Connecting device and method for supercritical fluid chromatography-mass spectrometry

Abstract

The present application relates to a connection device and method for supercritical fluid chromatography-mass spectrometry wherein the device comprises: a fluid introduction device for introducing a sample-containing high pressure fluid flowing out of a chromatographic column to an outlet of an ion source; the fluid outflow device is used for introducing the high-pressure fluid into the mass spectrum system and refluxing the rest of the fluid so as to maintain the pressure in the connecting device; and the pressure control device is connected with the fluid outflow device, and the pressure control device controls the pressure of the high-pressure fluid from the inlet to the outlet based on the pressure in the connecting device and the pressure of the automatic back pressure regulator ABPR so as to control the pressure in the structure to meet preset stable conditions. According to the embodiment of the invention, the fluid introduction device, the fluid outflow device and the pressure control device are included, all the parts have a synergistic effect, fluid transmission and pressure stability in a high-pressure environment are effectively guaranteed, and stable transmission of supercritical fluid is achieved by improving a flow channel structure.

Description

Technical Field

[0001] The present application relates to the technical field of mass spectrometry ion sources, and in particular to a connection device and method for supercritical fluid chromatography-mass spectrometry. Background Art

[0002] Currently, the interface designs for supercritical fluid chromatography-mass spectrometry can be divided into two categories: full-flow interfaces and split-flow interfaces.

[0003] In related technologies, full-flow interfaces are mainly implemented through the following methods: (1) direct introduction using a throttle; (2) pressure control using a liquid pump; (3) use of an ABPR (Automated Back-Pressure Regulator).

[0004] However, related technologies usually find it difficult to maintain sufficient pressure at the outlet of the ion source, which may cause precipitation of substances in the internal mobile phase, resulting in pressure fluctuations and affecting the ionization efficiency of the sample; usually more liquid flows to the mass spectrometer, which increases the liquid processing burden in mass spectrometry analysis and may also lead to a decrease in ionization efficiency; due to the use of a three-way mixer, a large extra-column dead volume is often generated, resulting in a decrease in sample separation effect; in existing mobile phase systems, additional liquid is often required to maintain the solubility of the mobile phase, which increases the complexity of the system and urgently needs to be improved. Summary of the Invention

[0005] The present application provides a connection device and method for supercritical fluid chromatography-mass spectrometry to solve the problems that related technologies usually have difficulty in maintaining sufficient pressure at the outlet of the ion source, which may cause precipitation of substances in the internal mobile phase, resulting in pressure fluctuations and affecting the ionization efficiency of the sample; usually a large amount of liquid flows to the mass spectrometer, which increases the liquid processing burden in mass spectrometry analysis and may also lead to a decrease in ionization efficiency; due to the use of a three-way mixer, a large extra-column dead volume is often generated, resulting in a decrease in sample separation effect; in existing mobile phase systems, additional liquid is often required to maintain the solubility of the mobile phase, which increases the complexity of the system.

[0006] In a first aspect, an embodiment of the present application provides a connecting device for supercritical fluid chromatography-mass spectrometry, comprising: a fluid introduction device for introducing a high-pressure fluid containing a sample flowing out of a chromatographic column to an outlet of an ion source; a fluid outflow device for introducing the high-pressure fluid into a mass spectrometry system and reflowing the remaining fluid to maintain the pressure inside the connecting device; a pressure control device, the pressure control device being connected to the fluid outflow device, and the pressure control device controlling the pressure of the high-pressure fluid from the inlet to the outlet based on the pressure inside the connecting device and the pressure of an automatic back pressure regulator (ABPR) to control the pressure inside the structure to meet a preset stability condition.

[0007] Optionally, in one embodiment of the present application, the fluid introduction device includes: a long tube, which is a double-layer sleeve structure and is used to maintain the high-pressure fluid to the outlet of the ion source.

[0008] Optionally, in one embodiment of the present application, the long tube includes: a thin tube, which is an inner tube extending from the inlet to the outlet and is used to control the outlet diameter and flow rate of the high-pressure fluid; and a hose, which is an outer tube used to wrap the thin tube.

