JP5589750B2 - Ionizer for mass spectrometer and mass spectrometer equipped with the ionizer - Google Patents

Description

  The present invention relates to an ionization apparatus for a mass spectrometer for ionizing a sample solution used in a liquid chromatograph mass spectrometer and the like, and a mass spectrometer including the ionization apparatus.

  The mass spectrometer performs ionization of the sample in the ionization unit, takes the ionized sample into the mass analysis unit, and then separates and detects the sample according to the mass-to-charge ratio (m / z) using a quadrupole mass filter or the like. It has the structure of.

  As a method of ionizing a sample solution sent from a liquid chromatograph or the like, a method of electrostatically spraying the sample solution in an ionization chamber under atmospheric pressure (electrospray ionization method: ESI) or an ionization chamber under atmospheric pressure There is a method of ionizing a sample by reacting droplets sprayed on the substrate with carrier gas ions generated by corona discharge (atmospheric pressure chemical ionization method: APCI).

  In ESI, when the sample liquid is sprayed from the capillary, the sample is given a biased charge, and the atomization of the droplet is promoted by the Coulomb repulsive force in the sprayed droplet. Is ionized. On the other hand, in APCI, a discharge electrode is disposed in front of the capillary outlet, and solvent gas ions generated by the corona discharge are chemically reacted with fine droplets to ionize the target component. Regardless of which method is used, the degree of micronization of the droplet greatly affects the ionization efficiency in the ionization unit and the subsequent measurement accuracy in the mass analysis unit.

JP 2005-197141 A US Pat. No. 5,412,208

  As a method for promoting the refinement of droplets, there is a method in which a nebulizer gas is ejected from around a liquid ejected from a capillary (see, for example, Patent Document 1). In this method, the liquid ejected from the capillary is sheared by the nebulizer gas, so that the refinement of the droplet is promoted. There is a problem of getting worse.

  For example, in ESI, if the diameter of the charged droplet is large, evaporation of ions due to Coulomb repulsion does not occur. Therefore, when the diameter of the charged droplet is large, it is necessary to dry the droplet to the limit (Rayleigh limit) at which evaporation due to Coulomb repulsion occurs (see, for example, Patent Document 2). However, in order to dry such large droplets, a large amount of heat is required. Conventionally, drying gas heated to several hundred degrees Celsius is supplied at a rate of several tens of L / min. It was necessary to equip the apparatus with a large drying mechanism.

  The problem to be solved by the present invention is to provide an ionization apparatus for a mass spectrometer capable of more efficiently miniaturizing droplets with a nebulizer gas.

The present invention made to solve the above problems
In an ionizer for a mass spectrometer that introduces a sample solution through a sample conduit and ionizes the sample by injecting a nebulizer gas along the sample solution,
An inner gas conduit for injecting the nebulizer gas and an outer gas for injecting the nebulizer gas provided on the outer peripheral side of the sample conduit provided at the outlet of the sample conduit at the central axis side of the sample conduit A conduit ,
The inner peripheral surface of the outlet end of the outer gas conduit is inclined toward the sample conduit toward the tip,
The inner peripheral surface of the outlet end of the inner gas conduit and said that you have inclined the sample conduit side to the tip.

Since the conventional sample conduit is a simple tube, the sample liquid is ejected from the sample conduit in the form of a solid column, whereas in the present invention, the inner gas conduit is provided on the central axis side of the sample conduit. It erupts in a columnar shape. As a result, the surface area of the ejected sample liquid is increased as compared with the conventional case, and comes into contact with the nebulizer gas and the gas inside the ionizer (ionizer) over a wider area. Furthermore, in the conventional apparatus, since the nebulizer gas was in contact from the outside of the solid columnar sample liquid, the sample liquid was insufficiently dispersed by the nebulizer gas. However, in the apparatus of the present invention, the inner periphery of the outlet end was insufficient. The nebulizer gas is ejected from an outer gas conduit whose surface is inclined toward the sample conduit toward the tip and an inner gas conduit whose inner peripheral surface is inclined toward the sample conduit toward the tip. Therefore, the nebulizer gas with increased straightness pushes the wall-shaped sample liquid from the inside to the outside, greatly promoting the dispersion of the sample liquid.

