A microporous oscillating atomization electrospray extraction and ionization device for mass spectrometry analysis

Abstract

The present invention discloses a microporous oscillating atomization electrospray extraction ionization device for mass spectrometry analysis, comprising a sample spray device, a solvent electrospray device and an extraction ionization chamber; the extraction ionization chamber is provided with a sample spray droplet inlet, a solvent spray droplet inlet and an outlet respectively; the extension line of the sample spray droplet inlet to the inner cavity of the extraction ionization chamber intersects with the extension line of the solvent spray droplet inlet to the inner cavity of the extraction ionization chamber; the sample spray droplet inlet of the extraction ionization chamber is connected to the outlet of the sample spray device, the solvent spray droplet inlet is connected to the outlet of the solvent electrospray device, and the outlet is used to be connected to the inlet of a mass spectrometer. Through this solution, droplet collision and extraction ionization occur in the extraction ionization chamber, and the spray angles of the sample spray device and the solvent electrospray device, as well as the spatial positions between them and the inlet of the mass spectrometer are fixed, thereby helping to improve the stability and repeatability of electrospray extraction ionization.

Description

Technical Field

[0001] The present invention relates to the technical field of mass spectrometry analysis, and in particular to a microporous oscillating atomization electrospray extraction ionization device for mass spectrometry analysis. Background Art

[0002] A mass spectrometer is an instrument that separates and analyzes charged ions under the influence of an electromagnetic field. It primarily consists of an ionization source, a mass analyzer, and a detector. The ionization source, which ionizes the substance being analyzed into a charged state, is the first and most critical step in mass spectrometry analysis, and is therefore often referred to as the heart of the mass spectrometer.

[0003] Electrospray ionization is the most common and widely used ionization source. A sample solution containing the analyte flows through a capillary tube. A high DC voltage is applied at the capillary outlet, while a heated nebulizing gas is coaxially connected to the capillary tube. Under the combined effects of the electric field and the nebulizing gas, the solvent molecules are atomized at the capillary outlet, atomizing into micron-sized, charged droplets. Through solvent evaporation and Coulomb explosion, the analyte is converted into gaseous ions that enter the mass spectrometer for analysis.

[0004] Among them, electrospray extraction ionization: an electrospray extraction ionization device composed of two intersecting electrosprays. One electrospray is the sample solution, and the other electrospray is the extraction ionization solvent. Extraction and charge transfer occur at the intersection of the two electrosprays to achieve extraction ionization of the analyte, which then enters the mass spectrometer for analysis. In other words, the sample solution of electrospray extraction ionization is not directly electrosprayed into the mass spectrometer, but is extracted and charge transferred with the electrospray of another pure solvent to achieve ionization of the analyte. This technical method reduces the interference of the matrix in the sample solution on the ionization of the analyte. Extraction solvents of different polarities have a better extraction effect on analyte molecules with different polarities.

[0005] In addition, electrospray extraction ionization is an extraction ionization process that occurs in an open environment with the assistance of two nebulizer gas beams and electrospray cross-collision. However, it still has the following disadvantages:

[0006] 1. Affected by external factors such as ambient airflow, the stability is poor;

[0007] 2. The angles of the two electrospray beams and the spatial position between them and the mass spectrometer inlet are difficult to adjust, resulting in poor repeatability;

[0008] 3. The extraction solvent is single, which makes it impossible to analyze polar and weakly polar substances simultaneously;

[0009] 4. Both the sample solution and the extraction solvent are electrosprayed with the assistance of nebulizing gas, which relies on gas cylinders or serial gas lines, making it impossible to achieve portable integration and mobility of the ionization source device. In addition, the gas usage cost is high.

[0010] 5. The direction of the high-speed airflow of the two electrospray beams is inconsistent with the direction of the mass spectrometer inlet, which will affect the transmission efficiency of the substance to be tested to the mass spectrometer inlet and cause signal loss. Summary of the Invention

[0011] In view of this, the present invention provides a microporous oscillating atomization electrospray extraction ionization device for mass spectrometry analysis, in which droplet collision and extraction ionization occur within the extraction ionization chamber, and the spray angles of the sample spray device and the solvent electrospray device, as well as the spatial positions between them and the mass spectrometer inlet are fixed, thereby helping to improve the stability and repeatability of electrospray extraction ionization.

