WO2016066062A1 - Electrospray ionization apparatus and mass spectrometer - Google Patents

Abstract

An electrospray ionization apparatus for ionizing the substance to be analyzed in solution comprises an ionization chamber (1), a liquid sucker (2), one or more air ducts (3) and an ion sampling port (4). The liquid sucker (2) introduces the solution from the outlet end of the liquid sucker (2) into the ionization chamber (1) in the form of droplet, and a potential difference is maintained in a predetermined period between at least a part of the liquid sucker (2) and the surface of the ionization chamber (1) so as to charge the droplets. The one or more air ducts (3) introduce one or more air flows towards the outlet end of the liquid sucker (2) into the ionization chamber (1), and the movement direction of the air flows is at a predetermined angle with the extension direction of the liquid sucker (2). The air ducts (3) and the liquid sucker (2) are freely detachable. The opening end of the ion sampling port (4) is towards the ionization chamber (1) for introducing the ions of the substance to be analyzed in the solution into the mass spectrometer at the next stage of the electrospray ionization apparatus. The ionization apparatus with direct, rapid mass analysis, good reproducibility and without cross contamination can be realized, and the electrospray ionization can be realized on the disposable sucker having a larger tip end size without the electrode being contacting with the solution.

Description

Electrospray ionization device and mass spectrometer Technical field

The invention relates to the technical field of mass spectrometry, in particular to an electrospray ionization device and a mass spectrometer.

Background technique

Chromatography-mass spectrometry combines the high separation efficiency of chromatography with the high selectivity and sensitivity of mass spectrometry. It is still the most effective method for complex sample analysis. However, because the chromatographic separation process cannot be completed in a short period of time, the chromatographic-mass spectrometry method is not a high-throughput analytical method, and it is not sufficient to meet certain analytical tasks that require results to be available or large sample sizes.

The flow injection-mass spectrometry analysis technique is a method with high throughput analysis capabilities. Instrumentation for flow injection mass spectrometry typically includes a solvent delivery device, an injection valve, and a mass spectrometer ionization source that are connected together by a solvent delivery line. When the injection valve is in the load position, the sample solution is injected into the sample loop through the syringe. At this point, the solvent flows into the mass spectrometry ion source through a separate channel on the valve; when the sample is injected, the injection valve is switched. To the injection state, the flow of solvent on the valve is routed to the sample loop by the separate channel described above, and the injected sample is brought into the mass spectrometry ionization source. The use of the auto-injection robot greatly improves the analysis speed of the flow injection-mass spectrometry method, making the technology a metabolomics, clinical test and related pharmacodynamics, toxicology and mechanism research requiring large sample and large data volume acquisition and analysis. Have certain advantages.

However, this method also has the disadvantages of: 1) requiring proper sample preparation to remove a large amount of background matrix that inhibits ionization in the sample solution, which limits the increase in analytical throughput; 2) syringes, tubing, and ionization sources The needle will have analyte residue, even a small amount of residue will make the quantitative analysis of the quantitative analysis have obvious deviation; 3) After the contamination occurs, the replacement of the needle, the pipeline and the ionization source needle is very cumbersome.

The document of U.S. Patent No. 6,858,437 B2 discloses a direct flow injection analysis atomization electrospray technique which is unique in that a syringe is used in place of a conventional electrospray ionization source. When the syringe draws the sample solution, it is directly inserted into the probe that closely fits the syringe, and a DC voltage is applied to the syringe, and if necessary, an auxiliary atomizing gas is passed through the gap between the needle and the probe. To achieve electrospray ionization of the analyte of interest. The syringe can be a multi-use needle or a disposable tip. Simple sample preparation can be achieved by filling the sample with a chromatographic packing to reduce the suppression of ionization by the background matrix. In addition, the use of atomizing gas can reduce the voltage amplitude required for electrospray, improve spray stability and desolvation efficiency. Although this method solves the defects of partial flow injection-mass spectrometry, there are still two shortcomings: 1) After the syringe is aspirated, it needs to be inserted into the probe which is closely matched with it, and remains on the syringe. The solution may contaminate the probe. Contaminants left on the probe may interfere with the next analysis; 2) if plastic is used The disposable tip of the material, the direct electricity needs to be contacted with the sample solution in the tip through a metal part, which not only increases the complexity of the device, but also the possibility of contaminants remaining on the metal part.