Similar to be conventional in the present invention is provided with outer gas conduit for injecting the nebulizer gas from the outlet outer periphery of the sample conduit. The outer gas conduit provided on the outer peripheral side of the outlet of the sample conduit has a protrusion protruding from the outlet, and the inner peripheral surface of the protrusion is inclined toward the center axis of the sample conduit toward the tip. It is desirable. With this shape, the nebulizer gas acts to the inside of the sample liquid, and the dispersion of the sample liquid can be further promoted. It is desirable to provide gas flow rate adjusting means for adjusting the flow rate of the nebulizer gas in the inner gas conduit and the outer gas conduit, respectively. As a result, it is possible to generate a pressure difference due to the difference in gas flow velocity between the central axis side and the outside of the sample liquid ejected from the sample conduit, and the nebulizer gas can be applied to the inside of the sample liquid or the gas in the ionizer Can be mixed in.

The present invention, as a gas conduit for nebulizer gas, a gas conduit inner peripheral surface of the outlet end on the outer side of the sample conduit guiding the sample liquid to the ionizer is inclined to said sample conduit side to the distal end, the inner By providing a gas conduit in which the inner peripheral surface of the outlet end is inclined toward the sample conduit toward the tip, the sample solution can be sheared from the outside and the central axis side of the sample solution ejected from the sample conduit. Is. Conventionally, since the gas conduit was provided only outside the sample conduit, the shearing action by the nebulizer gas did not reach the central axis, and as a result, a droplet having a large diameter was formed. Or since nebulizer gas is also injected from the vicinity, the refinement | miniaturization of a droplet can be promoted more.

  In addition, since the droplets are further miniaturized, drying of the droplets is promoted more than before, so that the flow rate and temperature are kept low even when a drying mechanism for supplying a drying gas is installed in the apparatus. Can do. Thereby, a drying mechanism can be reduced in size and it becomes possible to reduce the cost and space for that. Furthermore, since fine droplets are difficult to adsorb on the wall surface, contamination of the ion source can be reduced.

The schematic block diagram of the principal part of a mass spectrometer. The schematic diagram (a) which shows the structure of the conventional ionization part in the case of performing ionization by ESI, and the schematic diagram (b) which shows the structure of the conventional ionization part in the case of performing ionization by APCI. BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a schematic sectional view (a) showing an embodiment of an ionization probe according to the present invention, and a front view (b) of an outlet opening thereof. The schematic diagram which shows the gas flow around the exit of the capillary of a present Example. The schematic sectional drawing which shows the modification of the ionization probe of a present Example. The schematic sectional drawing which shows another modification of the ionization probe of a present Example.

  FIG. 1 is a schematic diagram showing a general configuration of a main part of a mass spectrometer. As shown in this figure, a mass spectrometer includes an ionization unit 1 that ionizes an introduced sample solution, and a mass analysis unit that separates and detects sample ions obtained by the ionization unit 1 according to m / z. 2 and a control unit (not shown) for controlling the operation of each part of the apparatus.

  In the ionization part 1, the ionization probe 12 is protrudingly provided in the ionization chamber 11 which is a substantially atmospheric pressure atmosphere. In front of the tip of the ionization probe 12, an inlet opening of a desolvation tube 13 is provided for transporting sample ions generated by evaporation of the solvent from droplets sprayed from the tip to the subsequent stage. Further, a drain 14 for discharging droplets that have not been vaporized is disposed in front of the drain 14. The central axis of the inlet opening of the desolvation tube 13 is obliquely intersected with the central axis of the spray from the tip of the ionization probe 12 (in this case, substantially orthogonal), so that a large droplet in which the solvent is not sufficiently evaporated is removed. Jumping into the solvent tube 13 is prevented.

  The mass analyzer 2 is provided with a first intermediate vacuum chamber 21 and a second intermediate vacuum chamber 24 that are separated from each other by a partition wall between the mass analysis chamber 27 and the ionization chamber 11. In the mass analysis chamber 27, a quadrupole filter 28 and an ion detector 29 as a mass separation unit are provided. An ion lens 22 and a second ion lens 25 are provided. Between the ionization chamber 11 and the first intermediate vacuum chamber 21, a small-diameter desolvation tube 13 is provided, and between the first intermediate vacuum chamber 21 and the second intermediate vacuum chamber 24, a very small diameter passage hole is formed at the top. It communicates through a conical skimmer 23.

