Electrospray ionization mass spectrometry ionization source and application thereof

Abstract

The invention relates to an electrospray ionization mass spectrometry ionization source, which drives a sample to be matched with a mass spectrometer to realize separation and detection of the sample, and comprises a tube body, the tube body is provided with a channel, the channel is provided with a first end and a second end, the cross section area of the first end is smaller than that of the second end, the second end is electrically connected with a power supply, and the power supply is electrically connected with the tube body. A plurality of polarity areas matched with samples are arranged in the channel, and the samples are sequentially sprayed out from the first end under the action of a power supply. A plurality of polarity areas are formed in a channel through a sample, the polarity of the plurality of polarity areas is gradually weakened from a first end to a second end, so that a polar solvent gradient is established in the channel, in the solvent gradient, voltage applied to an electrode can form an electric field, and generated electromigration force pushes target molecules to a mass spectrum end; and non-polar or weak-polar substances in the polar gradient generate hydrophobic acting force on the target molecules, so that the target molecules are pulled to the opposite direction.

Description

Technical Field

[0001] The invention relates to the field of mass spectrometry analysis, and in particular to an electrospray mass spectrometry ionization source and application thereof. Background Art

[0002] For mass spectrometry, it is usually used in conjunction with liquid chromatography and gas chromatography to achieve the best detection effect. Liquid chromatography and gas chromatography are used to separate the target substances in complex matrix samples to achieve more accurate quantitative and qualitative analysis of complex mixtures, while simplifying the sample pretreatment process. This combined technology greatly improves the selectivity and sensitivity of the analysis and is widely used in detection and analysis in the fields of chemistry, food, environment, biology, etc.

[0003] However, when conventional liquid chromatography is used in conjunction with mass spectrometry, the structure of the instrument becomes complex and large, and the cost is also greatly increased. When liquid chromatography or gas chromatography is used in conjunction with mass spectrometry, a specific interface is required. This interface is responsible for ionizing the separated mobile liquid and sending it to the mass spectrometer, so this interface is both an ion source and an indispensable adapter for coupling liquid chromatography and mass spectrometry. Liquid chromatography itself is also a complex and large instrument, and the liquid phase that can be used in conjunction with mass spectrometry is ultra-high performance liquid chromatography (UHPLC), which can withstand very high liquid pressure, which is also an important factor leading to the complexity of the instrument and the increase in cost. In recent years, in response to the high sensitivity requirements brought about by the analysis of small volumes or precious samples, nano-liquid chromatography (Nano-LC)-mass spectrometry has gradually become a development trend. Nano-liquid chromatography has a low flow rate and high sensitivity. The manufacture of nano-liquid chromatographs requires the use of high-precision processing technology and high-quality materials to ensure their performance and durability. The cost of these high-precision and high-quality materials and components is very high, which leads to a further increase in instrument prices.

[0004] Therefore, there is an urgent need for a method with a new principle that can integrate the functions of nano-liquid chromatography and an adapter, which can not only achieve the separation function but also ionize the sample; and this method can reduce the complexity of the instrument and significantly reduce the cost, while realizing low-flow-rate and high-sensitivity mass spectrometry analysis of small-volume or precious samples. Summary of the invention

[0005] In order to achieve the purpose of the present invention, the technical solution adopted by the present invention is: an electrospray mass spectrometry ionization source, which drives the sample to cooperate with the mass spectrometer to achieve sample separation and detection, including: a tube body, the tube body is provided with a channel, the channel is provided with a first end and a second end, the cross-sectional area of ​​the first end is smaller than the cross-sectional area of ​​the second end, and the second end is electrically connected to a power supply, a plurality of polar regions that cooperate with the sample are provided in the channel, and the sample is ejected from the first end in sequence under the action of the power supply.

[0006] Preferably, at least one solution is disposed in the channel, and a plurality of polar regions are formed by mixing the solution with the sample, and the polarities of the plurality of polar regions gradually weaken from the first end to the second end.

[0007] Preferably, the solution comprises: one or more combinations of acetonitrile, methanol, ethanol, acetone and tetrahydrofuran.

[0008] Preferably, at least one coating is axially disposed in the channel, and the polarity of the coating gradually weakens from the first end to the second end.

[0009] Preferably, the coating is synthesized in the channel, and the coating includes one or more combinations of octadecylsilane bonded silica gel, octadecylsilane bonded silica gel, tetradecylsilane bonded silica gel, silica gel, amino bonded silica gel, polyethylene glycol, a mixture of 50% phenyl and 50% dimethylarylene siloxane, and dimethyl polyoxysilane.

[0010] Preferably, the channel gradually contracts from the second end to the first end and approaches a point structure.

