A surface extraction device, mass spectrometry system and method

Abstract

The present invention relates to the field of biological and chemical analysis, and discloses a surface extraction device, a mass spectrometry analysis system and a method. The surface extraction device of the present invention comprises: a sampling unit, an injection unit, a back-suction unit, a six-way valve with a quantitative loop, an electrically controlled multi-way valve and an air supply unit; the sampling unit is coaxially provided with a back-suction channel, an injection channel and a dry gas channel from the inside to the outside; the same side ends of the back-suction channel, the injection channel and the dry gas channel are respectively connected to the back-suction port, the injection port and the dry gas port of the sampling unit, and the other ends jointly form a sampling port; a sampling cavity is formed at the sampling port; the dry gas channel is provided with an air hole at a position higher than the sampling cavity; the injection unit is respectively connected to the six-way valve and the injection port through an electrically controlled multi-way valve; the back-suction unit and the back-suction port are respectively connected to the six-way valve; and the air supply unit is connected to the dry gas port. The scheme of the present invention can maintain the liquid flow stability of continuous analysis, optimize the operation platform, reduce the difficulty of operation, and improve the ionization effect.

Description

Technical Field

[0001] The present invention relates to the field of biological and chemical analysis, and in particular to a surface extraction device, a mass spectrometry analysis system and a method. Background Art

[0002] Mass spectrometry is an important means of material analysis. In recent years, mass spectrometry has been widely used in many fields such as life sciences, food safety, environmental monitoring, clinical testing, and pesticide residue monitoring. Most traditional mass spectrometry analyses require a pretreatment process and cannot meet the needs of on-site online measurements. In 2004, Professor Cooks and others developed the analytical electrospray ionization (DESI) technology, which can be used to perform direct mass spectrometry analysis on samples on the surface of materials without sample pretreatment. Since then, researchers have successively developed a variety of environmental ionization sources that can be used for direct surface analysis of different complex sample systems without pretreatment conditions.

[0003] In addition to using an ambient ionization source to directly complete the ionization process on the sample surface, surface extraction methods based on liquid phase extraction and electrospray ionization technology are also important methods for surface mass spectrometry analysis. In 2002, Professor Berkel's research and development team proposed a liquid microjunction surface sampling probe (LMJ-SSP), which uses a robotic probe composed of two coaxial tubes for surface extraction. The solvent in the external pipeline extracts the sample surface molecules while flowing, and relies on the Venturi effect to transfer the liquid through the internal pipeline to the electrospray ionization source (ESI) for mass spectrometry analysis. Later in 2010, the research group proposed liquid extraction surface analysis (LESA) based on LMJ-SSP, using a robotic arm to inject a certain amount of liquid on the sample surface through the extraction probe. After the surface extraction is completed, the liquid is sucked back into the probe and transferred to the ESI nozzle through the robotic arm to complete ionization and mass spectrometry analysis. Another nano-DESI method based on DESI requires two capillaries placed at a certain angle. The extraction liquid forms a liquid bridge between the two pipes, which is ionized using DESI, and the generated ions are transmitted into the mass spectrometry sampling port. In 2018, Livia S. Eberlin's research group developed a three-channel mass spectrometry pen (MasSpec Pen), which also uses liquid surface extraction technology, assisted by auxiliary gas and vacuum propulsion, and can transfer the extracted samples to the mass spectrometry injection end to meet the needs of long-distance transmission.

[0004] Although the above methods can use liquid surface extraction and direct surface analysis of different samples, they all have technical limitations. For example, LESA involves probe movement during the extraction and ionization process, and the analysis process must be completed in conjunction with a precise mechanical control platform. Nano-ESI also has strict requirements on the placement angles of the two pipes. At the same time, neither method can meet the needs of direct in-situ analysis of remote samples. The method represented by MasSpec Pen that uses vacuum to transmit liquid flow has high requirements for vacuum pressure difference. Slight differences in vacuum will affect the liquid flow rate and liquid flow stability, thereby affecting the ionization effect. Summary of the invention

[0005] In order to overcome the above technical problems, the present invention provides a surface extraction device, a mass spectrometry analysis system and a method, which can maintain the liquid flow stability of continuous analysis, optimize the operation platform, reduce the operation difficulty, and improve the ionization effect.

