Mass spectrometer ion introduction device, ion introduction method, mass spectrometry system, mass spectrometry method, ionization device, and ionization method

Abstract

The ion introduction device of the present application is provided with a mixed gas generating section, a sample supply section, and an interface section. The mixed gas generating section generates and discharges a mixed gas of a rare gas and nitrogen. The sample supply section is arranged to contact the mixed gas discharged from the mixed gas generating section with a sample under atmospheric pressure to form a mixed gas containing a sample component. The interface section has a gas discharge port that communicates with an external gas exhaust system, forms a sealed region that communicates with a mass spectrometer, and maintains the sealed region at a negative pressure by the external gas exhaust system. The mixed gas containing the sample component is introduced into the sealed region, the mixed gas containing the sample component is excited and ionized by dark discharge, and the sample component ionized is introduced into the mass spectrometer from a transfer port of the mass spectrometer. The present application provides an ion introduction device that can stably and continuously maintain low voltage dark discharge under atmospheric pressure, is not affected by the surrounding environment, can stably ionize, and can be safely used.

Description

Technical Field

[0001] This invention relates to a method and apparatus for atmospheric pressure ionization of samples used in mass spectrometry analysis. Background Technology

[0002] Mass spectrometry is an indispensable method in the analysis of various substances. In recent years, atmospheric pressure ionization (environmental ionization) has developed rapidly. This method can achieve ionization in an atmospheric atmosphere without special sample preparation and pretreatment of the target sample, thus enabling real-time in-situ mass spectrometry analysis.

[0003] For example, methods combining helium with glow discharge are known (Patent Document 1, Patent Document 2), but in recent years, the supply stability of helium used as a carrier gas has been problematic. As an alternative to helium, a method combining nitrogen with corona discharge has been developed (Patent Document 3). However, due to side reactions caused by nitrogen (N2) free radicals, it is difficult to qualitatively identify unknown substances. Furthermore, discharge methods using hydrogen pose safety hazards because hydrogen is a flammable gas. Some studies have also attempted methods without using a special carrier gas (Patent Document 5). However, this method utilizes continuous discharge accompanied by luminescence, and is affected by nitrogen free radicals, exhibiting the same technical problems as Patent Document 3.

[0004] Furthermore, all known atmospheric pressure ionization methods employing discharge require the application of high voltages. For example, in related methods using helium (Patent Document 1, Patent Document 2), the DART method requires approximately 5 kV, the DCBI method requires approximately 3 kV, and the APCI method requires approximately 3 kV; even Patent Document 5, which does not use a carrier gas, requires a high voltage of 2.5 kV or higher.

[0005] Patent document 4 discloses a method for ionizing a sample using dark discharge. This method utilizes a discharge without luminescence, i.e., dark discharge, which is generated by applying a voltage to argon gas in an atmospheric atmosphere. Although dark discharge can be generated under low voltage (1.8 kV and above), it is difficult to maintain a stable dark discharge state during the sample ionization process, which has become a technical problem that urgently needs to be solved.

[0006] Patent Document 1: International Publication No. WO2009 / 009228 Patent Document 2: International Publication No. WO2010 / 075769 Patent Document 3: US Patent No. 7977629B2 Patent Document 4: Japanese Patent No. 6382166 Patent document 5: Japanese Patent No. 7453642.

[0007] In the technical approach of applying voltage to argon gas under atmospheric conditions to achieve sample ionization via dark discharge, there is an urgent need in the industry to develop an ionization device that can stably maintain dark discharge at low voltages and achieve stable ionization of various samples, including gaseous, liquid, and even difficult-to-vaporize solids, unaffected by nitrogen free radicals. Furthermore, there is also an urgent need to develop an ionization device that uses a stable, safe, low-cost, and easy-to-use carrier gas. Summary of the Invention

[0008] The present invention is constituted as follows: (1) An ion introduction device for introducing ions into a mass spectrometry analyzer, the ion introduction device comprising a mixed gas generating section, a sample supply section, and an interface section; the mixed gas generating section mixes argon and nitrogen to generate a mixed gas; the sample supply section is disposed in an atmospheric atmosphere; a sample is disposed in the sample supply section, such that the mixed gas discharged from the mixed gas generating section comes into contact with the sample to form a mixed gas containing sample components; the interface section is provided with an exhaust port communicating with an external exhaust system, and is tightly attached to a surface of the mass spectrometry analyzer to form an ionization region; the ionization region is maintained at a negative pressure lower than the atmospheric atmosphere by the external exhaust system; within the ionization region, the mixed gas containing sample components is introduced from the sample supply section, and the mixed gas containing sample components is excited by dark discharge to generate sample ions; the sample ions are introduced from the ionization region into the mass spectrometry analyzer via the ion transfer port of the mass spectrometry analyzer.

[0009] (2) Based on (1), the ion introduction device of the present invention further comprises: a discharge electrode is provided between the introduction path of the mixed gas containing sample components and the ion transfer port in the ionization region; a dark discharge is generated between the discharge electrode and the ion transfer port to generate sample ions from the sample components in the mixed gas containing sample components. (3) In addition, based on (2), the iontophoresis device of the present invention is characterized in that: the discharge electrode, except for the front end, is covered by an insulator; (4) Furthermore, based on (2), the ion import 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) Based on (1), the ion-importing device of the present invention is characterized in that: in the mixed gas generated by the mixed gas generating unit, the volume ratio of argon is more than 2% and less than 67%, preferably more than 17% and less than 25%; (6) In addition, based on (1), the mixed gas generating unit also has a mechanism for heating the mixed gas; (7) In addition, based on (1), the sample supply unit also has a mechanism for heating the sample; (8) Based on (1), the ion import device of the present invention is characterized in that: the sample supply unit is equipped with a sample container replacement mechanism, which can accommodate multiple sample containers containing samples. (9) In addition, based on (1), the sample container replacement mechanism can continuously and automatically replace multiple sample containers; (10) Based on (1), the ion introduction device of the present invention is characterized in that: the ionization region maintains a higher pressure than the mass spectrometry analysis device, and the gas flow passes through the mixed gas generation unit, the sample supply unit and the ionization region in sequence before flowing into the mass spectrometry analysis device.

