Ion introduction device and ion introduction method for introducing ions into mass spectrometer, mass spectrometry system, mass spectrometry method, ionization device, and ionization method

Abstract

[Problem] To provide an ionization device and an ionization method which are capable of stably sustaining dark discharge at a low voltage and enable stable ionization of various samples from gas to solid. [Solution] The present invention pertains to an ionization device which: ionizes a sample by applying a voltage to a mixture gas of argon gas and nitrogen gas under an air atmosphere and exciting the argon with dark discharge; and comprises a mixture gas generation unit, a sample supply unit, and an ionization means. In the mixture gas generation unit, the mixture gas is generated by mixing the argon and the nitrogen. In the sample supply unit, a sample component is generated by bringing the mixture gas into contact with the sample. In the ionization means, sample ions are generated by exciting the sample component with the dark discharge. The present invention further pertains to: an ion introduction device and an ion introduction method for introducing said sample ions into a mass spectrometer; and a mass spectrometry system for analyzing the mass of the sample by ionizing and introducing the sample into the mass spectrometer.

Description

Ion introduction device and ion introduction method for mass spectrometer, mass spectrometry system, mass spectrometry method, ionization device and ionization method

[0001] The present invention relates to a method and apparatus for atmospheric pressure ionization of a sample for mass spectrometry.

[0002] Mass spectrometry is an essential method for analyzing a variety of substances. In recent years, atmospheric pressure ionization (ambient ionization) has been actively developed, which enables real-time, in situ mass analysis by ionizing target sample components in the ambient atmosphere without any special sample preparation or pretreatment.

[0003] For example, methods combining helium gas and glow discharge (Patent Document 1 and Patent Document 2) are known, but in recent years, there have been issues with the supply stability of helium gas used as a carrier gas. As an alternative to helium gas, a method combining nitrogen gas and corona discharge (Patent Document 3) has been developed. However, there is an issue that the identification of unknown substances becomes difficult due to the influence of side reactions caused by nitrogen (N2) radicals. Furthermore, discharge methods using hydrogen have safety issues due to the flammable gas. A method that does not use a special carrier gas (Patent Document 5) has also been attempted. However, because it utilizes a sustained discharge accompanied by a luminescence phenomenon, there are issues similar to those in Patent Document 3 due to the influence of nitrogen radicals.

[0004] Furthermore, known atmospheric pressure ionization methods that utilize discharge require high voltages. For example, when helium gas is used (Patent Documents 1 and 2), a high voltage of 5 kV is required for the DART method, 3 kV for the DCBI method, and about 3 kV for the APCI method, and even Patent Document 5, which does not use a carrier gas, requires a high voltage of 2.5 kV or more.

[0005] Patent Document 4 discloses a method for ionizing a sample using dark discharge. This method utilizes a discharge that does not accompany a light emission phenomenon, i.e., a dark discharge. A voltage is applied only to argon gas in an atmospheric environment to generate a dark discharge. While dark discharge can be performed at a low voltage (1.8 kV or higher), it has been difficult to maintain a stable dark discharge state during sample ionization.

[0006] WO2009 / 009228 publication WO2010 / 075769 publication US7977629B2 publication Patent No. 6382166 publication Patent No. 7453642 publication

[0007] In a method of ionizing samples by applying a voltage to argon gas in an atmospheric environment and generating a dark discharge, there is a need to develop an ionization device that can stably maintain a dark discharge at a low voltage and that can stably ionize a variety of samples, from gases and liquids to solids that are difficult to vaporize, without being affected by nitrogen radicals. Furthermore, there is a need to develop an ionization device that uses a carrier gas that is stable, safe, inexpensive, and easy to use.

[0008] The means (present invention) for solving the above problem is (1) an iontophoresis device for introducing ions into a mass spectrometer, the iontophoresis device comprising a mixed gas generation unit, a sample supply unit, and an interface unit, the mixed gas generation unit generates a mixed gas by mixing argon and nitrogen, the sample supply unit is provided in an atmospheric environment, a sample is placed in the sample supply unit, the mixed gas discharged from the mixed gas generation unit is brought into contact with the sample to form a mixed gas containing a sample component, the interface unit has an exhaust port communicating with an external exhaust system and is in close contact with one surface of the mass spectrometer to form an ionization region, the ionization region is maintained at a pressure lower than the atmospheric atmosphere by the external exhaust system, the sample component-containing mixed gas is introduced from the sample supply unit into the ionization region, the sample component-containing mixed gas is excited by dark discharge to generate sample ions, and the sample ions are introduced from the ionization region into the mass spectrometer via an ion transfer port of the mass spectrometer.

[0009] (2) In addition to (1), the iontophoresis device of the present invention is characterized in that it has a discharge electrode positioned in the ionization region between the inlet path for introducing the sample component-containing mixed gas and the ion transfer port, and generates a dark discharge between the discharge electrode and the ion transfer port to generate sample ions from the sample components in the sample component-containing mixed gas. (3) In addition to (2), the iontophoresis device of the present invention is characterized in that the discharge electrode is covered with an insulator except for its tip. (4) In addition to (2), the iontophoresis device of the present invention is characterized in that the voltage applied between the discharge electrode and the ion transfer port is 1.8 kV or more and 3.0 kV or less.

[0010] (5) In addition to (1), the iontophoresis device of the present invention is also characterized in that the volume ratio of argon in the mixed gas generated in the mixed gas generator is 2% to 67%, preferably 17% to 25%. (6) In addition to (1), the mixed gas generator further comprises a means for heating the mixed gas. (7) In addition to (1), the sample supply unit further comprises a means for heating the sample. (8) In addition to (1), the iontophoresis device of the present invention is also characterized in that the sample supply unit is equipped with a sample container exchange mechanism that can accommodate multiple sample containers containing samples. (9) In addition to (1), the sample container exchange mechanism can automatically exchange multiple sample containers continuously. (10) In addition to (1), the ionization region is maintained at a higher pressure than the mass spectrometer, and the gas flow passes through the mixed gas generator, the sample supply unit, and the ionization region before entering the mass spectrometer.

[0011] (11) A mass spectrometry system of the present invention, which ionizes a sample, introduces it into a mass spectrometer, and analyzes its mass, comprises a mixed gas generation unit, a sample supply unit, and an interface unit, wherein the mixed gas generation unit generates a mixed gas by mixing argon and nitrogen, the sample supply unit is provided in an atmospheric environment, a sample is placed in the sample supply unit, and the mixed gas discharged from the mixed gas generation unit is brought into contact with the sample to form a mixed gas containing a sample component, the interface unit has an exhaust port communicating with an external exhaust system and is in close contact with one surface of the mass spectrometer to form an ionization region, the ionization region is maintained at a pressure lower than the atmospheric pressure by the external exhaust system, the sample component-containing mixed gas is introduced from the sample supply unit into the ionization region, the sample component-containing mixed gas is excited by dark discharge to generate sample ions, and the sample ions are introduced from the ionization region through an ion transfer port of the mass spectrometer to analyze the mass.

[0012] (12) The ion introduction method of the present invention for introducing ions into a mass spectrometer comprises the steps of: mixing argon and nitrogen to generate a mixed gas; discharging the mixed gas into an atmospheric atmosphere; contacting the mixed gas with a sample placed in the atmospheric atmosphere to form a mixed gas containing a sample component; introducing the mixed gas containing a sample component into an ionization region maintained at a negative pressure relative to the atmospheric atmosphere by an external exhaust system; exciting the mixed gas containing a sample component in the ionization region by dark discharge to generate sample ions; and introducing the sample ions from the ionization region into a mass spectrometer.

[0013] (13) In addition to (12), the iontophoresis method of the present invention further comprises a step of heating the mixed gas after the step of generating the mixed gas. (14) In addition to (12), the iontophoresis method of the present invention further comprises a step of heating the sample placed in the atmospheric environment in the step of forming the sample component-containing mixed gas. (15) In addition to (12), the iontophoresis method of the present invention further comprises a sample exchange step of exchanging the sample that has been contacted with the mixed gas for a sample that has not been contacted with the mixed gas in the atmospheric environment in the step of forming the sample component-containing mixed gas. (16) In addition to (15), the sample exchange step is characterized in that the contact-treated sample is exchanged for an untreated sample using a mechanism for automatically exchanging multiple samples.