[0011] Preferably, a columnar reaction zone is provided between the first end and the second end of the channel, and a plurality of polar zones are provided in the channel, and the polarities of the plurality of polar zones gradually weaken from one end to the other end.

[0012] Preferably, the power supply adopts a DC voltage of 5-30KV.

[0013] Preferably, the cross-section of the first end and the cross-section of the second end of the channel include: a regular shape or an irregular shape.

[0014] Compared with the prior art, the present invention has the following beneficial effects: The sample forms multiple polar zones in the channel, and the polarity of the multiple polar zones gradually weakens from the first end to the second end, thereby establishing a polar solvent gradient in the channel. In the solvent gradient, the voltage applied to the electrode will form an electric field, and the generated electromigration force will push the target molecules to the mass spectrometry end. The non-polar or weakly polar substances in the polarity gradient produce a hydrophobic force on the target molecules, thereby pulling them in the opposite direction.

[0015] Under the action of these two forces, on the one hand, the capillary electrophoresis liquid chromatography micro-separation of target molecules in a small volume is achieved; on the other hand, the separated target molecules are ionized online and analyzed by mass spectrometry. This new separation principle can be widely used in mass spectrometry analysis of various complex matrix samples, greatly reducing sample usage and analysis costs. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] Figure 1 Schematic diagram of the structure of the electrospray mass spectrometry ionization source of Example 2 of the present invention; Figure 2It is a structural cross-sectional view of an electrospray mass spectrometry ionization source according to Example 2 of the present invention; Figure 3 Schematic diagram of the structure of the electrospray mass spectrometry ionization source of Example 4 of the present invention; Figure 4 It is a structural cross-sectional view of an electrospray mass spectrometry ionization source according to Example 4 of the present invention; Figure 5 It is a schematic structural diagram of the electrospray mass spectrometry ionization source with a bracket and a mass spectrometry cone hole of the present invention; Figure 6 A schematic diagram of the polarity gradient formed by the electrospray mass spectrometry ionization source of the present invention; Figure 7 This is a comparison chart of the separation effects of the present invention and the prior art (the sample is an aqueous solution of 10 μg / ml reserpine and 100 mM sodium chloride); Figure 8 Ion currents and mass spectra of various substances analyzed by conventional electrospray mass spectrometry ionization sources (samples were aqueous solutions of 1 μg / ml tributyl methyl ammonium chloride, 1 μg / ml trioctyl methyl ammonium chloride and 1 μg / ml trihexadecyl methyl ammonium chloride); Fig. 9 The ion currents and mass spectra of various substances analyzed by the electrospray mass spectrometry ionization source of the present invention (the samples are aqueous solutions of 1 μg / ml tributyl methylammonium chloride, 1 μg / ml trioctyl methylammonium chloride and 1 μg / ml trihexadecyl methylammonium chloride).

[0017] In the figure: 1. Tube body; 101. Columnar reaction area; 2. Mass spectrometer end. DETAILED DESCRIPTION

[0018] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. 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 creative work are within the scope of protection of the present invention.

[0019] Embodiment 1: like Figure 1 to Figure 2As shown, the present invention provides a technical solution: an electrospray mass spectrometry ionization source, which is used in mass spectrometry analysis to drive the sample to cooperate with the mass spectrometer to achieve sample separation and detection, including: a tube body 1, the tube body 1 is provided with a micron-level channel, the channel is provided with a first end and a second end, the cross-sectional area of ​​the first end is smaller than the cross-sectional area of ​​the second end, and the cross-sectional shapes of the first end and the second end are both circular, the second end is electrically connected to a power supply, the power supply adopts a DC voltage of 5KV, a plurality of polarity zones that cooperate with the sample are provided in the channel, and the sample is ejected from the first end in sequence under the action of the power supply.

[0020] The cross section of the first end is a circle with a diameter of 1 micron, and the cross section of the second end is a circle with a diameter of 10 microns. The channel of the tube body 1 is configured in a cone shape as a whole, and gradually and smoothly shrinks from the second end to the first end.

[0021] A solution is arranged in the channel. The solution is acetonitrile. The solution and the sample (the sample contains water) are sucked into the tube body 1 by negative pressure. Multiple polar regions are formed during the mixing of acetonitrile and the sample.

[0022] like Figures 5 to 9 As shown, multiple polar regions are formed by mixing the solution with the sample to be detected, and the polarity of the multiple polar regions gradually weakens from the first end to the second end, thereby establishing a polar solvent gradient in the channel. In the solvent gradient, the voltage applied to the electrode will form an electric field, and the generated electromigration force will push the target molecules to the mass spectrometry end 2. The non-polar or weakly polar substances in the polarity gradient produce a hydrophobic force on the target molecules, thereby pulling them in the opposite direction.