[0011] (11) A mass spectrometry analysis system for ionizing a sample and introducing it into a mass spectrometry analysis device for mass analysis, the mass spectrometry analysis system comprising a mixed gas generation unit, a sample supply unit, and an interface unit; the mixed gas generation unit mixes argon and nitrogen to generate a mixed gas; the sample supply unit is disposed in an atmospheric atmosphere; a sample is disposed in the sample supply unit, so that the mixed gas discharged from the mixed gas generation unit comes into contact with the sample to form a mixed gas containing sample components; the interface unit is provided with an exhaust port communicating with an external exhaust system, and is tightly attached to a surface of the mass spectrometry analysis device to form an ionization region; the ionization region is maintained at a negative pressure lower than the atmospheric atmosphere by the external exhaust system; within the ionization region, the mixed gas containing sample components is introduced from the sample supply unit, and the mixed gas containing sample components is excited by dark discharge to generate sample ions; the sample ions are introduced from the ionization region through the ion transfer port of the mass spectrometry analysis device to the mass spectrometry analysis device, thereby performing mass analysis.

[0012] (12) An ion introduction method for introducing ions into a mass spectrometry analyzer, comprising the following steps: mixing argon and nitrogen to generate a mixed gas; discharging the mixed gas into the atmosphere; contacting a sample disposed in the atmosphere with the mixed gas to form a mixed gas containing sample components; introducing the mixed gas containing sample components into an ionization region, the ionization region being maintained at a negative pressure below the atmosphere 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 the mass spectrometry analyzer.

[0013] (13) Based on (12), the ion introduction method of the present invention further includes: after the step of generating the mixed gas, an additional step of heating the mixed gas is added; (14) Furthermore, based on (12), in the step of forming the mixed gas containing the sample components, the sample disposed in an atmospheric atmosphere is heated; (15) Based on (12), the ion introduction method of the present invention further includes a sample replacement step: in the step of forming the mixed gas containing the sample components, the sample that has been in contact with the mixed gas and the sample that has not been in contact with the mixed gas are replaced in an atmospheric atmosphere. (16) Furthermore, based on (15), the sample replacement step replaces the sample that has completed the contact treatment with the sample to be treated by means of a mechanism that can automatically replace multiple samples.

[0014] (17) An ionization apparatus for ionizing a sample, the ionization apparatus comprising a mixed gas generating section, a sample supply section, and an interface section; the mixed gas generating section mixes argon and nitrogen to generate a mixed gas; the sample supply section is disposed in an atmospheric atmosphere; a sample is disposed in the sample supply section, such that the mixed gas discharged from the mixed gas generating section comes into contact with the sample to form a mixed gas containing sample components; the interface section has an ionization region, and the mixed gas containing sample components is introduced into the ionization region from the sample supply section; in the ionization region, the mixed gas containing sample components is excited by dark discharge to generate sample ions.

[0015] (18) In addition, an ionization method for ionizing a sample includes the following steps: mixing argon and nitrogen to generate a mixed gas; discharging the mixed gas into an atmospheric atmosphere; contacting the sample disposed in the atmospheric atmosphere with the mixed gas to form a mixed gas containing sample components; introducing the mixed gas containing sample components into an ionization region; and exciting the mixed gas containing sample components in the ionization region by dark discharge to generate sample ions.

[0016] According to the present invention, by using a carrier gas composed of argon and nitrogen, which are stable and non-flammable inert gases, an ionization method for achieving ionization by stable dark discharge under low voltage conditions can be provided, as well as a simple and low-cost ion introduction device and ion introduction method for introducing ions into a mass spectrometry analysis device. In addition, by heating the sample, it is possible to achieve the ionization of substances such as high-boiling-point samples that cannot be achieved by existing dark discharge ionization technology. Furthermore, heating the carrier gas and / or the sample can enhance the detection sensitivity of mass spectrometry analysis. Attached Figure Description

[0017] Figure 1 A flowchart illustrating the steps of the ion importation method for mass spectrometry analysis of the present invention; Figure 2 A schematic diagram illustrating the structure of the ion-importing device for mass spectrometry analysis of the present invention; Figure 3 A cross-sectional view showing the ion-importing device for mass spectrometry analysis of the present invention. Figure 3 It is a cross-sectional view including the mixed gas flow path and the mixed gas inlet path containing the sample components; Figure 4 This is a schematic diagram showing the state of an ionization unit installed in a mass spectrometer. The ionization unit integrates a mixed gas generation unit, a sample supply unit, and an interface unit. The ionization unit is installed in the mass spectrometer via a hinge. Figure 5 A cross-sectional view showing the mixed gas flow path within the mixed gas generation section and the mixed gas introduction path containing the sample components; Figure 6 Observing from another direction Figure 4 A schematic diagram of an iontophoresis device; Figure 7 This diagram illustrates an ionization unit in an open state relative to the mass spectrometer. The ionization unit consists of a mixed gas generation section, a sample supply section, and an interface section, and is connected to the mass spectrometer via a hinge, and is in an open state. Figure 8 Enlarged view of the interface section; Figure 9 A schematic diagram showing the installation status of the ionization unit and the mass spectrometer, clearly indicating the ionization region; Figure 10 A schematic diagram of an ion introduction device equipped with a sample heating mechanism; Figure 11 A schematic diagram of an ion introduction device having a cover and a sample container exchange mechanism; Figure 12 Remove Figure 11 A state diagram of the upper part of the cover section; Figure 13 A cross-sectional view including the mixed gas flow path and the mixed gas inlet path containing the sample components; Figure 14 An example graph showing the relationship between heating temperature and mass spectrometry analysis intensity; Figure 15 Tables showing the results of Examples 1 to 8 and Comparative Examples 1 to 4; Figure 16 A graph showing the results of Example 9-1; Figure 17 A graph showing the results of Example 9-2; Figure 18 A schematic diagram showing the integration of the ionization unit and the mass spectrometer. Detailed Implementation

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

[0019] In this specification, the gas containing the sample components is also referred to as a mixed gas.

