De-solvation transmission-type desorption electrospray low-pressure ion mobility spectrometry

Abstract

The utility model relates to a desolvation transmission-type desorption electrospray low-pressure ion mobility spectrometry, which comprises a transmission-type desorption electrospray ion source, an interface electrode and a low-pressure ion migration tube, the transmission-type desorption electrospray ion source is connected with the low-pressure ion migration tube through the interface electrode, the ion mobility spectrometry can realize high-efficiency desorption electrospray ionization of substances difficult to volatilize in the detection process, the sample detection process is simplified, the working pressure is lower than the atmospheric pressure, the detection sensitivity can be improved, and further, the detection accuracy is improved. The ion mobility spectrometry is provided with the desolvation area and is combined with the desolvation gas, so that the detection sensitivity can be further improved, and the application scene of IMS field detection is expanded.

Description

TECHNICAL FIELD

[0001] The utility model belongs to the field of analytical chemistry instrument, concretely relates to a kind of desolvation transmission type analytical electric spray low pressure ion mobility spectrometry. BACKGROUND

[0002] The combined effective infusion of intraoperative sedative analgesics and blood drug concentration monitoring have important clinical significance for the precise implementation of anesthesia. The research team used photoionization pyrolysis ion mobility spectrometry (IMS) to achieve high-sensitivity detection of volatile compounds such as explosives, but the measurement sensitivity of polar and non-volatile compounds was not high. There is no technology to measure polar and non-volatile anesthetics in the blood at the bedside.

[0003] The utility model designs desolvation transmission type analytical electric spray-low pressure IMS technology, solves the effective ionization of polar and non-volatile compounds, and the development of transmission type analytical electric spray technology is very important for expanding the application range of IMS technology. Like traditional electric spray (ESI), the ions generated by ionization exist in the form of ion droplets, which are used as the ionization source of ion mobility spectrometry. These ion droplets need to be completely desolvated. Ion mobility spectrometry identifies compounds based on mobility. If the ion droplets are not completely desolvated, their mobility will change, causing ion mobility spectrometry to be unable to accurately identify. In addition, the solvent in the ion droplets that are not completely desolvated will continue to evaporate in the ion mobility tube and cause severe ion clustering reactions, reducing the resolution and sensitivity of IMS. Traditional IMS works at atmospheric pressure, with small volume and simple structure, but the ion mobility speed is low, and the sensitivity is lower than that of mass spectrometry working in high vacuum. The development of low-pressure IMS technology working between atmospheric pressure and vacuum can improve detection sensitivity and expand the application scenarios of IMS on-site detection. Blood drug concentration monitoring of analgesics and sedatives during surgery is crucial for the precise implementation of clinical anesthesia.

[0004] The utility model works at the pressure of IMS between mass spectrometry vacuum and atmospheric pressure, improves the ion number density and mobility speed per unit space, improves the sensitivity of trace substances, and develops a rapid blood drug monitoring method for bedside anesthetics. The transmission grid is used as the base material of the electric spray ion source, and the direct Joule heat analysis assisted anesthetic gasification through rapid temperature change is used to realize the pre-separation and analytical ionization of target substances, develop low-pressure high-sensitivity IMS technology, further improve the sensitivity, and achieve anesthetic drug sensitivity of ng / ml. This provides a new technical means for bedside anesthetic concentration monitoring and precise implementation of anesthesia. UTILITY MODEL CONTENTS

[0005] The desolvation transmission type analytical electrospray low-pressure ion mobility spectrometer can shield or eliminate the influence of other interfering substances in the blood sample on the detection of anesthetic drugs, and through desolvation of ions in the ion mobility tube, the sensitivity of ionization detection of the substance is improved, and high-sensitivity detection of anesthetic drugs in a complex matrix of a blood sample is realized.

