Mass spectrometry on-line detection device based on double-beam pulse nanoelectrospray ionization source

Abstract

The application discloses a mass spectrum online detection device based on a double-beam pulse nanoelectrospray ionization source, which comprises a double-spray assembly, a power supply, a first adjusting platform and two second adjusting platforms, the first adjusting platform comprises a three-axis driving mechanism and a mounting table driven by the three-axis driving mechanism, and each second adjusting platform is symmetrically arranged on the mounting table and is provided with one spray assembly. The first adjusting platform is used for adjusting the second adjusting platform in X, Y and Z directions, so that the coarse adjustment of the spray assembly is realized; the second adjusting platform can realize the precise adjustment of each spray assembly, so that the sample is fully ionized before entering the sample inlet of the mass spectrometer, the sample feeding speed of the ionized sample is improved, and the intensity and sensitivity of the mass spectrum signal are improved; due to the high ionization efficiency and high sample feeding efficiency, the loss of ions in the transmission process can be reduced, the stability and repeatability of the detection signal are improved, and the reliability and repeatability of the analysis result of the analyte are further ensured.

Description

Technical Field

[0001] This invention relates to the field of online mass spectrometry detection, and in particular to an online mass spectrometry detection device based on a dual-beam pulsed nanoliter electrospray ionization source. Background Technology

[0002] In recent years, online mass spectrometry (MS / MS) detection technology has developed rapidly. This technology, with its ease of operation, rapid analysis, and in-situ detection capabilities, has shown broad prospects for development and application. Traditional online MS / MS detection mainly focuses on analytes with high stability and high ionization efficiency, making it difficult to meet the online detection needs of highly volatile, highly reactive, and low ionization efficiency analytes. Currently, the commonly used method is to improve the stability and ionization efficiency of these analytes through offline derivatization techniques, but this method is complex and time-consuming. To achieve rapid online detection of highly volatile, highly reactive, and low ionization efficiency analytes, and to expand the application scope of online MS / MS detection technology, there is an urgent need for an analytical device that can overcome the above-mentioned technical shortcomings. To this end, existing manufacturers have produced mass spectrometers with dual electrospray ionization sources (such as Waters' LockSpray dual electrospray ionization source), which utilizes the dual electrospray ionization source to improve the ionization efficiency of samples. However, the spray position of this dual ionization source cannot be adjusted, resulting in relatively low sample introduction efficiency, making it impossible to achieve rapid sample introduction of highly volatile and highly reactive analytes, and the low sample introduction efficiency affects the mass spectrometry signal. It is evident that improving both the ionization efficiency and sample introduction efficiency of a mass spectrometer is one of the challenges in expanding the application scope of online mass spectrometry detection. Summary of the Invention

[0003] In view of this, the present invention proposes an online mass spectrometry detection device based on a dual-beam pulsed nanoliter electrospray ionization source. This device can achieve high-precision adjustment of the spray position of the spray component, realize rapid sample injection of the ion source, and thus expand the detection objects of the online mass spectrometry detection device.

[0004] To achieve the above objectives, the present invention adopts the following technical solution: The online mass spectrometry detection device based on a dual-beam pulsed nanoliter electrospray ionization source of the present invention includes a dual spray assembly and a power supply. The sensing electrodes of the spray assembly and the power supply are connected in pairs, and the power supply is a high-voltage pulsed power supply. The online reaction detection device also includes a first adjustment platform and two second adjustment platforms. The first adjustment platform includes a three-axis drive mechanism and a mounting platform driven by the three-axis drive mechanism. The second adjustment platforms are symmetrically arranged on the mounting platform, and the second adjustment platforms are XYR three-axis displacement platforms or XYZR four-axis displacement platforms. Each second adjustment platform is equipped with a spray assembly, and the spray assembly also includes a... The invention comprises a sample loading module and an air inlet module connected via a three-way connector. The three-way connector has a first straight cylinder and a second straight cylinder perpendicularly connected to the first straight cylinder. The sensing electrode is cylindrical and is installed at the first port of the first straight cylinder via a connecting connector. The sample loading module includes a sample injection pump and a nanoliter capillary nozzle connected via a sample injection line. The nanoliter capillary nozzle is coaxially disposed within the first straight cylinder and the sensing electrode, with its tip extending out from the sensing electrode. One end of the nanoliter capillary nozzle is fixed at the second port of the first straight cylinder by a mounting component. The air inlet module is connected to the first straight cylinder and the sensing electrode via the second straight cylinder. The beneficial effects are: This invention has two high-precision adjustable spray components, enabling symmetrical spraying or cross-spraying modes, improving the mixing efficiency of samples and reagents, and promoting sample ionization. This invention utilizes a first adjustment platform to adjust a second adjustment platform in the X, Y, and Z directions, thereby achieving coarse adjustment of the spray components. The second adjustment platform enables precise adjustment of each spray component, ensuring that the sample is fully ionized before entering the mass spectrometer inlet. It also increases the injection rate of the ionized sample, thereby improving the intensity and sensitivity of the mass spectrometry signal. Due to the high ionization and injection efficiency, ion loss during transmission is reduced, increasing the stability and repeatability of the detection signal, and further ensuring the reliability and repeatability of the analyte analysis results.