[0012] To achieve the above object, the present invention provides the following technical solutions:

[0013] A microporous oscillating atomization electrospray extraction ionization device for mass spectrometry analysis, comprising a sample spray device, a solvent electrospray device and an extraction ionization chamber;

[0014] The extraction ionization chamber is respectively provided with a sample spray droplet inlet, a solvent spray droplet inlet and an outlet; an extension line of the sample spray droplet inlet to the inner cavity of the extraction ionization chamber intersects with an extension line of the solvent spray droplet inlet to the inner cavity of the extraction ionization chamber;

[0015] The sample spray droplet inlet of the extraction ionization chamber is connected to the outlet of the sample spray device, the solvent spray droplet inlet is connected to the outlet of the solvent electrospray device, and the outlet is used to be connected to the inlet of a mass spectrometer.

[0016] Preferably, the sample spray device comprises:

[0017] A high-frequency microporous oscillator is provided at the sample spray droplet inlet of the extraction ionization chamber and is used for injecting or dripping the sample.

[0018] Preferably, the sample spray droplet inlet is opened at the top of the extraction ionization chamber, and the solvent spray droplet inlet is opened at the side wall of the extraction ionization chamber.

[0019] Preferably, the sample spray device further comprises a sample solution injection pump and a sample solution transmission capillary;

[0020] The inlet end of the sample solution transmission capillary is connected to the outlet end of the sample solution injection pump, and the outlet end is used to align with the high-frequency microporous oscillating plate.

[0021] Preferably, the solvent spray droplet inlet includes a polar solvent spray droplet inlet and a weak polar solvent spray droplet inlet;

[0022] The solvent electrospray device comprises a polar solvent electrospray device and a weak polar solvent electrospray device; the outlet of the polar solvent electrospray device is connected to the polar solvent spray droplet inlet, and the outlet of the weak polar solvent electrospray device is connected to the weak polar solvent spray droplet inlet.

[0023] Preferably, the polar solvent electrospray device comprises a polar solvent spray body;

[0024] The weak polar solvent electrospray device comprises a weak polar solvent spray body;

[0025] The solvent electrospray device also includes a DC high-voltage power supply and a high-frequency switching switch;

[0026] The DC high-voltage power supply is communicatively connected to the high-frequency switching switch, and the high-frequency switching switch is electrically connected to the capillary of the polar solvent spray body and the capillary of the weak polar solvent spray body respectively.

[0027] Preferably, the polar solvent spray body includes a polar solvent injection pump and a polar solvent capillary; the inlet end of the polar solvent capillary is connected to the outlet end of the polar solvent injection pump, the outlet end is connected to the polar solvent spray droplet inlet, and is electrically connected to the high-frequency switch;

[0028] The weak polar solvent spray body includes a weak polar solvent injection pump and a weak polar solvent capillary; the inlet end of the weak polar solvent capillary is connected to the outlet end of the weak polar solvent injection pump, the outlet end is connected to the weak polar solvent spray droplet inlet, and is electrically connected to the high-frequency switching switch.

[0029] Preferably, the polar solvent spray body further comprises a polar solvent metal two-way valve;

[0030] The polar solvent metal two-way is connected to the middle part of the polar solvent capillary and is electrically connected to the high-frequency switching switch;

[0031] The weak polar solvent spray body further comprises a weak polar solvent metal two-way valve; the weak polar solvent metal two-way valve is connected to the middle part of the weak polar solvent capillary and is electrically connected to the high-frequency switching switch.

[0032] Preferably, the polar solvent spray droplet inlet and the weak polar solvent spray droplet inlet are opened on the same side wall of the extraction ionization chamber, and the outlet is opened on the other side wall of the extraction ionization chamber and is respectively arranged opposite to the polar solvent spray droplet inlet and the weak polar solvent spray droplet inlet;

[0033] The outlet end of the polar solvent capillary is tilted downward in the horizontal direction and connected to the polar solvent spray droplet inlet, and the outlet end of the weak polar solvent capillary is tilted upward in the horizontal direction and connected to the weak polar solvent spray droplet inlet.

[0034] Preferably, the extraction ionization chamber is manufactured by 3D printing.

[0035] As can be seen from the above technical solution, in the microporous oscillating atomization electrospray extraction ionization device for mass spectrometry analysis provided by the present invention, droplet collision and extraction ionization occur within the extraction ionization chamber, and the spray angles of the sample spray device and the solvent electrospray device, as well as the spatial positions between them and the mass spectrometer inlet are fixed, thereby helping to improve the stability and repeatability of electrospray extraction ionization. BRIEF DESCRIPTION OF THE DRAWINGS

[0036] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the embodiments or the description of the prior art. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0037] Figure 1 A simplified structural diagram of a microporous oscillating atomization electrospray extraction and ionization device for mass spectrometry analysis provided by an embodiment of the present invention;

[0038] Figure 2 Flowchart of a microporous oscillating atomization electrospray extraction and ionization device for mass spectrometry analysis provided by an embodiment of the present invention.