[0020] The dark discharge referred to in this invention refers to a discharge that produces light emission without the presence of visible light when a low voltage is applied to the carrier gas. In other words, the dark discharge of this invention refers to a state in which, although no visible light emission is produced when a voltage is applied between the needle electrode and the counter electrode and the current value is measured, the current flows stably (the current variation is within ±50% of the average current value).

[0021] The present invention is characterized by using a mixture of argon and nitrogen as the carrier gas for the sample ions. The argon-nitrogen mixture of the present invention refers to argon containing nitrogen. Through in-depth research, the inventors have discovered that using the argon-nitrogen mixture under low voltage conditions can excite argon without luminescence. The inventors have further discovered that by using the argon-nitrogen mixture of the present invention, no nitrogen free radicals are generated, and dark discharge can be stably maintained even in the presence of sample components, thereby enabling continuous ionization.

[0022] In this invention, the voltage that generates dark discharge is preferably in the range of 1.8kV to 3.0kV. When the voltage exceeds 3.0kV, dark discharge without light emission will not occur, but discharge with light emission will occur. On the other hand, when the voltage is below 1.8kV, no discharge will occur.

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

[0024] In this invention, in order to ionize the sample components through dark discharge, the current needs to be set to between 0.1 μA and 1.0 μA. Dark discharge will not occur if the current is less than 0.1 μA, and it becomes unstable if it exceeds 1.0 μA. That is, the current value at which dark discharge is stably maintained is between 0.1 μA and 1.0 μA.

[0025] The steps of the present invention will be described using Figure 1. Figure 1 is a schematic diagram of the steps of the ion introduction method for introducing ions into a mass spectrometry analyzer according to the present invention. First, (1) a mixed gas consisting of argon and nitrogen is generated. (2) The mixed gas is heated as needed. Next, (3) the mixed gas at room temperature or heated is discharged into an atmospheric atmosphere containing moisture. Then, (4) the discharged mixed gas is brought into contact with a sample disposed in the atmospheric atmosphere containing moisture to form a mixed gas containing sample components. (5) The mixed gas containing sample components is introduced into an ionization region under reduced pressure. (6) In the ionization region, argon in the mixed gas containing sample components is excited by dark discharge without luminescence under reduced pressure, and sample ions are generated from the sample components by means of the mediation of the excited argon and moisture. Afterward, (7) the mixed gas containing the sample ions is introduced into a mass spectrometry analyzer for mass determination.

[0026] In the sample ionization process of this invention, since moisture in the atmospheric atmosphere participates in the reaction, the sample needs to be placed in an atmospheric atmosphere containing moisture. Moisture in the atmosphere is considered sufficiently present under typical laboratory conditions (humidity 20 to 85%). This is evident from the fact that atmospheric pressure (normal pressure) ionization methods have been practically applied in the past. Any environment suitable for these ionization methods is acceptable.

[0027] In this invention, the "sample" can be any substance capable of generating ions that can be measured by a mass spectrometer, regardless of its state (solid, liquid, gas, etc.). In particular, metal complexes such as titanium phthalocyanine, which are difficult to measure in conventional methods, are also applicable. Furthermore, in principle, no pretreatment is required; simply placing the sample in the mixed gas is sufficient. The "sample composition" in this invention refers to the substance generated by the sample through contact with the mixed gas, including any state such as sample vaporization, atomization, or becoming droplets or microparticles.

[0028] In this invention, nitrogen is present in the mixed gas, but unlike nitrogen-excited (100% nitrogen) ionization steps, argon is excited in the ionization region with an excitation energy lower than that required to excite nitrogen molecules. This excited argon ionizes clusters of water molecules in the atmosphere. These water molecule clusters efficiently ionize the sample, thus suppressing byproducts originating from nitrogen radicals. Therefore, this invention can suppress the generation of sample fragments (decomposition components) and can gently and efficiently ionize samples that were previously difficult to measure.

[0029] Figure 2 is a schematic diagram illustrating the ion introduction device for introducing ions into a mass spectrometry analysis apparatus according to the present invention. The ion introduction device includes a mixed gas generation unit 100 for performing steps (1) and (2), a sample supply unit 200 for performing step (4), and an interface unit 300 for performing step (6). 100, 200, and 300 are integrated to form an ionization unit 900. In addition, the means in the interface unit 300 for performing step (6) is also referred to as an ionization means (the same applies below).

[0030] The mixed gas generating unit 100 includes a mixed gas generating mechanism 11 for mixing argon and nitrogen, and a gas heating mechanism 12 for heating the mixed gas. Argon and nitrogen are introduced into the mixed gas generating mechanism 11 to generate a mixed gas of argon and nitrogen (hereinafter referred to as "mixed gas"). The mixed gas is heated in the gas heating mechanism 12. For simplicity, a heater 122 can be used for heating the gas. The generated mixed gas 123, with or without heating, is discharged from the mixed gas generating unit 100 and sent to the sample supply unit 200.

[0031] In the sample supply unit 200, under atmospheric conditions 22, the mixed gas 123 comes into contact with the sample 21 to generate a sample component. The mixed gas 123 mixes with the sample component 21 and the atmospheric conditions 22, thereby forming a sample component containing the mixed gas 23. This sample component containing the mixed gas 23 is then sent to the interface unit 300.

[0032] An ionization region 31 is provided in the interface section 300. In this ionization region, a voltage is applied to the discharge electrode 34 to generate a dark discharge. Through this dark discharge, only the argon gas in the sample component mixed gas 23 is excited. Through this excited argon gas, the sample is ionized via water molecule clusters. The sample ions containing the ionized sample components in the sample-containing mixed gas 37 are sent to the mass spectrometer 600 for mass determination.

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

[0034] The structure of the mixed gas generating unit 100 in this invention (though not particularly limited) includes at least a mixed gas generating mechanism 11 for mixing argon and nitrogen to generate a mixed gas, and also includes, as needed, a mixed gas heating mechanism 12 for heating the mixed gas.