[0005] Preferably, the air intake module includes a mass flow meter and a gas heater connected in sequence via an air intake pipe. The air outlet of the air intake pipe enters the first straight cylinder from the second straight cylinder. The air intake module introduces sheath gas into the inner cavity of the induction electrode through the first straight cylinder, where it carries micro-droplets and is ejected. The high-temperature sheath gas accelerates the volatilization of interfering reagents and the matrix, thereby reducing the influence of the matrix effect and improving the ionization efficiency.

[0006] Preferably, the injection pump is a micro-injection pump with a flow rate of 0.001 μL / min to 50 μL / min; the inner diameter of the nano-capillary nozzle is 0.1 μm to 10 μm; and the radial distance between the inner wall of the sensing electrode and the nano-capillary nozzle is 50 μm to 1000 μm, thereby allowing the sheath gas to encapsulate the sample and promote sample ionization.

[0007] Preferably, the output voltage of the high-voltage pulse power supply is ±5000V, its waveform is a square wave, the pulse frequency is 0~20 kHz, and the duty cycle is 1%~100%. This invention uses a high-voltage pulse power supply to form tiny charged spray droplets from the sample, promoting the spray ionization of the sample.

[0008] In a preferred embodiment of the present invention, the second adjustment platform is an XYR triaxial displacement platform or an XYZR quadriaxial displacement platform. The XYR triaxial displacement platform has an adjustment accuracy of 10 μm in the X and Y directions and an adjustment accuracy of 0.01° in the R axis. The XYZR quadriaxial displacement platform has an adjustment accuracy of 10 μm in the X, Y, and Z directions and an adjustment accuracy of 0.01° in the R axis. More preferably, a high-precision XYZR quadriaxial displacement platform is selected as the second adjustment platform. The present invention can first use the first adjustment platform for coarse adjustment in the X, Y, and Z directions, and then use the second adjustment platform for precise adjustment of the spray assembly in the X, Y, Z, and R directions, thereby improving the accuracy of the spray assembly and further improving the mixing efficiency of the sample and reagent.

[0009] In a preferred embodiment of the present invention, the gas delivery module delivers nitrogen gas into the induction electrode at a flow rate of 0.5-10 L / min and a heating temperature of ≤250℃.

[0010] Preferably, the connecting joint is a Luer joint; the mounting component is a sealing plug disposed in the second port of the first straight cylinder, and the nano-capillary nozzle is fixedly connected to the first straight cylinder through the sealing plug.

[0011] Compared with existing technologies, this invention features two highly precise adjustable spray components, enabling symmetrical or cross-spray modes to improve sample and reagent mixing efficiency and promote sample ionization. This invention utilizes a first adjustment platform to adjust the second adjustment platform in the X, Y, and Z directions, thereby achieving coarse adjustment of the spray components; the second adjustment platform allows for precise adjustment of each spray component, ensuring sufficient ionization of the sample before it enters the mass spectrometer inlet, and increasing the injection rate of the ionized sample, thus improving the intensity and sensitivity of the mass spectrometry signal. Due to the high ionization and injection efficiency, ion loss during transmission is reduced, increasing the stability and repeatability of the detection signal, further ensuring the reliability and repeatability of analyte analysis results. Attached Figure Description

[0012] Figure 1 This is a schematic diagram of the structure of the present invention.

[0013] Figure 2 This is a schematic diagram of the spray assembly of the present invention.

[0014] Figure 3This is an internal schematic diagram of the spray assembly of the present invention (the air intake module is omitted). Detailed Implementation

[0015] The embodiments of the present invention will be described in detail below with reference to the accompanying drawings. These embodiments are implemented based on the technical solution of the present invention, and detailed implementation methods and specific operation processes are given. However, the scope of protection of the present invention is not limited to the following embodiments.

[0016] It should be noted that, in the description of this invention, relational terms such as “first” and “second” are used only to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any such actual relationship or order between these entities or operations.