[0014] (17) An ionization device of the present invention for ionizing a sample comprises a mixed gas generation unit, a sample supply unit, and an interface unit, wherein the mixed gas generation unit generates a mixed gas by mixing argon and nitrogen, the sample supply unit is provided in an atmospheric environment, a sample is placed in the sample supply unit, and the mixed gas discharged from the mixed gas generation unit is brought into contact with the sample to form a mixed gas containing a sample component, the interface unit has an ionization region into which the sample component-containing mixed gas is introduced from the sample supply unit, and the sample component-containing mixed gas is excited by dark discharge in the ionization region to generate sample ions.

[0015] (18) Furthermore, the ionization method of the present invention for ionizing a sample is characterized by comprising the steps of: mixing argon and nitrogen to generate a mixed gas; discharging the mixed gas into an atmospheric environment; contacting the mixed gas with a sample placed in the atmospheric environment to form a mixed gas containing a sample component; introducing the mixed gas containing a sample component into an ionization region; and exciting the mixed gas containing a sample component in the ionization region by dark discharge to generate sample ions.

[0016] According to the present invention, by using a carrier gas consisting of argon and nitrogen, which are inert gases (non-flammable gases) with stable supply, an ionization method using stable dark current discharge under low voltage conditions, and a simple and inexpensive ion introduction device and ion introduction method for introducing ions into a mass spectrometer can be provided. Furthermore, by heating the sample, it is possible to ionize high-boiling point samples, etc., which have not been achieved by known dark current discharge ionization methods. Furthermore, by heating the carrier gas and / or sample, the sensitivity of mass spectrometry can be improved.

[0017] FIG. 1 is a process diagram illustrating a method for forming sample ions for introducing ions into a mass spectrometer according to the present invention. FIG. 2 is a schematic diagram illustrating an iontophoresis device for introducing ions into a mass spectrometer according to the present invention. FIG. 3 is a simplified diagram illustrating one embodiment of an iontophoresis device for introducing ions into a mass spectrometer according to the present invention. In FIG. 3, a mixed gas flow path and a sample component-containing mixed gas inlet path are shown in cross section, and the surrounding structure is also shown in cross section. In FIG. 3, an ionization region is formed by an interface unit and one surface of the mass spectrometer. The iontophoresis device of FIG. 3 includes a mixed gas generation unit, a sample supply unit, and an interface unit. FIG. 4 is a diagram illustrating the iontophoresis device with a sample stage and a sample container arranged thereon. In FIG. 4, the mixed gas generation unit, the sample supply unit, and the interface unit are integrally configured to form an ionization unit. The ionization unit is attached to the mass spectrometer using a hinge. Furthermore, FIG. 4 also illustrates a schematic diagram of a mass spectrometer. Note that the following figures do not show the entire mass spectrometer, but only its essential parts. FIG. 5 is a cross-sectional view of FIG. 4 taken along a plane including the mixed gas flow path and the sample component-containing mixed gas introduction path within the mixed gas generation unit. In FIG. 5, the interface unit is also shown as a cross-sectional view. Furthermore, FIG. 5 also shows the ionization region formed by the interface unit and one surface of the mass spectrometer. FIG. 6 is a view of the iontophoresis device of FIG. 4 viewed from another direction. In FIG. 6, the mixed gas generation unit, the sample supply unit, and the interface unit are integrally configured to form an ionization unit. The ionization unit is connected to the mass spectrometer using a hinge. Also, as described in FIG. 4, FIG. 6 shows only a portion of the mass spectrometer. FIG. 7 is a view of FIG. 6 showing the ionization unit opened and closed relative to the mass spectrometer. In FIG. 7, the interface unit constituting the ionization unit is connected to the mass spectrometer via a hinge, and the ionization region is open. FIG. 8 is a top view of the state of FIG. 7. FIG. 9 is a view showing the ionization region formed by the interface unit and the mass spectrometer.In Figure 9, hatching is used to clarify the ionization region. Figure 10 is a diagram showing an embodiment in which a heating plate is provided on a support base on which a sample container is placed. Figure 11 is a diagram showing the configuration of Figure 10 further equipped with a covering member and a sample container exchange mechanism. Figure 12 is a diagram showing the configuration of Figure 11 with the top of the covering member removed. Figure 13 is a diagram showing the cross section of Figure 12 along a plane including the mixed gas flow path and the sample component-containing mixed gas inlet path. Figure 14 is a diagram showing an example of the difference in mass spectrometry signals when the sample is heated and when it is not heated. Figure 15 is a table summarizing the experiments of Examples 1 to 8 and Comparative Examples 1 to 4. Figure 16 is a diagram showing the results of the experiment of Example 9-1. Figure 17 is a diagram showing the results of the experiment of Example 9-2. Figure 18 is a diagram showing an embodiment in which the iontophoresis device of the present invention is mounted on a mass spectrometer equipped with a built-in voltage unit.

[0018] The present invention will be described in detail below.

[0019] In the present invention, the gas that contains the sample components and is used for ionization is called a carrier gas.

[0020] The term "dark discharge" as used herein refers to the generation of a discharge that does not emit light in the visible light region when a low voltage is applied to a carrier gas. That is, the dark discharge of the present invention refers to a state in which, when a voltage is applied between a needle electrode and a counter electrode and the current value is measured, no visible light is emitted but a stable current flows (with the current fluctuation being within ±50% of the average current value).

[0021] The present invention is characterized by using a mixed gas of argon and nitrogen as a carrier gas for sample ions. The mixed gas of argon and nitrogen in the present invention refers to a state in which nitrogen gas is contained in argon. After extensive research, the inventors have found that when a mixed gas of argon and nitrogen is used under low voltage conditions, argon can be excited without emitting light. The inventors have further found that by using the mixed gas of argon and nitrogen in the present invention, nitrogen radicals are not generated, and a stable dark discharge is maintained even in the presence of sample components, enabling continuous ionization.

[0022] In the present invention, the voltage for generating dark discharge is preferably in the range of 1.8 kV to 3.0 kV. If the voltage exceeds 3.0 kV, a discharge accompanied by light emission occurs, rather than a dark discharge without light emission. On the other hand, if the voltage is less than 1.8 kV, no discharge occurs.

[0023] When discharge was performed using nitrogen (100%), helium (100%), or hydrogen (100%), which are commonly used as carrier gases in conventional atmospheric pressure ionization methods, no dark discharge occurred. Furthermore, when discharge was performed using argon (100%) as the carrier gas, the dark discharge was unstable.

[0024] In the present invention, in order to ionize sample components by dark discharge, the current must be set to 0.1 μA or more and 1.0 μA or less. If the current is less than 0.1 μA, dark discharge will not occur, and if the current is more than 1.0 μA, the dark discharge will not be stable. In other words, the current value when dark discharge is maintained stably is 0.1 μA or more and 1.0 μA or less.

[0025] The steps of the present invention are explained using FIG. 1 . FIG. 1 is a simplified flowchart illustrating the ion introduction method of the present invention for introducing ions into a mass spectrometer. First, (1) a mixed gas consisting of argon and nitrogen is generated. (2) The mixed gas is heated as necessary. Next, (3) this room-temperature or heated mixed gas is discharged into a moisture-containing atmosphere. Furthermore, (4) a sample placed in the moisture-containing atmosphere is contacted with the discharged mixed gas to form a mixed gas containing sample components. (5) The mixed gas containing the sample components is introduced into an ionization region under reduced pressure. (6) In the ionization region, argon in the mixed gas containing the sample components is excited by a dark discharge without light emission under reduced pressure, and sample ions are generated from the sample components through the interaction of the excited argon and moisture. Thereafter, (7) the mixed gas containing the sample ions is introduced into a mass spectrometer, where the mass is measured.