[0039] Among them, 1 is a high-frequency microporous oscillator, 2 is an extraction ionization chamber, 3 is a sample solution injection pump, 4 is a sample solution transfer capillary, 5 is a polar solvent injection pump, 6 is a polar solvent transfer capillary, 7 is a polar solvent metal two-way valve, 8 is a polar electrospray capillary, 9 is a weak polar solvent injection pump, 10 is a weak polar solvent transfer capillary, 11 is a weak polar solvent metal two-way valve, 12 is a weak polar electrospray capillary, 13 is a DC high-voltage power supply, 14 is a high-frequency switching switch, 15 is a mass spectrometer inlet transfer capillary, and 16 is a mass spectrometer. DETAILED DESCRIPTION

[0040] The following will clearly and completely describe the technical solutions in the embodiments of the present invention in conjunction with the accompanying drawings. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of the present invention.

[0041] The microporous oscillating atomization electrospray extraction and ionization device for mass spectrometry provided in the embodiment of the present invention is as follows: Figure 1 As shown, it includes a sample spray device, a solvent electrospray device and an extraction ionization chamber (2);

[0042] The extraction ionization chamber 2 is respectively provided with a sample spray droplet inlet, a solvent spray droplet inlet and an outlet; an extension line of the sample spray droplet inlet to the inner cavity of the extraction ionization chamber 2 intersects with an extension line of the solvent spray droplet inlet to the inner cavity of the extraction ionization chamber 2;

[0043] The sample spray droplet inlet of the extraction ionization chamber 2 is connected to the outlet of the sample spray device, the solvent spray droplet inlet is connected to the outlet of the solvent electrospray device, and the outlet is used to be connected to the inlet of the mass spectrometer 16.

[0044] It should be noted that the inner extension line of the sample spray droplet inlet intersects the inner extension line of the solvent spray droplet inlet, so that the spray droplets of the sample spray device and the solvent electrospray device form an intersection point in the extraction ionization chamber 2, and then the spray droplets of the two paths undergo collision extraction and charge transfer in the extraction ionization chamber 2, extracting and ionizing the test substance in the sample, and then under the vacuum negative pressure of the mass spectrometer 16, the test substance extracted and ionized in the extraction ionization chamber 2 is transferred to the mass spectrometer 16 for mass spectrometry analysis. In other words, the electrospray extraction ionization of this scheme occurs in the extraction ionization chamber 2, which can avoid being affected by external factors such as ambient airflow, and the angle of the two spray droplets and the spatial position between them and the inlet of the mass spectrometer 16 are fixed, which helps to improve the stability and repeatability of the electrospray extraction ionization.

[0045] It can be seen from the above technical solution that in the microporous oscillating atomization electrospray extraction ionization device for mass spectrometry analysis provided by the embodiment of the present invention, droplet collision and extraction ionization occur in the extraction ionization chamber, and the spray angles of the sample spray device and the solvent electrospray device, as well as the spatial positions between them and the mass spectrometer inlet are fixed, thereby helping to improve the stability and repeatability of electrospray extraction ionization.

[0046] In this program, if Figure 1 As shown, the sample spray device includes:

[0047] A high-frequency microporous oscillator 1 is provided at the sample spray droplet inlet of the extraction ionization chamber 2 and is used to inject or drip the sample. When the sample is applied to the high-frequency microporous oscillator 1, under the action of high-frequency oscillation, the sample quickly passes through the microporous plate of the high-frequency microporous oscillator 1 and is broken into micron-sized droplet sprays before entering the extraction ionization chamber 2. Furthermore, this solution uses the high-frequency microporous oscillator 1 as a sample spray device to facilitate atomizing the sample into a micron-sized droplet plume. This is not only suitable for continuously flowing solution samples, but also for droplet samples, cell samples, and the like. Furthermore, when the cell sample passes through the high-frequency oscillator 1, the cell membrane, organelles, etc. are fragmented and cut by the micron-sized pores, and the intracellular substances are completely released into the sample droplets, enabling complete and efficient analysis of cellular substances.

[0048] Specifically, the sample spray droplet inlet is located at the top of the extraction ionization chamber 2, and the solvent spray droplet inlet is located on the sidewall of the extraction ionization chamber 2. This design allows the sample spray droplets to fall vertically and naturally into the extraction ionization chamber 2. Furthermore, the bottom end of the high-frequency microporous oscillator 1 is connected to the top of the extraction ionization chamber 2.