[0023] Under the action of these two forces, on the one hand, the capillary electrophoresis liquid chromatography micro-separation of target molecules in a small volume is achieved; on the other hand, the separated target molecules are ionized online and analyzed by mass spectrometry. This new separation principle can be widely used in mass spectrometry analysis of various complex matrix samples, greatly reducing sample usage and analysis costs.

[0024] Embodiment 2: like Figure 1 to Figure 2 As shown, the present invention provides a technical solution: an electrospray mass spectrometry ionization source, which is used in mass spectrometry analysis to drive the sample to cooperate with the mass spectrometer to achieve sample separation and detection, including: a tube body 1, the tube body 1 is provided with a micron-level channel, the channel is provided with a first end and a second end, the cross-sectional area of ​​the first end is smaller than the cross-sectional area of ​​the second end, and the cross-sectional shapes of the first end and the second end are both circular, the second end is electrically connected to a power supply, the power supply adopts a DC voltage of 30KV, a plurality of polarity zones that cooperate with the sample are provided in the channel, and the sample is ejected from the first end in sequence under the action of the power supply.

[0025] The cross section of the first end is a circle with a diameter of 100 microns, the cross section of the second end is a circle with a diameter of 300 microns, the channel of the tube body 1 is set in a cone shape as a whole, and gradually and smoothly shrinks from the second end to the first end. Multiple truncated cones are connected end to end through a capillary connector to form a complete tube body 1.

[0026] Three solutions are arranged in the channel, and the solutions are acetonitrile, methanol and ethanol. The various solutions and samples (the samples contain water) are sucked into the tube body 1 by negative pressure.

[0027] like Figures 5 to 9 As shown, multiple polar regions are formed by mixing the solution with the sample to be detected, and the polarity of the multiple polar regions gradually weakens from the first end to the second end, thereby establishing a polar solvent gradient in the channel. In the solvent gradient, the voltage applied to the electrode will form an electric field, and the generated electromigration force will push the target molecules to the mass spectrometry end 2. The non-polar or weakly polar substances in the polarity gradient produce a hydrophobic force on the target molecules, thereby pulling them in the opposite direction.

[0028] Under the action of these two forces, on the one hand, the capillary electrophoresis liquid chromatography micro-separation of target molecules in a small volume is achieved; on the other hand, the separated target molecules are ionized online and analyzed by mass spectrometry. This new separation principle can be widely used in mass spectrometry analysis of various complex matrix samples, greatly reducing sample usage and analysis costs.

[0029] Embodiment 3: like Figure 1 to Figure 2 As shown, the present invention provides a technical solution: an electrospray mass spectrometry ionization source, which is used in mass spectrometry analysis to drive the sample to cooperate with the mass spectrometer to achieve sample separation and detection, including: a tube body 1, the tube body 1 is provided with a micron-level channel, the channel is provided with a first end and a second end, the cross-sectional area of ​​the first end is smaller than the cross-sectional area of ​​the second end, and the cross-sectional shapes of the first end and the second end are both circular, the second end is electrically connected to a power supply, the power supply adopts a DC voltage of 25KV, a plurality of polarity zones that cooperate with the sample are provided in the channel, and the sample is ejected from the first end in sequence under the action of the power supply.

[0030] The cross section of the first end is a circle with a diameter of 50 microns, and the cross section of the second end is a circle with a diameter of 150 microns. The channel of the tube body 1 is configured in a cone shape as a whole, and gradually and smoothly shrinks from the second end to the first end.

[0031] Five solutions, acetonitrile, methanol, ethanol, acetone and tetrahydrofuran, are arranged in the channel, and the solutions and samples (the samples contain water) are sucked into the tube body 1 by negative pressure.

[0032] like Figures 5 to 9As shown, multiple polar regions are formed by mixing the solution with the sample to be detected, and the polarity of the multiple polar regions gradually weakens from the first end to the second end, thereby establishing a polar solvent gradient in the channel. In the solvent gradient, the voltage applied to the electrode will form an electric field, and the generated electromigration force will push the target molecules to the mass spectrometry end 2. The non-polar or weakly polar substances in the polarity gradient produce a hydrophobic force on the target molecules, thereby pulling them in the opposite direction.

[0033] Under the action of these two forces, on the one hand, the capillary electrophoresis liquid chromatography micro-separation of target molecules in a small volume is achieved; on the other hand, the separated target molecules are ionized online and analyzed by mass spectrometry. This new separation principle can be widely used in mass spectrometry analysis of various complex matrix samples, greatly reducing sample usage and analysis costs.