[0035] While dark discharge can be generated when using argon (100%), maintaining this dark discharge state and ensuring its stability is a challenge. This is believed to be because, with 100% argon, for example, the evaporation of the sample can alter the conductivity near the electrodes, causing a decrease in resistance and generating overcurrent, thus making it impossible to maintain the dark discharge state. In this invention, a mixture of argon and nitrogen is used as the carrier gas. When this mixture is used as the carrier gas, the dark discharge is stably maintained, and the sample components can be continuously ionized.

[0036] In Figure 3, the mixed gas generating mechanism 11 is extremely simple, requiring only a structure capable of mixing argon and nitrogen. It at least includes an argon inlet path 111, a nitrogen inlet path 112, and a mixed gas outlet path 113 for argon and nitrogen. In a very simple manner, this mixed gas generating mechanism 11 can be implemented by combining T-shaped, V-shaped, or U-shaped pipes formed from resin tubing, such as polytetrafluoroethylene (PTFE), or metal tubing.

[0037] A mixed gas 114, generated by mixing argon and nitrogen, is sent from the mixed gas outlet 113 to the mixed gas flow path 121. A mixed gas heating mechanism 12 is provided on the mixed gas flow path 121. In this mixed gas heating mechanism 12, a heater 122 is arranged around the mixed gas flow path 121 to heat the mixed gas as needed. Regardless of whether it is heated, the mixed gas is discharged from the mixed gas outlet 13 as mixed gas 123 to the sample supply section 200.

[0038] In the argon and nitrogen mixture of the present invention, the argon is mixed in a volume ratio ranging from 2% to 67%. For stable dark discharge, a volume ratio of 10% to 30% is preferred; and for maintaining stable dark discharge unaffected by atmospheric conditions and the sample, a volume ratio of 17% to 25% is particularly preferred. The volume ratio of the argon is controlled by adjusting the flow rate. Using these argon and nitrogen mixtures 123, stable dark discharge can be maintained, and continuous ionization is possible.

[0039] The flow rates of argon and nitrogen can be adjusted and controlled using general pressure regulating valves, without particular limitation. Alternatively, a known gas flow meter can be used for precise control based on the sample condition, atmospheric conditions of the sample supply system (described later), and other relevant factors. The flow rates of argon and nitrogen are displayed by the flow meter, and the displayed flow rates can be adjusted using a needle valve. The resulting argon-nitrogen mixture 114 exits from the mixed gas outlet 113, flows through the mixed gas flow path 121, and is introduced into the sample supply unit 200 as mixed gas 123. The flow rate of the mixed gas 114 is determined by the relationship between the pressures of the sample supply unit 200 (approximately atmospheric pressure), the ionization region 31 (maintained at a negative pressure relative to the sample supply unit 200 via an exhaust system connected to this region), and the mass spectrometry analyzer 600 (further maintained at a reduced pressure via the exhaust system of the analyzer itself).

[0040] In Figure 3, the mixed gas 123 discharged from the mixed gas generation unit 100 to the sample supply unit 200 comes into contact with the sample in the sample supply unit 200, forming a sample component containing mixed gas 23. This sample component containing mixed gas 23 is introduced into the ionization region 31 via the sample component containing mixed gas inlet path 35. The ionization region 31 includes a discharge electrode 34 and an exhaust port 32 connected to an external exhaust system. Through the external exhaust system connected to the exhaust port 32, the atmosphere within the ionization region 31 is exhausted and controlled to a predetermined pressure. The atmosphere in the sample supply unit 200 is opened to the atmospheric atmosphere, reaching approximately atmospheric pressure. Therefore, the pressure within the ionization region 31 and the pressure in the sample supply unit 200 are in a relationship of "pressure in the sample supply unit 200 > pressure in the ionization region 31". On the other hand, the internal pressure of the mass spectrometry analyzer 600 body is regulated by the exhaust system of the apparatus body. The gas suction rate (exhaust rate) of a typical 600-type mass spectrometer varies depending on the device, ranging from approximately 0.5 to 5 L / min. An external vacuum exhaust unit can further increase the suction rate to approximately 10 L / min. The pressure within the ionization region 31 is consistently higher than the pressure within the mass spectrometer 600, maintaining a relationship of "pressure within the ionization region 31 > pressure inside the mass spectrometer 600". Through this pressure relationship, sample ions are naturally introduced from the ionization region 31 into the mass spectrometer 600. Therefore, a relationship of "pressure in the sample supply unit 200 > pressure in the ionization region 31 > pressure inside the mass spectrometer 600" is established between the sample supply unit 200, the interior of the ionization region 31, and the interior of the mass spectrometer 600.

[0041] The flow rate of the sample component containing the mixed gas 23 introduced into the ionization region 31 also affects the pressure within that region. This flow rate depends on the flow rate of the mixed gas 123 discharged to the sample supply unit 200. If the flow rate of the mixed gas 123 is less than a specified range, sensitivity will decrease. This is because the sample component is not sufficiently mixed with the mixed gas 123 in the sample supply unit 200 and is diluted by the surrounding atmospheric atmosphere 22. On the other hand, if the flow rate of the mixed gas 123 exceeds the specified range by a significant amount, sensitivity will also decrease. This is because, under these conditions, the sample component is not sufficiently mixed with the moisture-containing atmospheric atmosphere 22 before the sample component containing the mixed gas 23 reaches the sample component containing the mixed gas inlet path 35, thus hindering the sufficient mixing of moisture and sample necessary for ionization. Furthermore, excessive gas will unnecessarily pressurize the ionization region 31, placing a load on the vacuum state of the mass spectrometer 600. Simultaneously, it will also cause a shortened lifespan of the device due to excessive gas.

[0042] In this invention, a gas heating mechanism 12 can be provided in the mixed gas generation unit 100. This allows the mixed gas 114 of argon and nitrogen to be heated as needed. For example, a heater 122 can be provided around the mixed gas flow path 121 as the gas heating mechanism 122. Specifically, heating can be achieved by using a metal pipe for the mixed gas flow path 121 and surrounding it with a ceramic heater.