[0049] Further, if Figure 1 As shown, the sample spray device further includes a sample solution injection pump 3 and a sample solution transmission capillary 4;

[0050] The inlet end of the sample solution transfer capillary 4 is connected to the outlet end of the sample solution injection pump 3, wherein the sample solution injection pump 3 is a stepper motor micro-injection pump, which is used with a 1 mL syringe and can set the sample solution delivery flow rate. The syringe is driven by the stepper motor micro-injection pump to pre-extract the sample solution, and then the outlet end of the syringe is connected to the inlet end of the sample solution transfer capillary 4 to wait for the sample solution to be delivered; the outlet end of the sample solution transfer capillary 4 is used to align with the high-frequency microporous oscillation plate 1, that is, the outlet end of the sample solution transfer capillary 4 forms a corresponding fit with the microporous plate of the high-frequency microporous oscillation plate 1. This solution is designed in this way to facilitate the automatic injection of the sample solution into the high-frequency microporous oscillation plate 1, and also uses a sample solution injection pump 3 without the assistance of atomizing gas to provide power for the sample solution transmission, that is, the sample spray device is a sample spray device without the assistance of atomizing gas, which helps to get rid of the limitation of using cylinder gas, reduces the cost of use, and makes the device easy to be portable, integrated, and moved.

[0051] In this solution, the solvent spray droplet inlet includes a polar solvent spray droplet inlet and a weak polar solvent spray droplet inlet;

[0052] The solvent electrospray device includes a polar solvent electrospray device and a weak polar solvent electrospray device; the outlet of the polar solvent electrospray device is connected to the inlet of the polar solvent spray droplets, and the outlet of the weak polar solvent electrospray device is connected to the inlet of the weak polar solvent spray droplets. This solution is designed in such a way that, on the one hand, the polar solvent electrospray device generates a polar solvent electrospray under the action of a high DC voltage, and interacts and collides with the sample spray droplets in the extraction and ionization chamber 2, and extracts and ionizes polar substances to be tested in the sample droplets; on the other hand, the weak polar solvent electrospray device generates a weak polar solvent electrospray under the action of a high DC voltage, and interacts and collides with the sample spray droplets in the extraction and ionization chamber 2, and extracts and ionizes weak polar substances to be tested in the sample droplets. In other words, this solution uses two solvent electrospray devices of different polarities so that polar and weak polar substances in the sample droplets can be extracted and ionized, thereby maximizing the simultaneous ionization analysis of polar and weak polar substances.

[0053] Specifically, the polar solvent electrospray device includes a polar solvent spray body;

[0054] The weak polar solvent electrospray device comprises a weak polar solvent spray body;

[0055] like Figure 1 As shown, the solvent electrospray device further includes a DC high voltage power supply 13 and a high frequency switching switch 14;

[0056] The DC high-voltage power supply 13 is communicatively connected to the high-frequency switching switch 14, and the high-frequency switching switch 14 is electrically connected to the capillary of the polar solvent spray body and the capillary of the weak polar solvent spray body, respectively. This solution is designed so that the high-voltage electricity provided by the DC high-voltage power supply 13 can be switched and output to the capillaries of the polar solvent spray body and the weak polar solvent spray body through the high-frequency switching switch 14, thereby achieving alternating electrospraying of polar and weak polar solvents, thereby facilitating the extraction and ionization of polar and weak polar substances in sample droplets. In other words, this solution uses a dual-solvent electrospray device with different polarities to facilitate alternating electrospraying of polar and weak polar solvents, thereby facilitating the extraction and ionization of polar and weak polar substances in sample droplets, thereby maximizing the simultaneous ionization analysis of multiple substances. In addition, it is not difficult to see that the polar solvent electrospray device and the weak polar solvent electrospray device of this solution share a single DC high-voltage power supply 13.

[0057] Further, if Figure 1As shown, the polar solvent spray body includes a polar solvent injection pump 5 and a polar solvent capillary; the inlet end of the polar solvent capillary is connected to the outlet end of the polar solvent injection pump 5, wherein the polar solvent injection pump 5 is a stepper motor micro-injection pump, which is matched with a 1 mL syringe and can set the flow rate of the polar solvent to be delivered. The syringe is driven by the stepper motor micro-injection pump to pre-extract the polar solvent, and then the outlet end of the syringe is connected to the inlet end of the polar solvent capillary to wait for the delivery of the polar solvent; the outlet end of the polar solvent capillary is connected to the inlet of the polar solvent spray droplet and is electrically connected to the high-frequency switching switch 14;