The inside of the ionization chamber 11 is in an almost atmospheric pressure atmosphere due to vaporized molecules of the sample liquid supplied almost continuously from the ionization probe 12. The first intermediate vacuum chamber 21 is evacuated to about 10 ² Pa by a rotary pump 30, and the second intermediate vacuum chamber 24 is evacuated to about 10 ⁻¹ to 10 ⁻² Pa by a turbo molecular pump 31. The chamber 27 is evacuated to a high vacuum state of about 10 ⁻³ to 10 ⁻⁴ Pa by a turbo molecular pump 32. In this way, the ionization chamber 11, the first intermediate vacuum chamber 21, the second intermediate vacuum chamber 24, the mass analysis chamber 27, and the multistage differential exhaust system that increases the degree of vacuum stepwise can be used for mass analysis. A high degree of vacuum in the chamber 27 is maintained.

  The analysis operation in the ionization unit 1 and the mass analysis unit 2 will be described. The sample liquid is sprayed into the ionization chamber 11 from the tip of the ionization probe 12, and the sample molecules in the spray flow are ionized as described later. The generated ions are drawn into the desolvation tube 13 by the differential pressure between the ionization chamber 11 and the first intermediate vacuum chamber 21 together with the fine droplets that have not yet been ionized. The first ion lens 22 helps the ions to be drawn through the desolvation tube 13 by the electric field, and converges the ions in the vicinity of the passage hole of the skimmer 23. The ions introduced into the second intermediate vacuum chamber 24 through the passage hole of the skimmer 23 are converged and accelerated by the second ion lens 25 and then sent to the mass analysis chamber 27 through the small hole 26. In the mass analysis chamber 27, only ions having a specific m / z pass through the quadrupole filter 28, reach the ion detector 29, and are detected as an ion current.

  In this mass spectrometer, the ionization method such as ESI or APCI can be selectively changed by exchanging the ionization probe 12. The configuration of an ionization probe conventionally used in ESI and APCI will be described below with reference to FIG.

  FIG. 2A is a schematic cross-sectional view of an ionization probe 12 conventionally used in ESI. The ionization probe 12 includes a capillary 121 to which a sample solution is supplied, a gas outer tube 122 disposed so as to surround the capillary 121 as an outer tube, and a metal tube (not shown) provided around the capillary 121 itself or its periphery. And a DC power supply 123 for applying a DC high voltage of about several kV. In ESI, the sample liquid flowing through the capillary 121 is biased by the influence of the electric field formed by the voltage applied from the DC power source 123, and in this state, nebulizer gas (usually nitrogen gas) injected from the gas outer tube 122 is charged. Gas) and is ejected as fine droplets. The ejected microdroplet comes into contact with, for example, dry nitrogen gas ejected from the periphery of the desolvation tube 13, and the mobile phase and the solvent in the droplet rapidly evaporate, thereby reducing the size of the droplet. Then, the droplets are finely divided by the Coulomb repulsive force of the charged charge, and gas ions derived from the sample molecules are generated in the process.

  FIG. 2B is a schematic cross-sectional view of an ionization probe 12 conventionally used in APCI. The ionization probe 12 includes a capillary 121, a gas outer tube 122, a heater 124 surrounding a space in front of the outlet opening of the capillary 121, and a needle-like discharge electrode 125 provided in front of the heater 124. The sample solution that has reached the tip of the capillary 121 (uncharged unlike ESI) is sheared by the nebulizer gas ejected from the gas outer tube 122 and ejected as fine droplets. Since the space in front of it is surrounded by the heater 124, the solvent in the droplets is evaporated by the heating of the heater 124 and becomes a solvent gas. When a high voltage is applied to the discharge electrode 125 from a high voltage source (not shown), corona discharge occurs, and the solvent gas molecules become solvent ions. The solvent ions and the sample molecules in the droplets chemically react, and the sample molecules are ionized to become sample ions.