[0043] The differences in mass spectrometry results were observed between the case where the heater 122 (without using the gas heating mechanism 12) was not used to heat the mixed gas, and the case where the heater 122 was used to heat the argon and nitrogen mixed gas. The results showed that, compared to the case where the mixed gas was not heated, heating the mixed gas resulted in fewer impurity peaks, and the target substance peaks were relatively easier to observe, thus improving analytical sensitivity. (This is explained in Examples 9-1 and 9-2 below.)

[0044] In this invention, when heating the mixed gas, the set temperature of the heater 122 (though not particularly limited) can generally be set in the range of 10°C to 600°C. To realize the effect of heating the carrier gas, it is preferable to heat it to above room temperature, for example, in the range of 50°C to 500°C. Considering factors such as heater lifespan, it is particularly preferable to set it 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. That is, a gaseous sample can be supplied from the outside through a tube of appropriate diameter and directly mixed with the mixed gas 123 and the atmospheric atmosphere 22. There are no particular limitations on liquid and solid samples or mixtures thereof. For example, the sample can be coated on the front end of a glass rod and placed in the flow path of the mixed gas 123, or it can be continuously supplied from the outside through a capillary tube (thin tube).

[0046] Alternatively, for liquid or solid samples, a container can be placed within the atmospheric atmosphere 22 inside the sample supply section 200, and the sample can be contained therein and exposed to the atmospheric atmosphere. The sample inside the container is vaporized or atomized, or becomes droplets or particles, through the flow of heated or unheated mixed gas 123, thus generating sample components. These sample components mix with the mixed gas 123 and the atmospheric atmosphere 22, resulting in a sample component containing the mixed gas 23. Furthermore, heating the container can also promote the generation of sample components.

[0047] Figure 4 This is a diagram illustrating another embodiment of the iontophoresis device of the present invention. Figure 4 This diagram clearly shows the positional relationships of the mixed gas generating unit 100 (equipped with a mixed gas generating mechanism 11 and a gas heating mechanism 12), the sample supply unit 200, the interface unit 300, and the mass spectrometry analysis device 600. Additionally, Figure 4 The diagram shows the configuration of the sample stage 212 and the sample container 211 in the sample supply unit 200.

[0048] exist Figure 4 In this configuration, a mixed gas generation unit 100, a sample supply unit 200, and an interface unit 300 are mounted on a substrate 91. Thus, units 100, 200, and 300 are integrally formed to create an ionization unit 900. Furthermore, in... Figure 4 In this figure, the mass spectrometry analysis apparatus 600 is schematically illustrated. Furthermore, in the following figures, the mass spectrometry analysis apparatus 600 is not shown in its entirety, but only its main parts are illustrated. Figure 4 In this configuration, the ionization unit 900 is mounted to the mass spectrometry analyzer 600 using hinges 36a and 36b.

[0049] Figure 5 Is Figure 4 The diagram shows the surface of the mixture gas flow path 121 within the mixture gas generation section 100 and the sample component mixture gas inlet path 35 provided at the interface section 300 when cut. That is, in Figure 5 In the diagram, the mixed gas flow path 121 and the sample composition mixed gas inlet path 35 are shown in cross-section, and the surrounding structures are also shown in cross-section. Figure 5In the mass spectrometer, an ion transfer port 61 of the mass spectrometer is disposed on the outer wall surface 62 of the mass spectrometer, and one side 62 of the mass spectrometer forms an ionization region 31 with the interface portion 300.

[0050] Figure 5 The gas mixture generating unit 100 includes a gas mixture generating mechanism 11 and a gas heating mechanism 12, and the gas heating mechanism 12 includes a heater 122 capable of heating the gas mixture. Figure 5 The relative positions of the sample stage 212 and the sample container 211 in the sample supply unit 200 are also shown.

[0051] Mixed gas 123 is discharged from the mixed gas generating unit 100 to the sample supply unit 200 via the mixed gas flow path 121. The discharged mixed gas 123 comes into contact with the sample in the sample container 211, generating the components constituting the sample, i.e., the sample component. This sample component mixes with the mixed gas 123 and the atmospheric atmosphere 22 to form a sample component containing mixed gas 23. This sample component containing mixed gas 23 is introduced into the ionization region 31 via the sample component containing mixed gas introduction path 35.

[0052] When using liquids, solids, or mixtures thereof as samples, it is possible to use Figure 5 The sample container 211 is used. The sample is placed in the sample container 211 and positioned on the sample stage 212 located within the sample supply unit 200. The sample within the sample container 211 is vaporized or atomized, or becomes droplets or microparticles, depending on the flow and temperature of the mixed gas 123, thereby generating a sample component. This sample component mixes with the mixed gas 123 and the atmospheric atmosphere 22, resulting in a sample component containing the mixed gas 23. The sample container 211 can be any container capable of holding a liquid or solid sample, and can be a commonly used resin or metal container.

[0053] Additionally, as described later, a sample heating mechanism can be provided on the sample stage 212 to promote the vaporization, atomization, spraying, and microparticle formation of liquid or solid samples. When the sample in the sample container 211 is heated by the sample heating mechanism on the sample stage 212, the mixed gas 123 may be supplied at room temperature without using the gas heating mechanism 12. Alternatively, the heated mixed gas 123 may be used in conjunction with the sample heating mechanism.

[0054] Figure 6 It is a different perspective. Figure 4 A diagram of an iontophoresis device. In this diagram, [the device is shown in the image]. Figure 4Similarly, the mixed gas generation unit 100, the sample supply unit 200, and the interface unit 300 are mounted on the substrate 91. The 100, 200, and 300 are integrally formed on this substrate 91 to create an ionization unit 900. This integrally formed ionization unit 900 is mounted to the mass spectrometry analyzer 600 via hinges 36a (and 36b, not shown).