[0058] The weak polar solvent spray body includes a weak polar solvent injection pump 9 and a weak polar solvent capillary; the inlet end of the weak polar solvent capillary is connected to the outlet end of the weak polar solvent injection pump 9, wherein the weak polar solvent injection pump 9 is a stepper motor micro-injection pump, which is matched with a 1 mL syringe and can set the flow rate of the weak polar solvent. The syringe is driven by the stepper motor micro-injection pump to pre-extract the weak polar solvent, and then the outlet end of the syringe is connected to the inlet end of the weak polar solvent capillary to wait for the weak polar solvent to be delivered; the outlet end of the weak polar solvent capillary is connected to the weak polar solvent spray droplet inlet and is electrically connected to the high-frequency switching switch 14. This solution is designed so that both solvent spray bodies use solvent injection pumps without atomizing gas assistance to provide power for electrospray solvent transmission, that is, both solvent electrospray devices are solvent electrospray devices without atomizing gas assistance, which helps to get rid of the limitation of using cylinder gas, reduces the cost of use, and makes the device easy to be portable, integrated and mobile.

[0059] Furthermore, if Figure 1 As shown, the polar solvent spray body further includes a polar solvent metal two-way 7;

[0060] The polar solvent metal two-way valve 7 is connected to the middle part of the polar solvent capillary and is electrically connected to the high-frequency switching switch 14;

[0061] The weak polar solvent spray body also includes a weak polar solvent metal two-way valve 11; the weak polar solvent metal two-way valve 11 is connected to the middle part of the weak polar solvent capillary and is electrically connected to the high-frequency switching switch 14. This solution is designed so that the capillaries of the two solvent spray bodies can be connected to the DC high voltage. In addition, if Figure 1As shown, the weak polar solvent capillary includes a polar solvent transfer capillary 6 and a polar electrospray capillary 8; wherein, the inlet end of the polar solvent transfer capillary 6 is connected to the outlet end of the polar solvent injection pump 5, and the outlet end is connected to one end of the polar solvent metal two-way 7; the inlet end of the polar electrospray capillary 8 is connected to the other end of the polar solvent metal two-way 7, and the outlet end is connected to the polar solvent spray droplet inlet; in addition, the weak polar solvent capillary includes a weak polar solvent transfer capillary 10 and a weak polar electrospray capillary 12; wherein, the inlet end of the weak polar solvent transfer capillary 10 is connected to the outlet end of the weak polar solvent injection pump 9, and the outlet end is connected to one end of the weak polar solvent metal two-way 11; the inlet end of the weak polar electrospray capillary 12 is connected to the other end of the weak polar solvent metal two-way 11, and the outlet end is connected to the weak polar solvent spray droplet inlet.

[0062] In this program, if Figure 1 As shown, the polar solvent spray droplet inlet and the weak polar solvent spray droplet inlet are opened on the same side wall of the extraction ionization chamber 2, and the outlet is opened on the other side wall of the extraction ionization chamber 2, and is respectively arranged opposite to the polar solvent spray droplet inlet and the weak polar solvent spray droplet inlet;

[0063] The outlet end of the polar solvent capillary is tilted downward in the horizontal direction and is connected to the polar solvent spray droplet inlet, and the outlet end of the weak polar solvent capillary is tilted upward in the horizontal direction and is connected to the weak polar solvent spray droplet inlet. In other words, the polar and weak polar solvent electrosprays of this scheme are successively introduced from the extraction ionization chamber 2 side wall at a certain angle in the horizontal direction, and interact and collide with the vertically falling sample spray droplets in the extraction ionization chamber 2, respectively extracting the ionization polarity and weak polarity of the test substance, and then entering the mass spectrometer for analysis. This scheme is designed so that the high-speed airflow direction of the two beams of solvent electrospray is consistent with the mass spectrometer 16 inlet direction, avoiding affecting the transmission efficiency of the test substance to the mass spectrometer 16 inlet, in case of causing signal loss.

[0064] Specifically, the extraction ionization chamber 2 is manufactured by 3D printing, featuring high manufacturing efficiency and a long service life. Preferably, the extraction ionization chamber 2 is a cylindrical chamber with an opening at the top. The opening serves as the sample spray droplet inlet for the extraction ionization chamber 2. The top of the cylindrical chamber is connected to the bottom of the high-frequency microporous oscillator 1, and the solvent spray droplet inlet and outlet are located on the sidewalls of the cylindrical chamber.

[0065] The present invention will be further described below with reference to specific embodiments:

[0066] The present invention involves constructing a new atmospheric pressure ionization source device. A solution sample first contacts a microporous oscillating plate and is rapidly atomized into micron-sized droplets. The sample then undergoes collision extraction and charge transfer with polar electrospray and weak polar electrospray (two-way) droplets, respectively extracting and ionizing polar and non-polar substances in the sample before entering a mass spectrometer for analysis.