[0006] In order to achieve the above object, the present invention provides a surface extraction device, comprising:

[0007] Sampling unit, injection unit, back suction unit, six-way valve with quantitative loop, electric multi-way valve and air supply unit;

[0008] The sampling unit is coaxially provided with a back-suction channel, an injection channel and a dry gas channel from the inside to the outside; the back-suction channel, the injection channel and the dry gas channel are connected to the back-suction port, the injection port and the dry gas port of the sampling unit at one end on the same side respectively, and the other ends together form a sampling port; a sampling cavity is formed at the sampling port; the dry gas channel is provided with an air hole at a position higher than the sampling cavity;

[0009] The injection unit is connected to the six-way valve and the injection port respectively through the electrically controlled multi-way valve; the back-suction unit and the back-suction port are connected to the six-way valve respectively; and the air supply unit is connected to the dry gas port.

[0010] In an optional embodiment, the ends of the re-absorption channel and the injection channel are retracted inwardly at the sampling port relative to the end of the dry gas channel to form the sampling cavity.

[0011] In an optional embodiment, at least two liquid flow channels are arranged in the electrically controlled multi-way valve.

[0012] In an optional embodiment, the surface extraction device further comprises an electric control unit; the electric control unit is electrically connected to the injection unit, the suck-back unit, the six-way valve and the electric-controlled multi-way valve respectively.

[0013] In an optional embodiment, the injection unit and the electrically controlled multi-way valve, the sampling unit and the electrically controlled multi-way valve, the six-way valve and the air supply unit, and the six-way valve and the back-suction unit are connected by pipelines through hoses.

[0014] In an optional embodiment, the surface extraction device further comprises: an integrated component;

[0015] The suck-back unit, the electrically controlled multi-way valve, the six-way valve and the electrically controlled unit are fixedly arranged on the integrated component.

[0016] In another aspect, the present invention provides a mass spectrometry system, comprising a mass spectrometer and an ion source, and further comprising any one of the surface extraction devices described above;

[0017] The surface extraction device is coupled to the mass spectrometer via the ion source.

[0018] In another aspect, the present invention further provides a surface extraction method for use in any one of the surface extraction devices or mass spectrometry systems described above, the method comprising:

[0019] The electrically controlled multi-way valve is adjusted to the first liquid flow channel, the six-way valve is in a sampling state, the back-sucking unit is in a closed state, and the injection unit pushes the extraction liquid at a first flow rate for a first period of time, so that the extraction liquid reaches the sampling cavity through the electrically controlled multi-way valve and the injection port of the sampling unit to contact the sample;

[0020] The electrically controlled multi-way valve is adjusted to the second liquid flow channel, the states of the suction unit and the six-way valve are kept unchanged, the injection unit pushes the extraction liquid at a second flow rate, and the extraction liquid in the sampling cavity remains in contact with the sample for a second period of time;

[0021] The suction unit is adjusted to an open state, and the states of the electrically controlled multi-way valve and the six-way valve are kept unchanged for a third period of time, so that the extraction liquid in the sampling cavity is sucked back into the quantitative loop of the six-way valve through the suction port;

[0022] The six-way valve is adjusted to the injection state, the electrically controlled multi-way valve is kept in the second liquid flow channel, and the injection unit pushes the extraction liquid at the second flow rate for a fourth time period, so that the liquid in the quantitative ring is pushed toward the analysis device.

[0023] In an optional embodiment, the method further includes:

[0024] Before the first time period, the gas supply unit is turned on and lasts for a zero time period, so that the dry gas reaches the sample through the dry gas port and the sampling port.

[0025] In an optional embodiment, the method further includes:

[0026] In the initial state, the six-way valve is adjusted to the sampling state, and the electrically controlled multi-way valve is adjusted to the second liquid flow channel.

[0027] The surface extraction device, mass spectrometry system and method described in the present invention include: a sampling unit, an injection unit, a back-suction unit, a six-way valve with a quantitative loop, an electrically controlled multi-way valve and an air supply unit; the sampling unit is coaxially provided with a back-suction channel, an injection channel and a dry gas channel from the inside to the outside; the back-suction channel, the injection channel and the dry gas channel are connected to the back-suction port, the injection port and the dry gas port of the sampling unit at one end on the same side, and the other end forms a sampling port together; a sampling cavity is formed at the sampling port; the dry gas channel is provided with an air hole at a position higher than the sampling cavity; the injection unit is connected to the six-way valve and the injection port respectively through the electrically controlled multi-way valve; the back-suction unit and the back-suction port are connected to the six-way valve respectively; the air supply unit is connected to the dry gas port. The technical solution of the present invention overcomes the technical limitations of various existing surface extraction technologies, reduces the dependence on precision mechanical control and the difficulty of operation, avoids the influence of vacuum transmission on liquid flow rate and liquid flow stability, realizes in-situ analysis of remote samples, optimizes the liquid flow stability of continuous analysis and improves the ionization effect. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 This is a schematic structural diagram of a surface extraction device according to the present invention;

