of metabolites. BRIEF DESCRIPTION OF THE DRAWINGS

[0046] Figure 1 It is a schematic structural diagram of a sampling pen tip according to a preferred embodiment of the present invention.

[0047] Figure 2 Schematic diagram of the structure of a sampler according to a preferred embodiment of the present invention.

[0048] Figure 3 FIG. 4 is a schematic structural diagram of a pressure sensing assembly according to another embodiment of the present invention.

[0049] Figure 4 Flow chart of a method for sampling a biological tissue surface according to a preferred embodiment of the present invention.

[0050] Description of reference numerals:

[0051] Sampling pen 1

[0052] Sampling end 11

[0053] Connection terminal 12

[0054] Clamp 13

[0055] Connecting sleeve 14

[0056] Pen holder 15

[0057] Pipeline connector 16

[0058] Disc 17

[0059] Ejector 18

[0060] Pressure sensor 19

[0061] Liquid channel 2

[0062] Gas channel 3

[0063] Recycling channel 4

[0064] Biological tissue 5

[0065] First crossbar 6

[0066] First vertical bar 7

[0067] Second crossbar 8

[0068] The third crossbar 9

[0069] The second vertical rod 10

[0070] Fourth Crossbar 101

[0071] Elastic member 102

[0072] Pressure sensor 103 DETAILED DESCRIPTION

[0073] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, rather than all the embodiments. The following description of at least one exemplary embodiment is actually only illustrative and is by no means intended to limit the present invention and its application or use. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0074] For ease of description, spatially relative terms such as "above", "above", "on the upper surface of", "above", etc. may be used here to describe the spatial positional relationship between a device or feature and other devices or features as shown in the figure. It should be understood that spatially relative terms are intended to include different orientations of the device in use or operation in addition to the orientation described in the figure. For example, if the device in the accompanying drawings is inverted, the device described as "above other devices or structures" or "above other devices or structures" will be positioned as "below other devices or structures" or "below other devices or structures". Thus, the exemplary term "above" can include both "above" and "below". The device can also be positioned in other different ways (rotated 90 degrees or in other orientations), and the spatially relative descriptions used here are interpreted accordingly.

[0075] like Figure 1 and Figure 2 As shown, this embodiment discloses a sampler, which includes a multi-channel micro-droplet generation component, a pressure sensing component and a connecting component.

[0076] The multi-channel micro-droplet generation component includes a sampling pen head 1, and the sampling pen head 1 has a sampling end 11 and a connecting end 12, and the sampling end 11 and the connecting end 12 are respectively located at the two ends of the length direction of the sampling pen head 1. Figure 1In the figure, the sampling end 11 is the lower end of the sampling pen tip 1, and the connecting end 12 is the upper end of the sampling pen tip 1. The sampling pen tip 1 is provided with a liquid channel 2, a gas channel 3 and a recovery channel 4, the lower end of the gas channel 3 (the outlet of the gas channel 3) is connected to the side wall of the liquid channel 2, and the lower end of the liquid channel 2 (the outlet of the liquid channel 2) and the lower end of the recovery channel 4 (the inlet of the recovery channel 4) intersect at the sampling end 11. The upper end of the gas channel 3 (the inlet of the gas channel 3), the upper end of the liquid channel 2 (the inlet of the liquid channel 2) and the upper end of the recovery channel 4 (the outlet of the recovery channel 4) are all provided at the connecting end 12 of the sampling pen tip 1. The multi-channel micro-droplet generation component is composed of at least 3 micro-channels, namely at least 1 liquid channel 2, at least 1 gas channel 3, and at least 1 recovery channel 4.

[0077] In this embodiment, the diameter of the sampling end 11 is smaller than the diameter of the connecting end 12 to reduce interference and facilitate sampling.

[0078] Further, the gas channel 3 is located between the liquid channel 2 and the recovery channel 4. The liquid channel 2 includes a first upper section and a first lower section, the gas channel 3 includes a second upper section and a second lower section, and the recovery channel 4 includes a third upper section and a third lower section. The first upper section, the second upper section and the third upper section are arranged vertically and in parallel along the length direction of the sampling pen tip 1, the lower end of the first lower section (the outlet of the liquid channel 2) and the lower end of the third lower section (the inlet of the recovery channel 4) are close to each other and meet at the sampling end 11 of the sampling pen tip 1, and the lower end of the second lower section (the outlet of the gas channel 3) is connected to the first lower section.

[0079] Furthermore, the sampler also includes a clamp 13, a connecting sleeve 14, a pen holder 15, a pipe joint 16, a liquid conduit, a gas conduit and a recovery conduit.

[0080] The clamp 13 is detachably mounted on the sampling pen tip 1. Therefore, the detachable sampling pen tip can be replaced according to the sample tissue type and sampling accuracy. The clamp 13 is used to lock the liquid channel 2, gas channel 3 and recovery channel 4 reserved in the sampling pen tip 1 and the pipe joint at the connecting sleeve to ensure the sealing effect.