[0055] Figure 7 Is Figure 6 The diagram shows the opening and closing state of the ionization unit 900 relative to the mass spectrometry analyzer 600. The mixed gas generation unit 100, the sample supply unit 200, and the interface unit 300 are integrally formed by the substrate 91, constituting the ionization unit 900. The opening and closing of the ionization unit 900, which is integrally formed by the substrate 91, and the mass spectrometry analyzer 600 is indicated by the opening and closing direction 38 of the interface unit. Figure 7 The diagram shows the interface 300 constituting the ionization unit 900 connected to the mass spectrometry analysis device 600 via hinges 36a and 36b, with the ionization region open.

[0056] Figure 8 Viewed from above Figure 7 The diagram shows the state of the graph. Figure 8 A detailed explanation is provided. Figure 8 In the ionization unit 900, the interface portion 300 has a recess 31a. When the ionization unit 900 and the mass spectrometry analyzer 600 are closed along the opening and closing direction 38 of the interface portion, the outer wall surface 62 of the mass spectrometry analyzer 600 comes into contact with the interface portion 300, and the recess 31a becomes an internal space, thereby forming an ionization region 31. Figure 9 This indicates the state. Additionally, Figure 9 The details will be explained later.

[0057] exist Figure 8 In this configuration, the interface portion 300 is constructed of a metal component, preferably a lightweight and highly conductive aluminum component, and is connected to the outer wall surface 62 of the mass spectrometry analyzer 600 via a conductive component. The interface portion 300 and the outer wall surface 62 are reliably electrically connected via the conductive component.

[0058] exist Figure 8 In the interface portion 300, the recess 31a is typically a generally cylindrical space. An exhaust port 32 communicating with an external exhaust system and a voltage unit 33 for dark discharge are provided on the side region of this generally cylindrical space. The interface portion 300 also has a sample composition mixed gas inlet path 35 on the bottom surface of the generally cylindrical recess 31a, opposite to the mass spectrometry analyzer 600. Figure 8 In the middle, the recess 31a is connected to the sample supply section 200 in the atmospheric atmosphere via the sample component containing mixed gas inlet passage 35.

[0059] Figure 9 Is Figure 8 In the diagram, the ionization unit 900 and the mass spectrometry analysis device 600 are closed along the opening / closing direction 38, thereby forming the ionization region 31. Figure 9 In order to clearly define the ionization region 31, a cross-sectional line is applied to the ionization region. The interface portion 300 integrated with the ionization unit 900 has a sample composition mixed gas inlet 35 and an exhaust port 32 connected to an external exhaust system.

[0060] exist Figure 9 In this process, the ionization region 31 needs to be sealed by the surface of the interface 300 that contacts the outer wall surface 62 of the mass spectrometry analyzer 600. The sealing method is not particularly limited; for example, the two can be sealed via an O-ring. The material of the O-ring is not particularly limited. Figure 9 In this state, the ionization region 31 becomes an electromagnetically shielded space, capable of dark discharge unaffected by external influences. The conductive components can most simply be the aforementioned hinges 36a and 36b. Since the ionization region 31 is located adjacent to the mass spectrometry analyzer 600, measures must be taken to prevent contamination of the mass spectrometry analyzer 600. Therefore, 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 assembled mass spectrometry analyzer 600, but as previously mentioned, a compact structure is required to form a clean region. Typically, Figure 8 The roughly cylindrical space formed by the recess 31a shown has an inner diameter of 80mm to 100mm at the bottom and a depth (height) of approximately 50mm to 80mm. The combined space has a volume of approximately 200 to 600 × 10³ mm³.

[0062] exist Figure 9In this configuration, the ionization region 31 is isolated from the external atmosphere, except that it is connected to the sample supply unit 200 in the atmospheric atmosphere via the sample component mixed gas inlet 35, to the mass spectrometer 600 body via the ion transfer port 61 of the mass spectrometer, and to the external exhaust system via the exhaust port 32. Through the external exhaust system connected to the exhaust port 32 of the interface unit 300, the ionization region 31 is vented at a flow rate of approximately 1 to 40 L / min, ideally approximately 10 L / min. This venting maintains the ionization region 31 at a negative pressure of approximately 1 to 70 kPa lower than atmospheric pressure, ideally approximately 10 kPa. The external exhaust system can use any known venting method and is not particularly limited. For example, a diaphragm pump or similar device can be used to vent the ionization region.

[0063] The atmospheric atmosphere 22 of the sample supply unit 200 is approximately at atmospheric pressure. In contrast, the ionization region 31, which is vented by the external exhaust system, is at a negative pressure lower than atmospheric pressure. Through this pressure difference, the sample component containing the mixed gas 23 formed in the sample supply unit 200 is introduced into the ionization region 31. Furthermore, through the exhaust from the external exhaust system, the pressure in the ionization region 31 is maintained at a level lower than atmospheric atmosphere 22 (approximately 1 to 70 kPa) and higher than the pressure of the mass spectrometer 600. Thus, the gas flow from the mixed gas generation unit 100 to the sample supply unit 200, then to the ionization region 31, and finally to the mass spectrometer 600 is stably maintained. That is, the pressures of each unit maintain the following relationship: "Sample supply unit 200 > Ionization region 31 > Mass spectrometer 600".

[0064] use Figure 5 The dark discharge of the present invention will be described. Figure 5 In this process, a discharge electrode 34 (for dark discharge) is provided at the front end of the voltage unit 33 in the ionization region 31. The sample component introduced into the ionization region 31 contains argon gas in the mixed gas 23, which is excited by dark discharge. Through the mediating interaction between the excited argon gas and the moisture in the mixed gas 23, the sample component in the mixed gas 23 is ionized.

[0065] exist Figure 5 In the ionization region 31, the discharge electrode 34 (for dark discharge) is positioned between the sample component mixed gas inlet path 35 (from the sample supply unit 200) and the ion transfer port 61 of the mass spectrometer 600. Figure 5In this configuration, the ion transfer port 61 serves as the counter electrode of the discharge electrode 34. A voltage is applied between the ion transfer port 61, which acts as the counter electrode, and the discharge electrode 34, thereby generating a dark discharge. The ion transfer port 61, which serves as the counter electrode for the dark discharge, is kept at the same potential as the interface portion 300 and the outer wall surface 62 of the mass spectrometry analyzer 600 via a conductive member, thereby preventing electromagnetic phenomena other than those described above.