The traditional pipetting method uses a pipette and uses a visual method to perform a volumetric pipetting method. The pipette used can be reused after washing. Although the pipetting method has high accuracy, the efficiency is too low. Pipetting methods using pipetting guns combined with low-cost disposable plastic tips have become mainstream. The method has the advantages of high pipetting speed, low cost and no cross-contamination between multiple pipetting. The plastic tips used are standardized for mass production and the current purchase price is very low. Williams et al. (Rapid Communication in Mass Spectrometry, 2001, Vol. 15, pp. 1890-1891) used a disposable pipette tip as an electrospray needle to achieve mass spectrometric analysis of organic synthesis intermediates. , reducing cross-contamination of multiple analyses. However, in this method, in order to achieve electrospray ionization, the applied DC voltage is applied to the tip of the tip by a metal needle inserted into the tip to contact the solution. Since the metal needle is directly in contact with the solution, it needs to be cleaned in multiple analyses, making the analysis process still complicated. Since the atomization gas is not used to assist the generation of electrospray, the spray voltage required for the method is high, and the stability and reproducibility of the electrospray are insufficient.

Franzke et al. (Analytical Bioanaytical Chemistry, 2010, Vol. 397, pp. 1767-1772) proposed a dielectric barrier electrospray method in 2010. The applied voltage is a square wave AC high voltage, electrode and sample solution. Separated by a layer of dielectric, not in direct contact with the sample solution. Qiao et al. (Analytical Chemistry, 2012, Vol. 84, pp. 7422-7430) proposes a method similar to the principle of dielectric barrier electrospray, and proposes a new name for this method - electrostatic spray ionization. In this article, attempts have been made to combine a dielectric barrier electrospray technique with a tip electrospray method which obscures the drawbacks of using a metal needle to contact a solution in a nozzle spray method as disclosed by Williams et al. Qiao et al. used a direct electrospray method. In this case, in order to stabilize the electrospray, the tip of the selected tip should be as small as possible. The tip of the pipette tip of the disposable polypropylene material selected by Qiao et al. is about 350 μm. The rigidity of the tip of such a fine polypropylene plastic is insufficient, and the degree of bending between the tip and the tip is not Again, this obviously affects the reproducibility of the tip electrospray. In order to improve reproducibility, it is necessary to use a tip with a more rigid tip, for example, a 20 μL tip having a tip outer diameter of 750 μm. However, in the direct electrospray mode, the dielectric barrier electrospray is required to achieve a spray of the solution, which requires that the peak-to-peak value of the applied square wave AC voltage is higher than that of the DC electrospray, and with the diameter of the tip of the needle. It increases and increases, and when the peak-to-peak value of the AC voltage is too high, it is easy to cause discharge of the electrode and the surrounding environment.

Based on the shortcomings of the above methods, in order to develop an electrospray ionization mass spectrometry method which can be used for direct rapid analysis, good reproducibility and no cross-contamination, the above method should be improved to achieve on a tip with a larger tip size. Electrospray ionization.

Summary of the invention

In view of the above-mentioned shortcomings of the prior art, the object of the present invention is to develop an electrospray ionization device which can be used for direct and rapid analysis of a mass spectrometer, has good reproducibility and is free of cross-contamination, and can be used without the electrode contacting the solution. To achieve electrospray ionization on a disposable tip with a larger tip size.

In order to achieve the above object and other related objects, the present invention provides an electrospray ionization device for ionizing an analyte in a solution, the electrospray ionization device comprising: an ionization chamber; a liquid tip for guiding the The solution enters the ionization chamber in the form of droplets from the outlet end of the liquid tip, and at least a portion of the liquid tip maintains a potential difference relative to the surface of the ionization chamber for a predetermined time to allow liquid to enter the ionization chamber Dropping electrification; one or more air guiding tubes for guiding one or more air currents into the ionization chamber, the one or more air currents directed to the outlet end of the liquid suction head, and the air guiding tube and the liquid suction The extending direction of the head is at a predetermined angle; wherein the air guiding tube and the liquid suction head are disposed to be freely separable; the ion sampling port has an open end facing the ionization chamber for guiding the analyte ions of the solution to enter A mass analyzer located below the electrospray ionization device.