[0026] In the ionization of a sample in the present invention, moisture in the atmosphere is involved in the reaction, so the sample must be placed in an atmosphere containing moisture. It can be assumed that there is sufficient moisture in the atmosphere in a normal laboratory environment (humidity 20-85%). This is also evident from the fact that conventional atmospheric pressure (ambient) ionization methods are used in practice. Any environment in which these ionization methods can be applied will suffice.

[0027] The "sample" in this invention can be in any state, such as solid, liquid, or gas, as long as it can generate ions that can be measured by a mass spectrometer. In particular, metal complexes such as titanyl phthalocyanine, which have been difficult to measure using conventional methods, can also be used. Furthermore, essentially, the sample can be simply held over the mixed gas without any pretreatment. The "sample component" in this invention refers to a substance that is generated by contacting the sample with the mixed gas, and includes any state of the sample, such as vaporization, atomization, droplets, or fine particles.

[0028] In the present invention, nitrogen gas is present in the mixed gas, but in the ionization region, unlike the nitrogen excitation type (100% nitrogen) ionization process, argon is excited with lower excitation energy than that used to excite nitrogen molecules. The excited argon ionizes water molecule clusters in the atmosphere. These water molecule cluster ions efficiently ionize the sample, suppressing the generation of by-products derived from nitrogen radicals. Therefore, in the present invention, the generation of sample fragments (decomposition components) is suppressed, allowing for soft and efficient ionization of samples that were previously difficult to measure.

[0029] 2 is a schematic diagram of an iontophoresis device for introducing ions into a mass spectrometer according to the present invention. The iontophoresis device includes a mixed gas generator 100 for carrying out steps (1) and (2), a sample supply unit 200 for carrying out step (4), and an interface unit 300 for carrying out step (6). Components 100, 200, and 300 are integrated to form an ionization unit 900. The means for carrying out step (6) in interface unit 300 is also referred to as the ionization means (hereinafter the same).

[0030] The mixed gas generating unit 100 includes a mixed gas generating means 11 that mixes argon and nitrogen and a gas heating means 12 that can heat the mixed gas. The mixed gas generating means 11 introduces argon gas and nitrogen gas to generate a mixed gas of argon and nitrogen (hereinafter abbreviated as "mixed gas"). The gas heating means 12 can heat the mixed gas. A heater 122 can be used to heat the gas conveniently. The generated mixed gas 123 is discharged from the mixed gas generating unit 100 with or without heating, and sent to the sample supply unit 200.

[0031] In the sample supply section 200, the mixed gas 123 comes into contact with the sample 21 in the environment of the atmospheric atmosphere 22 to generate sample components, and the mixed gas 123 is mixed with the sample components 21 and the atmospheric atmosphere 22 to form a sample component-containing mixed gas 23. Next, the sample component-containing mixed gas 23 is sent to the interface section 300.

[0032] The interface section 300 is provided with an ionization region 31, and in this ionization region, a dark discharge is generated by applying a voltage to the discharge electrode 31. The dark discharge excites only argon in the sample component-containing mixed gas 23, and the excited argon ionizes the sample via water molecule clusters. The sample ion-containing mixed gas 37 containing the ionized sample components is sent to the mass spectrometer 600, where the mass is measured.

[0033] FIG. 3 is a simplified diagram illustrating one embodiment of an iontophoresis device for introducing ions into a mass spectrometer according to the present invention. In FIG. 3, the iontophoresis device, like that shown in FIG. 2, includes a mixed gas generation unit 100 for implementing steps (1) and (2), a sample supply unit 200 for implementing step (4), and an interface unit 300 for implementing step (6). In FIG. 3, the mixed gas flow path 121 and the sample component-containing mixed gas inlet path 35 are shown in cross section, with the surrounding structure also shown in cross section. Also in FIG. 3, the interface unit 300 and the outer wall surface 62 of the mass spectrometer form an ionization region 31. An ion transfer port 61 of the mass spectrometer 600 is located on the outer wall surface 62 of the mass spectrometer 600, which forms the ionization region 31.

[0034] The configuration of the mixed gas generation unit 100 in the present invention (although not particularly limited) includes at least a mixed gas generation means 11 that mixes argon and nitrogen to generate a mixed gas, and further includes a mixed gas heating means 12 that can heat the mixed gas as needed.

[0035] When discharging using 100% argon gas, it is possible to generate a dark discharge, but maintaining the dark discharge state is difficult and unstable. One possible reason for this is that, when using 100% argon gas, the conductivity near the electrode changes due to volatilized sample, reducing electrical resistance and causing an overcurrent, making it impossible to maintain the dark discharge state. In the present invention, a mixed gas of argon and nitrogen is used as the carrier gas. Using a mixed gas of argon and nitrogen as the carrier gas allows for stable dark discharge and continuous ionization of sample components.

[0036] 3, the mixed gas generating means 11 may simply be any means capable of mixing argon and nitrogen, and is provided with at least an argon gas inlet channel 111, a nitrogen gas inlet channel 112, and an argon and nitrogen mixed gas outlet channel 113. In simple terms, this can be realized by a T-shaped pipe, a V-shaped pipe, a U-shaped pipe, or the like, which is a combination of a resin tube, typically made of polytetrafluoroethylene (PTFE), or a metal pipe.

[0037] Mixed gas 114, generated by mixing argon gas and nitrogen gas, is sent from mixed gas outlet channel 113 to mixed gas flow path 121. Mixed gas heating means 12 is provided in mixed gas flow path 121. In mixed gas heating means 12, heater 122 is arranged around mixed gas flow path 121, and the mixed gas can be heated as needed. The mixed gas is discharged as mixed gas 123 from mixed gas outlet 13 to sample supply unit 200, with or without heating.

[0038] In the argon and nitrogen mixed gas of the present invention, argon is mixed in a volume ratio range of 2% to 67%. To obtain a stable dark current discharge, a volume ratio of 10% to 30% is preferable, but to maintain a stable dark current discharge regardless of the atmospheric environment or sample, a volume ratio of 17% to 25% is particularly preferable. The volume ratio of argon is mixed by adjusting and controlling the flow rate. When this argon and nitrogen mixed gas 123 is used, a stable dark current discharge is maintained and continuous ionization is possible.

[0039] The flow rates of argon and nitrogen can be adjusted and controlled using a general pressure regulator valve and are not particularly limited. For precise control based on various conditions, such as the state of the sample and the atmospheric pressure of the sample supply system (described later), well-known gas flow meters can also be used. The flow rates of argon and nitrogen are displayed on the flow meters, and the displayed flow rates can be adjusted using needle valves. The argon and nitrogen mixed gas 114 thus generated is discharged from the mixed gas outlet channel 113 and introduced into the sample supply unit 200 as the mixed gas 123 via the mixed gas flow path 121. The flow rate of the mixed gas 114 is determined based on the pressures of the sample supply unit 200 (which is approximately atmospheric pressure), the ionization region 31 (which is maintained at a negative pressure relative to the sample supply unit 200 by an exhaust system connected to the ionization region 31), and the mass spectrometer 600 (which is maintained at a further reduced pressure by the exhaust system of the mass spectrometer body).

[0040] In FIG. 3 , the mixed gas 123 discharged from the mixed gas generator 100 to the sample supply unit 200 comes into contact with the sample in the sample supply unit 200 to form a sample component-containing mixed gas 23. The sample component-containing mixed gas 23 is introduced into the ionization region 31 via a sample component-containing mixed gas inlet 35. The ionization region 31 is equipped with a discharge electrode 34 and an exhaust port 32 communicating with an external exhaust system. The atmosphere in the ionization region 31 is exhausted and controlled to a predetermined pressure by the external exhaust system communicating with the exhaust port 32. The atmosphere in the sample supply unit 200 is open to the atmosphere and is maintained at approximately atmospheric pressure. Therefore, the pressure in the ionization region 300 and the pressure in the sample supply unit 200 have the following relationship: pressure in the sample supply unit 200 > pressure in the ionization region 31. Meanwhile, the internal pressure of the mass spectrometer 600 is regulated by the exhaust system of the device itself. The gas suction speed (exhaust speed) of a typical mass spectrometer 600 varies depending on the instrument, but is approximately 0.5 to 5 L / min. By connecting a separate vacuum exhaust unit, the suction speed can be increased by approximately 10 L / min. The pressure in the ionization region 31 is always kept higher than the pressure inside the mass spectrometer 600, maintaining the following relationship: pressure in the ionization region 31 > pressure inside the mass spectrometer 600. This pressure relationship allows sample ions to be naturally introduced from the ionization region 31 into the mass spectrometer 600. Therefore, the following relationship holds between the sample supply unit 200, the inside of the ionization region 31, and the inside of the mass spectrometer 600: pressure in the sample supply unit 200 > pressure in the ionization region 31 > pressure inside the mass spectrometer 600.

