An electrospray ion source device without auxiliary gas bottle

Abstract

The present invention relates to the technical field of mass spectrometry detection, and discloses an electrospray ion source device without an auxiliary gas cylinder, comprising a peristaltic pump, a syringe, an electrophoresis capillary, a metal spray needle, an ionization voltage source, and a negative pressure ionization chamber; the metal spray needle is fixed in the negative pressure ionization chamber and connected to one end of the electrophoresis capillary; the syringe is connected to the electrophoresis capillary, and the peristaltic pump pushes the sample solution in the syringe into the electrophoresis capillary and reaches the metal spray needle; the ionization voltage source is electrically connected to the metal spray needle; the negative pressure ionization chamber is provided with an intracavity air pressure regulating valve; and a mass spectrometer injection port is provided in the negative pressure ionization chamber relative to the metal spray needle. The electrospray ion source device of the present invention can realize electrospraying without an additional auxiliary gas cylinder, significantly reduces the complexity of the system, has high ionization efficiency, and strong anti-pollution robustness, and is convenient for expanding its functions while miniaturizing a miniature mass spectrometer.

Description

Technical Field

[0001] The invention relates to the technical field of mass spectrometry detection, in particular to an electrospray ion source device without an auxiliary gas bottle. Background Art

[0002] As a highly sensitive chemical analysis method that can quantify and quantify, mass spectrometry has been widely used in the field of analysis and detection. Mass spectrometry systems are usually composed of ion sources, transmission systems, mass analysis systems, etc. Electrospray ionization (ESI) technology can detect non-volatile and thermally unstable samples and macromolecular samples. Its soft ionization characteristics make it possible to detect and analyze macromolecules such as proteins. Electrospray ionization technology is mainly used in liquid chromatography-mass spectrometry devices. At a large liquid flow rate, in order to assist in atomization and desolvation, additional gas cylinders must be added to provide atomizing gas and drying gas. The addition of additional gas cylinders makes the electrospray ionization device larger and less compatible with other open ionization methods. Summary of the invention

[0003] In order to overcome the above technical problems, the present invention provides an electrospray ion source device without auxiliary gas cylinders, which realizes electrospray without the need for additional auxiliary gas cylinders and simplifies the complexity of the instrument.

[0004] In order to achieve the above object, on the one hand, the present invention provides an electrospray ion source device without an auxiliary gas cylinder, comprising:

[0005] Peristaltic pump, syringe, electrophoresis capillary, metal spray needle, ionization voltage source, negative pressure ionization chamber;

[0006] The metal spray needle is fixed in the negative pressure ionization chamber and connected to one end of the electrophoresis capillary; the syringe is connected to the electrophoresis capillary, and the peristaltic pump pushes the sample solution in the syringe into the electrophoresis capillary and reaches the metal spray needle; the ionization voltage source is electrically connected to the metal spray needle;

[0007] The negative pressure ionization chamber is provided with an intra-cavity air pressure regulating valve; and a mass spectrometer injection port is located at a distance of 0.5 cm to 2 cm relative to the metal spray needle in the negative pressure ionization chamber.

[0008] In an optional embodiment of the present invention, the metal spray needle is connected to one end of the electrophoresis capillary through a metal coupler, and the ionization voltage source is connected to the metal spray needle through the metal coupler.

[0009] In an optional embodiment of the present invention, the metal spray needle is connected to one end of the electrophoresis capillary through a metal tee, and the ionization voltage source is electrically connected to the metal spray needle through the metal tee.

[0010] In an optional embodiment of the present invention, the liquid flow rate of the peristaltic pump is: 0.1 μL / min to 10 μL / min.

[0011] The electrospray ion source device without auxiliary gas cylinder described in the present invention comprises a peristaltic pump, a syringe, an electrophoresis capillary, a metal spray needle, an ionization voltage source, and a negative pressure ionization chamber; the metal spray needle is fixed in the negative pressure ionization chamber and connected to one end of the electrophoresis capillary, the syringe is connected to the electrophoresis capillary, the peristaltic pump pushes the sample solution in the syringe into the electrophoresis capillary and reaches the metal spray needle, the ionization voltage source is electrically connected to the metal spray needle, the negative pressure ionization chamber is a sealed space, and an intracavity air pressure regulating valve is provided on it; a mass spectrometer injection port is provided at a certain distance relative to the metal spray needle in the negative pressure ionization chamber. The technical solution of the present invention autonomously inhales air through the pressure difference between the metal spray needle in the negative pressure ionization chamber and the mass spectrometer injection port to assist the formation of micro-electrospray, without the need for auxiliary gas cylinders and auxiliary pipelines, significantly reducing the complexity of the system, with high ionization efficiency and strong anti-pollution robustness, facilitating the miniaturization of the micro mass spectrometer while expanding its functions, and can also be compatible with liquid chromatography, electrophoresis and open ion sources. BRIEF DESCRIPTION OF THE DRAWINGS