Optionally, the liquid tip is a tapered liquid tip having a tapered tip as the outlet end.

Optionally, the outer diameter of the tapered tip of the liquid tip has a diameter ranging from 10 to 50 μm; or 50 to 200 μm; or 200 to 500 μm; or 500 to 1000 μm; or 1000 to 2000 μm.

Optionally, a chromatographic packing is disposed in the liquid tip.

Optionally, the material used for the chromatographic packing comprises: one or more mixtures of porous silica gel particles, paper fiber porous monolithic materials, polymer monolithic columns, and polymer coated particles.

Optionally, the solution passes through the liquid tip under the pressure difference applied between the inlet end and the outlet end of the liquid tip, wherein the pressure at the inlet end of the liquid tip is stronger than the pressure at the outlet end of the liquid tip.

Optionally, the airflow sent by the air guiding tube passes through the outlet end of the liquid suction head to form a pressure difference between the inlet end of the liquid suction head and the outlet end of the liquid suction head, and the solution passes through the liquid suction head by the pressure difference. .

Optionally, the inlet end of the liquid suction head is connected to atmospheric pressure, and the pressure at the outlet end of the liquid suction head is a negative pressure.

Optionally, the potential difference is a DC high voltage potential difference, and the DC potential difference is directly applied to the liquid in the liquid tip.

Optionally, the potential difference is an alternating high voltage potential difference, and the alternating current potential difference is directly applied to the liquid in the liquid tip.

Optionally, the potential difference is an alternating high voltage potential difference, and the alternating current potential difference is applied to the liquid in the liquid tip through the dielectric.

Optionally, the material of the liquid tip comprises: one of a metal, a quartz tube, an organic polymer material, and glass.

Optionally, the DC high voltage potential difference ranges from 1000 to 3000V; or 3000 to 5000V; or 5000 to 8000V; or 8000 to 12000V.

Optionally, the peak-to-peak value of the alternating high voltage potential ranges from 1000 to 3000V; or 3000 to 5000V; or 5000 to 8000V; or 8000 to 12000V.

Optionally, the frequency of the alternating current potential is 2 to 1000 Hz.

Optionally, the end of the air guiding tube pointing to the outlet end of the liquid suction head has a circular shape, a flat shape, or a circular arc shape.

Optionally, the angle between the air guiding tube and the liquid tip is in the range of 20° to 60°; or 60° to 90°; or 90° to 120°.

Optionally, the air flow is a heated air flow.

Optionally, the airflow speed ranges from 10 to 100 m/s; or from 100 to 300 m/s; or from 300 to 600 m/s; or from 600 to 800 m/s.

To achieve the above and other related objects, the present invention provides a mass spectrometer comprising: an electrospray ionization device as described above; and the mass analyzer located below the electrospray ionization device.

As described above, the present invention provides an electrospray ionization apparatus for ionizing a solution to be analyzed, comprising: an ionization chamber; a liquid tip, guiding the solution into the ionization chamber from the outlet end of the tip in the form of droplets. a body, at least a portion of the tip maintains a potential difference relative to the surface of the ionization chamber for a predetermined time to charge the droplets entering the ionization chamber; one or more air tubes directing a portion of the outlet end of the liquid tip or The plurality of air flows enter the ionization chamber, and the direction of the air flow moves at a predetermined angle with the extending direction of the liquid tip; wherein the air pipe and the liquid tip are freely separable; the ion sampling port has an open end facing the ionization cavity, guiding The analyte ions of the solution enter the mass analyzer located in the lower stage of the electrospray ionization device; the ionization device that achieves direct rapid mass analysis, good reproducibility and no cross-contamination can be realized at the tip size without the electrode contacting the solution. Electrospray ionization is achieved on larger disposable tips.

DRAWINGS

1 is a schematic view showing the structure of an electrospray ionization apparatus according to an embodiment of the present invention.