[0067] The present invention provides a new ionization source technology and device for mass spectrometry analysis. The overall process of the present invention is as follows: Figure 2 As shown. Continuous flow solutions / droplets / cell samples are applied to the microporous oscillator through contact connection or dripping. Under the action of high-frequency oscillation, the solution sample, droplet sample, or cell sample quickly passes through the microporous sheet and is broken into micron-sized droplet sprays, which enter the extraction ionization chamber. At the same time, DC high voltage electricity successively triggers the non-nebulizer gas-assisted microliter electrospray of polar solvents and weak polar solvents, which collide with the sample droplets in the extraction ionization chamber for extraction and charge transfer reactions, achieving efficient ionization of polar and weak polar substances to be analyzed. Under the attraction of the vacuum negative pressure of the mass spectrometer, the substances enter the mass spectrometer for analysis.

[0068] Working principle of this device:

[0069] Driven by a 24V DC voltage, the microporous vibrator, with its center plate covered in micron-sized pores, can vibrate up and down at high frequencies. For solution samples, the moment they come into contact with the vibrator, they are driven by high-frequency oscillations through the plate, being cut into micron-sized spray droplets that vertically enter the semi-enclosed extraction and ionization chamber. For cell samples, the cell-containing solution or droplets come into contact with the vibrator, instantly shattering the cell membrane. Organelles and cytoplasm pass through the microporous plate, further fragmenting larger organelles such as mitochondria, and completely releasing intracellular substances into the micron-sized sample droplets.

[0070] Simultaneously, the electric field and Coulombic force generated by the 3-6kV DC high voltage form a Taylor cone spray at the tip of the spray capillary (10 microns in diameter), producing micron-sized solvent spray droplets. Solvents of different polarity generate electrospray plumes of different polarities. Polar and weakly polar electrosprays are introduced horizontally and at a certain angle from one side of the extraction and ionization chamber. Within the chamber, they interact and collide with the vertical sample spray droplets, extracting and ionizing the polar and weakly polar analytes, respectively, before entering the mass spectrometer for analysis.

[0071] The structure and function of components of this device:

[0072] The schematic diagram of the device structure of the present invention is as follows Figure 1 As shown, where:

[0073] The high-frequency microporous oscillator 1, with a selectable diameter (10-30mm) and number of micropores (1000-3000 mesh), is driven by a 24V DC voltage. During operation, the sample solution penetrates the microporous plate under the action of high-frequency oscillation, being cut into micron-sized droplet sprays. During cell sample analysis, the cell membrane is also broken, releasing intracellular substances; the sample droplets enter the extraction and ionization chamber 2.

[0074] The extraction ionization chamber 2 is manufactured by 3D printing. It has an open top connected to the microporous oscillator and openings on its sidewalls, which connect to the polar electrospray capillary 8, the weakly polar electrospray capillary 12, and the mass spectrometer inlet transfer capillary 15. The extraction ionization chamber 2 is where the spray converges and the extraction ionization occurs.

[0075] The sample solution injection pump 3 provides power for sample solution transmission and adjusts the flow rate.

[0076] The sample solution transmission capillary 4 has an outer diameter of 360 μm and an inner diameter of 50 μm.

[0077] The polar solvent injection pump 5 provides power for the transmission of polar electrospray solvent and adjusts the flow rate.

[0078] The polar solvent transmission capillary 6 has an outer diameter of 360 μm and an inner diameter of 50 μm.

[0079] The metal union (ie, the polar solvent metal union 7 ) connects the polar solvent transfer capillary 6 and the polar electrospray capillary 8 , and is also the point for applying a DC high voltage.

[0080] The polar electrospray capillary 8 has an outer diameter of 360 μm, an inner diameter of 20 μm, and a tip inner diameter of 10 μm. It generates polar electrospray under the action of a DC high voltage (3-5 kV). The spray plume interacts and collides with the sample droplets in the extraction and ionization chamber 2, and extracts and ionizes the polar analytes in the sample droplets.

[0081] The weak polar solvent injection pump 9 provides power for the transmission of the weak polar electrospray solvent and adjusts the flow rate.

[0082] The weak polar solvent transmission capillary 10 has an outer diameter of 360 μm and an inner diameter of 50 μm.

[0083] The metal union (ie, the weak polar solvent metal union 11 ) connects the weak polar solvent transfer capillary 10 and the weak polar electrospray capillary 12 , and is also the point for applying a DC high voltage.

[0084] The weak polarity electrospray capillary 12 has an outer diameter of 360 μm, an inner diameter of 20 μm, and a tip inner diameter of 10 μm. It generates weak polarity electrospray under the action of a DC high voltage (4-6 kV). The spray plume interacts and collides with the sample droplets in the extraction and ionization chamber 2, and extracts and ionizes the weak polarity analyte in the sample droplets.