[0009] Optionally, in one embodiment of the present application, the fluid outflow device includes: an outer tube, one end of the outer tube is fixed to a tee, and the other end forms a compression-resistant port for wrapping the long tube to control the amount of liquid flowing into the mass spectrometry system, and the outer tube serves as the outlet of the ion source.

[0010] Optionally, in one embodiment of the present application, the pressure control device includes: an automatic back pressure regulator ABPR, used to maintain the pressure of the high-pressure fluid from the inlet to the outlet.

[0011] Optionally, in one embodiment of the present application, the pressure control device further includes: an air pump, configured to control the pressure of the mass spectrometry system to meet the preset stability condition.

[0012] Optionally, in one embodiment of the present application, the pressure control device further includes: a liquid storage bottle for collecting the high-pressure fluid passing through the automatic back pressure regulator.

[0013] A second aspect of the present application provides a connection method for supercritical fluid chromatography-mass spectrometry, comprising the following steps: directing a high-pressure fluid containing a sample flowing out of a chromatographic column to the outlet of an ion source; introducing the high-pressure fluid into a mass spectrometry system, and refluxing the remaining fluid to maintain the pressure inside the connection device; and controlling the pressure of the high-pressure fluid from the inlet to the outlet based on the pressure inside the connection device and the pressure of an automatic back pressure regulator (ABPR) to control the pressure inside the structure to meet a preset stability condition.

[0014] Optionally, in one embodiment of the present application, introducing the high-pressure fluid containing the sample flowing out of the chromatographic column into the outlet of the ion source includes: maintaining the high-pressure fluid to the outlet of the ion source.

[0015] Optionally, in one embodiment of the present application, maintaining the pressure to the outlet of the ion source includes: extending from the inlet to the outlet to control the outlet diameter and flow rate of the high-pressure fluid.

[0016] Optionally, in one embodiment of the present application, introducing the high-pressure fluid into the mass spectrometry system includes: controlling the amount of liquid flowing into the mass spectrometry system.

[0017] The embodiment of the present application can adopt a double-layer sleeve (glass capillary and PEEK (Poly ether etherketone) hose) structure, so that high-pressure fluid can be transmitted in a more stable manner. At the same time, the outer PEEK hose provides additional physical protection, extending the service life of the device. Through the necking design and stretching treatment of the glass capillary, the outlet diameter and flow rate of the fluid can be better controlled, ensuring the controllability and accuracy of the liquid flow during mass spectrometry analysis. Through the synergistic effect of ABPR and the air pump, the pressure from fluid introduction to fluid outflow can be effectively maintained stable, avoiding problems such as reduced solubility of the mobile phase caused by unstable pressure in the prior art, improving the reliability of the system and simplifying the operating process. The separated components enter the ionization region with almost zero dead volume, which can maximize the resolution of the chromatography. This solves the problems that related technologies usually have difficulty in maintaining sufficient pressure at the outlet of the ion source, which may cause precipitation of substances in the internal mobile phase, resulting in pressure fluctuations and affecting the ionization efficiency of the sample; usually more liquid flows to the mass spectrometer, which increases the liquid processing burden in mass spectrometry analysis and may also lead to a decrease in ionization efficiency; due to the use of a three-way mixer, a large extra-column dead volume is often generated, resulting in a decrease in sample separation effect; in existing mobile phase systems, additional liquid is often required to maintain the solubility of the mobile phase, which increases the complexity of the system.

[0018] Additional aspects and advantages of the present application will be given in part in the description below, and in part will become apparent from the description below, or will be learned through practice of the present application. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] The above and / or additional aspects and advantages of the present application will become apparent and easily understood from the following description of the embodiments in conjunction with the accompanying drawings, in which:

[0020] Figure 1 Schematic diagram of a full-flow SFC (Supercritical Fluid Chromatography)-MS (Mass Spectrometry) interface in related technology;

[0021] Figure 2 Schematic diagram of a split-flow SFC-MS interface in the related art;

[0022] Figure 3 Schematic diagram of a structural connection device for supercritical fluid chromatography-mass spectrometry provided according to an embodiment of the present application;

[0023] Figure 4 Schematic diagram of a high-pressure fluid connection device according to one embodiment of the present application;

[0024] Figure 5 This is a physical diagram of an outlet of a fluid outflow device according to one embodiment of the present application;

[0025] Figure 6 The present invention provides a flow chart of a method for connecting supercritical fluid chromatography-mass spectrometry according to an embodiment of the present application. DETAILED DESCRIPTION

[0026] The following describes in detail embodiments of the present application, examples of which are shown in the accompanying drawings, wherein the same or similar reference numerals throughout represent the same or similar elements or elements having the same or similar functions. The embodiments described below with reference to the accompanying drawings are exemplary and are intended to be used to explain the present application, and should not be construed as limiting the present application.