[0029] Figure 2 A schematic cross-sectional view of a sampling port according to the present invention;

[0030] Figure 3 A longitudinal cross-sectional schematic diagram of a sampling port according to the present invention;

[0031] Figure 4 It is a three-dimensional assembly schematic diagram of the integrated component of the present invention;

[0032] Figure 5 A flow chart of a surface extraction method according to the present invention;

[0033] Figure 6 A flow chart of another surface extraction method according to the present invention;

[0034] Figure 7 A timing state diagram of the surface extraction method of the present invention;

[0035] Figure 8 Another timing state diagram of the surface extraction method of the present invention;

[0036] Fig. 9 The mass spectrometry ion flow diagram and mass spectrum diagram obtained by combining the surface extraction device of the present invention with a mass spectrometer;

[0037] Fig.10 A mass spectrum of a finger surface subjected to mass spectrometry analysis using the surface extraction device and method of the present invention;

[0038] Fig.11 The present invention provides a mass spectrum of celery subjected to mass spectrometry analysis using the surface extraction device and method of the present invention. DETAILED DESCRIPTION

[0039] Embodiments of the present invention are described below with reference to the accompanying drawings. Elements and features described in one drawing or one embodiment of the present invention may be combined with elements and features shown in one or more other drawings or embodiments. It should be noted that for the purpose of clarity, the representation and description of components or processes that are not related to the present invention and are known to those of ordinary skill in the art are omitted in the drawings and descriptions.

[0040] The embodiment of the present invention provides a surface extraction device, such as Figure 1 As shown, the device comprises:

[0041] The sampling unit 11, the injection unit 12, the back suction unit 13, the six-way valve 14, the electric control multi-way valve 15 and the air supply unit (not shown in the figure). The six-way valve 14 has a quantitative ring 141 in it.

[0042] The sampling unit 11 is coaxially provided with a back-suction channel 111, an injection channel 112 and a dry gas channel 113 from the inside to the outside. The coaxial arrangement of the back-suction channel 111, the injection channel 112 and the dry gas channel 113 is as follows: Figure 2 and Figure 3 shown.

[0043] The same ends of the suction channel 111, the injection channel 112 and the dry gas channel 113 are respectively connected Figure 1 The sampling unit 11 shown has a suction port 114, an injection port 115 and a drying gas port 116; the other end together forms a sampling port 117. Figure 3 As shown, a sampling cavity 118 is formed at the sampling port 117 . The dry gas channel 113 is provided with an air hole 1131 at a position higher than the sampling cavity 118 .

[0044] like Figure 1 As shown, the injection unit 12 is connected to the electrically controlled multi-way valve 15, and further connected to the six-way valve 14 and the injection port 115 of the sampling unit 11 through different pipelines. The back-suction unit 13 and the back-suction port 114 of the sampling unit 11 are connected to the six-way valve 14 through pipelines. In addition, the air supply unit is connected to the dry gas port 116 through a pipeline.

[0045] The embodiment of the present invention provides a surface extraction device, which includes a sampling unit, an injection unit, a back-suction unit, a six-way valve with a quantitative loop, an electrically controlled multi-way valve and an air supply unit. The sampling unit is coaxially provided with a back-suction channel, an injection channel and a dry gas channel from the inside to the outside; the same side ends of the back-suction channel, the injection channel and the dry gas channel are respectively connected to the back-suction port, the injection port and the dry gas port of the sampling unit, and the other ends together form a sampling port; a sampling cavity is formed at the sampling port, and an air hole is provided in the dry gas channel at a position higher than the sampling cavity; the injection unit is respectively connected to the six-way valve and the injection port through the electrically controlled multi-way valve; the back-suction unit and the back-suction port are respectively connected to the six-way valve; and the air supply unit is connected to the dry gas port. The technical solution of the embodiment of the present invention realizes handheld automatic in-situ extraction, overcomes the technical limitations of various existing surface extraction technologies, reduces the dependence on precision mechanical control and the difficulty of operation, avoids the influence of vacuum transmission on liquid flow rate and liquid flow stability, realizes remote sample in-situ analysis, optimizes the liquid flow stability of continuous analysis and improves the ionization effect.

[0046] For biological tissue sampling, dry gas can be blown onto the moist surface of sample tissue through the dry gas channel to quickly create a dry surface. The airflow can also disperse blood, flushing water and other liquids to reduce background interference from irrelevant variables in subsequent analysis.

[0047] By providing the air hole, the sampling space is connected to the atmosphere, so as to avoid the sampling port 117 being close to the sample surface to cause a local vacuum, and ensure the normal operation of the re-absorption unit 13, so that the liquid can be smoothly re-absorbed. In addition, since the air hole is located higher than the sampling cavity, the liquid can be effectively prevented from flowing out of the cavity, thereby ensuring local sampling.