[0006] In order to achieve the above object, the utility model adopts the following technical scheme:

[0007] A desolvation transmission type analytical electrospray low-pressure ion mobility spectrometer, comprising a transmission type analytical electrospray ion source, an interface electrode, and a low-pressure ion mobility tube, the interface electrode is a metal sheet electrode with a through hole at the center, the transmission type analytical electrospray ion source is connected with the low-pressure ion mobility tube through the interface electrode;

[0008] The low-pressure ion mobility tube is a hollow closed cavity, comprising an ion gate, a desolvation zone on the left side of the ion gate, and an ion molecule detection zone on the right side of the ion gate, the desolvation zone and the ion molecule detection zone are respectively composed of alternating coaxial superimposed annular electrodes and annular insulators, the middle part of the annular electrodes and the annular insulators forms a hollow cavity, the middle 1 / 3 of the hollow cavity of the desolvation zone is swollen to form an ampulla shape, and ions can form a vortex with desolvation gas in the swollen hollow cavity to realize complete desolvation effect on the ions.

[0009] A desolvation gas inlet is arranged on the middle 1 / 3 of the lower wall of the desolvation zone close to the ion gate, and the desolvation gas enters the desolvation zone of the ion mobility tube through the desolvation gas inlet.

[0010] The transmission type analytical electrospray ion source comprises a flow injection pump, a capillary electrospray needle, a capillary high-voltage power supply device, a transmission grid, and an ion funnel device, the ion funnel device is connected with the interface electrode through an insulating ring, and the ion funnel device and the center through hole of the interface electrode are coaxial;

[0011] The transmission grid and the capillary electrospray needle are sequentially arranged on the left side of the ion funnel device, the transmission grid is located between the capillary electrospray needle and the ion funnel device, the capillary electrospray needle comprises a capillary tube body with an axial through hole and a spraying tip, the tube body of the capillary electrospray needle is fixed in a horizontal direction on a fixed frame, the spraying tip of the capillary electrospray needle points to the transmission grid and is coaxial with the ion funnel device and the interface electrode, and the transmission grid is arranged between two parallel PEEK sheets on the fixed frame.

[0012] The copper foil is connected with a high-voltage power supply device of the capillary, and the transmission grid, ion funnel device and interface electrode are directly connected with an external power source; different axial voltages are loaded on the spraying tip of the capillary electrospray needle, the transmission grid, the ion funnel device and the interface electrode in order from high to low; an ionization zone is formed between the capillary electrospray needle and the transmission grid, and an ion convergence zone is formed between the transmission grid and the interface electrode.

[0013] The ion funnel device comprises a plurality of polar plates with through holes in the middle, and the plurality of polar plates are arranged in parallel, at equal intervals and coaxially through the through holes.

[0014] An ion migration tube gas inlet is arranged on the middle part of the left side wall of the desolvation zone, coaxially with the center through hole of the interface electrode, and connected with the transmission type desorption electrospray ion source through the center through hole of the interface electrode; an ion migration tube gas outlet is arranged on the upper wall of the desolvation zone close to the gas inlet, and connected with the atmosphere through a connecting pipeline sequentially provided with a first pressure gauge, an adjusting needle valve and a diaphragm pump.

[0015] A Faraday cup is arranged on the right side wall of the ion molecule detection zone opposite to the ion migration tube gas inlet, connected with a signal acquisition and processing system, and a drift gas inlet is arranged on the upper part of the Faraday cup, connected with a drift gas source.

[0016] The end of the capillary tube of the capillary electrospray needle away from the spraying tip is connected with a syringe of a flow injection pump; the capillary tube of the capillary electrospray needle has an outer diameter of 1.5-2 mm, an inner diameter of 0.8-1.5 mm and a length of 10-15 cm, and the inner diameter of the spraying tip of the capillary electrospray needle is about 0.5 μm.

[0017] The distance between the spraying tip of the capillary electrospray needle and the transmission grid is 1-2 mm, the distance between the transmission grid and the ion funnel device is 6-8 mm, and the distance between the spraying tip of the capillary electrospray needle and the ion funnel device is 7-10 mm.

[0018] The base material of the transmission grid is iron-chromium-aluminum or nickel-chromium alloy which is high-temperature resistant, corrosion resistant, fast heat conduction and not easy to deform, the size of the transmission grid is 1 cm*1 cm, the thickness is 1-1.5 mm, the aperture of the wire diameter is about 200-300 μm, the wire diameter of the grid is about 100-200 μm, and the scanning speed of the transmission grid is 100-500 μm / s.