[0017] In the description of this invention, unless otherwise explicitly specified and limited, the terms "connected" and "linked" should be interpreted broadly. For example, they can refer to a fixed connection, a detachable connection, or an integral connection; they can refer to a mechanical connection or an electrical connection; they can refer to a direct connection or an indirect connection through an intermediate medium; and they can refer to the internal connection of two components. Those skilled in the art will understand the specific meaning of the above terms in this invention based on the specific circumstances.

[0018] like Figure 1 As shown, the online mass spectrometry detection device based on a dual-beam pulsed nano-liter electrospray ionization source of the present invention includes dual-beam spray components 1 (for samples and reagents respectively) and power supplies 2. The sensing electrode 1.2 of each spray component 1 is connected to a power supply 2. The two power supplies 2 are preferably high-voltage pulse power supplies 2 with an output voltage of ±5000V, a square wave waveform, a pulse frequency of 0-20 kHz, and a duty cycle of 1%-100%. The pulse amplitude, frequency, polarity, and duty cycle of each power supply 2 can be flexibly set, thereby realizing individual control of each electrospray. By optimizing the ionization conditions, mass spectrometry detection of different analytes can be achieved, expanding the application range of the mass spectrometer.

[0019] Combination Figure 1-3It is understood that the online reaction detection device of the present invention also includes a first adjustment platform 3 and two second adjustment platforms 4. The first adjustment platform 3 includes a three-axis drive mechanism 3.1 (which adopts a scissor lifting structure with high stability in the Z direction) and a mounting platform 3.2 driven by the three-axis drive mechanism 3.1. The two second adjustment platforms 4 are symmetrically arranged on the mounting platform 3.2. Each second adjustment platform 4 is provided with a spray component 1. During operation, the second adjustment platform 4 is adjusted in the X, Y, and Z directions by the first adjustment platform 3 to achieve coarse adjustment of the position of the spray component 1. The second adjustment platform 4 is preferably a high-precision XYZR four-axis displacement platform, with an adjustment accuracy of 10μm in the X, Y, and Z directions and an adjustment accuracy of 0.01° in the R axis, which can achieve high-precision adjustment in the X, Y, Z, and rotation directions. In actual operation, the second adjustment platform 4 can be used to adjust the spatial position of each spray assembly 1 so that the spray end of the spray assembly 1 and the sample inlet 5 of the mass spectrometer are optimally positioned, ensuring that the ionized sample enters the sample inlet 5 of the mass spectrometer unimpeded, improving the sample introduction efficiency, thereby reducing the loss of ions during transmission and increasing the stability and repeatability of the detection signal. The spray assembly 1 includes a sample loading module and an air inlet module connected via a three-way connector 1.1. The three-way connector 1.1 has a first straight cylinder 1.1a and a second straight cylinder 1.1b perpendicularly connected to the first straight cylinder 1.1a (i.e., the three-way connector 1.1 is a T-shaped connector). The sensing electrode 1.2 is cylindrical and is installed at the first port of the first straight cylinder 1.1a via a connecting connector 1.3 (preferably a Luer connector). The sample loading module includes a sample injection pump 1.4b connected via a sample injection line 1.4a. The nano-capillary nozzle 1.4c is coaxially disposed inside the first straight cylinder 1.1a and the sensing electrode 1.2. The needle tip of the nano-capillary nozzle 1.4c extends out from the sensing electrode 1.2, and the fixed end of the nano-capillary nozzle 1.4c is fixed at the second port of the first straight cylinder 1.1a by a sealing plug. The sample pump 1.4b injects the sample or reagent into the nano-capillary nozzle 1.4c through the sample injection line 1.4a, forming ionized droplets at its spray end. The air intake module is used to introduce sheath gas (nitrogen with a purity ≥ 99.99% is preferred in this invention) into the sensing electrode 1.2. It includes a mass flow meter 1.5b (for monitoring flow rate) and a gas heater 1.5c (for heating nitrogen, with a flow rate controlled at 0.5-10 L / min and a temperature preferably below 250°C) connected in sequence through the air intake pipe 1.5a. The air inlet of the air intake pipe 1.5a is connected to a nitrogen source (such as a nitrogen tank), and its outlet extends through the second straight cylinder 1.1b to the first straight cylinder 1.1a. Since the second port of the first straight cylinder 1.1a is sealed by a sealing plug, the heated nitrogen enters the sensing electrode 1.2 through the first straight cylinder 1.1a and exits through the spray end of the sensing electrode 1.2. The high temperature of the nitrogen can accelerate the volatilization of interfering reagents and matrix, reduce the influence of matrix effect, and improve ionization efficiency.