[0048] Specifically, the six-way valve 14 may be a two-position six-way valve. The six-way valve of the embodiment of the present invention is provided with six ports. Figure 1 As shown, the S1-S3 liquid flow channel of the electric multi-way valve 15 is connected to the port 6 of the six-way valve 14. The suction port 114 of the sampling unit 11 is connected to the port 2 of the six-way valve, and the suction unit 13 is connected to the port 3 of the six-way valve 14. The port 5 of the six-way valve is connected to the ion source and other equipment at the rear end. The quantitative ring 141 is connected to the port 1 and the port 4 inside the six-way valve 14. Figure 1 As shown, there are two working positions inside the six-way valve 14, namely position A and position B. In position A, port 1 and port 2, port 3 and port 4, port 5 and port 6 are connected respectively; in position B, port 1 and port 6, port 2 and port 3, port 4 and port 5 are connected respectively.

[0049] Optionally, the injection unit 12 may be a syringe pump, and the suction unit 13 may be a peristaltic pump.

[0050] Optionally, the electrically controlled multi-way valve 15 may be a three-way solenoid valve or a valve element provided with at least two fluid flow channels. Figure 1 As shown, the electrically controlled multi-way valve 15 may be a three-way solenoid valve provided with a first liquid flow channel S1 - S2 and a second liquid flow channel S1 - S3 .

[0051] Optionally, the gas supply unit may be a gas cylinder, a gas pump or other gas supply devices.

[0052] One of the core aspects of the embodiments of the present invention is to utilize an injection unit 12, such as an injection pump, a back suction unit 13, such as a peristaltic pump, and an electrically controlled multi-way valve 15, such as a three-way solenoid valve, to achieve automated surface extraction, thereby reducing the operational complexity of the surface extraction process of the existing conventional technology and providing a stable liquid flow without involving vacuum requirements.

[0053] The peristaltic pump provides a stable suction speed for the extraction liquid on the sample surface. The suction speed can be adjusted according to the viscosity of different extractants to ensure the continuity of the suction liquid. Compared with the sub-vacuum suction, the peristaltic pump is simpler and more controllable.

[0054] In addition, the syringe pump provides continuous power to the analyte, with a more uniform speed, and the pushing speed can be adjusted according to the properties of the liquid, with higher stability.

[0055] In some specific embodiments, Figure 3 As shown, the ends of the re-absorption channel 111 and the injection channel 112 of the surface extraction device according to the embodiment of the present invention are retracted inwardly relative to the end of the dry gas channel 113 at the sampling port 117 to form a sampling cavity 118. By setting the sampling cavity, it is beneficial for the extraction liquid to fully contact with the sample, and the surface extraction is effectively realized.

[0056] Figure 3 The end of the back-inhalation channel 111 is flush with the end of the injection channel 112, and this relative position relationship is schematic. In actual scenarios, the end of the back-inhalation channel 111 can also be recessed or protruded relative to the end of the injection channel 112 without affecting the sampling cavity 118.

[0057] Further, such as Figure 1 As shown, a waste liquid outlet is provided in the suction back unit 13, such as a peristaltic pump, and is connected to a waste liquid bottle.

[0058] In some specific embodiments, the surface extraction device further includes an electric control unit. The electric control unit is electrically connected to the injection unit 12, the resuspension unit 13, the six-way valve 14 and the electric-controlled multi-way valve 15, respectively, and is used to control state changes and pipeline switching, such as controlling the injection unit 12 to inject buffer at different speeds, controlling the opening and closing of the resuspension unit 13, controlling the six-way valve 14 to switch between different working positions, and controlling the electric-controlled multi-way valve 15 to switch between different liquid flow channels.

[0059] The electronic control unit includes a control circuit. Optionally, a power module may also be integrated into the electronic control unit.

[0060] In some specific embodiments, the injection unit 12 and the electrically controlled multi-way valve 15, the sampling unit 11 and the electrically controlled multi-way valve 15, the six-way valve 14 and the air supply unit, and the six-way valve 14 and the back-sucking unit 13 can be connected by a hose. Using a flexible hollow hose to connect the various units and valves can reduce the difficulty of operation and improve the scalability of the system.

[0061] Further, the hose can be a hose with adjustable length and inner diameter. The use of a hose with adjustable length can further coordinate long-distance sampling. For surfaces that are far away and inconvenient to move, by increasing the length of the hose, it is achieved that the sampling unit 11 reaches the surface of the object to be measured without moving the rear-end mass spectrometer. At the same time, the hose with adjustable length is also convenient for meeting the assembly conditions of different valves and other equipment, such as different valves or pumps have different pipeline requirements or different placement requirements. In addition, the use of a hose with adjustable inner diameter can match the thickness of the pipelines of the six-way valve and the three-way valve, and is also convenient for coordinating the length of its own pipeline and the pumping speed of the peristaltic pump.