[0081] Both ends of the connecting sleeve 14 are provided with external threads, one end is detachably connected to the clamp 13 by means of threaded connection, and the pen holder 15 is detachably connected to the other end of the connecting sleeve 14 by means of threaded connection.

[0082] The liquid conduit is arranged in the pen barrel 15 and communicated with the liquid channel 2 through a pipe joint. The gas conduit is arranged in the pen barrel and communicated with the gas channel 3 through a pipe joint. The recovery conduit is arranged in the pen barrel and communicated with the recovery channel 4 through a pipe joint. The sealing can be ensured by setting the pipe joint.

[0083] In this embodiment, the sampler further includes a disc 17, a push rod 18 and a pressure sensor 19. The pressure sensor 19 is arranged in the pen barrel and contacts the push rod. One end of the disc 17 is arranged at the connection end of the sampling pen tip, and is provided with a through hole for the liquid conduit, the gas conduit and the recovery conduit to pass through. The push rod 18 is fixedly installed on the other end of the disc by screws, that is, one side of the push rod is connected to the sampling pen tip through the bottom disc, and the other side contacts the pressure sensor for pressure transmission and feedback. In another embodiment, Figure 3 As shown, the pressure sensing component is installed at the connecting end 12 of the sampling pen head 1, as shown in FIG. Figure 2 As shown, the pressure sensing assembly includes an upper braking structure, a lower braking structure, an elastic member 102 and a pressure sensor 103 .

[0084] The upper braking structure comprises a first cross bar 6, a first vertical bar 7 and a second cross bar 8 which are connected in sequence.

[0085] The lower braking structure comprises a third cross bar 9, a second vertical bar 10 and a fourth cross bar 101 which are connected in sequence.

[0086] The elastic member 102 connects the lower end of the first crossbar 6 and the upper end of the third crossbar 9 . In this embodiment, the elastic member 102 is a spring, but is not limited thereto.

[0087] The lower end of the third cross bar 9 and the upper end of the second cross bar 8 are arranged opposite to each other, and a gap is maintained between them.

[0088] The pressure sensor 103 is disposed in the gap between the lower end of the third crossbar 9 and the upper end of the second crossbar 8 , and is used to detect the distance of the second crossbar 8 relative to the third crossbar 9 .

[0089] The fourth crossbar 101 is fixed on the structural member. When pressure is applied, the first crossbar 6 is displaced under the pressure, and the second crossbar 8 will be away from the pressure sensor 103. The smaller the pressure applied, the closer the second crossbar 8 is to the pressure sensor 103; the greater the pressure applied, the further the second crossbar 8 is away from the pressure sensor 103.

[0090] Thus, the pressure sensor or pressure sensing assembly can realize pressure detection and feedback control. By setting the normal working pressure value / pressure range and providing an indicator light to indicate the normal / abnormal working status, the normal sampling of the sampler and the corresponding sampling accuracy can be ensured between different operators, different sampling tissue surfaces, and different sampling points. (The sampling volume accuracy and sampling concentration accuracy are closely related to the sealing of the sampler-tissue surface, and the sealing is determined by the pressure applied when the sampler contacts the tissue surface.)

[0091] The pressure feedback indicates the operator's working status and adjusts the normal working pressure range of the sampler to avoid the sampling accuracy being affected by uneven pressure caused by different operators' usage habits, which helps to improve sampling accuracy and sampling repeatability.

[0092] The connecting component includes a connecting rod, a rivet, a knob cover, etc. The connecting component is used to connect the sampling pen head 1 and the pressure sensor component.

[0093] This embodiment also discloses a sampling module, which includes the above-mentioned sampler. In addition, the sampling module also includes a microfluidic gas-liquid control unit and a connecting conduit.

[0094] The microfluidic gas-liquid control unit generates the continuous pure water flow required by the sampler and the gas flow required to cut the sample droplets.

[0095] The connecting conduit is a flexible conduit used for connecting the sampler and the microfluidic gas-liquid control unit.

[0096] like Figure 4 As shown, this embodiment also discloses a method for sampling the surface of a biological tissue 5, which uses the above-mentioned sampling module. The method for sampling the surface of the biological tissue 5 includes the following steps:

[0097] Preparation step: pass the metabolite dilution solution into liquid channel 2, and stop when the liquid level reaches the intersection. At this time, the sampler is in the preparation completion stage.