[0027] The following describes the connection device and method for supercritical fluid chromatography-mass spectrometry in accordance with an embodiment of the present application with reference to the accompanying drawings. In view of the fact that the related technologies mentioned in the above background technology are generally difficult to maintain sufficient pressure at the outlet of the ion source, which may cause the precipitation of substances in the internal mobile phase, resulting in pressure fluctuations and affecting the ionization efficiency of the sample; generally, more liquid flows to the mass spectrometer, which increases the processing burden of the liquid in the mass spectrometry analysis and may also lead to a decrease in the ionization efficiency; due to the use of a three-way mixer, a large dead volume outside the column is often generated, resulting in a decrease in the sample separation effect; in the existing mobile phase system, additional liquid is often required to maintain the solubility of the mobile phase, which increases the complexity of the system. The present application provides a connection method for supercritical fluid chromatography-mass spectrometry, in which a double-layer sleeve (glass capillary and P) can be used. The PEEK hose) structure enables high-pressure fluids to be transmitted in a more stable manner. At the same time, the outer PEEK hose provides additional physical protection, extending the service life of the device. The necking design and stretching of the glass capillary can better control the outlet diameter and flow rate of the fluid, ensuring the controllability and accuracy of the liquid flow during mass spectrometry analysis. Through the synergistic effect of ABPR and the air pump, the pressure from fluid introduction to fluid outflow can be effectively maintained stable, avoiding problems such as reduced mobile phase solubility caused by unstable pressure in the existing technology, improving the reliability of the system and simplifying the operating process. The separated components enter the ionization area with almost zero dead volume, which can maximize the resolution of the chromatography. This solves the problems that related technologies usually have difficulty in maintaining sufficient pressure at the outlet of the ion source, which may cause precipitation of substances in the internal mobile phase, resulting in pressure fluctuations and affecting the ionization efficiency of the sample; usually more liquid flows to the mass spectrometer, which increases the liquid processing burden in mass spectrometry analysis and may also lead to a decrease in ionization efficiency; due to the use of a three-way mixer, a large extra-column dead volume is often generated, resulting in a decrease in sample separation effect; in existing mobile phase systems, additional liquid is often required to maintain the solubility of the mobile phase, which increases the complexity of the system.

[0028] Before introducing the connection device for supercritical fluid chromatography-mass spectrometry, the relevant background of this application is introduced:

[0029] Methods of introducing full flow using a restrictor, such as Figure 1 (A) As shown. The restrictor acts as a passive pressure regulator. Heating the outlet of the restrictor or heating the entire restrictor can alleviate the cooling of the SFC mobile phase and the precipitation of analytes caused by rapid decompression. The main advantages of using a restrictor are simple structure and small dead volume outside the column. The corresponding disadvantages are reduced operational flexibility and lack of stability. The pressure drop across the restrictor is passively controlled by the density, viscosity and mass flow rate of the internal liquid. Therefore, in scenarios where the mobile phase flow rate and composition vary, it is difficult to achieve the desired effect using a designed restrictor.

[0030] Full flow interface solution for pressure flow control such as Figure 1 As shown in (B). All components effluent from the chromatographic column first pass through an ultraviolet (UV) detector. A liquid pump then delivers a pressure-regulated fluid miscible with CO2, which mixes with the mobile phase in a zero-dead-volume T-piece before flowing to the ionization source. This pressure-regulated flow can incorporate components completely different from the mobile phase, providing the opportunity to introduce different solvents and additives to enhance the mass spectrometric signal without affecting the supercritical fluid chromatography (SFC) separation process. However, despite these advantages, pressure flow control interfaces are not flexible enough because the inner diameter of the transfer tubing determines the range of compatible flow / pressure combinations, requiring different tubing to be selected under different conditions. Furthermore, this method requires a liquid pump and T-piece capable of providing pulse-free flow, which increases the dead volume outside the column, and the additional liquid flow also increases the solvent load in the ionization source. Depending on the target pressure, the required amount of solvent addition also varies, which in turn changes the analyte concentration and affects the quantitative results.