[0041] The flow rate of the sample component-containing mixed gas 23 introduced into the ionization region 31 also affects the pressure within the region. The flow rate of the sample component-containing mixed gas 23 depends on the flow rate of the mixed gas 123 discharged to the sample supply unit 200. If the flow rate (flow rate) of the mixed gas 123 is lower than a predetermined range, sensitivity decreases. This is because the sample components are not sufficiently mixed with the mixed gas 123 in the sample supply unit 200 and are diluted by the surrounding atmosphere 22. On the other hand, if the flow rate (flow rate) of the mixed gas 123 exceeds the predetermined range, sensitivity also decreases. This is because, under these conditions, the sample component-containing mixed gas 23 reaches the sample component-containing mixed gas inlet 35 before the sample components are sufficiently mixed with the moisture-containing atmosphere 22, preventing sufficient mixing of the moisture and sample, which is essential for ionization. Furthermore, excess gas overpressures the ionization region 31, placing a strain on the vacuum state of the mass spectrometer 600. This excess gas also shortens the life of the instrument.

[0042] In the present invention, the mixed gas generating unit 100 can be provided with a gas heating means 12. This makes it possible to heat the argon and nitrogen mixed gas 114 as needed. As the gas heating means 12, for example, a heater 122 can be provided around the mixed gas flow path 121. Specifically, the mixed gas flow path 121 can be made of metal piping, and the periphery of the metal piping can be covered with a ceramic heater, thereby enabling heating.

[0043] In fact, the difference in mass spectrometry measurement results was observed between a case where the mixed gas was not heated without using the heater 122 of the gas heating means 12 and a case where the mixed gas of argon and nitrogen was heated using the heater 121. As a result, when the mixed gas was heated, the peaks of impurities were reduced and the peak of the target substance was relatively easier to see, improving the analytical sensitivity, compared to when the mixed gas was not heated (as will be described later in Examples 9-1 and 9-2).

[0044] When heating the mixed gas in the present invention, the set temperature of the heater 122 can be set (although not particularly limited) in the range of usually 10° C. to 600° C. In order to obtain the effect of heating the carrier gas, it is preferable to heat the carrier gas to a temperature above room temperature, for example, in the range of 50° C. to 500° C. Furthermore, taking into consideration the life of the heater, it is particularly preferable to set the temperature in the range of 100° C. to 450° C.

[0045] In the sample supply unit 200 of the present invention, the sample is supplied as follows: In the case of a gas sample, it may be supplied from the outside using a tube of an appropriate diameter, and the sample is directly mixed with the mixed gas 123 and the atmospheric environment 22. In the case of a liquid or solid sample or a mixture thereof, there is no particular limitation, but for example, the sample may be applied to the tip of a glass rod and placed in the flow path of the mixed gas 123, or the sample may be continuously supplied from the outside using a capillary (thin tube).

[0046] Alternatively, a liquid or solid sample can be placed in a container provided in the atmospheric atmosphere 22 in the sample supply unit 200 and exposed to the atmospheric atmosphere. The sample in the container is vaporized or atomized, or turned into droplets or fine particles by the flow of heated or unheated mixed gas 123, to generate sample components. The sample components are mixed with the mixed gas 123 and the atmospheric atmosphere 22 to generate a sample component-containing mixed gas 23. Furthermore, the generation of sample components can be promoted by heating the container.

[0047] Fig. 4 is a diagram showing another embodiment of the iontophoresis device of the present invention. Fig. 4 is a diagram clarifying the positional relationship between the mixed gas generation unit 100 (equipped with mixed gas generation means 11 and gas heating means 12), the sample supply unit 200, the interface unit 300, and the mass spectrometer 600. Furthermore, Fig. 4 shows the case where a sample stage 212 and a sample container 211 are arranged in the sample supply unit 200.

[0048] In Fig. 4, a mixed gas generation section 100, a sample supply section 200, and an interface section 300 are mounted on a base 91. As a result, the sections 100, 200, and 300 are integrally configured to form an ionization unit 900. Furthermore, Fig. 4 also shows a schematic diagram of a mass spectrometer 600. Note that in the following figures, the entire mass spectrometer 600 is not shown, but only the essential parts are shown. In Fig. 4, the ionization unit 900 is attached to the mass spectrometer 600 using hinges 36a and 36b.

[0049] 5 is a cross-sectional view of the mixed gas flow path 121 in the mixed gas generation unit 100 and the sample component mixed gas inlet path 35 provided in the interface unit 300 in FIG. 4. That is, in FIG. 5, the mixed gas flow path 121 and the sample component-containing mixed gas inlet path 35 are shown in cross section, and the surrounding structure is also shown in cross section. In FIG. 5, an ion transfer port 61 of the mass spectrometer 600 is disposed on an outer wall surface 62 of the mass spectrometer 600, and the surface 62 of the mass spectrometer and the interface unit 300 form an ionization region 31.

[0050] The mixed gas generating unit 100 in Fig. 5 includes a mixed gas generating means 11 and a gas heating means 12, and the gas heating means 12 includes a heater 121 that can heat the mixed gas. Fig. 5 also shows the relative positions of a sample stage 212 and a sample container 211 in the sample supply unit 200.

[0051] Mixed gas 123 is discharged from mixed gas generator 100 to sample supply unit 200 via mixed gas flow path 121. The discharged mixed gas 123 comes into contact with the sample in sample container 211 to produce sample components, which are components that make up the sample. The sample components are mixed with mixed gas 123 and ambient air 22 to form sample component-containing mixed gas 23. Sample component-containing mixed gas 23 is introduced into ionization region 31 via sample component-containing mixed gas introduction path 35.

[0052] When a liquid, solid, or mixture thereof is used as the sample, the sample container 211 in FIG. 5 can be used. The sample is placed in the sample container 211 and placed on the sample stage 212 provided in the sample supply unit 200. The sample in the sample container 211 is vaporized or atomized, or turned into droplets or fine particles, depending on the flow and temperature of the mixed gas 123, to generate sample components. The sample components are mixed with the mixed gas 123 and the ambient atmosphere 22 to generate a sample component-containing mixed gas 23. The sample container 211 can be any commonly used resin or metal container as long as it can hold a liquid or solid sample.

[0053] As will be described later, in order to promote vaporization, atomization, droplet formation, and microparticulation of a liquid or solid sample, a sample heating means may be provided on the sample stage 212. When the sample in the sample container 211 is heated by the sample heating means provided on the sample stage 212, the mixed gas 123 may be supplied at room temperature without using the gas heating means 12. Alternatively, the heated mixed gas 123 and the sample heating means may be used in combination.

[0054] Figure 6 is a view of the iontophoresis device of Figure 4 from another side. In this figure, as in Figure 4, the mixed gas generation unit 100, the sample supply unit 200, and the interface unit 300 are mounted on a base 91. The base 91 integrally configures the units 100, 200, and 300 to form an ionization unit 900. The integrally configured ionization unit 900 is attached to the mass spectrometer 600 using hinges 36a (and 36b, not shown).

[0055] 7 is a diagram showing a state in which the ionization unit 900 in FIG. 6 is opened and closed relative to the mass spectrometer 600. The mixed gas generation unit 100, the sample supply unit 200, and the interface unit 300 are integrally configured by the base 91 to constitute the ionization unit 900. The opening and closing of the ionization unit 900 and the mass spectrometer 600 integrated by the base 91 is indicated by an opening and closing direction 38 of the interface unit. FIG. 7 shows a state in which the interface unit 300 constituting the ionization unit 900 is connected to the mass spectrometer 600 by hinges 36a and 36b, and the ionization region is opened.