  As shown in FIG. 2, the ionization probe 12 conventionally used in a mass spectrometer ejects nebulizer gas only from the outside of the capillary 121 regardless of the method of ESI or APCI. In the present invention described below, the sample liquid can be sheared with the nebulizer gas of the ionization probe 12 more efficiently than before.

  FIG. 3 is a schematic sectional view showing an embodiment of the ionization probe 12 according to the present invention and a front view of the outlet opening. In the ionization probe 12 of the present embodiment, the capillary 121A has a double tube structure of a capillary inner tube 1211 and a capillary outer tube 1212. The nebulizer gas flows through the capillary inner tube 1211 and the sample solution flows through the capillary outer tube 1212. It has a structure.

In the capillary 121A of the present embodiment, when the radii of the capillary inner tube 1211 and the capillary outer tube 1212 are R _in = R and R _out = 2R, respectively, the cross-sectional area of the sample solution is πR _out ² -πR _in ² = 3πR ² . On the other hand, a comparison is made with the case where R _s = 3 ^1/2 R is set so that the radius of the capillary 121 having the conventional structure as shown in FIG.

When the flow path cross-sectional areas of the sample liquid are the same, assuming that the sample liquid is introduced at the same flow rate into the capillary 121A of this embodiment and the capillary 121 having the conventional structure, the flow rates of the sample liquid in the respective capillaries are the same. On the other hand, the surface area ratio of the sample liquid directly sheared by the nebulizer gas assumes that the sample liquid ejected from the capillary goes straight as it is.
(2πR _in + 2πR _out ) / (2πR _s ) = 3 ^1/2
It becomes. Therefore, in the above example, by using the capillary 121A of the present embodiment, the liquid surface area directly sheared by the nebulizer gas is increased by 3 ^1/2 times that of the capillary 121 having the conventional structure.

Even if the flow path cross-sectional area of the sample liquid is the same, the sample liquid is ejected from the capillary 121 having the conventional structure with a diameter of 2 × 3 ^1/2 R, and R _out from the capillary 121A of the present embodiment. Sample liquid is ejected with a width of -R _in = R. Therefore, in the capillary 121A of the present embodiment, the width of the sample liquid after ejection is (2 × 3 ^1/2 ) ^-1 times that of the capillary 121 having the conventional structure, and the nebulizer gas and the outside air (ionization) are reduced by the width. It becomes easy to act on the inside of the sample liquid from which the gas in the room is ejected.
Due to the above effects, it is possible to suppress the generation of large droplets compared to the prior art and improve the yield of fine droplet generation.

FIG. 4 shows the vicinity of the outlet of the capillary 121A when a gas flow rate adjusting unit (not shown) is provided in the mass spectrometer and the flow rates of the nebulizer gas in the capillary inner tube 1211 and the gas outer tube 122 are adjusted. It is a schematic diagram which shows the flow of gas. In the example of this figure, the air pressure on the central axis side of the sample liquid ejected from the capillary outer tube 1212 is increased by making the flow velocity v ₁ of the nebulizer gas in the capillary inner tube 1211 larger than the flow velocity v ₂ in the gas outer tube 122. The pressure is lower than the outside pressure so that the nebulizer gas injected from the gas outer tube 122 side is easily drawn into the central axis side of the liquid flow path. Further, since the atmospheric pressure difference between the central axis side and the outside of the sample liquid is easily drawn into the sample liquid from which the outside air is ejected, the shear efficiency and the spray efficiency of the sample liquid are improved.

Hereinafter, modifications of the ionization probe 12 of the present embodiment will be shown.
The ionization probe 12 of FIG. 5 is an example in which the capillary 121B has a triple tube structure. In this modification, the sample liquid branched in the ionization probe 12 flows in the innermost first tube 1213 and the outermost third tube 1215, and in the second tube 1214 sandwiched between the first tube 1213 and the third tube 1215. Nebulizer gas flows. By having such a structure, the liquid surface area on which the nebulizer gas acts is further increased as compared with the embodiment shown in FIG.

  FIG. 6 is a modification regarding the shape of the ionization probe 12. The inner capillary tube 1211A shown in FIG. 6A is subjected to processing for controlling the directionality of the nebulizer gas flowing through the tube. As seen in a rocket engine or the like, in the configuration as shown in FIG. 6 (a), the nebulizer gas flowing through the capillary inner tube 1211A increases the straightness, and thus has the effect of converging the gas flow in the desolvation tube 13.