[0012] Figure 1 A schematic diagram of an electrospray ion source device without an auxiliary gas cylinder according to the present invention;

[0013] Figure 2 A schematic diagram of another electrospray ion source device without an auxiliary gas cylinder according to the present invention;

[0014] Figure 3 A physical picture of the electrospray ion source device without an auxiliary gas bottle according to the present invention;

[0015] Figure 4 A mass spectrum collected by the electrospray ion source device without auxiliary gas cylinder using the present invention;

[0016] Figure 5 This is a graph showing the mass spectrometry stability test of the electrospray ion source device without an auxiliary gas cylinder of the present invention;

[0017] Figure 6a-Figure 6b The schematic diagram is for testing and characterizing protein samples using the electrospray ion source device without an auxiliary gas cylinder as described in the present invention. DETAILED DESCRIPTION

[0018] 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.

[0019] The embodiment of the present invention provides an electrospray ion source device of an auxiliary gas bottle, such as Figure 1 As shown, the device comprises:

[0020] Electrophoresis capillary 1, metal spray needle 2, ionization voltage source 3, negative pressure ionization chamber 4, peristaltic pump, syringe.

[0021] The peristaltic pump and the syringe are not shown in the figure.

[0022] The metal spray needle 2 is fixed in the negative pressure ionization chamber 4 , and the metal spray needle 2 is connected to one end of the electrophoresis capillary 1 .

[0023] The syringe is connected to the electrophoresis capillary 1 . Specifically, the needle of the syringe can be connected to the electrophoresis capillary 1 through a two-way connection.

[0024] The peristaltic pump can push the sample solution in the syringe into the electrophoresis capillary 1 and reach the metal spray needle 2. The ionization voltage source 3 is electrically connected to the metal spray needle 2 and applies an ionization spray voltage.

[0025] The negative pressure ionization chamber 4 is provided with an intracavity air pressure regulating valve 5, through which the air pressure inside the chamber is regulated to adjust the size of the passive airflow, thereby adjusting the state of the spray and optimizing different spray conditions.

[0026] The mass spectrometer injection port 6 is located in the negative pressure ionization chamber 4 at a position opposite to the metal spray needle 2. The mass spectrometer injection port 6 is maintained at a relatively low pressure due to the operation of the instrument's mechanical pump. The pressure difference formed with the negative pressure ionization chamber 4 causes the external gas to passively flow to the mass spectrometer injection port 6 along the coaxial direction of the liquid flow. Due to the shear force of the passively introduced coaxial gas and the spray voltage, the sample solution is pulled out and broken into small droplets. The solvent is further evaporated to obtain gas ions that enter the mass spectrometer for detection and analysis.

[0027] The embodiment of the present invention provides an electrospray ion source device without an auxiliary gas cylinder, comprising: a peristaltic pump, a syringe, an electrophoresis capillary, a metal spray needle, an ionization voltage source, and a negative pressure ionization chamber; the metal spray needle is fixed in the negative pressure ionization chamber and connected to one end of the electrophoresis capillary, the syringe is connected to the electrophoresis capillary, the peristaltic pump pushes the sample solution in the syringe into the electrophoresis capillary and reaches the metal spray needle, the ionization voltage source is electrically connected to the metal spray needle, and the negative pressure ionization chamber is provided with an intracavity air pressure regulating valve; a mass spectrometer injection port is provided at a certain distance relative to the metal spray needle in the negative pressure ionization chamber. The certain distance is 0.5 cm to 2 cm.

[0028] The technical solution provided by the embodiment of the present invention is applied to the state of relatively low liquid flow rate, and realizes microliter electrospray under passive gas assistance. The pressure difference between the metal spray needle in the negative pressure ionization chamber and the mass spectrometer injection port is used to autonomously inhale air to assist the formation of micro electrospray. Microliter electrospray is realized without the need for auxiliary gas cylinders and auxiliary gas pipelines to generate auxiliary gas flow, which significantly reduces the complexity of the system, has high ionization efficiency, and strong anti-pollution robustness. It is convenient to expand its functions while miniaturizing the micro mass spectrometer, and can also be compatible with liquid chromatography, electrophoresis and open ion sources. Compared with the complex auxiliary gas circuit and huge gas cylinder equipment required for traditional electrospray, the embodiment of the present invention utilizes the gas flow assisted atomization formed by the pressure difference between the inside and outside of the capillary to realize microliter electrospray ionization on the micro mass spectrometer on a simple device, which greatly reduces the complexity and volume of the instrument, and greatly expands the application range and field of the micro mass spectrometer.