2 is a schematic view showing the structure of an electrospray ionization apparatus according to still another embodiment of the present invention.

3 is a schematic view showing the structure of an electrospray ionization apparatus in still another embodiment of the present invention.

4 is a schematic view showing the structure of an electrospray ionization apparatus according to another embodiment of the present invention.

Fig. 5 is a view showing the experimental results of the mass spectrometry application of the electrospray ionization apparatus in an application example of the present invention.

6 is a schematic view showing experimental results of mass spectrometry application of an electrospray ionization apparatus in an application example of the present invention.

7 is a schematic view showing experimental results of mass spectrometry application of an electrospray ionization apparatus in an application example of the present invention.

Figure 8 is a graph showing experimental results of mass spectrometry application of an electrospray ionization apparatus in an applied embodiment of the present invention.

Figure 9 is a graph showing experimental results of mass spectrometry application of an electrospray ionization apparatus in an applied embodiment of the present invention.

detailed description

The embodiments of the present invention are described below by way of specific examples, and those skilled in the art can readily understand other advantages and effects of the present invention from the disclosure of the present disclosure. The present invention may be embodied or applied in various other specific embodiments, and various modifications and changes can be made without departing from the spirit and scope of the invention. It should be noted that the embodiments in the present application and the features in the embodiments may be combined with each other without conflict.

As shown in Figure 1, the present invention provides an embodiment of an electrospray ionization apparatus for ionizing a substance to be analyzed in a solution, the electrospray ionization apparatus being usable as a component of a mass spectrometry system such as a mass spectrometer; The electrospray ionization device comprises: an ionization chamber 1, a liquid suction head 2, an air guiding tube 3, an ion sampling port 4, and the like.

In an embodiment, the liquid tip 2 is tubular, and the solution may be sucked from one end (for example, the upper end of the drawing) of the liquid tip 2 by means of a pipetting gun, or may be injected from the opposite end (for example, the lower end of the figure). Referring to the illustrated arrow indicating the direction of movement of the solution, the liquid tip 2 is used to guide the solution into the ionization chamber 1 from the outlet end (lower end in the drawing) of the liquid tip 2 in the form of droplets. The liquid tip 2 is preferably a liquid tip (ie, a disposable tip), wherein at least a portion of the liquid tip 2 maintains a potential difference with respect to the surface of the ionization chamber 1 for a predetermined time to allow entry. The droplet of the ionization chamber 1 is charged; in the embodiment, the potential difference is a DC high voltage potential difference, and the applied DC high voltage potential difference can be directly applied to the tip of the liquid tip, or can be applied to the tip of the tip through a dielectric, and the dielectric can be The outer wall of the air or the insulating tip or other dielectric material; the DC high voltage potential difference ranges from 1000 to 3000V; or 3000 to 5000V; or 5000 to 8000V; or 8000 to 12000V; in addition, the DC high voltage potential Preferably the suction head 2 is engaged through a high resistance (e.g., 10 M [Omega) resistance of the liquid. The material of the liquid tip 2 includes one of a metal, a quartz tube, an organic polymer material, and glass. A DC or AC power is applied to the liquid tip 2 of the metal material as a preferred solution.