[0019] The gas pressure range of the low-pressure ion mobility spectrometer is 200-500 Pa, the gas pumping speed of the pump is controlled by controlling the tightness of the adjusting needle valve, so as to adjust the gas pressure in the migration tube. The ion migration tube has an ionization zone with a length of 62 mm and an electric field strength of 160~1000 V·cm -1 , a migration zone with a length of 134 mm and an electric field strength of 370~600 V·cm -1 , and an ion gate in the form of a Tyndall-Powell structure ion gate. The resolution of the ion migration tube is 70-80.

[0020] The spray solvent used in the electrospray is a polar organic compound, specifically one or a mixture of two of the following: analytical grade methanol, methanol / water, water, acetonitrile, etc. The flow rate of the spray solvent is 2-10 μl / min. The desolvation gas is air, N2, He or a mixture of any proportion of the two, and the flow rate of the desolvation gas is 50-200 ml / min. The temperature of the desolvation gas is 50-120 ℃.

[0021] The carrier gas is clean air purified by silica gel, activated carbon and 13X molecular sieve in sequence, and the humidity is controlled to be below 10 ppm.

[0022] Compared with the prior art, the advantages of the utility model are that: the transmission grid is used as the base material of the blood sample, which can be replaced, avoids cross interference, improves the repeatability of analysis, does not need complex sample pretreatment, and simplifies the sample processing process; in addition, the rapid temperature change joule thermal analysis technology is adopted, which can realize rapid gasification balance of different boiling point components in sequence, primary pre-separation, improve the gaseous sample concentration per unit time, increase the gasification analysis rate of strong volatile methanol and the like through the analysis of the solvent auxiliary gasification, improve the gasification efficiency, shorten the single analysis time, realize the high-sensitivity online detection of the anesthetic drugs in the blood on the bed. The traditional IMS works under atmospheric pressure, has small volume and simple structure, but the ion migration speed is low, and the sensitivity is low compared with the mass spectrum working under high vacuum. The low-pressure IMS technology working between atmospheric pressure and vacuum is developed, and the detection sensitivity can be further improved by combining the desolvation of ions, so that the application scene of IMS on-site detection is expanded. BRIEF DESCRIPTION OF DRAWINGS

[0023] Figure 1This is a schematic diagram of the structure of a desolvation transmission analytical electrospray low-pressure ion migration spectrum according to the present invention. In the diagram, 1 is a flow injection pump, 2 is a capillary electrospray needle, 3 is a capillary high-voltage power supply device, 4 is a transmission grid, 5 is an ion funnel device, 6 is an interface electrode, 7 is a migration tube high-voltage power supply device, 8 is an ionization region, 9 is an ion aggregation region, 10 is a desolvation region, 11 is an ion molecule detection region, 12 is a signal acquisition and processing system, 13 is a drift gas inlet, 14 is a heating jacket, 15 is a ring-shaped insulator, 16 is a ring-shaped electrode, 17 is an ion migration tube outlet, 18 is a first pressure gauge, 19 is a regulating needle valve, 20 is a diaphragm pump, 21 is a diaphragm pump exhaust outlet, 22 is a second pressure gauge, 23 is an exhaust pump, 24 is an exhaust pump exhaust outlet, and 25 is a desolvation gas inlet. Detailed Implementation

[0024] To make the objectives, technical solutions, and advantages of this utility model clearer, the present utility model will be described in detail below with reference to the accompanying drawings and specific embodiments. Example

[0025] like Figure 1 As shown, this utility model provides a desolvation transmission-desorption electrospray low-pressure ion migration spectrum, including a transmission-desorption electrospray ion source, an interface electrode 6, and a low-pressure ion migration tube. The interface electrode 6 is a metal sheet electrode with a through hole in the center. The transmission-desorption electrospray ion source is connected to the low-pressure ion migration tube through the interface electrode 6.

[0026] The transmission-type analytical electrospray ion source includes a flow injection pump 1, a capillary electrospray needle 2, a capillary high-voltage power supply device 3, a transmission grid 4, an ion funnel device 5, and the ion funnel device 5 is connected to the interface electrode 6 through an insulating ring. The ion funnel device 5 and the central through hole of the interface electrode 6 are coaxial.