[0029] Specifically, the metal spray needle 2 is connected to one end of the electrophoresis capillary 1 through the metal two-way 7. The ionization voltage source 3 is connected to the metal spray needle 2 through the metal two-way 7, such as Figure 1 shown.

[0030] The mass spectrometer injection port 6 is located in the negative pressure ionization chamber 4 at a position relative to the metal spray needle 2. The mass spectrometer injection port 6 is maintained at a relatively low pressure due to the operation of the instrument mechanical pump. The pressure difference formed with the negative pressure ionization chamber 4 causes the external gas to passively flow to the mass spectrometer injection port 6 along the coaxial direction of the liquid flow. Due to the shear force of the passively introduced coaxial gas and the spray voltage loaded on the metal second pass 7, the sample solution is pulled out and broken into small droplets. The solvent can be further evaporated to obtain gas ions that enter the mass spectrometer for detection and analysis.

[0031] In some optional embodiments, the metal spray needle 2 is connected to one end of the electrophoresis capillary 1 through a metal tee 8, and the ionization voltage source 3 is electrically connected to the metal spray needle 2 through the metal tee 8. Figure 2 As shown,

[0032] The mass spectrometer injection port 6 is located at a certain distance from the metal spray needle 2 in the negative pressure ionization chamber 4. The distance can be specifically 0.5 cm to 2 cm. The mass spectrometer injection port 6 is maintained at a relatively low air pressure due to the operation of the instrument mechanical pump. The pressure difference formed with the negative pressure ionization chamber 4 causes the external gas to passively flow to the mass spectrometer injection port 6 along the coaxial direction of the liquid flow. Due to the shear force of the passively introduced coaxial gas and the spray voltage loaded on the metal tee 8, the sample solution is pulled out and broken into small droplets. The solvent is further evaporated to obtain gas ions that enter the mass spectrometer for detection and analysis.

[0033] The first end of the metal tee 8 is connected to the electrophoresis capillary 1, the second end is connected to the metal spray needle 2, and the third end is in an open state for air intake. When the flow rate is large, air is passively introduced through the third end of the metal tee 8, which can be used to assist spraying and desolvation.

[0034] In some specific embodiments, the flow rate of the peristaltic pump is 0.1 μL / min to 10 μL / min.

[0035] Furthermore, the liquid flow rate of the peristaltic pump may specifically be 1 μL / min.

[0036] Furthermore, the inner diameter of the electrophoresis capillary may be 75 μm, the syringe capacity may be 100 μL, and the applied ionization voltage may be about 2 kV.

[0037] The embodiment of the present invention proposes a passive gas-assisted microliter electrospray ionization source based on a miniaturized mass spectrometer. Under a relatively low liquid flow rate (e.g., 1 μL / min), a negative pressure ionization chamber formed by a mass spectrometer vacuum system inhales air as a carrier gas under the action of the internal and external pressure difference to assist in the atomization of the sample at the electrospray needle. No additional auxiliary gas cylinder is required, thus streamlining the electrospray ion source device and facilitating the miniaturization of the micro mass spectrometer while expanding its functions. The instrument is compatible with liquid chromatography, electrophoresis, and various open ion sources.

[0038] Figure 3 A physical diagram of an electrospray ion source device without an auxiliary gas bottle provided in an embodiment of the present invention is shown, a peristaltic pump is used to set the liquid flow rate to 1 μL / min, the volume of the syringe used is 100 μL, the inner diameter of the electrophoresis capillary used is 75 μm, and the applied spray voltage is about 2 kV. The mass spectrometer injection port is located in the negative pressure ionization chamber relative to the ion source micro-nozzle, i.e., the metal spray needle.

[0039] Figure 3 The auxiliary airflow here refers to the auxiliary spray airflow that passively assists inhalation under the action of negative pressure, so there is no need for additional auxiliary gas cylinders to provide airflow to assist spraying.

[0040] The sample pretreatment system refers to the device being compatible with pretreatment parts such as liquid chromatography (LC). The constant temperature heating interface means that after the sample spray enters the mass spectrometer injection capillary, there is a heating device inside the instrument to help desolvation.