[0034] Embodiment 4: like Figure 3 to Figure 4 As shown, the present invention provides a technical solution: an electrospray mass spectrometry ionization source, which is used in mass spectrometry analysis to drive the sample to cooperate with the mass spectrometer to achieve sample separation and detection, including: a tube body 1, the tube body 1 is provided with a micron-level channel, the channel is provided with a first end and a second end, the cross-sectional area of ​​the first end is smaller than the cross-sectional area of ​​the second end, and the cross-sectional shapes of the first end and the second end are both circular, the second end is electrically connected to a power supply, the power supply adopts a DC voltage of 15KV, a plurality of polarity zones that cooperate with the sample are provided in the channel, and the sample is ejected from the first end in sequence under the action of the power supply.

[0035] Among them, the cross-section of the first end is a circle with a diameter of 5 microns, and the cross-section of the second end is a circle with a diameter of 15 microns. A columnar reaction zone 101 is provided between the first end and the second end in the channel of the tube body 1. A plurality of polar zones are provided in the columnar reaction zone 101, and the polarity of the plurality of polar zones gradually weakens from one end to the other end.

[0036] The tube body 1 is composed of two truncated cones and a cylindrical tube body 1, wherein the large end of one truncated cone is connected to one end of the cylindrical tube body 1, and the other end of the cylindrical tube body 1 is connected to the small end of another conical cone through a capillary connector to form a complete tube body 1.

[0037] Three solutions, acetonitrile, acetone and tetrahydrofuran, are arranged in the channel, and the solutions and samples are sucked into the tube body 1 by negative pressure.

[0038] like Figures 5 to 9As shown, multiple polar regions are formed by mixing the solution with the sample to be detected, and the polarity of the multiple polar regions gradually weakens from the first end to the second end, thereby establishing a polar solvent gradient in the channel. In the solvent gradient, the voltage applied to the electrode will form an electric field, and the generated electromigration force will push the target molecules to the mass spectrometry end 2. The non-polar or weakly polar substances in the polarity gradient produce a hydrophobic force on the target molecules, thereby pulling them in the opposite direction.

[0039] Under the action of these two forces, on the one hand, the capillary electrophoresis liquid chromatography micro-separation of target molecules in a small volume is achieved; on the other hand, the separated target molecules are ionized online and analyzed by mass spectrometry. This new separation principle can be widely used in mass spectrometry analysis of various complex matrix samples, greatly reducing sample usage and analysis costs.

[0040] Embodiment 5: like Figure 3 to Figure 4 As shown, the present invention provides a technical solution: an electrospray mass spectrometry ionization source, which is used in mass spectrometry analysis to drive the sample to cooperate with the mass spectrometer to achieve sample separation and detection, including: a tube body 1, the tube body 1 is provided with a micron-level channel, the channel is provided with a first end and a second end, the cross-sectional area of ​​the first end is smaller than the cross-sectional area of ​​the second end, and the cross-sectional shapes of the first end and the second end are both circular, the second end is electrically connected to a power supply, the power supply adopts a DC voltage of 20KV, a plurality of polarity zones that cooperate with the sample are provided in the channel, and the sample is ejected from the first end in sequence under the action of the power supply.

[0041] Among them, the cross-section of the first end is a circle with a diameter of 1 micron, and the cross-section of the second end is a circle with a diameter of 10 microns. A columnar reaction zone 101 is provided between the first end and the second end in the channel of the tube body 1. A plurality of polar zones are provided in the columnar reaction zone 101. The polarity of the plurality of polar zones gradually weakens from one end to the other end. The tube body 1 adopts an integrally formed structure.

[0042] Two solutions, acetone and tetrahydrofuran, are arranged in the channel, and the solutions and samples are sucked into the tube body 1 by negative pressure.

[0043] like Figures 5 to 9 As shown, multiple polar regions are formed by mixing the solution with the sample to be detected, and the polarity of the multiple polar regions gradually weakens from the first end to the second end, thereby establishing a polar solvent gradient in the channel. In the solvent gradient, the voltage applied to the electrode will form an electric field, and the generated electromigration force will push the target molecules to the mass spectrometry end 2. The non-polar or weakly polar substances in the polarity gradient produce a hydrophobic force on the target molecules, thereby pulling them in the opposite direction.

[0044] Under the action of these two forces, on the one hand, the capillary electrophoresis liquid chromatography micro-separation of target molecules in a small volume is achieved; on the other hand, the separated target molecules are ionized online and analyzed by mass spectrometry. This new separation principle can be widely used in mass spectrometry analysis of various complex matrix samples, greatly reducing sample usage and analysis costs.