[0098] Sampling steps: the sampling end 11 of the sampling pen head 1 is brought into contact with the surface of the biological tissue 5 to be sampled, the metabolite diluent continues to be introduced into the liquid channel 2, and the gas (air) is introduced into the gas channel 3 at the same time, and by controlling the flow rate ratio of the diluent / gas, the quantitative segmentation of the trace droplets is achieved at the intersection of the lower ends of the liquid channel 2 and the gas channel 3; after the droplets are segmented, the liquid channel 2 is kept stable (the pressure can be stable, the pump can be stopped, etc.), and the gas is continued to be introduced into the gas channel 3, and the segmented droplets are pushed to the sampling end 11 where the lower end of the liquid channel 2 (the outlet of the liquid channel 2) contacts the surface of the biological tissue 5, thereby, the metabolites on the surface of the biological tissue 5 are dissolved and diffused into the droplets; during the dissolution and diffusion process, the gas channel 3 and the liquid channel 2 remain stationary to ensure that the contact process between the droplets and the surface of the biological tissue 5 is stationary and stable, and the substances are fully dissolved and diffused into the droplets.

[0099] Collection step: After the dissolution and diffusion are completed, the sampling stage is completed. Continue to introduce gas into the gas channel 3, keep the liquid level in the liquid channel 2 stable, and the sampled droplets enter the recovery channel 4 from the lower end of the recovery channel 4 (the entrance of the recovery channel 4) under the action of the gas pressure. A detection module / equipment can be further added downstream of the recovery channel 4 to perform relevant detection on the metabolites inside the sampled droplets.

[0100] After the sampling process is completed, if it is necessary to clean the inside of the sampler (such as removing the residual liquid inside the channel during the previous sampling process to avoid affecting the metabolite detection of the next sampling point), a cleaning process is required.

[0101] S1: The sampling end 11 of the sampling pen tip 1 contacts a clean surface (sealing surface) (without the influence of the corresponding interfering molecules of metabolites), the metabolite diluent / cleaning liquid is introduced into the liquid channel 2, and the gas is introduced into the gas channel 3 at the same time. By adjusting the liquid flow rate of the liquid channel 2 and the gas flow rate of the gas channel 3, the liquid cannot enter the gas channel 3 at the intersection of the gas / liquid channel, and only enters the recovery channel 4 after contacting the clean surface from below. The downstream of the recovery channel 4 can be connected to a liquid storage tank, etc. to collect the cleaning liquid.

[0102] S2: After cleaning, stop the liquid injection of liquid channel 2, adjust the gas flow rate of gas channel 3, so that the liquid is divided at the intersection of gas / liquid channels, and the liquid below the intersection is pushed by the gas into the recovery channel 4 and finally completely discharged from the sampler. The sampler state returns to the preparation completion stage of the sampling process.

[0103] The sampler and sampling system of this embodiment can realize non-destructive extraction of metabolites and high spatiotemporal resolution extraction of metabolites. Non-destructive extraction of metabolites refers to the contact between the tiny droplets formed by the micro-droplet generation component and the sampling area of ​​the biological tissue 5. The target metabolites on the surface of the biological tissue 5 (such as hydrogen protons, glutamate, ammonia, ROS, proteases, etc.) have good water solubility, so the droplets can directly extract the above-mentioned metabolites from the surface of the biological tissue 5 through diffusion and transport them to the detection system. During the whole process, only the tiny droplets generated by the sampling pen head 1 contact the biological tissue area non-destructively, and will not cause damage to the biological tissue to be detected. In this way, rapid online extraction of metabolites on the surface of the biological tissue 5 is achieved, which can be applied to the next step of the metabolite detection process. High spatiotemporal resolution extraction of metabolites refers to the formation of microliter-level droplets with controllable volume through the micro-droplet generation component. On the one hand, droplet volume control reduces the contact area between the droplet and the biological tissue 5 and improves the spatial resolution of the sampling point. On the other hand, it also increases the material transfer performance between the droplet and the metabolites on the surface of the biological tissue 5, that is, it reduces the mixing time of the droplet and the metabolites (within milliseconds to seconds), achieving high sampling time resolution.

[0104] The sampler and sampling module of this embodiment optimize the sampling droplet segmentation logic by changing the multi-channel gas / liquid structure inside the sampler to ensure that the volume of the micro-droplets formed at each sampling point is not affected by the sampling process and mechanical structure; at the same time, for the application scenario of real biological tissue 5, the sampler is equipped with a pressure sensor 103, which regulates the normal working pressure range of the sampler through pressure feedback to ensure that the working pressure of each sampling point remains consistent, thereby ensuring that the diffusion behavior of metabolites on the surface of each biological tissue 5 is consistent, and finally, by detecting the metabolite concentration of the sampling droplet, the metabolite distribution characteristics of the corresponding sampling point on the surface of the biological tissue 5 are obtained. In addition. The sampler and sampling module of the present invention can also be used for sampling on the surface of non-biological tissues.