[0031] With the practical application of small-volume automatic back pressure regulators (ABPRs), it has become possible to introduce ABPRs into the interface. Standard-size ABPRs usually significantly increase the dead volume, resulting in chromatographic peak broadening and loss of chromatographic resolution. The use of small-volume ABPRs effectively avoids this problem. However, this move has caused another problem. The mobile phase flowing out of the ABPR is a completely decompressed CO2 phase, and its solubility may not guarantee that all analytes are transmitted to the mass spectrometer. In particular, if the tubing is too long, this problem will be more serious. For example Figure 1 As shown in (C), this scheme adds a make-up pump to address analyte precipitation. The make-up pump can be added before or after ABPR. Duval et al. compared the addition of the make-up pump before and after ABPR using APCI as the ionization source and achieved similar quantitative results.

[0032] In a split flow interface, only a small portion of the SFC mobile phase is diverted to the ionization source, while the majority exits through the ABPR. Depending on the relative position of the mass spectrometer and UV detector, two schemes can be used: pre-split flow and post-split flow.

[0033] Figure 2(A) is a pre-split interface solution. A zero dead volume tee is used at the outlet of the SFC column to transfer a small portion (1%-20%) of the mobile phase to the ionization source inlet, and the rest enters the ABPR through the UV detector. In order to ensure that the flow to the MS is small, the flow channel to the MS should provide a stronger flow resistance than the ABPR. Since the splitter is under the control of the ABPR, the interface has good flexibility and the pressure in the interface can be adjusted by the ABPR to adapt to different conditions. Under the premise of limiting the length of the pipeline and ensuring the minimum dead volume of the interface, the chromatographic separation results can be completely transferred from the SFC to the MS using this interface. However, this setting means that both the UV and MS detectors do not detect the entire mobile phase flowing out of the chromatographic column, which may lead to inaccurate and incomplete measurement results.

[0034] Figure 2 (B) is the mainstream interface solution currently offered by SFC-MS instrument vendors. This interface consists of two zero-dead-volume tees connected in series. A make-up liquid pumped by a liquid pump is added to the first tee, while a small portion of the mobile phase is transferred to the ionization source through the second tee, with the remainder discharged through the ABPR. This interface fully utilizes the ABPR and make-up liquid pump to flexibly adjust the liquid flow rate and composition delivered to the ionization source, reducing sample precipitation within the interface and achieving higher sensitivity.

[0035] Specifically, Figure 3 This is a schematic structural diagram of a connection device for supercritical fluid chromatography-mass spectrometry provided in an embodiment of the present application.

[0036] like Figure 3 As shown, the connecting device 10 for supercritical fluid chromatography-mass spectrometry includes: a fluid introduction device 100, a fluid outflow device 200 and a pressure control device 300.

[0037] Specifically, the fluid introducing device 100 is used to introduce the high-pressure fluid containing the sample flowing out of the chromatographic column to the outlet of the ion source.

[0038] The fluid introduction device 100 in the embodiment of the present application is used to guide the high-pressure fluid containing the sample flowing out of the chromatographic column to a position very close to the outlet of the ion source. The present application achieves stable transmission of supercritical fluid by improving the flow channel structure.

[0039] Optionally, in one embodiment of the present application, the fluid introduction device 100 includes: a long tube, which is a double-layer sleeve structure and is used to maintain the high-pressure fluid to the outlet of the ion source.

[0040] It is understandable that if Figure 4 As shown, the long tube (No. 2) in the embodiment of the present application is the core component of the fluid introduction device.

[0041] During the actual implementation process, the long tube in the embodiment of the present application adopts a double-layer sleeve structure to maintain the high-pressure fluid to the outlet of the ion source. Through the innovative double-layer sleeve structure, the pressure is effectively maintained to the outlet of the ion source, solving the problem of the inability to maintain pressure in the prior art.