  FIG. 6B is an example in which the nebulizer gas injection port of the gas outer tube 122 is processed to control the directionality of the gas flow. In this example, the direction of the outer nebulizer gas is changed so that the nebulizer gas acts inside the sample liquid ejected from the capillary outer tube 1212. Further, as shown in FIGS. 6C and 6D, either the capillary inner tube 1211 or the capillary outer tube 1212 may be protruded on the outlet side.

  In the case of performing ionization by ESI, when any of the tubes in the ionization probe 12 protrudes at the tip as shown in FIGS. 6B to 6D, the potential of the protruding tube is changed. It is desirable to make the potential higher than that of other tubes because the sample solution can be charged.

  Further, the miniaturization of droplets by the nebulizer gas can be promoted also by increasing the gas temperature. Therefore, it is desirable for the mass spectrometer to have a heating unit for heating the nebulizer gas supplied to the ionization probe 12.

  As mentioned above, although the ionization probe of this invention was demonstrated using the Example, these are an example to the last, and can be suitably corrected or changed in the range of the main point of this invention. Moreover, it can be easily conceived that the structure of the ionization probe shown in the above embodiment can be applied to various ionization methods such as ESI and APCI in which a sample solution is sheared with a nebulizer gas.

DESCRIPTION OF SYMBOLS 1 ... Ionization part 11 ... Ionization chamber 12 ... Ionization probe 121, 121A, 121B ... Capillary 1211, 1211A ... Capillary inner tube 1212 ... Capillary outer tube 1213 ... First tube 1214 ... Second tube 1215 ... Third tube 122 ... Out of gas Tube 123 ... DC power supply 124 ... Heater 125 ... Discharge electrode 13 ... Desolvation tube 14 ... Drain 2 ... Mass analyzer 21 ... First intermediate vacuum chamber 22 ... First ion lens 23 ... Skimmer 24 ... Second intermediate vacuum chamber 25 ... Second ion lens 26 ... Small hole 27 ... Mass analysis chamber 28 ... Quadrupole filter 29 ... Ion detector 30 ... Rotary pump 31, 32 ... Turbo molecular pump

Claims (7)

In an ionizer for a mass spectrometer that introduces a sample solution through a sample conduit and ionizes the sample by injecting a nebulizer gas along the sample solution,
At the outlet of the sample conduit, an inner gas conduit for injecting the nebulizer gas provided on the central axis side of the sample conduit and an outer gas conduit for injecting the nebulizer gas provided on the outer peripheral side of the sample conduit It equipped with a door,
The inner peripheral surface of the outlet end of the outer gas conduit is inclined toward the sample conduit toward the tip,
Inner circumferential surface mass spectrometer for ionization and wherein that you have inclined the sample conduit side to the tip of the outlet end of the inner gas conduit. In an ionizer for a mass spectrometer that introduces a sample solution through a sample conduit and ionizes the sample by injecting a nebulizer gas along the sample solution,
At the outlet of the sample conduit, an inner gas conduit for injecting the nebulizer gas provided on the central axis side of the sample conduit and an outer gas conduit for injecting the nebulizer gas provided on the outer peripheral side of the sample conduit And
The outer gas conduit has a protrusion protruding from the outlet of the sample conduit, and an inner peripheral surface of the protrusion is inclined toward the center axis of the sample conduit toward the tip. Ionizer for analyzers. The ionization device for a mass spectrometer according to claim 1 or 2, further comprising gas flow rate adjusting means for adjusting the flow rate of the nebulizer gas in each of the inner gas conduit and the outer gas conduit.   The ionization apparatus for a mass spectrometer according to any one of claims 1 to 3, further comprising heating means for heating the nebulizer gas.   The ionization apparatus for a mass spectrometer according to any one of claims 1 to 4, wherein the ionization is performed by an electrospray ionization method.   The ionization apparatus for a mass spectrometer according to any one of claims 1 to 4, wherein the ionization is performed by an atmospheric pressure chemical ionization method.   A mass spectrometer comprising the ionization apparatus for a mass spectrometer according to claim 1.

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