The air ducts 3 may be one or more in number for guiding one or more air streams into the ionization chamber 1 , the air stream being directed to the outlet end of the liquid tip 2 . The function of the air flow of the air guiding tube 3 is described below: generally, the outer diameter of the outlet end (or the tip end) of the liquid suction head used in the prior art is generally larger than 350 μm, and the outlet of the outer diameter of 350 μm can be applied by applying a voltage of more than 4 kV to the suction head. Produces a beam of electrospray at the end, however its spray stability is poor, and as the liquid flow rate increases, The spray stability is gradually reduced. In the embodiment of the present invention, when a gas stream is introduced through the air guiding tube 3, the air current is blown to the outlet end of the liquid suction head 2, and at this time, it is possible to apply, for example, a suction head outlet having an outer diameter of 350 μm or even 750 μm without applying electricity. A stable spray is generated at the end, and a voltage greater than 2.0 kV is applied to the tip of the liquid tip 2 to convert the spray into an electrospray, which in turn produces a stable ion current within the ion analyzer. Conventional electrospray ion sources, the auxiliary atomizing gas and the liquid conduit are usually placed coaxially, and the gap between the liquid conduit and the auxiliary atomizing gas conduit is small, which makes it difficult to achieve instant separation between the liquid conduit and the auxiliary atomizing gas conduit; By some designs, the instantaneous separation of the liquid conduit from the auxiliary atomizing gas conduit can be achieved, but it is difficult to avoid contamination of the gas conduit for atomization by the liquid in the tube when the liquid conduit is replaced; in this embodiment, the side blowing airflow is used. As a means of assisting the atomizing gas, the liquid suction head 2 and the air guiding tube 3 can be instantly separated, which enables the liquid suction head 2 to be frequently replaced without contaminating the air guiding tube 3, thereby avoiding mutual interference between multiple analyses. In an embodiment, the inner diameter of the air guiding tube 3 is preferably 0.5 mm to 2 mm, and the gas flow rate can be adjusted by a manual or computer controlled manner, for example, by a pressure valve. Optionally, the air flow speed ranges from 10 to 100 m / s; or 100 ~ 300 m / s; or 300 ~ 600 m / s; or 600 ~ 800 m / s, preferably, the air flow rate is controlled between 100 to 200 m / s.

It should be noted that, in order to make the solution droplets flow out from the outlet end of the liquid suction head, in addition to using the potential difference of the liquid suction head 2, pressure control may be used alone or in combination, for example: The solution passes through the liquid tip 2 under the pressure difference applied between the inlet end and the outlet end of the liquid tip 2, wherein the pressure at the inlet end of the liquid tip 2 is stronger than the pressure at the outlet end of the liquid tip 2. The airflow sent by the air guiding tube 3 passes through the outlet end of the liquid suction head 2 to form a pressure difference between the inlet end of the liquid suction head 2 and the outlet end of the liquid suction head 2; the solution can also be passed under the pressure difference The liquid tip 2; preferably, the pressure difference is generated, for example, such that the inlet end of the liquid tip 2 is connected to atmospheric pressure, and the pressure at the outlet end of the liquid tip 2 forms a negative pressure due to the action of the gas flow.

Accordingly, the formation of the electrospray can be achieved, for example, by forming a pressure difference between the outlet end of the liquid tip 2 and the inlet end, so that the liquid in the tip can flow out from the tip, and the discharged liquid can be electrosprayed under the action of voltage and gas flow. For another example, a rapidly moving gas stream flowing through the tip of the liquid tip 2 can reduce the static pressure at the outlet end of the liquid tip 2 by the jet effect, and the other end of the liquid tip 2, that is, the inlet end can be, for example, At atmospheric pressure, under the action of the pressure difference between the two ends of the liquid tip 2, the liquid therein is pushed out, and the discharged liquid can also be electrosprayed under the action of voltage and air flow.

In addition, the gas may be heated in the air guiding tube 3, and the heated gas contributes to desolvation of the spray droplets.

In an embodiment, the air guiding tube 3 and the liquid suction head 2 extend at a predetermined angle; optionally, the angle between the air guiding tube 3 and the liquid suction head 2 ranges from 20° to 60°. Or 60 ° ~ 90 °; or 90 ° ~ 120 °, in order to obtain better auxiliary spray efficiency, 70 ° ~ 85 ° is a more preferred solution.

The open end of the ion sampling port 4 faces the ionization chamber 1 and is used to guide the analyte ions of the solution after the ion detachment liquid tip 2 enters the ionization chamber 1 in the direction indicated by the arrow in the figure. Entering the electrospray ionization The quality analyzer of the lower stage of the device is used to complete the mass analysis; the angle between the ion sampling port 4 and the direction of the air flow may vary from 0° to 90°, in order to reduce the contamination of the ion analyzer by the spray droplets, 45° to 90° is a more preferred solution.