[0062] In some specific embodiments, the surface extraction device provided by the embodiments of the present invention further comprises an integrated component. The back-sucking unit, the electrically controlled multi-way valve, the six-way valve and the electrically controlled unit are fixedly arranged on the integrated component. The integrated component realizes the integrated and integrated arrangement of the components such as the back-sucking unit, the electrically controlled multi-way valve, the six-way valve and the electrically controlled unit.

[0063] Figure 4 A specific implementation of the integrated component is shown. The integrated component is a box body, and there is an installation space on the bottom plate and at least one side plate of the box body. Figure 4As shown, the control circuit 41 and the power module 42 are fixedly arranged on the side plate, and the peristaltic pump 43, the three-way solenoid valve 44 and the six-way valve 45 are fixedly arranged on the bottom plate. The structure integrates the control circuit 41, the power module 42, the peristaltic pump 43, the three-way solenoid valve 44 and the six-way valve 45 into a whole. In addition, the control circuit 41 and the power module 42 as a part of the electric control unit are integrated on the side plate, and the peristaltic pump 43, the three-way solenoid valve 44 and the six-way valve 45 are integrated on the bottom plate, so that the overall structural layout is more reasonable. The injection pump and the sampling unit are independent of the overall structure for sampling and replacement of the extractant. The integrated component can be moved as needed, connected with the back-end analysis equipment to complete the subsequent complete analysis process. In addition, a display screen and a control interface can be set on the side of the integrated component to observe data and adjust the preset time and flow rate of each stage.

[0064] The surface extraction device provided by the embodiment of the present invention overcomes the technical limitations of various existing surface extraction technologies, reduces the dependence on precision mechanical control and the difficulty of operation, avoids the influence of vacuum transmission on liquid flow rate and liquid flow stability, realizes in-situ analysis of remote samples, optimizes the liquid flow stability of continuous analysis and improves the ionization effect. The technical solution of the embodiment of the present invention solves the problems faced by the current liquid surface extraction mass spectrometry analysis technology, such as the complex extraction process and the need for the extraction probe to continuously move back and forth between the sample surface and the analytical instrument. The technical solution of the embodiment of the present invention also gets rid of the need for vacuum extraction. It only needs to align the sampling port of the sampling unit with the analysis area, and one-button operation can be achieved. And the technical solution of the embodiment of the present invention supports the selection of different extractants for different analytes and surface materials to achieve non-invasive in-situ extraction of the surface. In addition, for samples at a distance, the in-situ analysis requirements can be met by replacing the pipeline.

[0065] Furthermore, an embodiment of the present invention also provides a mass spectrometry system, which includes an ion source and a mass spectrometer, and also includes any surface extraction device as described above in the embodiment of the present invention. The surface extraction device is coupled to the mass spectrometer via an ion source. The ion source can specifically be an electrospray ion source or an atmospheric pressure chemical ion source, etc. The surface extraction device completes sample surface collection and sends the solution into the mass spectrometer through the ion source to complete mass spectrometry analysis.

[0066] The mass spectrometry analysis system provided in the embodiment of the present invention realizes handheld automatic in-situ extraction, overcomes the technical limitations of various existing surface extraction technologies, reduces the dependence on precision mechanical control and the difficulty of operation, avoids the influence of vacuum transmission on liquid flow rate and liquid flow stability, realizes long-distance in-situ analysis of samples, optimizes the liquid flow stability of continuous analysis and improves the ionization effect.

[0067] The present invention also provides a surface extraction method, which is used in any of the surface extraction devices or mass spectrometry analysis systems in the above embodiments. Figure 5 As shown, the method includes:

[0068] S501. Adjust the electrically controlled multi-way valve to the first liquid flow channel, put the six-way valve in a sampling state, put the back-sucking unit in a closed state, and use the injection unit to push the extraction liquid at a first flow rate for a first period of time, so that the extraction liquid reaches the sampling cavity through the electrically controlled multi-way valve and the injection port of the sampling unit to contact the sample.

[0069] Figure 7 A timing state diagram of the surface extraction method provided by an embodiment of the present invention is shown. Figure 1 and Figure 7 S501 is described.