[0085] The DC high voltage power supply 13 provides DC high voltage for polar and weak polar electrospray.

[0086] The high-frequency switching switch 14 switches the high-voltage power provided by the DC high-voltage power supply 13 to the polar / weak-polarity electrospray capillary at high frequency, thereby realizing the alternating generation of polar and weak-polarity electrosprays, and extracting and ionizing polar and weak-polar substances in the sample droplets respectively.

[0087] The mass spectrometer inlet transmission capillary 15 transmits the polar and weak polar substances to be tested extracted and ionized in the extraction ionization chamber 2 to the mass spectrometer inlet under the vacuum negative pressure of the mass spectrometer for mass spectrometry analysis.

[0088] The working process of this device:

[0089] The extraction ionization chamber 2 is connected to the mass spectrometer's inlet transfer capillary 15. The polar solvent injection pump 5, weakly polar solvent injection pump 9, DC high-voltage power supply 13, and high-frequency switching switch 14 are turned on. After the solvent fills the capillary and forms a stable electrospray (approximately 2 minutes), the high-frequency microporous oscillator 1 is turned on. For solution samples, the sample solution injection pump 3 is turned on, the flow rate is adjusted, and mass spectrometry analysis begins. For droplet or cell samples, the droplet or cell-containing droplet is directly applied to the high-frequency microporous oscillator 1 to begin mass spectrometry analysis.

[0090] In addition, the extraction ionization chamber 2 is processed by 3D printing, and other high-frequency microporous oscillator, DC high-voltage power supply, transmission capillary, electrospray capillary, etc. are commercial parts.

[0091] Advantages of the present invention:

[0092] 1. The high-frequency oscillating plate is used to atomize the sample into a micron-sized droplet beam, which is not only suitable for continuously flowing solution samples, but also for droplet samples, cell samples, etc.

[0093] 2. The cell sample passes through the high-frequency oscillator, and the cell membrane, organelles, etc. are fragmented and cut by micron-level pores. The intracellular substances are completely released into the sample droplets, which can achieve complete and efficient cell substance analysis.

[0094] 3. The design of the dual electrospray extraction probe performs alternating electrospray of polar and weak polar solvents to extract and ionize polar and weak polar substances in the sample droplets, respectively, thereby maximizing the simultaneous ionization analysis of multiple substances.

[0095] 4. The high-frequency oscillating plate is used to atomize the sample solution, and the microliter electrospray atomization without the assistance of atomizing gas is used to atomize the extraction solvent. Both get rid of the limitation of using cylinder gas, reduce the cost of use, and are easy to integrate and move.

[0096] 5. Droplet collision and extraction ionization occur in the semi-enclosed cavity of 3D printing, and the spatial position and relative angle are fixed, which improves the stability and repeatability of the technical method.

[0097] The key points and points to be protected of the present invention are:

[0098] 1. Use high-frequency oscillating plate to atomize samples and perform efficient electrospray extraction and ionization of continuous flow liquids, droplets, and cell samples.

[0099] 2. Use high-frequency oscillating plates to fragment cell samples and atomize them into sample droplets for complete and efficient analysis of intracellular substances.

[0100] 3. Use two alternating electrosprays of polar and weak polar solvents to achieve simultaneous extraction and ionization of polar and weak polar analytes.

[0101] 4. Use 3D printed semi-enclosed extraction ionization chamber to improve the stability and repeatability of extraction ionization.

[0102] The various embodiments in this specification are described in a progressive manner, and each embodiment focuses on the differences from other embodiments. The same or similar parts between the various embodiments can be referenced to each other.