[0045] Embodiment 6: The present invention provides a technical solution: an electrospray mass spectrometry ionization source, which is used in mass spectrometry analysis to drive the sample to cooperate with the mass spectrometer to achieve sample separation and detection, comprising: a tube body 1, the tube body 1 is provided with a micron-level channel, the channel is provided with a first end and a second end, the cross-sectional area of ​​the first end is smaller than the cross-sectional area of ​​the second end, and the cross-sectional shapes of the first end and the second end are both irregular shapes, the second end is electrically connected to a power supply, the power supply adopts a DC voltage of 17KV, a plurality of polarity zones that cooperate with the sample are provided in the channel, and the sample is ejected from the first end in sequence under the action of the power supply.

[0046] The cross section of the first end is an irregular polygon with a diameter of 1 square micron, and the cross section of the second end is an irregular polygon with a diameter of 10 square microns. The channel of the tube body 1 is generally conical and gradually and smoothly shrinks from the second end to the first end.

[0047] Three types of coatings are provided axially in the channel. The coatings are synthesized in the channel, and the polarity of the coatings gradually weakens from the first end to the second end. Polyethylene glycol is used for strong polarity, a mixture of 50% phenyl and 50% dimethyl arylene siloxane is used for medium polarity, and dimethyl polyoxysilane is used for non-polarity. The channel is divided into multiple polarity zones by multiple coatings, and the polarity of multiple polarity zones gradually weakens from the first end to the second end.

[0048] like Figures 5 to 9 As shown, the sample is sucked into the tube body 1 by negative pressure, and the sample to be detected enters multiple polarity zones, thereby establishing a polar solvent gradient in the channel. In the solvent gradient, the voltage applied to the electrode will form an electric field, and the generated electromigration force will push the target molecules to the mass spectrometer end 2. The non-polar or weakly polar substances in the polarity gradient produce a hydrophobic force on the target molecules, thereby pulling them in the opposite direction.

[0049] Under the action of these two forces, on the one hand, the capillary electrophoresis liquid chromatography micro-separation of target molecules in a small volume is achieved; on the other hand, the separated target molecules are ionized online and analyzed by mass spectrometry. This new separation principle can be widely used in mass spectrometry analysis of various complex matrix samples, greatly reducing sample usage and analysis costs.

[0050] Embodiment 7: The present invention provides a technical solution: an electrospray mass spectrometry ionization source, which is used in mass spectrometry analysis to drive the sample to cooperate with the mass spectrometer to achieve sample separation and detection, comprising: a tube body 1, the tube body 1 is provided with a micron-level channel, the channel is provided with a first end and a second end, the cross-sectional area of ​​the first end is smaller than the cross-sectional area of ​​the second end, and the cross-sectional shapes of the first end and the second end are both triangular, the second end is electrically connected to a power supply, the power supply adopts a DC voltage of 23KV, a plurality of polarity zones cooperating with the sample are provided in the channel, and the sample is ejected from the first end in sequence under the action of the power supply.

[0051] The cross section of the first end is a triangle with a diameter of 3 square microns, and the cross section of the second end is a triangle with a diameter of 10 square microns. The channel is configured in a cone shape as a whole, and gradually and smoothly shrinks from the second end to the first end.

[0052] A coating is provided axially in the channel, the coating is synthesized in the channel, and the polarity of the coating gradually weakens from the first end to the second end. Polyethylene glycol is used for strong polarity, and no coating is formed in other areas of the channel. The strong polarity coating forms a polarity gap with other areas. The channel is divided into multiple polarity zones by the coating, and the polarity of the multiple polarity zones gradually weakens from the first end to the second end.

[0053] like Figures 5 to 9 As shown, the sample is sucked into the tube body 1 by negative pressure, and the sample to be detected enters multiple polarity zones, thereby establishing a polar solvent gradient in the channel. In the solvent gradient, the voltage applied to the electrode will form an electric field, and the generated electromigration force will push the target molecules to the mass spectrometer end 2. The non-polar or weakly polar substances in the polarity gradient produce a hydrophobic force on the target molecules, thereby pulling them in the opposite direction.

[0054] Under the action of these two forces, on the one hand, the capillary electrophoresis liquid chromatography micro-separation of target molecules in a small volume is achieved; on the other hand, the separated target molecules are ionized online and analyzed by mass spectrometry. This new separation principle can be widely used in mass spectrometry analysis of various complex matrix samples, greatly reducing sample usage and analysis costs.