[0042] Optionally, in one embodiment of the present application, the long tube includes: a thin tube, which is an inner tube extending from the inlet to the outlet and is used to control the outlet diameter and flow rate of the high-pressure fluid; and a hose, which is an outer tube used to wrap the thin tube.

[0043] Specifically, the capillary tube in the embodiment of the present application is an inner tube, extending from the inlet to the outlet, and is used to control the outlet diameter and flow rate of the high-pressure fluid, and the hose is an outer tube, which is used to wrap the capillary tube.

[0044] The embodiment of the present application adopts a double-layer sleeve design, with the inner tube directly connected to the outlet, which can effectively maintain the pressure to the outlet of the ion source. This design makes the pressure transmission more uniform and stable, thereby improving the ionization efficiency and sensitivity of the analyte.

[0045] Among them, the capillary in the embodiment of the present application is a glass or quartz capillary. The design of the glass capillary is such that it extends from the inlet to the outlet. The outlet is processed by laser stretching technology to reduce the diameter so that it can be closer to the outlet of the glass outer tube (number 3) to achieve more precise fluid control. The introduction device is connected to the outlet of the chromatographic column (number 1) to ensure stable transmission of high-pressure fluid. The hose in the embodiment of the present application is a polyetheretherketone (PEEK) hose, which is used to wrap the glass capillary and provide protection.

[0046] The fluid outflow device 200 is used to introduce high-pressure fluid into the mass spectrometry system and to return the remaining fluid to maintain the pressure inside the connecting device.

[0047] In the actual implementation process, Figure 5 As shown, all liquids except those introduced into the mass spectrometer will flow back. Therefore, the fluid outflow device 200 in the embodiment of the present application is responsible for introducing a portion of the high-pressure fluid into the mass spectrometry system while ensuring that the remaining fluid flows back to maintain the pressure inside the connecting device.

[0048] The embodiments of the present application greatly reduce the amount of liquid flowing to the mass spectrometer by optimizing the structural design, thereby reducing the impact of the liquid on the mass spectrometer system and improving the ionization efficiency of the analyte. This not only simplifies the ionization process but also helps to improve the sensitivity of the analysis.

[0049] Optionally, in one embodiment of the present application, the fluid outflow device 200 includes: an outer tube, one end of the outer tube is fixed to a tee, and the other end forms a compression-resistant port for wrapping the long tube to control the amount of liquid flowing into the mass spectrometry system, and the outer tube serves as the outlet of the ion source.

[0050] It is understandable that if Figure 4 As shown, the outer tube in the embodiment of the present application can be a glass outer tube (number 3), which is a key component.

[0051] In the actual implementation process, the outer tube in the embodiment of the present application is used to wrap the long tube, one end is fixed to the three-way joint (number 4), and the other end is formed into a compression-resistant port by melt-resolidification technology. The inner diameter of the constriction can reach 10 microns, which can effectively control the internal pressure and reduce the amount of liquid flowing out. The outer tube serves as the outlet of the ion source. The fluid outflow device ensures that a very small part of the fluid flows out for mass spectrometry analysis, and the other part flows to the three-way joint (number 4) through the space between the glass outer tube and the long tube to enter the pressure regulating system. Through this device, the liquid flowing out of the chromatogram enters the ionization region of the mass spectrum in a manner of almost zero dead volume, maintaining the resolution of the chromatographic separation to the greatest extent.

[0052] This embodiment utilizes a double-layer cannula (glass capillary and PEEK hose) to ensure a more stable transmission of high-pressure fluids. The outer PEEK hose provides additional physical protection, extending the life of the device. The necking design and stretched glass capillary tube allow for better control of the fluid outlet diameter and flow rate, ensuring controllable and precise flow during mass spectrometry analysis.

[0053] The pressure control device 300 is connected to the fluid outflow device 200. The pressure control device 300 controls the pressure of the high-pressure fluid from the inlet to the outlet based on the pressure inside the connecting device and the pressure of the automatic back pressure regulator ABPR to meet the preset stability conditions according to the pressure inside the pressure control structure.

[0054] It can be understood that the preset stability condition in the embodiment of the present application can be to stabilize the high-pressure environment inside the entire structure.