[0066] The discharge electrode 34 is made of a needle-shaped metal material. Preferably, it is a material whose tip is easy to machine, exhibits minimal wear due to dark discharge, and has high durability. In this invention, needle-shaped stainless steel is used.

[0067] Between the discharge electrode 34 and the counter electrode 61, it is undesirable for any current other than discharge current (leakage current) to occur. Therefore, it is necessary to cover the portion of the discharge electrode 34 other than the front end with an insulator. As this insulator, a material with high insulation properties, which does not produce decomposition products even under high voltage, and which is difficult to charge. For example, resin materials such as silicone, polyimide, and PEEK (polyether ether ketone) are preferred.

[0068] Compared to conventional atmospheric pressure ionization methods, the dark discharge of this invention is performed at a lower voltage. That is, at a low voltage, if a mixture of argon and nitrogen is used as the carrier gas, a stable dark discharge can be maintained even in the presence of sample components.

[0069] The voltage required for dark discharge, which is a discharge without accompanying light emission, is lower than the voltage required for conventional discharges accompanied by light emission. Even in a mixture of argon and nitrogen gases, if the voltage required for dark discharge is applied, the dark discharge only excites the argon gas and does not generate nitrogen free radicals. Furthermore, this invention has found that when using a mixture of argon and nitrogen gases, stable dark discharge can be maintained even in the presence of sample components. There are no particular limitations on the applied voltage as long as it falls within the range where dark discharge is stable; it is typically applied within the voltage range of 1.8 kV to 3.0 kV. Above 3.0 kV, no dark discharge occurs, but a discharge accompanied by light emission occurs; below 1.8 kV, the discharge is unstable.

[0070] exist Figure 5In this invention, the electric field strength generated at the front end 34a of the discharge electrode 34 contributes to the generation of dark discharge. This electric field strength varies depending on the shape of the front end of the discharge electrode 34, the distance between the counter electrode 61 and the front end of the discharge electrode 34, the orientation (angle) of the front end of the discharge electrode relative to the counter electrode 61, and the voltage applied to the discharge electrode. After adjusting these conditions, by applying the aforementioned voltage (between 1.8 kV and 3.0 kV), a stable dark discharge without luminescence can be maintained. (Additionally, the counter electrode 61 is typically grounded.)

[0071] As another embodiment of the mass spectrometry analysis apparatus 600, there exists a mass spectrometry analysis apparatus equipped with a voltage unit. One example is shown in… Figure 18 That is, in Figure 18 In this configuration, 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. The ion transfer port 61 and one end of the voltage unit 33 are disposed within this recess 60a. These arrangements are shown in cross-section. The voltage unit 33 is connected to a circuit (not shown) of the mass spectrometer 600, thereby enabling the application of a voltage.

[0072] exist Figure 18 In the recess 60a, a discharge electrode 34 is mounted at one end of the voltage unit 33. On the other hand, the interface portion 300 of the present invention includes a sample component containing a mixed gas inlet 35 and an exhaust port 32 communicating with an external exhaust system; the figure shows a cross-section of the inlet 35 and the exhaust port 32. Furthermore, the interface portion 300 has a recess 31a. Additionally, in... Figure 18 The mixed gas generating unit 100 and the sample supply unit 200 of the present invention are omitted from the illustration.

[0073] exist Figure 18 In this configuration, the interface portion 300 is connected to the mass spectrometry analysis device 600 via hinges 36a and 36b (not shown). When the interface portion 300 and the mass spectrometry analysis device 600 are in a relative position via hinges 36a and 36b, the recess 31a on the interface portion 300 side faces and seals against the recess 60a on the mass spectrometry analysis device side, thereby forming an ionization region 31. Figure 18 In the diagram, the ionization region 31 is shown as a dashed line.

[0074] To form the ionization region 31, the recess 31a of the interface portion 300 is designed to fit the opening size of the recess 60a of the mass spectrometry analyzer. Figure 18 In this invention, the ion-importing device has the advantage of not requiring a voltage unit at the interface and being able to utilize the power supply of a mass spectrometry analysis device. Furthermore, Figure 18The ion implantation device of the present invention can be adapted to the structure of the mixed gas generation unit 100 and the sample supply unit 200 (omitted from the figure).

[0075] In this invention, a heating mechanism for heating the sample can also be provided to promote the generation of sample components from the sample, that is, to promote the vaporization, atomization, spraying, and microparticle formation of the sample. Figure 10 An embodiment is shown in which a heating plate 213 is mounted on a pedestal on which the sample container 211 is arranged. That is, Figure 10 Is Figure 4 The diagram shows the structure in which the heating plate 213 is also used as the sample stage of the sample container 211.

[0076] exist Figure 10 In this process, when heating the sample container 211, a heat-resistant metal container is used as the sample container 211. The sample container 211 is placed on a heating plate 213 for heating. Various types of heating plates, such as resistance heaters and infrared heaters, can be used as the heating plate 213. Figure 10 In this study, a heating plate made of resistance heater is used due to its simple structure, convenient temperature management, and ease of sample exchange (described later). In addition, heating mechanisms other than plate-shaped heating, such as laser heating, can also be used.

[0077] Furthermore, instead of directly heating the sample container 211 by the heating plate 213, a heating mechanism can also be built into the support platform of the sample container to heat the sample container. Figure 10 In this study, from the perspective of thermal efficiency, a flat resistance heater is used as the heating plate 213, and the sample container 211 is directly placed on the heating plate 213 for heating.

[0078] exist Figure 10 In this process, a sample container 211 is placed on a heating plate 213. The sample inside the sample container 211 is heated by applying voltage to the heating plate 213. The heating 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 This is an example of mass spectrometry analysis of solid and liquid samples that are difficult to vaporize or sublime at room temperature. That is, Figure 14 This is a diagram illustrating an example of the signal difference in a mass spectrometer when the sample is not heated versus when the sample is heated.