[0056] FIG. 8 is a diagram showing the state of FIG. 7 as viewed from above. FIG. 8 will be described in detail. In FIG. 8, the interface section 300 constituting the ionization unit 900 has a recess 31a. When the ionization unit 900 and the mass spectrometer 600 are closed along the opening / closing direction 38 of the interface section, the outer wall surface 62 of the mass spectrometer 600 comes into contact with the interface section 300, and the recess 31a becomes an internal space, forming the ionization region 31. FIG. 9 shows this state. Details of FIG. 9 will be described later.

[0057] 8, the interface unit 300 is made of a metal member, preferably an aluminum member which is lightweight and has good conductivity, and is connected to the outer wall surface 62 of the mass spectrometer 600 by a conductive member. By connecting the interface unit 300 and the outer wall surface 62 by the conductive member, the interface unit 300 and the outer wall surface 62 are reliably electrically connected to each other.

[0058] 8, recess 31a of interface unit 300 is typically a roughly cylindrical space, and an exhaust port 32 communicating with an external exhaust system and a voltage unit 33 for dark current discharge are provided in a side region of the roughly cylindrical recess 31a. The interface unit 300 further includes a sample component-containing mixed gas inlet channel 35 on the bottom side of the roughly cylindrical recess 31a facing the mass spectrometer 600. In Fig. 8, recess 31a communicates with sample supply unit 200 under atmospheric conditions via sample component-containing mixed gas inlet channel 35.

[0059] 9 is a diagram showing the ionization region 31 formed by closing the ionization unit 900 and the mass spectrometer 600 in the opening / closing direction 38 in FIG. 9. In FIG. 9, the ionization region 31 is hatched to clearly show it. An interface section 300 integrated with the ionization unit 900 includes a sample component-containing mixed gas inlet 35 and an exhaust port 32 communicating with an external exhaust system.

[0060] In FIG. 9 , the ionization region 31 must be sealed by the surface where the interface unit 300 and the outer wall surface 62 of the mass analyzer 600 meet. While the sealing method is not particularly limited, for example, both surfaces can be sealed using O-rings. The material of the O-rings is not particularly limited. In the state shown in FIG. 9 , the ionization region 31 becomes an electromagnetically shielded space, allowing dark current discharge to occur without being affected by the outside world. The most convenient conductive member is the hinges 36 a and 36 b. Because the ionization region 31 is located in close proximity to the mass analyzer 600, measures must be taken to prevent contamination of the mass analyzer 600. Therefore, the inside of the ionization region 31 must be kept clean by an external exhaust system connected via the exhaust port 32.

[0061] The size and shape of the ionization region 31 vary depending on the shape of the mass spectrometer 600 to be combined, but as mentioned above, a compact size is required to create a clean region. Typically, the roughly cylindrical space of the recess 31a shown in Figure 8 has an inner diameter of 80 mm to 100 mm at the bottom of the cylinder, and a depth, i.e., a height of the cylinder, of about 50 to 80 mm. The internal volume of the space formed as a result of the combination is 200 to 600 x 10 ３ mm ３ It will be about that level.

[0062] In Figure 9, the ionization region 31 is isolated from the outside air except for the following: it is connected to the sample supply unit 200 under atmospheric conditions via the sample component-containing mixed gas inlet 35; it is connected to the mass spectrometer 600 main body via the ion transfer port 61 of the mass spectrometer; and it is connected to an external exhaust system via the exhaust port 32. The ionization region 31 is evacuated at a flow rate of approximately 1 to 40 L / min, ideally approximately 10 L / min, by an external exhaust system connected to the exhaust port 32 provided in the interface unit 300. This exhaust maintains the ionization region 31 at a negative pressure of approximately 1 to 70 kPa below atmospheric pressure, ideally approximately 10 kPa. The external exhaust system can use any known exhaust means and is not particularly limited. For example, the ionization region is evacuated using a diaphragm pump or the like.

[0063] The atmospheric atmosphere 22 of the sample supply unit 200 is at approximately atmospheric pressure. In contrast, the ionization region 31, which is exhausted by the external exhaust system, is at a negative pressure relative to atmospheric pressure. This pressure difference from atmospheric pressure allows the sample component-containing mixed gas 23 formed in the sample supply unit 200 to be introduced into the ionization region 31. Furthermore, exhaust by the external exhaust system keeps the pressure in the ionization region 31 negative (approximately 1 to 70 kPa) relative to the atmospheric atmosphere 22 and higher than the pressure in the mass spectrometer 600, thereby maintaining a stable airflow from the mixed gas generator 100 to the sample supply unit 200 to the ionization region 31 and then to the mass spectrometer 600. In other words, the following relationship is maintained among the pressures in each section: sample supply unit 200 > ionization region 31 > mass spectrometer 600

[0064] The dark discharge of the present invention will be explained using Figure 5. In Figure 5, a discharge electrode 34 (for dark discharge) is provided at the tip of a voltage unit 33 provided in the ionization region 31. Argon in the sample component-containing mixed gas 23 introduced into the ionization region 31 is excited by the dark discharge. The sample components in the sample component-containing mixed gas 23 are ionized by the interaction between the excited argon and the moisture in the sample component-containing mixed gas 23.

[0065] In the ionization region 31 of Fig. 5, the discharge electrode 34 (for dark current discharge) is provided so as to be located between the sample component-containing mixed gas inlet 35 (from the sample supply unit 200) and the ion transfer port 61 of the mass spectrometer 600. In Fig. 5, the ion transfer port 61 serves as a counter electrode to the discharge electrode 34. A voltage is applied between the ion transfer port 61 serving as the counter electrode and the discharge electrode 34 to generate a dark current discharge. The ion transfer port 61, which serves as a counter electrode for the dark current discharge, is maintained at the same potential as the interface unit 300 and the outer wall surface 62 of the mass spectrometer 600 via a conductive member, preventing electromagnetic phenomena other than those described above from occurring.

[0066] A needle-shaped metal material is used for the discharge electrode 34. The material is preferably one that is easy to process the needle tip, has little wear due to dark discharge, and is highly durable. In the present invention, a needle-shaped stainless steel material is used.

[0067] It is undesirable for a current other than discharge (leak current) to occur between the discharge electrode 34 and the counter electrode 61. Therefore, it is necessary to cover the discharge electrode 34 except for its tip with an insulator. This insulator should be made of a material that has high insulating properties, does not generate decomposition products even at high voltages, and is resistant to charge-up. For example, resin materials such as silicone, polyimide, and PEEK (polyether ether ketone) are desirable.

[0068] The dark discharge of the present invention is performed at a lower voltage than that of conventional atmospheric pressure ionization methods. That is, by using a mixture of argon and nitrogen as a carrier gas at a low voltage, a stable dark discharge can be maintained even in the presence of sample components.

[0069] The voltage required for dark discharge, i.e., discharge without light emission, is lower than the voltage required for conventional discharge with light emission. Even in a mixed gas of argon and nitrogen, when the voltage required for dark discharge is applied, the dark discharge excites only argon and does not generate nitrogen radicals. Furthermore, the present invention has discovered that when a mixed gas of argon and nitrogen is used, stable dark discharge can be maintained even in the presence of sample components. The applied voltage is not particularly limited as long as it is within a range in which dark discharge is stable, but is usually applied in a voltage range of 1.8 kV to 3.0 kV. At voltages exceeding 3.0 kV, discharge accompanied by light emission rather than dark discharge occurs, and at voltages below 1.8 kV, the discharge is unstable.

[0070] In Figure 5, the strength of the electric field generated from the tip 34a of the discharge electrode 34 of the dark current discharge of the present invention contributes to the generation of dark current discharge. This electric field strength varies depending on the shape of the tip of the discharge electrode 34, the distance between the counter electrode 61 and the tip of the discharge electrode 34, the orientation (angle) of the tip of the discharge electrode relative to the counter electrode 61, and the voltage applied to the discharge electrode. By adjusting these conditions and applying the aforementioned voltage (1.8 kV or more to 3.0 kV or less), dark current discharge without light emission can be stably maintained. (Note that the counter electrode 61 is usually grounded.)