[0027] The ion funnel device 5 comprises a plurality of middle through-hole pole pieces, the plurality of pole pieces are parallel, equidistant, and coaxial through-hole, the pole pieces are circular or square ring pole pieces, the pole pieces are spaced by 2mm thick insulating rings, the inner diameters of the insulating rings are 16mm, 14mm, 12mm, 10mm and 8mm respectively, the number of the pole pieces of the ion funnel device 5 is 6, the middle part of the pole pieces of the ion funnel device 5 is a circular through-hole, the diameters of the through-holes are 18mm, 16mm, 14mm, 12mm, 10mm and 8mm respectively, and the diameters of the through-holes of the middle part of the pole pieces gradually decrease from left to right, the pole pieces are fixed on the insulating PEEK column, the interface electrode 6 is a metal sheet electrode with a through-hole at the center, the diameter of the center through-hole is 2mm, and the interface electrode 6 is connected with the rightmost pole piece of the ion funnel device 5 through an insulating ring, the ion funnel device 5 is coaxial with the center through-hole of the interface electrode 6, and an ionization source gas outlet 24 is arranged close to the interface electrode 6 of the ion funnel device 5, the ionization source gas outlet 24 is communicated with the atmosphere through the second pressure gauge 22 and the gas pump 23 arranged on the communication pipeline.

[0028] A transmission grid 4 and a capillary tube electrospray needle 2 are sequentially arranged on the left side of the ion funnel device 5, the transmission grid 4 is located between the capillary tube electrospray needle 2 and the ion funnel device 5, the capillary tube electrospray needle 2 comprises a capillary tube body with an axial through-hole and a spray tip, the capillary tube body of the capillary tube electrospray needle 2 is fixed in a horizontal direction on a fixed frame, the spray tip of the capillary tube electrospray needle 2 points to the transmission grid 4 and is coaxial with the ion funnel device 5 and the interface electrode 6, and the transmission grid 4 is fixed between the two parallel PEEK sheets of the fixed frame.

[0029] The end of the capillary tube body of the capillary tube electrospray needle 2 away from the spray tip is connected with the syringe of the flow injection pump 1, the size of the capillary tube body of the capillary tube electrospray needle 2 is an outer diameter of 1.5mm, an inner diameter of 0.86mm and a length of 10cm, and the size of the spray tip of the capillary tube electrospray needle 2 is about 0.5μm.

[0030] A copper foil is wound around the spray tip of the capillary tube electrospray needle 2, the copper foil is connected with the capillary high-voltage power supply device 3, the transmission grid 4, the ion funnel device 5 and the interface electrode 6 are all directly connected with an external power supply, the spray tip of the capillary tube electrospray needle 2, the transmission grid 4, the ion funnel device 5 and the interface electrode 6 are loaded with different axial voltages in the order of high to low voltage, an ionization zone 8 is formed between the capillary tube electrospray needle 2 and the transmission grid 4, and an ion convergence zone 9 is formed between the transmission grid 4 and the interface electrode 6.

[0031] The distance between the spray tip of the capillary electrospray needle 2 and the transmission grid 4 is 2 mm, the distance between the transmission grid 4 and the ion funnel device 5 is 8 mm, and the distance between the tip of the capillary electrospray needle 2 and the ion funnel device 5 is 10 mm.

[0032] The base material of the transmission grid 4 is a nickel-chromium alloy (purchased and processed from Dalian Showa Machinery Factory) which is high-temperature resistant, corrosion resistant, fast heat conducting and not easy to deform. The size of the transmission grid 4 is 1 cm*1 cm, the thickness is 1.5 mm, the aperture of the wire diameter is about 300 μm, the wire diameter of the grid is about 200 μm, and the scanning speed of the transmission grid is 100-500 μm / s.