[0055] Embodiment 8: The present invention provides a technical solution: an electrospray mass spectrometry ionization source, which is used in mass spectrometry analysis to drive the sample to cooperate with the mass spectrometer to achieve sample separation and detection, comprising: a tube body 1, the tube body 1 is provided with a micron-level channel, the channel is provided with a first end and a second end, the cross-sectional area of ​​the first end is smaller than the cross-sectional area of ​​the second end, and the cross-sectional shape of the first end is triangular, and the cross-sectional shape of the second end is circular, the second end is electrically connected to a power supply, the power supply adopts a DC voltage of 30KV, a plurality of polarity zones cooperating with the sample are provided in the channel, and the sample is ejected from the first end in sequence under the action of the power supply.

[0056] The cross section of the first end is a triangle with a diameter of 2 square microns, and the cross section of the second end is a circle with a diameter of 20 microns. The channel is configured in a cone shape as a whole, and gradually and smoothly shrinks from the second end to the first end.

[0057] Two coatings are provided axially in the channel, and the coatings are synthesized on the inner wall, and the polarity of the coatings gradually weakens from the first end to the second end. Polyethylene glycol is used for strong polarity, and dimethyl polysiloxane is used for non-polarity. The channel is divided into multiple polarity zones by multiple coatings, and the polarity of multiple polarity zones gradually weakens from the first end to the second end.

[0058] like Figures 5 to 9 As shown, the sample is sucked into the tube body 1 by negative pressure, and the sample to be detected enters multiple polarity zones, thereby establishing a polar solvent gradient in the channel. In the solvent gradient, the voltage applied to the electrode will form an electric field, and the generated electromigration force will push the target molecules to the mass spectrometer end 2. The non-polar or weakly polar substances in the polarity gradient produce a hydrophobic force on the target molecules, thereby pulling them in the opposite direction.

[0059] Under the action of these two forces, on the one hand, the capillary electrophoresis liquid chromatography micro-separation of target molecules in a small volume is achieved; on the other hand, the separated target molecules are ionized online and analyzed by mass spectrometry. This new separation principle can be widely used in mass spectrometry analysis of various complex matrix samples, greatly reducing sample usage and analysis costs.

[0060] Embodiment 9: The present invention provides a technical solution: an electrospray mass spectrometry ionization source, which is used in mass spectrometry analysis to drive the sample to cooperate with the mass spectrometer to achieve sample separation and detection, comprising: a tube body 1, the tube body 1 is provided with a micron-level channel, the channel is provided with a first end and a second end, the cross-sectional area of ​​the first end is smaller than the cross-sectional area of ​​the second end, and the cross-sectional shape of the first end is circular, and the cross-sectional shape of the second end is square, the second end is electrically connected to a power supply, the power supply adopts a DC voltage of 5KV, a plurality of polarity zones cooperating with the sample are provided in the channel, and the sample is ejected from the first end in sequence under the action of the power supply.

[0061] Among them, the cross-section of the first end is a circle with a diameter of 6 microns, and the cross-section of the second end is a square with a diameter of 200 square microns. A columnar reaction zone 101 is provided between the first end and the second end in the channel. A plurality of polar zones are provided in the columnar reaction zone 101. The polarity of the plurality of polar zones gradually weakens from one end to the other end. The tube body 1 adopts an integrally formed structure.

[0062] like Figures 5 to 9As shown, three types of coatings are provided axially in the channel, and the coatings are synthesized in the channel, and the polarity of the coatings gradually weakens from the first end to the second end. Polyethylene glycol is used for strong polarity, a mixture of 50% phenyl and 50% dimethyl arylene siloxane is used for medium polarity, and dimethyl polyoxysilane is used for non-polarity. The channel is divided into multiple polarity zones by multiple coatings, and the polarity of the multiple polarity zones gradually weakens from the first end to the second end.

[0063] The sample is sucked into the tube body 1 by negative pressure, and the sample to be tested enters multiple polarity zones, thereby establishing a polar solvent gradient in the channel. In the solvent gradient, the voltage applied to the electrode will form an electric field, and the generated electromigration force will push the target molecules to the mass spectrometer end 2. The non-polar or weakly polar substances in the polarity gradient produce hydrophobic forces on the target molecules, thereby pulling them in the opposite direction.

[0064] Under the action of these two forces, on the one hand, the capillary electrophoresis liquid chromatography micro-separation of target molecules in a small volume is achieved; on the other hand, the separated target molecules are ionized online and analyzed by mass spectrometry. This new separation principle can be widely used in mass spectrometry analysis of various complex matrix samples, greatly reducing sample usage and analysis costs.