[0055] In actual implementation, the pressure control device 300 in the embodiment of the present application is connected to the fluid introduction device 100 and the fluid outflow device 200. Based on the pressure within the connection device and the pressure of the automatic back pressure regulator (ABPR), the pressure control device 300 controls the pressure of the high-pressure fluid from the inlet to the outlet, thereby stabilizing the high-pressure environment within the pressure control structure. The pressure control device 300 ensures effective pressure maintenance throughout the entire process from fluid introduction to fluid outflow, ensuring the stability of the mobile phase.

[0056] The synergistic effect of the various components of this application effectively ensures fluid transmission and pressure stability under high-pressure environments, better maintaining system pressure and ensuring fluid solubility, without the need for additional supplemental fluid. This significantly simplifies the structure of the entire device, reducing operational difficulty and maintenance costs while also improving system reliability and stability. Due to better pressure maintenance, this application eliminates the need for additional supplemental fluid, simplifying system design and reducing maintenance and operational complexity.

[0057] By better maintaining pressure and reducing the amount of liquid entering the mass spectrometer, this application significantly improves the ionization efficiency and signal intensity of mass spectrometry analysis, thereby improving the accuracy and sensitivity of the overall analysis. By reducing the dead volume outside the column and optimizing the control of the mobile phase, the separation resolution of the system is improved. The elimination of the need for additional replenishing fluid makes the system structure simpler, operation and maintenance more convenient, and also reduces the risk of system errors. By reducing complex accessories and optimizing the design, the cost of the system in manufacturing and operation is also reduced, increasing economic benefits.

[0058] It should be noted that the preset stability conditions can be set by those skilled in the art according to actual conditions and are not specifically limited here.

[0059] Optionally, in one embodiment of the present application, the pressure control device 300 includes: an automatic back pressure regulator ABPR, which is used to maintain the pressure of the high-pressure fluid from the inlet to the outlet.

[0060] Among them, the automatic back pressure regulator ABPR (number 5) in the embodiment of the present application is used to maintain the pressure of the high-pressure fluid from the inlet to the outlet. After the fluid flows out of the tee 4, it enters the ABPR (number 5) through the pipeline.

[0061] Optionally, in one embodiment of the present application, the pressure control device 300 further includes: an air pump, configured to control the pressure of the mass spectrometry system to meet a preset stability condition.

[0062] Among them, the air pump (number 7) in the embodiment of the present application can assist the ABPR (number 5) in working and maintain the pressure stability of the entire system.

[0063] It should be noted that the preset stability conditions can be set by those skilled in the art according to actual conditions and are not specifically limited here.

[0064] Optionally, in one embodiment of the present application, the pressure control device 300 further includes: a liquid storage bottle for collecting high-pressure fluid passing through the automatic back pressure regulator.

[0065] It is understandable that if Figure 4As shown, the liquid storage bottle in the embodiment of the present application can be a waste liquid bottle (number 8). In the embodiment of the present application, the fluid passing through the ABPR (number 5) will enter the liquid storage bottle (number 8) through the pipeline to collect the high-pressure fluid passing through the automatic back pressure regulator.

[0066] The embodiments of the present application, through the synergistic effect of the ABPR and the air pump, effectively maintain stable pressure from fluid introduction to fluid discharge, avoiding problems such as reduced mobile phase solubility caused by unstable pressure in the prior art, improving system reliability and simplifying the operational process. This eliminates the need for a three-way mixing device, reduces extra-column dead volume, and allows separated components to enter the ionization region with virtually zero dead volume, maximizing chromatographic resolution.