[0033] The low-pressure ion mobility tube is a hollow sealed cavity, including an ion gate, a desolvation zone 10 on the left side of the ion gate, and an ion molecule detection zone 11 on the right side of the ion gate. The desolvation zone 10 and the ion molecule detection zone 11 are respectively composed of alternating coaxial superimposed ring electrodes 16 and ring insulators 15. The middle part of the ring electrodes 16 and the ring insulators 15 forms a hollow cavity, and the middle 1 / 3 of the hollow cavity of the desolvation zone 10 is swollen into an ampulla shape.

[0034] An ion mobility tube gas inlet is arranged on the middle part of the left side wall of the desolvation zone 10, which is coaxial with the center through hole of the interface electrode 6. The ion mobility tube gas inlet is connected with the transmission type analytical electrospray ion source through the center through hole of the interface electrode 6. An ion mobility tube gas outlet 17 is arranged on the upper wall of the desolvation zone close to the gas inlet. The ion mobility tube gas outlet 17 is connected with the atmosphere through the first pressure gauge 18, the adjusting needle valve 19 and the diaphragm pump 20 arranged in sequence on the connecting pipeline. A desolvation gas inlet 25 is arranged on the lower wall of the desolvation zone 10 close to the ion gate in the middle 1 / 3. The desolvation gas enters the ion mobility tube through the desolvation gas inlet 25.

[0035] A Faraday cup is arranged on the right side wall of the ion molecule detection zone 11 opposite to the ion mobility tube gas inlet. The Faraday cup is connected with the signal acquisition and processing system 12. A drift gas inlet 13 is arranged on the upper part of the Faraday cup, which is connected with a drift gas source.

[0036] The drift gas is clean air purified by silica gel, activated carbon and 13X molecular sieve in sequence, and the humidity is controlled below 10 ppm.

[0037] The pressure range of the low-pressure ion mobility spectrum is maintained at 200-500 Pa by adjusting the needle valve 19. The length of the desolvation zone of the ion mobility tube is 62 mm, the electric field strength is 160-1000 V·cm -1 , the length of the ion molecule detection zone is 134 mm, and the electric field strength is 370-600 V·cm -1The ion gate is a Tyndall-Powell structure ion gate, and the resolution in the ion transfer tube is 70-80.

Claims

1. A desolvation transmission resolving electrospray low pressure ion mobility spectrometer characterized in that: The desolvation transmission resolving electrospray ion source comprises an interface electrode (6), a low-pressure ion migration tube, and a transmission resolving electrospray ion source. The low-pressure ion migration tube is a hollow closed cavity, comprising an ion gate, a desolvation zone (10) on the left side of the ion gate, and an ion molecule detection zone (11) on the right side of the ion gate. The desolvation zone (10) and the ion molecule detection zone (11) are respectively composed of alternating coaxial stacked ring electrodes (16) and ring insulators (15). A desolvation gas inlet (25) is arranged on the lower wall of the desolvation zone (10) and near the ion gate. The transmission resolving electrospray ion source comprises a flow injection pump (1), a capillary electrospray needle (2), a capillary high-voltage power supply device (3), a transmission grid (4), and an ion funnel device (5). The transmission grid (4) is located between the capillary electrospray needle (2) and the ion funnel device (5). The capillary electrospray needle (2) comprises a capillary tube with an axial through hole and a spray tip. The capillary tube of the capillary electrospray needle (2) is fixed horizontally on a fixed frame. The spray tip of the capillary electrospray needle (2) points to the transmission grid (4) and coincides with the axial lines of the ion funnel device (5) and the interface electrode (6). The transmission grid (4) is fixed between two parallel polyether ether ketone sheets on the fixed frame. The spray tip of the capillary electrospray needle (2), the transmission grid (4), the ion funnel device (5), and the interface electrode (6) are loaded with different axial voltages in order from high to low. An ionization zone (8) is formed between the capillary electrospray needle (2) and the transmission grid (4).