[0070] At the beginning of the first time period T1, the electrically controlled multi-way valve 15, such as a three-way solenoid valve, switches the liquid flow channel to S1-S2. The injection unit 12, such as an injection pump, pushes the extraction liquid at a preset first flow rate V1, and the extraction liquid reaches the sample surface through the flow channel "S1-S2-injection port 115-sampling port 117". At T1, the six-way valve 14 is in the sampling state, that is, Figure 1 , Figure 7 In the shown position A, the sucking unit 13 is in a closed state.

[0071] S502, adjusting the electrically controlled multi-way valve to the second liquid flow channel, keeping the states of the suction unit and the six-way valve unchanged, the injection unit pushes the extraction liquid at a second flow rate, and the extraction liquid in the sampling cavity remains in contact with the sample for a second period of time.

[0072] Combination Figure 1 and Figure 7 S502 is described. At the beginning of the second time period T2, the electrically controlled multi-way valve 15 switches the liquid flow channel to S1-S3. The injection unit 12 pushes the liquid at a preset second flow rate V2 and continues until the end of the analysis process. During the entire T2, the extraction liquid in the sampling cavity 118 of the sampling unit 11 remains in contact with the sample, thereby completing the surface extraction.

[0073] exist Figure 7 In the embodiment, V1 is greater than V2, but this size relationship does not constitute the only limitation of the embodiment of the present invention. In practical applications, both speeds are adjustable, for example, V1 can be determined according to the amount of extract liquid required for the experiment, and V2 can be determined by the ionization speed of the back-end mass spectrometer.

[0074] S503, adjusting the suction unit to an open state, keeping the states of the electrically controlled multi-way valve and the six-way valve unchanged for a third period of time, so that the extraction liquid in the sampling cavity is sucked back into the quantitative loop of the six-way valve through the suction port.

[0075] Combination Figure 1 and Figure 7 S503 is described. At the beginning of the third time period T3, the re-absorption unit 13, such as a peristaltic pump, starts to work, and the solution in the sampling cavity 118 flows to the six-way valve 14 through the flow channel "re-absorption port 114-port 2-port 1-port 4-port 3-re-absorption unit 13". The solution enters and fills the quantitative loop 141 in T3. The re-absorption unit 13 remains in an open state and works until the analysis process ends.

[0076] S504, adjusting the six-way valve to the injection state, keeping the electrically controlled multi-way valve in the second liquid flow channel, and the injection unit pushing the extraction liquid at the second flow rate for a fourth time period, so that the liquid in the quantitative loop is pushed toward the analysis device.

[0077] Combination Figure 1 and Figure 7 S504 is described below. At the beginning of the fourth time period T4, the six-way valve 14 is adjusted to the injection state, that is, Figure 1 , Figure 7 The B position is shown. During T4, the electrically controlled multi-way valve 15 maintains the S1-S3 liquid flow channel, and the injection unit 12 continues to push the liquid at V2. Under the push of the injection unit 12, the solution in the quantitative loop 141 is pushed to the rear-end analysis device through the flow channel "S1-S3-Port 6-Port 1-Port 4-Port 5".

[0078] The liquid extraction method provided by the embodiment of the present invention overcomes the technical limitations of various existing surface extraction technologies, reduces the dependence on precision mechanical control and the difficulty of operation, avoids the influence of vacuum transmission on liquid flow rate and liquid flow stability, realizes remote sample in-situ analysis, optimizes the liquid flow stability of continuous analysis and can improve the ionization effect. The technical solution of the embodiment of the present invention is particularly suitable for analytes with dry surfaces.

[0079] Furthermore, the liquid extraction method provided by the embodiment of the present invention also includes:

[0080] In the initial state, the six-way valve is adjusted to the sampling state, and the electrically controlled multi-way valve is adjusted to the second liquid flow channel.

[0081] Combination Figure 1 and Figure 7 The initial state is described as follows: Before T1 begins, the six-way valve 14 is adjusted to the sampling state. The electric-controlled multi-way valve 15 is adjusted to the second liquid flow channel, namely S1-S3.

[0082] Furthermore, the back-sucking unit 13 is in the closed state.

[0083] Optionally, in the initial state, the electrically controlled multi-way valve 15 can also be adjusted to the first liquid flow channel and S1 - S2 .

[0084] Furthermore, an embodiment of the present invention also provides a surface extraction method, which is used in any surface extraction device or mass spectrometry analysis system as described in the above embodiments. Figure 6 As shown, the method includes:

[0085] S601, opening the gas supply unit and continuing for the zeroth time period, so that the dry gas reaches the sample through the dry gas port and the sampling port.

[0086] Figure 8 Another timing state diagram of the surface extraction method provided by the embodiment of the present invention is shown. Figure 1 and Figure 8 S601 is described.