As shown in Figure 2, an electrospray ionization apparatus in accordance with one embodiment of the present invention is shown. The difference from the above embodiment is that the potential difference is an alternating current potential difference, and the positive and negative ions are alternately generated with the periodic change of the voltage; the applied alternating current potential difference can be directly applied to the liquid suction head 2; or can be applied to the liquid suction head 2 through the dielectric. The dielectric can be air, an insulated outer wall of the tip or other dielectric material. The optional frequency of the alternating current potential difference is 2 to 1000 Hz, preferably a high frequency of 5 Hz to 50 Hz; optionally, the peak-to-peak value of the alternating high voltage potential ranges from 1000 to 3000 V; or 3000 to 5000 V; 5000 to 8000 V; or 8,000 to 12,000 V, preferably 6 kV to 10 kV.

As shown in Figure 3, an electrospray ionization apparatus of one embodiment of an embodiment of the invention is shown. The difference from the above embodiment is that the liquid suction head 5 is a conical liquid suction head having a tapered tip as the outlet end, and the liquid suction head 5 can be made of an organic polymer material, and an electrospray is realized by using an alternating high voltage. . The alternating high voltage is applied to the tip of the tip through the dielectric of the tip wall. Since the electrode to which the voltage is applied is not in contact with the solution, this embodiment can avoid interference of the analysis of the solution remaining on the electrode in the process of replacing the liquid tip. In an embodiment, the outer diameter of the tapered tip of the liquid tip 5 ranges from 10 to 50 μm; or from 50 to 200 μm; or from 200 to 500 μm; or from 500 to 1000 μm; or from 1000 to 2000 μm.

As shown in Fig. 4, another embodiment of the present invention which is based on the embodiment of Fig. 3 is shown. When the outer diameter of the tip of the liquid tip 5 is larger than 750 μm and the inner diameter is larger than 350 μm, since the flow resistance of the liquid is too small, the liquid flows out from the tip of the tip placed vertically under the action of its own weight, and even if the auxiliary airflow is used, it cannot be obtained. Stable spray. By filling a certain amount of the porous chromatography material 6 having good liquid permeability in the liquid tip 5, the flow resistance of the liquid can be increased to achieve stable electrospray under the aid of gas. Furthermore, the chromatographic packing 6 can be used for the removal of impurities and target analytes in complex sample analysis; the materials used for the chromatographic packing 6 include: porous silica particles, paper fiber porous monoliths, polymer monoliths and polymers Wrapped in one or more mixtures of particles.

As described above, the present invention forms an electrospray by a combination of a gas flow and a voltage, so that the action of the gas flow can effectively reduce the requirement for lowering the voltage applied to the liquid tip 5. When the outer diameter of the tip of the tip is greater than 750 μm, the alternating high voltage is applied to the tip of the tip through the dielectric of the tip wall. In the absence of the airflow assistance, a higher voltage is required to produce a stable electrospray at the tip of the tip, which can result in severe discharge; in the embodiment of the invention, when there is an auxiliary gas, the exchange is applied. The peak-to-peak value of the voltage is greater than 8kV.

The application of the present invention will be described below by several mass spectrometry examples for different analytes:

Figure 5 shows the mass spectrum of 50 ng/mL phenformin and rosiglitazone in methanol after detection on the apparatus of the present invention (horizontal to mass-to-charge ratio, vertical axis is ion current intensity). The mass spectrometer operates in positive ion mode. The liquid tip used was a polypropylene plastic pipette tip with a tip outer diameter of 350 μm. The solution can be directly absorbed using a pipette equipped with the liquid tip, or Inject from the other end of the tip of the liquid tip. The applied DC voltage was 3.0 kV and was directly contacted with the solution through a 10 MΩ resistor. The auxiliary gas flow rate used was 5 L/min.

Figure 6 shows the mass spectrum of 50 ng/mL phenformin and rosiglitazone in methanol after detection on the apparatus of the present invention. The mass spectrometer operates in positive ion mode. The liquid tip used was a polypropylene plastic pipette tip with a tip outer diameter of 350 μm. The solution can be directly aspirated using a pipette equipped with the tip or from the other end of the tip of the liquid tip. The applied DC voltage is a square wave AC voltage (±3.0kV, 50% duty cycle, 5Hz), and is directly in contact with the solution through a 10MΩ resistor. The auxiliary gas flow rate used was 5 L/min.