[0067] According to the connection device for supercritical fluid chromatography-mass spectrometry proposed in the embodiment of the present application, a double-layer sleeve (glass capillary and PEEK hose) structure can be adopted, so that high-pressure fluid can be transmitted in a more stable manner. At the same time, additional physical protection is provided by the outer layer of PEEK hose, thereby extending the service life of the device. Through the necking design and the stretching treatment of the glass capillary, the outlet diameter and flow rate of the fluid can be better controlled, ensuring the controllability and accuracy of the liquid flow rate during mass spectrometry analysis. Through the synergistic effect of ABPR and the air pump, the pressure from fluid introduction to fluid outflow can be effectively maintained stable, avoiding problems such as reduced solubility of the mobile phase caused by unstable pressure in the prior art, improving the reliability of the system and simplifying the operation process. The separated components enter the ionization region in a manner with almost zero dead volume, which can maximize the resolution of the chromatography. By avoiding the three-way mixing design, the extra-column dead volume can be significantly reduced, ensuring that the loss of the analyte during transmission is minimized, thereby maintaining the resolution of the chromatographic separation and improving the sensitivity of mass spectrometry detection. This solves the problem that related technologies usually have difficulty in maintaining sufficient pressure at the outlet of the ion source, which may cause precipitation of substances in the internal mobile phase, resulting in pressure fluctuations and affecting the ionization efficiency of the sample; usually more liquid flows to the mass spectrometer, which increases the liquid processing burden in mass spectrometry analysis and may also lead to a decrease in ionization efficiency; due to the use of a three-way mixer, a large extra-column dead volume is often generated, resulting in a decrease in sample separation effect; in existing mobile phase systems, additional liquid is often required to maintain the solubility of the mobile phase, which increases the complexity of the system.

[0068] Next, a connection method for supercritical fluid chromatography-mass spectrometry proposed according to an embodiment of the present application will be described with reference to the accompanying drawings.

[0069] Figure 6 This is a flow chart of a method for connecting supercritical fluid chromatography-mass spectrometry according to an embodiment of the present application.

[0070] like Figure 6As shown, the connection method for supercritical fluid chromatography-mass spectrometry includes the following steps:

[0071] In step S601 , a high-pressure fluid containing a sample flowing out of a chromatographic column is guided to an outlet of an ion source.

[0072] In step S602, the high-pressure fluid is introduced into the mass spectrometry system, and the remaining fluid is refluxed to maintain the pressure inside the connecting device.

[0073] In step S603, based on the pressure inside the connection device and the pressure of the automatic back pressure regulator ABPR, the pressure of the high-pressure fluid from the inlet to the outlet is controlled to control the pressure inside the structure to meet a preset stability condition.

[0074] Optionally, in one embodiment of the present application, introducing the high-pressure fluid containing the sample flowing out of the chromatography column into the outlet of the ion source includes: maintaining the high-pressure fluid at the outlet of the ion source.

[0075] Optionally, in one embodiment of the present application, maintaining the high-pressure fluid to the outlet of the ion source includes: extending from the inlet to the outlet for controlling the outlet diameter and flow rate of the high-pressure fluid.

[0076] It should be noted that the aforementioned explanation of the embodiment of the connection device for supercritical fluid chromatography-mass spectrometry is also applicable to the connection method for supercritical fluid chromatography-mass spectrometry in this embodiment, and will not be repeated here.

[0077] According to the connection method for supercritical fluid chromatography-mass spectrometry proposed in the embodiment of the present application, a double-layer sleeve (glass capillary and PEEK hose) structure can be adopted, so that the high-pressure fluid can be transmitted in a more stable manner. At the same time, additional physical protection is provided by the outer layer of PEEK hose to extend the service life of the device. Through the necking design and stretching treatment of the glass capillary, the outlet diameter and flow rate of the fluid can be better controlled, ensuring the controllability and accuracy of the liquid flow rate during mass spectrometry analysis. Through the synergistic effect of ABPR and the air pump, the pressure from fluid introduction to fluid outflow can be effectively maintained stable, avoiding problems such as reduced solubility of the mobile phase caused by unstable pressure in the prior art, improving the reliability of the system and simplifying the operating process. The separated components enter the ionization region with almost zero dead volume, which can maximize the resolution of the chromatography. This solves the problem that related technologies usually have difficulty in maintaining sufficient pressure at the outlet of the ion source, which may cause precipitation of substances in the internal mobile phase, resulting in pressure fluctuations and affecting the ionization efficiency of the sample; usually more liquid flows to the mass spectrometer, which increases the liquid processing burden in mass spectrometry analysis and may also lead to a decrease in ionization efficiency; due to the use of a three-way mixer, a large extra-column dead volume is often generated, resulting in a decrease in sample separation effect; in existing mobile phase systems, additional liquid is often required to maintain the solubility of the mobile phase, which increases the complexity of the system.