[0071] Another embodiment of the mass spectrometer 600 is one that includes a voltage unit. One example is shown in FIG. 18 . In FIG. 18 , a recess 60a is formed from the outer surface 63 of the mass spectrometer 600 toward the ion transfer port 61 of the mass spectrometer 600, and the ion transfer port 61 and one end of the voltage unit 33 are disposed within the recess 60a. These arrangements are shown in cross section. The voltage unit 33 is connected to an electrical circuit (not shown) of the mass spectrometer 600 so that a voltage can be applied.

[0072] In Figure 18, a discharge electrode 34 is attached to one end of the voltage unit 33 in the recess 60a. Meanwhile, the interface section 300 of the present invention is provided with a sample component-containing mixed gas inlet path 35 and an exhaust port 32 communicating with an external exhaust system, and is shown in a diagram cut at the inlet path 35 and the exhaust port 32. The interface section 300 also forms a recess 31a. Note that the mixed gas generation section 100 and sample supply section 200 of the present invention are not shown in Figure 18.

[0073] 18, the interface unit 300 is connected to the mass analyzer 600 by a hinge 36a and another hinge 36b (not shown). When the interface unit 300 and the mass analyzer 600 are positioned to face each other by the hinges 36a and 36b, the recess 31a on the interface 300 side and the recess 60a on the mass analyzer side face each other and are sealed to form the ionization region 31. In FIG. 18, the ionization region 31 is indicated by a dashed line.

[0074] To form the ionization region 31, the recess 31a of the interface unit 300 is designed to fit the size of the opening of the recess 60a of the mass spectrometer. The iontophoresis device of the present invention shown in Figure 18 has the advantage that it does not require a voltage unit to be provided in the interface unit and can utilize the power supply of the mass spectrometer. Furthermore, the iontophoresis device of the present invention shown in Figure 18 can be applied to the configurations of the mixed gas generation unit 100 and the sample supply unit 200, both of which are not shown.

[0075] In the present invention, a heating means for heating the sample can be provided to promote the generation of sample components from the sample, i.e., to promote the vaporization, atomization, droplet formation, and microparticulation of the sample. Fig. 10 shows an embodiment in which a heating plate 213 is provided on a stage on which a sample container 211 is placed. That is, Fig. 10 shows the configuration of Fig. 4 in which the heating plate 213 also serves as a sample stage for the sample container 211.

[0076] In Figure 10, when the sample container 211 is heated, a heat-resistant metal container is used as the sample container 211. The sample container 211 is placed on a heating plate 213 and heated. Various types of heating plate 213 can be used, such as a resistance heater or an infrared heater. In Figure 10, a heating plate made of a resistance heater is used because of its simple structure and ease of temperature control and sample replacement, which will be described later. Heating means other than a plate, such as laser heating, can also be used.

[0077] Furthermore, instead of directly heating the sample container 211 with the heating plate 213, it is also possible to heat the sample container by incorporating a heating means inside the support stand for the sample container. In Fig. 10, from the viewpoint of thermal efficiency, a flat resistance heater is used as the heating plate 213, and the sample container 211 is placed directly on the heating plate 213 and heated.

[0078] 10, a sample container 211 is placed on a heating plate 213. A voltage is applied to the heating plate 213 to heat the sample in the sample container 211. The temperature rise rate of the resistance heater used as the heating plate 213 is preferably in the range of 30 to 300°C / min. The maximum temperature of the resistance heater is set to 600°C.

[0079] Figure 14 shows an example of mass spectrometry for solid and liquid samples that are difficult to vaporize or sublimate at room temperature, showing an example of the difference in signals from a mass spectrometer when the sample is heated and when it is not heated.

[0080] In Figure 10, the time course of the signal from the mass spectrometer was observed when a solid sample of titanyl phthalocyanine was placed in the sample container 211 and a room temperature (i.e., unheated) mixed gas was discharged into the atmosphere of the sample supply unit 200. When the mixed gas was flowing without heating the sample container 211, no signal was observed. In other words, no sample ions derived from the sample components were present in the mass spectrometer 600. Next, when the sample container 211 was heated, a signal began to be observed. In other words, sample ions derived from the sample components were introduced into the mass spectrometer 600.

[0081] FIG. 14 is a diagram showing the time course of the signal from the mass spectrometer at this time. The horizontal axis of FIG. 14 shows the time course from when the sample container is not heated to when it is heated. The vertical axis shows the mass spectrometry signal of the sample ion derived from the sample components. That is, it was found that when the solid sample of titanyl phthalocyanine is not heated, the sample components are not present in the atmosphere, but when the sample is heated, the sample components are generated in the atmosphere. That is, by heating the sample using the heating plate 213 and sample container 211 of the present invention, it is possible to analyze samples that cannot be mass analyzed at room temperature, particularly refractory solid or liquid samples that are difficult to vaporize or sublimate at room temperature.

[0082] When heating a sample, as described above, it is possible to contact unheated, room temperature mixed gas 123 with the sample to form a mixed gas 213 containing sample components, but better data can be obtained by contacting heated mixed gas 123 with the sample to form a mixed gas 213 containing sample components.

[0083] Fig. 11 is a diagram showing the configuration of Fig. 10 further provided with covering members 41a and 41b and a sample container exchange mechanism 500. That is, Fig. 11 is a diagram showing the sample supply unit 200 provided with covering members 41a and 41b and a sample container exchange mechanism 500.

[0084] 11 , the sample supply unit 200 is provided with covering members 41 a and 41 b that cover the heating plate 213. The lower covering member 41 b also serves as a support for the heating plate 213. The lower covering member 41 b is placed on a base 91. The upper covering member 41 a is detachable from the lower covering member 41 b. The upper covering member 41 a covers the heating plate 213 and the sample container 211 when heating the sample (when applying a voltage to the heating plate 213). When replacing the sample container 211 or when arranging the aforementioned sample tube or glass capillary, the upper covering member 41 a can be removed from the sample supply unit 200 to perform the work.

[0085] The provision of the covering members 41 a and 41 b can suppress the diffusion of the mixed gas, sample components, and sample component-containing mixed gas 23 in the sample supply unit 200. It also mitigates the effects of temperature changes and air currents around the device, allowing for stable data to be obtained. It also prevents the experimenter from touching the heating area when heating the sample.

[0086] When replacing the sample container 211, the upper part 41a of the covering member can be removed as described above, but it is also possible to provide a means for supplying a plurality of samples in a replaceable manner in sequence. Such an embodiment is shown in FIG.

[0087] Figure 12 shows the state in Figure 11 with the upper covering member 41a removed. Figure 12 more clearly shows the positional relationship between the heating plate 213 and the sample container exchange mechanism 500. A plurality of samples are stored in a plurality of separate sample containers 51a, 51b, 51c, ..., which are arranged, for example, in a line in the sample container arrangement direction 52. The plurality of sample containers 51a, 51b, 51c, ... are made of the same shape and material for ease of sample handling.

[0088] Figure 13 is a cross-sectional view of Figure 12 taken along a plane including the mixed gas flow path 121 and the sample component-containing mixed gas inlet path 35. The mixed gas generating means 11, mixed gas heating means 12, and interface section 300 are also shown in cross section in Figure 13. An example of the sample container exchange mechanism 500 is shown in more detail in Figure 13. This example shows that a sample container arrangement direction 52 in which a plurality of sample containers 51a, 51b, 51c, etc. are arranged intersects with a sample supply / discharge direction 53 for exchanging sample containers by placing or removing the sample containers on or from the heating plate.

[0089] The sample container exchange mechanism 500 will be described with reference to Figure 13. Of the multiple sample containers arranged in a row along a sample container arrangement direction 52 on the sample container exchange mechanism 500, the sample container 51a closest to the heating plate is moved along the sample container arrangement direction 52 and then moved toward the heating plate 213 along the sample supply / discharge direction 53 that intersects with the sample container arrangement direction 52. After being brought into contact with the mixed gas 123 on the heating plate 213, the sample container 51a is moved in a direction away from the heating plate 213 along the sample supply / discharge direction 53. By repeating this series of operations in sequence for the sample containers 51a, 51b, 51c, ..., the sample components of multiple samples can be sequentially ionized and introduced into the mass spectrometer.