2. The desolvation transmission resolving electrospray low-pressure ion migration spectrum according to claim 1, wherein: The ion funnel device (5) comprises a plurality of middle through-hole pole pieces, a plurality of pole pieces are arranged in parallel, equidistantly and coaxially, the pole pieces are circular or square ring pole pieces, and each pole piece is spaced by an insulation ring with a thickness of 1-2 mm and an inner diameter of 1-19 mm; the number of pole pieces of the ion funnel device (5) is 4-50; the middle part of the pole piece of the ion funnel device (5) is a circular through-hole with a hole diameter of 1-20 mm, and the hole diameter of the middle part of the pole piece gradually decreases from left to right, and the pole piece is fixed on an insulation polyether ether ketone column; the interface electrode (6) is a metal sheet electrode with a through-hole at the center, and is connected with the rightmost pole piece of the ion funnel device (5) through an insulation ring; the ion funnel device (5) is coaxial with the center through-hole of the interface electrode (6); an ionization source gas extraction outlet (24) is arranged near the interface electrode (6) of the ion funnel device (5), and the ionization source gas extraction outlet (24) is communicated with the atmosphere through a second pressure gauge (22) and a gas extraction pump (23) arranged on the connecting pipeline.

3. The desolvation transmission-type resolved electrospray low-pressure ion mobility spectrometer according to claim 1, wherein: A ion mobility tube gas inlet is arranged in the middle of the left side wall of the desolvation zone (10), the ion mobility tube gas inlet is coaxial with the center through-hole of the interface electrode (6), the ion mobility tube gas inlet is connected with the transmission-type resolved electrospray ion source through the center through-hole of the interface electrode (6); an ion mobility tube gas outlet (17) is arranged on the upper wall of the desolvation zone (10) near the gas inlet, the ion mobility tube gas outlet (17) is communicated with the atmosphere through a first pressure gauge (18), an adjusting needle valve (19) and a diaphragm pump (20) arranged in sequence on the connecting pipeline; A Faraday cup is arranged at a position opposite to the ion mobility tube gas inlet on the right side wall of the ion molecule detection zone (11), the Faraday cup is connected with a signal acquisition and processing system (12), and a drift gas inlet (13) is arranged on the upper part of the Faraday cup and connected with a drift gas source.

4. The desolvation transmission resolved ambient electrospray low pressure ion mobility spectrometer of claim 1, wherein: One end of the capillary tube body of the capillary electrospray needle (2) far from the spray tip is connected with a syringe of a flow injection pump (1); the capillary tube body of the capillary electrospray needle (2) has a size of an outer diameter of 1.5-2 mm, an inner diameter of 0.8-1.5 mm and a length of 10-15 cm, and the inner diameter size of the spray tip of the capillary electrospray needle (2) is 0.5-1 μm.

5. The desolvation transmission resolved ambient electrospray low pressure ion mobility spectrometer of claim 1, wherein: The distance between the spray tip of the capillary electrospray needle (2) and the transmission grid (4) is 1-2 mm, the distance between the transmission grid (4) and the ion funnel device (5) is 6-8 mm, and the distance between the spray tip of the capillary electrospray needle (2) and the ion funnel device (5) is 7-10 mm.

6. The desolvation transmission resolved ambient electrospray low pressure ion mobility spectrometer of claim 1, wherein: The matrix material of the transmission grid (4) is iron-chromium-aluminum or nickel-chromium alloy, the size of the transmission grid (4) is 1 cm*1 cm, the thickness is 1-1.5 mm, the hole diameter of the wire diameter is about 200-300 μm, the wire diameter of the grid is about 100-200 μm, and the scanning speed of the transmission grid is 100-500 μm / s.

7. The desolvation transmission resolved ambient electrospray low pressure ion mobility spectrometer of claim 1, wherein: The air pressure range of the low air pressure ion mobility spectrometer is 200-500 Pa, the ion mobility tube ionization zone length is 62 mm, and the electric field intensity is 160-1000 V·cm -1 , the length of the migration zone is 134 mm, and the electric field intensity is 370-600 V·cm -1 , and the ion gate is a Tandem-Powell structure ion gate. The resolution in the ion mobility tube is 70-80.

8. The desolvation transmission resolved ambient electrospray low pressure ion mobility spectrometer of claim 1, wherein: The temperature of the desolvation gas is 50-120 ℃, the flow rate of the desolvation gas is 50-200 ml / min, the carrier gas is dry air purified by silica gel, activated carbon and 13X molecular sieve in turn, and the humidity is controlled to be less than 10 ppm.

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