[0087] At the beginning of the zeroth time period T0, the gas supply unit is turned on to input the dry gas, and the dry gas reaches the sample through the dry gas port 116 and the sampling port 117.

[0088] For the sampling of biological tissues, T0 is set before T1 and a gas delivery unit such as a gas pump or gas cylinder is used to deliver dry gas to the wet tissue surface of the analyte within T0 to quickly create a dry surface. At the same time, the airflow can also effectively blow away liquids such as blood and flushing water, reducing background interference caused by irrelevant variables in subsequent analysis. At the end of T0, the gas delivery unit is turned off. The subsequent T1-T4 timing control process after T0 is the same as Figure 7 The same is not repeated here.

[0089] For an ordinary dry surface, the sampling port 117 can be directly placed close to the surface of the analyte to perform subsequent processes.

[0090] S602, adjust the electrically controlled multi-way valve to the first liquid flow channel, put the six-way valve in the sampling state, put the back-suction unit in the closed state, and the injection unit pushes the extraction liquid at a first flow rate for a first period of time, so that the extraction liquid reaches the sampling cavity through the electrically controlled multi-way valve and the injection port of the sampling unit to contact the sample.

[0091] S603, adjust the electrically controlled multi-way valve to the second liquid flow channel, keep the states of the back-suction unit and the six-way valve unchanged, the injection unit pushes the extraction liquid at a second flow rate, and the extraction liquid in the sampling cavity remains in contact with the sample for a second period of time.

[0092] S604, adjusting the suction unit to an open state, maintaining the states of the electrically controlled multi-way valve and the six-way valve unchanged for a third period of time, so that the extraction liquid in the sampling cavity is sucked back into the quantitative loop of the six-way valve through the suction port.

[0093] S605, adjusting the six-way valve to the injection state, keeping the electrically controlled multi-way valve in the second liquid flow channel, and the injection unit pushing the extraction liquid at the second flow rate for a fourth time period, so that the liquid in the quantitative loop is pushed toward the analysis device.

[0094] Furthermore, after the fourth time period ends, the re-sucking unit 13, such as a peristaltic pump, can continue to remain in an open state for a period of time. At this time, the sampling port 117 of the sampling unit 11 is immersed in a standard solvent, and the pipeline is cleaned by re-sucking the standard solvent to reduce sample residues and reduce interference with subsequent experiments.

[0095] Furthermore, before S601, the liquid extraction method provided by the embodiment of the present invention further includes:

[0096] In the initial state, the six-way valve is adjusted to the sampling state, and the electrically controlled multi-way valve is adjusted to the second liquid flow channel.

[0097] The surface extraction method provided by the embodiment of the present invention overcomes the technical limitations of various existing surface extraction technologies, reduces the reliance on precision mechanical control and the difficulty of operation, avoids the influence of vacuum transmission on liquid flow rate and liquid flow stability, realizes in-situ analysis of remote samples, optimizes the liquid flow stability of continuous analysis and can improve the ionization effect. The technical solution of the embodiment of the present invention is particularly suitable for analytes with wet surfaces.

[0098] In some specific embodiments, T0, T1, T2, T3, T4, V1 and V2 can be controlled by an electronic control unit. The flow channel switching of the three-way solenoid valve and the six-way valve can be controlled by the electronic control unit. Each component can be powered by a power module.

[0099] Fig. 9 The mass spectrometry ion flow diagram and mass spectrum diagram obtained by combining the surface extraction device provided by the embodiment of the present invention with the mass spectrometer are shown. The upper part of the figure is the ion flow diagram of the imatinib sample on the surface of the sample plate. The ion flows of the three sampling points showed high consistency in analysis time, ion flow trend and intensity, proving the repeatability and stability of the surface extraction device provided by the embodiment of the present invention. Two pipeline cleanings were inserted in the middle of each sampling point. In the sampling point sampling experiment, the sampling unit directly contacts the sampling point on the sample plate, and during the cleaning process, the sampling unit contacts the blank position on the sample plate that does not contain the sample. Fig. 9 The three mass spectra in the middle and lower parts correspond to the mass spectra at t1, t2, and t3 in the EIC figure above from left to right. The relative intensities of the mass spectra at the three times are obtained by comparing the intensity of the m / z 494 peak at t1. From the comparison of the three peak intensities, it can be seen that the surface extraction device proposed in the embodiment of the present invention has a low residual amount, and the trace residual influence can be removed by cleaning the pipeline without replacing the sampling unit.