[0065] Embodiment 10: The present invention provides a technical solution: an electrospray mass spectrometry ionization source, which is used in mass spectrometry analysis to drive the sample to cooperate with the mass spectrometer to achieve sample separation and detection, comprising: a tube body 1, the tube body 1 is provided with a micron-level channel, the channel is provided with a first end and a second end, the cross-sectional area of ​​the first end is smaller than the cross-sectional area of ​​the second end, and the cross-sectional shapes of the first end and the second end are both irregular shapes, the second end is electrically connected to a power supply, the power supply adopts a DC voltage of 22KV, a plurality of polarity zones that cooperate with the sample are provided in the channel, and the sample is ejected from the first end in sequence under the action of the power supply.

[0066] The cross section of the first end is an irregular polygon with a diameter of 10 square microns, and the cross section of the second end is an irregular polygon with a diameter of 50 square microns. The inner wall of the tube body 1 is tapered as a whole and gradually and smoothly shrinks from the second end to the first end.

[0067] Three types of coatings are provided axially in the channel. The coatings are synthesized in the channel, and the polarity of the coatings gradually weakens from the first end to the second end. Tetraalkylsilane bonded silica gel is used for strong polarity, octadecylsilane bonded silica gel is used for medium polarity, and octadecylsilane bonded silica gel is used for non-polarity. The channel is divided into multiple polarity zones by multiple coatings, and the polarity of multiple polarity zones gradually weakens from the first end to the second end.

[0068] like Figures 5 to 9As shown, the sample is sucked into the tube body 1 by negative pressure, and the sample to be detected enters multiple polarity zones, thereby establishing a polar solvent gradient in the channel. In the solvent gradient, the voltage applied to the electrode will form an electric field, and the generated electromigration force will push the target molecules to the mass spectrometer end 2. The non-polar or weakly polar substances in the polarity gradient produce a hydrophobic force on the target molecules, thereby pulling them in the opposite direction.

[0069] Under the action of these two forces, on the one hand, the capillary electrophoresis liquid chromatography micro-separation of target molecules in a small volume is achieved; on the other hand, the separated target molecules are ionized online and analyzed by mass spectrometry. This new separation principle can be widely used in mass spectrometry analysis of various complex matrix samples, greatly reducing sample usage and analysis costs.

[0070] Embodiment 11: The present invention provides a technical solution: an electrospray mass spectrometry ionization source, which is used in mass spectrometry analysis to drive the sample to cooperate with the mass spectrometer to achieve sample separation and detection, comprising: a tube body 1, the tube body 1 is provided with a micron-level channel, the channel is provided with a first end and a second end, the cross-sectional area of ​​the first end is smaller than the cross-sectional area of ​​the second end, and the cross-sectional shapes of the first end and the second end are both irregular shapes, the second end is electrically connected to a power supply, the power supply adopts a DC voltage of 22KV, a plurality of polarity zones that cooperate with the sample are provided in the channel, and the sample is ejected from the first end in sequence under the action of the power supply.

[0071] The cross section of the first end is an irregular polygon with a diameter of 10 square microns, and the cross section of the second end is an irregular polygon with a diameter of 50 square microns. The inner wall of the tube body 1 is tapered as a whole and gradually and smoothly shrinks from the second end to the first end.

[0072] Three types of coatings are provided axially in the channel. The coatings are synthesized in the channel, and the polarity of the coatings gradually weakens from the first end to the second end. Silica gel is used for strong polarity, octadecylsilane bonded silica gel is used for medium polarity, and octadecylsilane bonded silica gel is used for non-polarity. The channel is divided into multiple polarity zones by multiple coatings, and the polarity of multiple polarity zones gradually weakens from the first end to the second end.

[0073] like Figures 5 to 9 As shown, the sample is sucked into the tube body 1 by negative pressure, and the sample to be detected enters multiple polarity zones, thereby establishing a polar solvent gradient in the channel. In the solvent gradient, the voltage applied to the electrode will form an electric field, and the generated electromigration force will push the target molecules to the mass spectrometer end 2. The non-polar or weakly polar substances in the polarity gradient produce a hydrophobic force on the target molecules, thereby pulling them in the opposite direction.

[0074] Under the action of these two forces, on the one hand, the capillary electrophoresis liquid chromatography micro-separation of target molecules in a small volume is achieved; on the other hand, the separated target molecules are ionized online and analyzed by mass spectrometry. This new separation principle can be widely used in mass spectrometry analysis of various complex matrix samples, greatly reducing sample usage and analysis costs.