[0090] These movements can be most easily achieved manually, but may also be achieved using a well-known mechanism (not shown). Use of such a sample container exchange mechanism eliminates the need to remove the upper cover member 41 a as described above when exchanging sample containers, thereby improving the efficiency of sample handling and the overall analytical experiment.

[0091] As an example of the well-known mechanism (not shown), a sample container can be automatically exchanged. After mass spectrometry or sample ionization is completed, the sample container 211 placed on the heating plate 213 can be automatically exchanged for the next sample container 51a to be measured using a sample container exchange mechanism 500 or the like. For example, the sample container can be automatically exchanged by moving it on a rail, or by using an automatic handling arm. By repeating the automatic exchange operation sequentially for 51b, 51c, ..., a large number of samples can be automatically measured in succession.

[0092] The present invention will be described in more detail below with reference to examples and comparative examples, but the present invention is not limited to these examples. The following shows the results of experiments using multiple carrier gas components. [Example 1] Mass analysis was performed in combination with a mass spectrometer using an iontophoresis device equipped with a mixed gas generator, a sample supply unit, and an interface unit of the present invention. Note that in Example 1 and following, the gas containing the sample components and used for ionization will be referred to as the carrier gas, including the mixed gas. In the mixed gas generator, the flow rates of argon gas and nitrogen were controlled to 1.7 L / min and 0.8 L / min, respectively, and the respective gases were introduced to generate the carrier gas. The temperature of the heater in the mixed gas heating means of the mixed gas generator was set to 400°C, and the heated carrier gas (argon:nitrogen = 2:1) was discharged at 2.5 L / min. In the sample supply section, 0.5 mg of titanyl phthalocyanine sublimation refined powder (Tokyo Chemical Industry Co., Ltd.) was placed in the sample cup LF (Frontier Labs, Inc.), which served as a sample container. The sample cup LF was rapidly heated to 400 °C to vaporize the titanyl phthalocyanine and extract the sample components in the ambient atmosphere. The ionization region was evacuated at 10 L / min to maintain a negative pressure below the ambient atmosphere, and a carrier gas containing atmospheric moisture and sample components was introduced into the ionization region. A voltage of 2.2 kV was applied to the voltage unit installed in the interface section to ionize the sample components. The generated sample ions were transferred to the mass spectrometer via the differential pressure with the mass spectrometer, where mass analysis was performed. A Shimadzu LCMS-2020 mass spectrometer was used. Prior to mass analysis of the sample components, heated carrier gas alone was allowed to flow for 30 minutes to confirm whether the dark current discharge changed between this condition and the sample component analysis. Hereinafter, "stable" means that dark discharge can be maintained without transitioning to discharge accompanied by light emission such as corona discharge or arc discharge. This definition was used as the criterion for judging the stability of dark discharge. Specifically, the following criteria were established: A: Stable discharge was maintained for 30 minutes before the measurement of the sample components, and was also maintained during subsequent measurement of the sample components. B: Stable discharge was maintained for 30 minutes before the measurement of the sample components, but became unstable during subsequent measurement of the sample components. C: Unstable. -: Dark discharge did not occur.

[0093] Examples 2 to 8, Comparative Examples 1 to 4 Mass spectrometry was performed in the same manner as in Example 1, except that the carrier gas was changed to the carrier gas shown in Figure 15. The flow rate of each carrier gas was 2.5 L / min. For the argon and nitrogen mixed gas, the argon flow rate was x L / min and the nitrogen flow rate was y L / min, with the ratio of x to y being the ratio shown in Figure 15, where x + y = 2.5. The stability of the dark discharge was evaluated in the experiments conducted in Examples 1 to 8 and Comparative Examples 1 to 4, and the results are summarized in Figure 15. That is, Figure 15 is a table summarizing the experiments in Examples 1 to 8 and Comparative Examples 1 to 4.

[0094] Examples 1 to 8 and Comparative Examples 1 to 4 demonstrated that dark discharge occurs when a carrier gas mixture of argon and nitrogen is used, and that the dark discharge is stable when only carrier gas is used and when sample components are measured at a specific ratio. On the other hand, dark discharge did not stably persist when argon alone was used. It was also revealed that dark discharge does not occur when nitrogen alone, helium, or hydrogen is used as the carrier gas. The present invention demonstrates that excitation at low voltage is possible using argon, which can be supplied more stably and is relatively inexpensive, instead of expensive helium gas, which has supply stability concerns. It was also demonstrated that a simple and inexpensive mass spectrometry system or method can be provided by using a carrier gas containing nitrogen, which is even cheaper than argon.

[0095] Example 9: An iontophoresis device equipped with a mixed gas generator, sample supply unit, and interface unit of the present invention was combined with a mass spectrometer to conduct a mass spectrometry experiment demonstrating the effect of carrier gas heating. Example 9-1: In the mixed gas generator, argon gas and nitrogen were introduced at flow rates of 0.5 L / min and 2.0 L / min, respectively, to generate a mixed gas. The mixed gas was discharged from the mixed gas generator at room temperature as a carrier gas without heating. The discharge rate was 2.5 L / min, the sum of the flow rates of the component gases. In the sample supply unit, a ceramic heater was installed on the heating plate, and a sample cup LF was placed. 0.5 mg of titanyl phthalocyanine sublimation refined powder was placed in the sample cup LF as a sample. The temperature setting of the ceramic heater was controlled to increase from room temperature to 400°C in 2 minutes (heating rate of 200°C / min), and sample components were obtained. The ionization region was evacuated at a flow rate of approximately 10 L / min, and a carrier gas containing the sample components was introduced into the ionization region. A voltage was applied to a needle electrode installed in the ionization region of the interface section to excite argon in the carrier gas containing the sample components. The excitation voltage was 2.2 kV. The generated sample ions were introduced into a mass spectrometer for measurement. A Shimadzu LCMS-9030 (9050 upgrade) mass spectrometer was used. The mass spectrometer settings were as follows: Positive m / z range 10-1500. The mass spectrometer was calibrated immediately before the experiment to confirm that it was in good condition. Figure 16 shows the results of the experiment in Example 9-1. In this experiment, impurity components appeared as impurity peaks, and the parent peak of titanyl phthalocyanine was relatively low (low sensitivity).

[0096] Example 9-2 A mass spectrometry experiment was conducted under the same conditions as in Example 9-1, except that the mixed gas was heated to a set temperature of 400°C in the heater installed in the mixed gas generator and discharged from the mixed gas generator as a carrier gas. A sample was placed in the sample supply unit as in Example 9-1 and rapidly heated to obtain sample components. The carrier gas containing the sample components was introduced into the ionization region. The argon excitation conditions in the ionization region and the mass spectrometer were the same as in Example 9-1. As in Example 9-1, the mass spectrometer was calibrated immediately beforehand to maintain good instrument condition. Figure 17 shows the results of the experiment in Example 9-2. It can be seen that in this experiment, highly volatile impurities were eliminated by contact with the heated carrier gas, and only the peak of the refractory component, titanyl phthalocyanine, was strongly detected. In other words, the sensitivity (S / N ratio) of the mass spectrometry was improved.

[0097] [Example 10] Mass spectrometry was performed in the same manner as in Example 5, except that 0.5 mg of aspartic acid powder (Sigma-Aldrich) was used as the sample. A peak (m / z = 134.1) derived from aspartic acid was clearly obtained. The stability of dark current discharge was also rated A. [Example 11] Mass spectrometry was performed in the same manner as in Example 5, except that 0.5 mg of glycine powder (Sigma-Aldrich) was used as the sample. A peak (m / z = 76.1) derived from glycine was clearly obtained. The stability of dark current discharge was also rated A.