Figure 7 shows the mass spectrum of 50 ng/mL phenformin and rosiglitazone in methanol after detection on the apparatus of the present invention. The mass spectrometer operates in positive ion mode. The liquid tip used was a polypropylene plastic pipette tip with a tip outer diameter of 350 μm. The solution can be directly aspirated using a pipette equipped with the tip or from the other end of the tip of the liquid tip. The applied AC voltage is a square wave AC voltage (±3.0 kV, 50% duty cycle, 5 Hz), applied to the tip of the tip by a layer of conductive metal coated on the outer wall of the tip. The auxiliary gas flow rate used was 5 L/min.

Figure 8 shows the mass spectrum of 50 ng/mL phenformin and rosiglitazone in methanol after detection on the apparatus of the present invention. The mass spectrometer operates in positive ion mode. The liquid tip used was a quartz capillary having an outer diameter of 300 μm. The solution is inhaled by capillary siphoning. The applied AC voltage is a square wave AC voltage (±3.0 kV, 50% duty cycle, 5 Hz), applied to the tip of the tip by a layer of conductive metal coated on the outer wall of the capillary. The auxiliary gas flow rate used was 5 L/min.

Figure 9 shows the mass spectrum of phenformin and rosiglitazone in a urine sample after detection on the apparatus of the present invention. The tip used was a commercial 20 μL polypropylene plastic pipette tip with an outer diameter of about 750 μm and 5 μL of chromatographic silica gel pre-blocked in the tip. The spiked concentration of the urine sample used was 200 ng/mL. First, 2 μL of the spiked urine sample was pipetted from the opposite end of the tip of the tip to the surface of the chromatographic silica gel, and then analyzed by 100 μL of acetonitrile-water (8:2) solution. At the same time as the analysis. The applied AC voltage is a square wave AC voltage (±4.0 kV, 50% duty cycle, 5 Hz) through a conductive metal layer coated on the outer wall of the tip and applied to the tip of the tip. The auxiliary gas flow rate used was 5 L/min.

The above results show that the gas-assisted electrospray ionization apparatus of the embodiment of the present invention can perform rapid analysis of analytes in simple solutions and even complex samples.

The above embodiments are merely illustrative of the possibilities of the present invention, and those skilled in the art can conveniently design various implementation configurations under the framework of the present invention. For example, the relative positions of the liquid suction head, the gas conduit and the ion introduction port are adjustable to meet the needs of different sizes of tips and different gas flow rates; the shape of the gas conduit outlet can be not only circular but also polygonal, arc Shape or other shape.

Referring to the above embodiments, the electrospray ionization apparatus of the present invention can be applied to a mass spectrometry system such as a mass spectrometer, which can include the electrospray ionization apparatus of the present invention, and a mass analyzer as a lower stage thereof.

In summary, the present invention provides an electrospray ionization device for ionizing a solution to be analyzed, the electrospray ionization device comprising: an ionization chamber; and a liquid tip for guiding the solution to a droplet Forming from the outlet end of the liquid tip into the ionization chamber, at least a portion of the liquid tip maintaining a potential difference relative to the surface of the ionization chamber for a predetermined time to charge the droplet entering the ionization chamber; Or a plurality of air guiding tubes for guiding one or more air currents into the ionization chamber, the one or more air currents directed to an outlet end of the liquid suction head, and an extending direction of the air guiding tube and the liquid suction head Forming a predetermined angle; wherein the air guiding tube and the liquid suction head are disposed to be freely separable; the ion sampling port has an open end facing the ionization cavity, and the ion to be analyzed for guiding the solution enters the electricity A mass analyzer for the lower stage of the spray ionization device; an electrospray ionization device for direct rapid mass analysis, good reproducibility and no cross-contamination, without the electrode being in contact with the solution, Now a larger size disposable tip head withdrawing achieve electrospray ionization.

The above-described embodiments are merely illustrative of the principles of the invention and its effects, and are not intended to limit the invention. Modifications or variations of the above-described embodiments may be made by those skilled in the art without departing from the spirit and scope of the invention. Therefore, all equivalent modifications or changes made by those skilled in the art without departing from the spirit and scope of the invention will be covered by the appended claims.