[0103] The above description of the disclosed embodiments is intended to enable one skilled in the art to implement or use the present invention. Various modifications to these embodiments will be readily apparent to one skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the present invention. Therefore, the present invention is not limited to the embodiments shown herein but is intended to conform to the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. A microporous oscillating atomization electrospray extraction and ionization device for mass spectrometry analysis, characterized in that: It includes a sample spray device, a solvent electrospray device and an extraction ionization chamber (2); The extraction ionization chamber (2) is respectively provided with a sample spray droplet inlet, a solvent spray droplet inlet and an outlet; an extension line of the sample spray droplet inlet toward the inner cavity of the extraction ionization chamber (2) intersects with an extension line of the solvent spray droplet inlet toward the inner cavity of the extraction ionization chamber (2); The sample spray droplet inlet of the extraction ionization chamber (2) is connected to the outlet of the sample spray device, and the solvent spray droplet inlet is connected to the outlet of the solvent electrospray device, and the outlet is used to be connected to the inlet of a mass spectrometer (16); wherein, the extension line of the sample spray droplet inlet to the inner cavity of the extraction ionization chamber (2) intersects with the extension line of the solvent spray droplet inlet to the inner cavity of the extraction ionization chamber (2), so that the spray droplets of the sample spray device and the solvent electrospray device form an intersection point in the extraction ionization chamber (2) and undergo collision extraction and charge transfer, thereby extracting and ionizing the substance to be tested in the sample; The sample spray device comprises: A high-frequency microporous oscillation plate (1) is provided at the sample spray droplet inlet of the extraction ionization chamber (2) and is used for injecting or dripping the sample; wherein the sample is applied to the high-frequency microporous oscillation plate (1), and under the high-frequency oscillation action of the high-frequency microporous oscillation plate (1), the sample quickly passes through the microporous plate of the high-frequency microporous oscillation plate (1) and is broken into micron-sized droplet spray; The sample spray droplet inlet is opened at the top of the extraction ionization chamber (2), and the solvent spray droplet inlet is opened at the side wall of the extraction ionization chamber (2); wherein the extraction ionization chamber (2) is a cylindrical chamber; The sample spray device further comprises a sample solution injection pump (3) and a sample solution transmission capillary (4); The inlet end of the sample solution transmission capillary (4) is connected to the outlet end of the sample solution injection pump (3), and the outlet end is used to align with the high-frequency microporous oscillating plate (1).

2. The microporous oscillating atomization electrospray extraction and ionization device for mass spectrometry analysis according to claim 1, characterized in that: The solvent spray droplet inlet includes a polar solvent spray droplet inlet and a weak polar solvent spray droplet inlet; The solvent electrospray device comprises a polar solvent electrospray device and a weak polar solvent electrospray device; the outlet of the polar solvent electrospray device is connected to the polar solvent spray droplet inlet, and the outlet of the weak polar solvent electrospray device is connected to the weak polar solvent spray droplet inlet.

3. The microporous oscillating atomization electrospray extraction and ionization device for mass spectrometry analysis according to claim 2, characterized in that: The polar solvent electrospray device includes a polar solvent spray body; The weak polar solvent electrospray device comprises a weak polar solvent spray body; The solvent electrospray device further comprises a DC high-voltage power supply (13) and a high-frequency switching switch (14); The DC high-voltage power supply (13) is communicatively connected to the high-frequency switching switch (14), and the high-frequency switching switch (14) is electrically connected to the capillary of the polar solvent spray body and the capillary of the weak polar solvent spray body, respectively.

4. The microporous oscillating atomization electrospray extraction and ionization device for mass spectrometry analysis according to claim 3, characterized in that: The polar solvent spray body comprises a polar solvent injection pump (5) and a polar solvent capillary; the inlet end of the polar solvent capillary is connected to the outlet end of the polar solvent injection pump (5), and the outlet end is connected to the polar solvent spray droplet inlet and is electrically connected to the high-frequency switching switch (14); The weak polar solvent spray body comprises a weak polar solvent injection pump (9) and a weak polar solvent capillary; the inlet end of the weak polar solvent capillary is connected to the outlet end of the weak polar solvent injection pump (9), the outlet end is connected to the weak polar solvent spray droplet inlet, and is electrically connected to the high-frequency switching switch (14).

5. The microporous oscillating atomization electrospray extraction and ionization device for mass spectrometry analysis according to claim 4, characterized in that: The polar solvent spray body further comprises a polar solvent metal two-way valve (7); the polar solvent metal two-way valve (7) is connected to the middle part of the polar solvent capillary and is electrically connected to the high-frequency switching switch (14); The weak polar solvent spray body further comprises a weak polar solvent metal two-way valve (11); the weak polar solvent metal two-way valve (11) is connected to the middle part of the weak polar solvent capillary and is electrically connected to the high-frequency switching switch (14).

6. The microporous oscillating atomization electrospray extraction and ionization device for mass spectrometry analysis according to claim 4, characterized in that: The polar solvent spray droplet inlet and the weak polar solvent spray droplet inlet are opened on the same side wall of the extraction ionization chamber (2), and the outlet is opened on the other side wall of the extraction ionization chamber (2), and is respectively arranged opposite to the polar solvent spray droplet inlet and the weak polar solvent spray droplet inlet; The outlet end of the polar solvent capillary is tilted downward in the horizontal direction and connected to the polar solvent spray droplet inlet, and the outlet end of the weak polar solvent capillary is tilted upward in the horizontal direction and connected to the weak polar solvent spray droplet inlet.

7. The microporous oscillating atomization electrospray extraction and ionization device for mass spectrometry analysis according to claim 1, characterized in that: The extraction ionization chamber (2) is manufactured by 3D printing.

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