[0098] Example 12: In Example 5, a glass rod was immersed in (R)-(+) limonene (Fujifilm Wako Pure Chemical Industries, Ltd.) as a sample, and the (R)-(+) limonene was attached to the glass rod. Mass spectrometry was performed in the same manner as in Example 5, except that in the sample supply section, the (R)-(+) limonene attached to the glass rod was held over the carrier gas discharged from the mixed gas generator, and the vaporized (R)-(+) limonene was introduced into the ionization region through the gas inlet. A peak (m / z = 137.2) derived from (R)-(+) limonene was clearly observed. Furthermore, the stability of the dark discharge was rated A.

[0099] Example 13: Mass spectrometry was performed in the same manner as in Example 12, except that a glass rod was immersed in a 0.01% acetonitrile solution of caffeine (Tokyo Chemical Industry Co., Ltd.) as the sample, and the caffeine was attached to the glass rod. A peak (m / z = 195.2) derived from caffeine was clearly obtained. The stability of the dark current discharge was also rated A. Example 14: Mass spectrometry was performed in the same manner as in Example 12, except that a peak (m / z = 369.4) derived from cholesterol (M-H2O+1) was clearly obtained. The stability of the dark current discharge was also rated A.

[0100] Although the above detailed description of the present invention has described an iontophoresis device and an iontophoresis method for introducing ions into a mass spectrometer, the technology of the present invention is not limited thereto. That is, the technology of the present invention can also be used as a method for generating ions in an atmospheric environment and as an iontophoresis device, and can be used in fields other than mass spectrometry.

[0101] 100... Mixed gas generation unit, 11... Mixed gas generation means, 111... Argon gas inlet channel, 112... Nitrogen gas inlet channel, 113... Mixed gas outlet channel, 114... Mixed gas, 12... Gas heating means, 121... Mixed gas flow channel, 122... Heater, 123... Mixed gas, 200... Sample supply unit, 21... Sample, 211... Sample container, 212... Sample stage, 213... Heating plate, 22... Atmospheric atmosphere, 23... Mixed gas containing sample component, 300... Interface unit, 31... Ionization region, 31a (of interface unit) recess, 32... Exhaust port, 33... Voltage unit, 34... Discharge electrode, 34a...discharge electrode tip, 35...sample component-containing mixed gas introduction path, 36a...upper hinge, 36b...lower hinge, 38...opening / closing direction of interface section, 41a...upper covering member, 41b...lower covering member, 500...sample container exchange mechanism, 51a...sample container, 51b...sample container, 51c...sample container, 52...sample container arrangement direction, 53...sample supply / discharge direction, 600...mass spectrometer, 60a...recess (of mass spectrometer), 61...ion transfer port of mass spectrometer, 62...outer wall surface of mass spectrometer, 63...outer surface of mass spectrometer, 900...ionization unit, 91...base

Claims

1. An iontophoresis device for introducing ions into a mass spectrometer, the iontophoresis device comprising: a mixed gas generation unit, a sample supply unit, and an interface unit; the mixed gas generation unit generates a mixed gas by mixing argon and nitrogen; the sample supply unit is provided in an atmospheric environment; a sample is placed in the sample supply unit, and the mixed gas discharged from the mixed gas generation unit is brought into contact with the sample to form a mixed gas containing a sample component; the interface unit has an exhaust port communicating with an external exhaust system and is in close contact with one surface of the mass spectrometer to form an ionization region; the ionization region is maintained at a pressure more negative than the atmospheric atmosphere by the external exhaust system; the sample component-containing mixed gas is introduced from the sample supply unit into the ionization region, and the sample component-containing mixed gas is excited by dark discharge to generate sample ions; and the sample ions are introduced from the ionization region into the mass spectrometer via an ion transfer port of the mass spectrometer.

2. The iontophoresis device according to claim 1, characterized in that it has a discharge electrode positioned in the ionization region between the ion transfer port and an inlet path for introducing the sample component-containing mixed gas (from the sample supply section), and generates a dark discharge between the discharge electrode and the ion transfer port to generate sample ions from the sample components in the sample component-containing mixed gas.

3. The iontophoresis device according to claim 2, wherein the discharge electrode is covered with an insulator except for the tip.

4. The iontophoresis device according to claim 2, wherein the voltage applied between the discharge electrode and the ion transfer port is 1.8 kV or more and 3.0 kV or less.

5. The iontophoresis device according to claim 1, wherein the volume ratio of argon in the mixed gas (generated) in the mixed gas generator is 2% or more and 67% or less, preferably 17% or more and 25% or less.

6. The iontophoresis device according to claim 1, wherein said mixed gas generator further comprises means for heating said mixed gas.

7. The iontophoresis device of claim 1, further comprising means for heating the sample in the sample supply section.

8. The iontophoresis device according to claim 1, wherein the sample supply unit is provided with a sample container exchange mechanism capable of being provided with a plurality of sample containers containing samples.

9. The iontophoresis device of claim 8, wherein the sample container exchange mechanism is capable of automatically exchanging a plurality of sample containers in succession.

10. The iontophoresis device of claim 1, wherein the ionization region is maintained at a higher pressure than the mass analyzer, and the gas flow passes through the mixed gas generator, the sample supply, and the ionization region before entering the mass analyzer.

11. A mass spectrometry system for ionizing a sample and introducing it into a mass spectrometer to analyze its mass, the mass spectrometry system comprising: a mixed gas generation unit, a sample supply unit, and an interface unit; the mixed gas generation unit generates a mixed gas by mixing argon and nitrogen; the sample supply unit is provided in an atmospheric environment; a sample is placed in the sample supply unit, and the mixed gas discharged from the mixed gas generation unit is brought into contact with the sample to form a mixed gas containing a sample component; the interface unit has an exhaust port communicating with an external exhaust system and is in close contact with one surface of the mass spectrometer to form an ionization region; the ionization region is maintained at a pressure more negative than the atmospheric atmosphere by the external exhaust system; the sample component-containing mixed gas is introduced from the sample supply unit into the ionization region, and the sample component-containing mixed gas is excited by dark discharge to generate sample ions; and the sample ions are introduced from the ionization region through an ion transfer port of the mass spectrometer to analyze the mass.

12. A method for introducing ions into a mass spectrometer, comprising the steps of: mixing argon and nitrogen to generate a mixed gas; discharging the mixed gas into an atmospheric environment; contacting the mixed gas with a sample placed in the atmospheric environment to form a mixed gas containing sample components; introducing the mixed gas containing sample components into an ionization region maintained at a negative pressure below the atmospheric environment by an external exhaust system; exciting the mixed gas containing sample components in the ionization region by dark discharge to generate sample ions; and introducing the sample ions from the ionization region into a mass spectrometer.

13. The iontophoresis method of claim 12, further comprising the step of heating the mixed gas after the step of generating the mixed gas.

14. The iontophoresis method according to claim 12, wherein the sample placed in the air atmosphere is heated in the step of forming the mixed gas containing the sample component.

15. The iontophoresis method according to claim 12, wherein the step of forming the sample component-containing mixed gas includes a sample exchange step of exchanging, under the atmospheric environment, a sample that has been contacted with the mixed gas for a sample that has not been contacted with the mixed gas.

16. The iontophoresis method according to claim 15, wherein the sample exchange step exchanges the contact-treated sample with the untreated sample using a mechanism for automatically exchanging multiple samples.

17. An ionization apparatus for ionizing a sample, comprising a mixed gas generation unit, a sample supply unit, and an interface unit, wherein the mixed gas generation unit generates a mixed gas by mixing argon and nitrogen, the sample supply unit is provided in an atmospheric environment, a sample is placed in the sample supply unit, and the mixed gas discharged from the mixed gas generation unit is brought into contact with the sample to form a mixed gas containing a sample component, the interface unit has an ionization region into which the sample component-containing mixed gas is introduced from the sample supply unit, and the sample component-containing mixed gas is excited by dark discharge in the ionization region to generate sample ions.

18. A method for ionizing a sample, comprising the steps of: mixing argon and nitrogen to generate a mixed gas; discharging the mixed gas into an atmospheric environment; contacting the mixed gas with a sample placed in the atmospheric environment to form a mixed gas containing a sample component; introducing the mixed gas containing a sample component into an ionization region; and exciting the mixed gas containing a sample component in the ionization region by dark discharge to generate sample ions.

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