[0105] It should be noted that in the claims and description of this patent, relational terms such as first and second, etc. are only used to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Moreover, the terms "include", "comprise" or any other variants thereof are intended to cover non-exclusive inclusion, so that a process, method, article or device including a series of elements includes not only those elements, but also other elements not explicitly listed, or also includes elements inherent to such process, method, article or device. In the absence of further restrictions, the elements defined by the sentence "including one" do not exclude the existence of other identical elements in the process, method, article or device including the elements.

Claims

1. A sampler, It is characterized in that include: A multi-channel micro-droplet generation component comprises a sampling pen tip, wherein one end of the sampling pen tip in the length direction is a sampling end, and the other end is a connecting end. A liquid channel, a gas channel and a recovery channel are provided in the sampling pen tip, the outlet of the gas channel is connected to the liquid channel, and the outlet of the liquid channel and the inlet of the recovery channel intersect at the sampling end.

2. The sampler according to claim 1, It is characterized in that Also includes: A clamp, detachably mounted on the sampling pen tip; A connecting sleeve, one end of which is detachably connected to the clamp; A pen holder, detachably connected to the other end of the connecting sleeve; Pipeline joints; A liquid conduit is disposed in the pen barrel and communicated with the liquid channel through the pipe joint; A gas conduit is disposed in the pen barrel and communicated with the gas channel through the pipe joint; The recovery conduit is arranged in the pen barrel and communicated with the recovery channel through the pipe joint.

3. The sampler according to claim 2, It is characterized in that Also includes: A disc, one end of which is arranged at the connection end of the sampling pen tip and is provided with a through hole for the liquid conduit, the gas conduit and the recovery conduit to pass through; A push rod is mounted on the other end of the disc; The pressure sensor is arranged in the pen barrel and contacts the push rod.

4. The sampler according to claim 2, It is characterized in that Also includes: A pressure sensing assembly is installed at the connecting end, and the pressure sensing assembly includes an upper braking structure, a lower braking structure, an elastic member and a pressure sensor; The upper brake structure comprises a first cross bar, a first vertical bar and a second cross bar connected in sequence; The lower brake structure comprises a third crossbar, a second vertical bar and a fourth crossbar connected in sequence; The elastic member connects the lower end of the first cross bar and the upper end of the third cross bar; The lower end of the third crossbar and the upper end of the second crossbar are arranged opposite to each other and keep a gap; The pressure sensor is disposed at the lower end of the third crossbar and is used to detect the distance between the second crossbar and the third crossbar.

5. The sampler according to claim 4, It is characterized in that Also includes: A connecting component is used to connect the sampling pen head and the pressure sensing component.

6. The sampler according to claim 1, It is characterized in that The gas channel is located between the liquid channel and the recovery channel.

7. The sampler according to claim 1, It is characterized in that The liquid channel comprises a first upper section and a first lower section; The gas channel includes a second upper section and a second lower section; The recovery channel includes a third upper section and a third lower section; The first upper section, the second upper section and the third upper section are arranged in parallel along the length direction of the sampling pen tip; The lower end of the first lower section and the lower end of the third lower section are close to each other and intersect; The lower end of the second lower section is communicated with the first lower section.

8. The sampler according to claim 1, It is characterized in that The diameter of the sampling end is smaller than the diameter of the connecting end.

9. A sampling module, It is characterized in that The sampler according to any one of claims 1 to 8 further comprises: A microfluidic gas-liquid control unit, which generates a continuous pure water flow required by the sampler and an air flow required for cutting sample droplets; A connecting conduit is connected to connect the sampler and the microfluidic gas-liquid control unit.

10. A method for sampling the surface of a biological tissue, It is characterized in that Using the sampling module as claimed in claim 9, the sampling method comprises the following steps: Preparation steps: pass the metabolite dilution solution into the liquid channel and stop when the liquid level reaches the intersection; Sampling steps: the sampling end of the sampling pen is brought into contact with the surface of the tissue to be sampled, the metabolite diluent continues to be introduced into the liquid channel, and the gas is introduced into the gas channel at the same time, and by controlling the flow rate ratio of the diluent / gas, quantitative segmentation of trace droplets is achieved at the intersection of the lower ends of the liquid channel and the gas channel; after the droplets are segmented, the liquid channel is kept stable, and the gas is continued to be introduced into the gas channel, and the segmented droplets are pushed to the sampling end where the lower end of the liquid channel contacts the tissue surface, thereby allowing metabolites on the tissue surface to dissolve and diffuse into the droplets; during the dissolution and diffusion process, the gas channel and the liquid channel remain stationary to ensure that the contact process between the droplets and the tissue surface is stationary and stable, and the substances are fully dissolved and diffused into the droplets; Collection steps: After the dissolution and diffusion are completed, continue to introduce gas into the gas channel, keep the liquid level in the liquid channel stable, and the sampling droplets enter the recovery channel from the lower end of the recovery channel under the action of gas pressure.

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