[0041] Figure 4 The sample UltraMark 1621 and the Agilent ion trap tuning fluid were tested using the electrospray ion source device without auxiliary gas cylinder provided in the embodiment of the present invention. The mass spectrometry signals collected are as follows: Figure 4 shown.

[0042] Further, in order to test the stability of the electrospray ion source device without auxiliary gas cylinder in the embodiment of the present invention, the sample was 1 ppm MRFA, and the signal intensity change was recorded for 16.7 minutes. The results are as follows: Figure 5 shown.

[0043] Further, the electrospray ion source device without auxiliary gas cylinder provided in the embodiment of the present invention is used to test and characterize the denatured protein and the non-denatured protein, specifically cytochrome C, and the results are as follows: Figure 6a and Figure 6b shown.

[0044] Figures 4 to 6b It is shown that from the perspectives of the measured mass range, ionization stability and detected samples, the electrospray ion source device without auxiliary gas cylinder provided in the embodiment of the present invention can achieve the effect of a conventional ESI device.

[0045] The electrospray ion source device without auxiliary gas cylinder provided in the embodiment of the present invention comprises a peristaltic pump, a syringe, an electrophoresis capillary, a metal spray needle, an ionization voltage source, and a negative pressure ionization chamber. The metal spray needle is fixed in the negative pressure ionization chamber and connected to one end of the electrophoresis capillary. The syringe is connected to the electrophoresis capillary. The peristaltic pump pushes the sample solution in the syringe into the electrophoresis capillary and reaches the metal spray needle. The ionization voltage source is electrically connected to the metal spray needle to provide a spray voltage. The negative pressure ionization chamber is provided with an intracavity air pressure regulating valve, and the air pressure inside the chamber is adjusted by the intracavity air pressure regulating valve to adjust the size of the passive airflow, so as to adjust the spray state, thereby optimizing different spray conditions. In the embodiment of the present invention, a metal two-way or metal three-way can be used to connect the electrophoresis capillary and the metal spray needle, and the ionization voltage of the ionization voltage source is applied to the metal two-way or three-way, so that the metal spray needle produces droplet spray. The metal three-way retains a passage joint for direct air inhalation under negative pressure, which can assist spraying and desolvation.

[0046] The embodiment of the present invention is suitable for the state of relatively low liquid flow rate, and realizes microliter electrospray under passive gas assistance. For example, the liquid flow rate of the peristaltic pump is set to 1 μL / min, a syringe with a volume of 100 μL and an electrophoresis capillary with an inner diameter of 75 μm are used, and a spray voltage of about 2 kV is applied, and the following can be obtained: Figures 4 to 6b The detection results shown show that the electrospray ion source device without auxiliary gas cylinder provided by the embodiment of the present invention has achieved the effect of a conventional ESI device from the perspective of the measured mass range, ionization stability and detection samples.

[0047] 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 steps 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 to be developed in the present and future can be used to perform the functions substantially the same as the corresponding embodiments described herein or to obtain the results substantially the same as the corresponding embodiments described herein. Therefore, the appended claims are intended to include such processes, equipment, means, methods or steps within their scope.

Claims

1. An electrospray ion source device without an auxiliary gas cylinder, characterized in that: include: Peristaltic pump, syringe, electrophoresis capillary, metal spray needle, ionization voltage source, negative pressure ionization chamber; The metal spray needle is fixed in the negative pressure ionization chamber and connected to one end of the electrophoresis capillary; the syringe is connected to the electrophoresis capillary, and the peristaltic pump pushes the sample solution in the syringe into the electrophoresis capillary and reaches the metal spray needle; the ionization voltage source is electrically connected to the metal spray needle; The negative pressure ionization chamber is provided with an intracavity air pressure regulating valve; a mass spectrometer injection port is located at a certain distance relative to the metal spray needle in the negative pressure ionization chamber; the certain distance is 0.5 cm to 2 cm; the liquid flow rate of the peristaltic pump is 1 μL / min; the inner diameter of the electrophoresis capillary is 75 μm, and the ionization voltage is 2 kV.

2. The electrospray ion source device without auxiliary gas cylinder according to claim 1, characterized in that: The metal spray needle is connected to one end of the electrophoresis capillary through a metal coupler, and the ionization voltage source is connected to the metal spray needle through the metal coupler.

3. The electrospray ion source device without auxiliary gas cylinder according to claim 1, characterized in that: The metal spray needle is connected to one end of the electrophoresis capillary through a metal tee, and the ionization voltage source is electrically connected to the metal spray needle through the metal tee.

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