[0078] In the description of this specification, the description with reference to the terms "one embodiment", "some embodiments", "example", "specific example", or "some examples" means that the specific features, structures, materials or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present application. In this specification, the schematic representations of the above terms do not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described can be combined in any one or N embodiments or examples in a suitable manner. In addition, those skilled in the art can combine and combine different embodiments or examples described in this specification and features of different embodiments or examples without contradiction.

[0079] Furthermore, the terms "first" and "second" are used for descriptive purposes only and should not be understood to indicate or imply relative importance or implicitly specify the number of technical features indicated. Thus, a feature specified as "first" or "second" may explicitly or implicitly include at least one such feature. In the description of this application, "N" means at least two, for example, two, three, etc., unless otherwise specifically defined.

[0080] Any process or method description in a flowchart or otherwise described herein may be understood to represent a module, fragment or portion of code comprising one or N executable instructions for implementing a custom logical function or process step, and the scope of the preferred embodiments of the present application includes alternative implementations in which functions may be performed in a different order than shown or discussed, including performing functions in a substantially simultaneous manner or in a reverse order depending on the functions involved, which should be understood by those skilled in the art to which the embodiments of the present application pertain.

Claims

1. A connection device for supercritical fluid chromatography-mass spectrometry, characterized in that: include: a fluid introducing device for introducing the high-pressure fluid containing the sample flowing out of the chromatographic column to the outlet of the ion source; a fluid outflow device, configured to introduce the high-pressure fluid into the mass spectrometry system and to return the remaining fluid to maintain the pressure inside the connecting device; A pressure control device is connected to the fluid outflow device. The pressure control device controls the pressure of the high-pressure fluid from the inlet to the outlet based on the pressure inside the connecting device and the pressure of the automatic back pressure regulator ABPR, so as to control the pressure inside the structure to meet the preset stability condition.

2. The device according to claim 1, characterized in that The fluid introduction device comprises: The long tube is a double-layer sleeve structure and is used to maintain the high-pressure fluid to the outlet of the ion source.

3. The device according to claim 2, characterized in that The long tube comprises: a capillary tube, the capillary tube being an inner tube, extending from the inlet to the outlet, and being used to control the outlet diameter and flow rate of the high-pressure fluid; The hose is an outer tube used to wrap the thin tube.

4. The device according to claim 2, characterized in that The fluid outflow device comprises: An outer tube, one end of which is fixed to a tee, and the other end of which forms a compression-resistant opening for wrapping the long tube to control the amount of liquid flowing into the mass spectrometry system, and the outer tube serves as the outlet of the ion source.

5. The device according to claim 1, characterized in that The pressure control device comprises: An automatic back pressure regulator (ABPR) is used to maintain the pressure of the high-pressure fluid from the inlet to the outlet.

6. The device according to claim 1, characterized in that The pressure control device further comprises: An air pump is used to control the pressure of the connecting device to meet the preset stability condition.

7. The device according to claim 1, characterized in that The pressure control device further comprises: A liquid storage bottle is used to collect the high-pressure fluid passing through the automatic back pressure regulator.

8. A method for connecting supercritical fluid chromatography-mass spectrometry, characterized in that: The supercritical fluid chromatography-mass spectrometry connection device according to any one of claims 1 to 7 comprises the following steps: directing the high-pressure fluid containing the sample flowing out of the chromatographic column to the outlet of the ion source; Introducing the high-pressure fluid into the mass spectrometry system and refluxing the remaining fluid to maintain the pressure inside the connecting device; Based on the pressure inside the connecting device and the pressure of the automatic back pressure regulator (ABPR), the pressure of the high-pressure fluid from the inlet to the outlet is controlled to control the pressure inside the structure to meet a preset stability condition.

9. The method according to claim 8, characterized in that The method of directing the high-pressure fluid containing the sample flowing out of the chromatographic column to the outlet of the ion source comprises: The high-pressure fluid is maintained to the outlet of the ion source.

10. The method according to claim 9, characterized in that The step of maintaining the high-pressure fluid to the outlet of the ion source comprises: Extending from the inlet to the outlet, it is used to control the outlet diameter and flow rate of the high-pressure fluid.

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