[0100] Fig.10 The mass spectrum obtained by direct mass spectrometry analysis of the finger surface without pre-treatment using the surface extraction device and method according to the embodiment of the present invention is shown. Fig.11 The mass spectrum obtained by direct mass spectrometry analysis of the surface of celery leaves without pre-treatment using the surface extraction device and method of the embodiment of the present invention is shown. The technical solution provided by the embodiment of the present invention can directly sample the surface of samples such as skin and vegetable leaves, without the need for additional sample pre-treatment before analysis. The entire sampling and analysis process is pre-set, and the operation is simpler.

[0101] Although the present invention and its advantages have been described in detail, it should be understood that various changes, substitutions and conversions can be made without exceeding the spirit and scope of the present invention defined by the appended claims. Moreover, the scope of the present application is not limited to the specific embodiments of the process, equipment, means, method and step described in the specification. It will be easily understood by those of ordinary skill in the art from the disclosure of the present invention that the process, equipment, means, method or step that performs the function substantially the same as the corresponding embodiment described herein or obtains the result substantially the same as the corresponding embodiment described herein, existing and future to be developed can be used according to the present invention. Therefore, the appended claims are intended to include such process, equipment, means, method or step within their scope.

Claims

1. A surface extraction device, characterized in that: include: A sampling unit, an injection unit, a back-suction unit, a six-way valve with a quantitative loop, an electrically controlled multi-way valve and an air supply unit; the sampling unit is coaxially provided with a back-suction channel, an injection channel and a dry gas channel from the inside to the outside; the back-suction channel, the injection channel and the dry gas channel are connected to the back-suction port, the injection port and the dry gas port of the sampling unit at one end on the same side, and the other end forms a sampling port together; a sampling cavity is formed at the sampling port; the dry gas channel is provided with an air hole at a position higher than the sampling cavity; the injection unit is connected to the six-way valve and the injection port respectively through the electrically controlled multi-way valve; the back-suction unit and the back-suction port are connected to the six-way valve respectively; the air supply unit is connected to the dry gas port; the ends of the back-suction channel and the injection channel are recovered inwardly at the sampling port relative to the end of the dry gas channel to form the sampling cavity; At least two liquid flow channels are arranged in the electrically controlled multi-way valve.

2. The surface extraction device according to claim 1, characterized in that: The surface extraction device further comprises an electric control unit; the electric control unit is electrically connected to the injection unit, the suck-back unit, the six-way valve and the electric-controlled multi-way valve respectively.

3. The surface extraction device according to claim 2, characterized in that: The injection unit and the electrically controlled multi-way valve, the sampling unit and the electrically controlled multi-way valve, the six-way valve and the air supply unit, and the six-way valve and the back-suction unit are connected by pipelines through hoses.

4. The surface extraction device according to claim 3, characterized in that: The surface extraction device further comprises: an integrated component; the suck-back unit, the electrically controlled multi-way valve, the six-way valve and the electrically controlled unit are fixedly arranged on the integrated component.

5. A mass spectrometry system, comprising a mass spectrometer and an ion source, characterized in that: It also includes a surface extraction device as described in any one of claims 1 to 4; the surface extraction device is coupled to the mass spectrometer via the ion source.

6. A surface extraction method, used in the surface extraction device according to any one of claims 1 to 4 or the mass spectrometry analysis system according to claim 5, characterized in that: include: The electrically controlled multi-way valve is adjusted to the first liquid flow channel, the six-way valve is in the sampling state, the back-sucking unit is in the closed state, the injection unit pushes the extraction liquid at a first flow rate for a first time period, so that the extraction liquid reaches the sampling cavity through the electrically controlled multi-way valve and the injection port of the sampling unit and contacts the sample; the electrically controlled multi-way valve is adjusted to the second liquid flow channel, the back-sucking unit and the six-way valve are kept unchanged, the injection unit pushes the extraction liquid at a second flow rate, the extraction liquid in the sampling cavity is kept in contact with the sample for a second time period; the back-sucking unit is adjusted to the open state, the electrically controlled multi-way valve and the six-way valve are kept unchanged for a third time period, so that the extraction liquid in the sampling cavity is sucked back into the quantitative loop of the six-way valve through the back-sucking port; the six-way valve is adjusted to the injection state, the electrically controlled multi-way valve is kept in the second liquid flow channel, the injection unit pushes the extraction liquid at the second flow rate for a fourth time period, so that the liquid in the quantitative loop is pushed toward the analysis device.

7. The surface extraction method according to claim 6, characterized in that: The method further includes: before the first time period, opening the gas delivery unit and continuing for a zeroth time period, so that the dry gas reaches the sample through the dry gas port and the sampling port.

8. The surface extraction method according to claim 7, characterized in that: The method further includes: in an initial state, adjusting the six-way valve to the sampling state, and adjusting the electrically controlled multi-way valve to the second liquid flow channel.

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