Claims (20)

An electrospray ionization device for an analyte in an ionized solution, characterized in that the electrospray ionization device comprises: Ionization chamber a liquid tip for guiding the solution into the ionization chamber from the outlet end of the liquid tip in the form of droplets, at least a portion of the liquid tip maintaining a potential difference relative to the surface of the ionization chamber for a predetermined time To charge the droplets entering the ionization chamber; One or more air conduits for directing one or more air streams into the ionization chamber, the one or more air streams directed toward the outlet end of the liquid nozzle, and an extension of the air conduit and the liquid nozzle The direction is a predetermined angle; wherein the air guiding tube and the liquid suction head are disposed to be freely separable; An ion sampling port, the open end facing the ionization chamber, and the analyte ion for guiding the solution enters a mass analyzer located below the electrospray ionization device. The electrospray ionization device of claim 1 wherein said liquid tip is a tapered liquid tip having a tapered tip as said outlet end. The electrospray ionization device according to claim 2, wherein the outer diameter of the tapered tip of the liquid tip has a value ranging from 10 to 50 μm; or from 50 to 200 μm; or from 200 to 500 μm; or from 500 to 1000 μm; or 1000 to 2000 μm. The electrospray ionization apparatus according to claim 2, wherein said liquid tip is provided with a chromatographic packing. The electrospray ionization apparatus according to claim 4, wherein said material for said chromatographic packing comprises: one or more of porous silica gel particles, paper fiber porous monolithic material, polymer monolithic column and polymer coated particles. . The electrospray ionization apparatus according to claim 1, wherein said solution passes through a liquid tip under a pressure difference applied between an inlet end and an outlet end of said liquid tip, wherein said liquid tip is at the inlet end The pressure is stronger than the pressure at the outlet end of the liquid tip. The electrospray ionization apparatus according to claim 6, wherein said air flow sent from said air duct passes through said liquid suction The electrospray ionization apparatus according to claim 7, wherein the inlet end of the liquid suction head is connected to atmospheric pressure, and the pressure at the outlet end of the liquid suction head is a negative pressure. The electrospray ionization apparatus according to claim 1, wherein said potential difference is a direct current high voltage potential difference, and said direct current potential difference is directly applied to the liquid in the liquid suction head. The electrospray ionization apparatus according to claim 1, wherein said potential difference is an alternating current high voltage potential difference, said alternating current potential difference being directly applied to the liquid in the liquid suction head. The electrospray ionization apparatus according to claim 1, wherein said potential difference is an alternating current high voltage potential difference, said alternating current potential difference being applied to a liquid in the liquid suction head by a dielectric. The electrospray ionization device according to claim 1, wherein the material of the liquid tip comprises: one of a metal, a quartz tube, an organic polymer material, and glass. The electrospray ionization device according to claim 9, wherein the DC high voltage potential difference ranges from 1000 to 3000 V; or 3000 to 5000 V; or 5000 to 8000 V; or 8000 to 12000 V. The electrospray ionization apparatus according to claim 10 or 11, wherein the peak-to-peak value of the alternating high voltage potential ranges from 1000 to 3000 V; or from 3,000 to 5,000 V; or from 5,000 to 8,000 V; or from 8,000 to 12,000 V. The electrospray ionization apparatus according to claim 10 or 11, wherein the alternating current potential has a frequency of 2 to 1000 Hz. The electrospray ionization apparatus according to claim 1, wherein the end portion of the air guiding tube that is directed toward the outlet end of the liquid suction head has a circular shape, a flat shape, or a circular arc shape. The electrospray ionization device according to claim 1, wherein the air guide tube and the liquid tip are at a predetermined angle ranging from 20 to 60; or from 60 to 90; or from 90 to 120. °. The electrospray ionization device of claim 1 wherein said gas stream is a heated gas stream. The electrospray ionization apparatus according to claim 1, wherein said gas flow rate is in the range of 10 to 100 m/s; or 100 to 300 m/s; or 300 to 600 m/s; or 600 to 800 m/s. . A mass spectrometer comprising the electrospray ionization device of any one of claims 1 to 19; and the mass analyzer located below the electrospray ionization device.

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