[0020] This invention features two highly precise adjustable spray components 1, one for sample spraying and the other for reagent spraying. In practical operation, symmetrical or cross-spraying can be employed to promote sample and reagent mixing and improve sample ionization efficiency. A first adjustment platform 3 adjusts the second adjustment platform 4 in the X, Y, and Z directions, thereby achieving coarse adjustment of the spray components 1. The second adjustment platform 4 enables precise adjustment of each spray component 1, ensuring sufficient ionization of the sample before it enters the mass spectrometer's inlet 5. This also increases the sample injection rate, enhancing the intensity and sensitivity of the mass spectrometry signal. Due to the high ionization and injection efficiency, ion loss during transmission is reduced, increasing the stability and repeatability of the detection signal, further ensuring the reliability and repeatability of the analyte analysis results.

[0021] In actual installation, the injection pump 1.4b is preferably a micro-injection pump with a flow rate of 0.001 μL / min to 50 μL / min, the inner diameter of the nano-capillary nozzle 1.4c is 0.1 μm to 10 μm, and the radial distance between the inner wall of the sensing electrode 1.2 and the nano-capillary nozzle 1.4c is 50 μm to 1000 μm, providing sufficient space for the sheath gas. During operation, the sheath gas enters the sensing electrode 1.2 and heats the sample inside the nozzle, improving the ionization efficiency of the sample.

[0022] Finally, it should be emphasized that the above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art can still make modifications to the technical solutions described in the foregoing embodiments without creative effort, or make equivalent substitutions for some of the technical features. Therefore, any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A mass spectrometry online detection device based on a dual-beam pulsed nanoliter electrospray ionization source, comprising a dual-spray assembly and a power supply, wherein the sensing electrodes of the spray assembly and the power supply are connected in pairs, characterized in that: The power supply is a high-voltage pulse power supply; the online detection device also includes a first adjustment platform and two second adjustment platforms. The first adjustment platform includes a three-axis drive mechanism and a mounting platform driven by the three-axis drive mechanism; the second adjustment platforms are symmetrically arranged on the mounting platform, and the second adjustment platforms are XYR three-axis displacement platforms or XYZR four-axis displacement platforms. Each second adjustment platform is equipped with a spray assembly, which also includes a sample loading module and an air inlet module connected via a three-way connector. The three-way connector has a first straight cylinder and a second straight cylinder perpendicularly connected to the first straight cylinder. The sensing electrode is cylindrical and is installed at the first port of the first straight cylinder via a connecting connector. The sample loading module includes a sample injection pump and a nano-capillary nozzle connected via a sample injection line. The nano-capillary nozzle is coaxially disposed inside the first straight cylinder and the sensing electrode. The tip of the nano-capillary nozzle extends out from the sensing electrode, and one end of the nano-capillary nozzle is fixed at the second port of the first straight cylinder by a mounting component. The air inlet module is connected to the first straight cylinder and the sensing electrode via the second straight cylinder. The air intake module includes a mass flow meter and a gas heater connected in sequence through an air intake pipe. The air outlet of the air intake pipe enters the first straight cylinder from the second straight cylinder. The air intake module supplies nitrogen gas into the sensing electrode. The flow rate of the nitrogen gas is 0.5-10 L / min, and the heating temperature is ≤250℃. The injection pump is a micro-injection pump with a flow rate of 0.001 μL / min to 50 μL / min; the inner diameter of the nano-capillary nozzle is 0.1 μm to 10 μm; and the radial distance between the inner wall of the sensing electrode and the nano-capillary nozzle is 50 μm to 1000 μm.

2. The online mass spectrometry detection device based on a dual-beam pulsed nano-liter electrospray ionization source according to claim 1, characterized in that: The output voltage of the high-voltage pulse power supply is ±5000V, its waveform is a square wave, the pulse frequency is 0~20kHz, and the duty cycle is 1%~100%.

3. The online mass spectrometry detection device based on a dual-beam pulsed nano-liter electrospray ionization source according to claim 1, characterized in that: The XYR three-axis displacement platform has an adjustment accuracy of 10 μm in the X and Y directions, and an adjustment accuracy of 0.01° in the R-axis direction; the XYZR four-axis displacement platform has an adjustment accuracy of 10 μm in the X, Y, and Z directions, and an adjustment accuracy of 0.01° in the R-axis direction.

4. The online mass spectrometry detection device based on a dual-beam pulsed nano-liter electrospray ionization source according to claim 1, characterized in that: The connecting connector is a Luer connector; the mounting component is a sealing plug located in the second port of the first straight cylinder, and the nano-capillary nozzle is fixedly connected to the first straight cylinder through the sealing plug.

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