[0075] Embodiment 12: The present invention provides a technical solution: an electrospray mass spectrometry ionization source, which is used in mass spectrometry analysis to drive the sample to cooperate with the mass spectrometer to achieve sample separation and detection, comprising: a tube body 1, the tube body 1 is provided with a micron-level channel, the channel is provided with a first end and a second end, the cross-sectional area of ​​the first end is smaller than the cross-sectional area of ​​the second end, and the cross-sectional shapes of the first end and the second end are both irregular shapes, the second end is electrically connected to a power supply, the power supply adopts a DC voltage of 22KV, a plurality of polarity zones that cooperate with the sample are provided in the channel, and the sample is ejected from the first end in sequence under the action of the power supply.

[0076] The cross section of the first end is an irregular polygon with a diameter of 10 square microns, and the cross section of the second end is an irregular polygon with a diameter of 50 square microns. The inner wall of the tube body 1 is tapered as a whole and gradually and smoothly shrinks from the second end to the first end.

[0077] Three types of coatings are provided axially in the channel. The coatings are synthesized in the channel, and the polarity of the coatings gradually weakens from the first end to the second end. Amino-bonded silica gel is used for strong polarity, octadecylsilane-bonded silica gel is used for medium polarity, and octadecylsilane-bonded silica gel is used for non-polarity. The channel is divided into multiple polarity zones by multiple coatings, and the polarity of multiple polarity zones gradually weakens from the first end to the second end.

[0078] like Figures 5 to 9 As shown, the sample is sucked into the tube body 1 by negative pressure, and the sample to be detected enters multiple polarity zones, thereby establishing a polar solvent gradient in the channel. In the solvent gradient, the voltage applied to the electrode will form an electric field, and the generated electromigration force will push the target molecules to the mass spectrometer end 2. The non-polar or weakly polar substances in the polarity gradient produce a hydrophobic force on the target molecules, thereby pulling them in the opposite direction.

[0079] Under the action of these two forces, on the one hand, the capillary electrophoresis liquid chromatography micro-separation of target molecules in a small volume is achieved; on the other hand, the separated target molecules are ionized online and analyzed by mass spectrometry. This new separation principle can be widely used in mass spectrometry analysis of various complex matrix samples, greatly reducing sample usage and analysis costs.

[0080] The embodiments of the present invention disclose preferred embodiments, but are not limited thereto. A person skilled in the art can easily understand the spirit of the present invention based on the above embodiments and make different extensions and changes. However, as long as they do not deviate from the spirit of the present invention, they are all within the protection scope of the present invention.

Claims

1. An electrospray mass spectrometry ionization source drives the sample to cooperate with the mass spectrometer to achieve sample separation and detection, characterized in that: include: The tube body is provided with a channel, the channel is provided with a first end and a second end, the cross-sectional area of ​​the first end is smaller than the cross-sectional area of ​​the second end, and the second end is electrically connected to a power source, a plurality of polarity zones cooperating with the sample are provided in the channel, and the sample is ejected from the first end in sequence under the action of the power source.

2. The electrospray mass spectrometry ionization source according to claim 1, characterized in that: At least one solution is arranged in the channel, and a plurality of polar regions are formed by mixing the solution with the sample, and the polarities of the plurality of polar regions gradually weaken from the first end to the second end.

3. The electrospray mass spectrometry ionization source according to claim 2, characterized in that: The solution comprises one or more combinations of acetonitrile, methanol, ethanol, acetone and tetrahydrofuran.

4. The electrospray mass spectrometry ionization source according to claim 1, characterized in that: At least one coating is axially disposed in the channel, and the polarity of the coating gradually weakens from the first end to the second end.

5. The electrospray mass spectrometry ionization source according to claim 1, characterized in that: The coating is synthesized in the channel, and the coating includes one or more combinations of octadecylsilane bonded silica gel, octadecylsilane bonded silica gel, tetradecylsilane bonded silica gel, silica gel, amino bonded silica gel, polyethylene glycol, a mixture of 50% phenyl and 50% dimethylarylene siloxane, and dimethyl polyoxysilane.

6. The electrospray mass spectrometry ionization source according to claim 1, characterized in that: The channel gradually contracts from the second end to the first end and approaches a point structure.

7. The electrospray mass spectrometry ionization source according to claim 1, characterized in that: A columnar reaction zone is arranged between the first end and the second end of the channel, and a plurality of polar zones are arranged in the channel, and the polarities of the plurality of polar zones gradually weaken from one end to the other end.

8. The electrospray mass spectrometry ionization source according to claim 1, characterized in that: The power supply adopts a direct current voltage of 5-30KV.

9. The electrospray mass spectrometry ionization source according to claim 1, characterized in that: The cross-section of the first end and the cross-section of the second end of the channel include: a regular shape or an irregular shape.

10. Use of the electrospray mass spectrometry ionization source according to any one of claims 1 to 9 in mass spectrometry analysis.

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