[0080] exist Figure 10In the process, a solid sample, titanium phthalocyanine, is placed in sample container 211. The change in the mass spectrometry signal over time is observed when a mixed gas at room temperature (i.e., unheated) is exhausted into the atmospheric environment of the sample supply unit 200. No signal is observed when the mixed gas is allowed to flow without heating the sample container 211. That is, there are no sample ions from the sample components in the mass spectrometry analyzer 600. Then, when the sample container 211 is heated, a signal is observed. That is, sample ions from the sample components are introduced into the mass spectrometry analyzer 600.

[0081] Figure 14 This is a schematic diagram showing how the signal from the mass spectrometer changes over time. Figure 14 The horizontal axis represents the time elapsed from when the sample container was not heated to when it was heated. The vertical axis represents the mass spectrometry signal of the sample ions from the sample components. That is, it can be seen that the solid sample phthalocyanine titanium oxide does not exist in the atmospheric atmosphere when it is not heated, but is generated in the atmospheric atmosphere by heating. In other words, when the sample is heated using the heating plate 213 and sample container 211 of the present invention, it is possible to analyze samples that cannot be analyzed by mass spectrometry at room temperature, especially non-volatile solid or liquid samples that are difficult to vaporize or sublimate at room temperature.

[0082] In addition, when heating the sample, as described above, the unheated room temperature mixed gas 123 can be brought into contact with the sample to form a sample composition containing mixed gas 23. However, when the heated mixed gas 123 is brought into contact with the sample to form a sample composition containing mixed gas 23, better data can be obtained.

[0083] Figure 11 Is Figure 10 The diagram further shows the addition of coated components 41a and 41b, and a sample container exchange mechanism 500 within the structure. That is, Figure 11 This diagram shows that the sample supply unit 200 includes covered parts 41a and 41b and a sample container exchange mechanism 500.

[0084] exist Figure 11 In this sample supply unit 200, there are covering parts 41a and 41b that cover the heating plate 213. The lower part 41b of the covering part also serves as a support for the heating plate 213. The lower part 41b of the covering part is mounted on the substrate 91. The upper part 41a of the covering part can be detached from the lower part 41b of the covering part. When the sample is heated (when voltage is applied to the heating plate 213), the upper part 41a of the covering part covers the heating plate 213 and the sample container 211. When changing the sample container 211, or when arranging the aforementioned sample tube or glass capillary, the upper part 41a of the covering part can also be removed from the sample supply unit 200 for operation.

[0085] By providing the coating components 41a and 41b, the diffusion of the mixed gas, sample components, and sample components containing mixed gas 23 in the sample supply section 200 can be suppressed. Furthermore, the effects of temperature changes and airflow around the device can be mitigated, thereby obtaining stable data. In addition, the danger of the experimenter coming into contact with the heated area during sample heating can be avoided.

[0086] When exchanging sample containers 211, as described above, the upper part 41a of the covered component can be removed for operation; however, a mechanism capable of sequentially and interchangeably supplying multiple samples can also be provided. An embodiment is shown below. Figure 12 .

[0087] Figure 12 It is to remove Figure 11 The state after the upper part 41a of the covered component. Figure 12 The positional relationship between the heating plate 213 and the sample container exchange mechanism 500 is shown more clearly. Multiple samples are respectively housed in their own independent sample containers 51a, 51b, 51c..., arranged, for example, along a column of sample containers 52. The sample containers 51a, 51b, 51c... use the same shape and material for sample processing.

[0088] Figure 13 Is Figure 12 The diagram shows the cross-section of the surface containing the mixed gas flow path 121 and the sample composition containing the mixed gas inlet path 35. Figure 13 In the diagram, the mixed gas generating mechanism 11, the mixed gas heating mechanism 12, and the interface portion 300 are also shown in cross-section. Figure 13 In this example, an example of the sample container exchange mechanism 500 is shown in more detail. In this example, a sample container arrangement direction 52, in which multiple sample containers 51a, 51b, 51c... are arranged, is shown, which intersects with a sample supply discharge direction 53 for exchanging sample containers in order to place or remove them from the heating plate.

[0089] use Figure 13The sample container exchange mechanism 500 will be described. In the sample container exchange mechanism 500, among a plurality of sample containers arranged in a row along the sample container arrangement direction 52, the sample container 51a closest to the heating plate is moved along the sample container arrangement direction 52, and then moved towards the heating plate 213 along the sample supply discharge direction 53, which intersects the sample container arrangement direction 52. After contacting it with the mixed gas 123 on the heating plate 213, it is moved away from the heating plate 213 along the sample supply discharge direction 53. By repeating this series of operations sequentially for sample containers 51a, 51b, 51c…, the sample components of multiple samples can be sequentially ionized and introduced into the mass spectrometry analysis device.

[0090] These movements can most easily be performed manually, but can also be performed using a well-known mechanism not shown. When using this sample container exchange mechanism, the aforementioned disassembly of the upper part 41a of the covered component is not required when exchanging sample containers, which improves the efficiency of sample handling and the overall analytical experiment.

[0091] As an example of the well-known mechanism (not shown), the sample container can also be automatically exchanged. For the sample container 211 disposed on the heating plate 213, when the mass spectrometry analysis or sample ionization is completed, it can be automatically exchanged for the next sample container 51a using a sample container exchange mechanism 500, etc. For example, the sample container can be automatically exchanged using track movement or an automatic operating arm. By further repeating the automatic exchange operation for 51b, 51c… in sequence, a large number of samples can be continuously and automatically measured. Example

[0092] The present invention will now be described in more detail by way of examples and comparative examples, but the present invention is not limited to these examples. The following shows the results of implementing the invention with multiple carrier gas components: [Example 1] Mass spectrometry analysis was performed using an ionization apparatus equipped with the mixed gas generation unit, sample supply unit, and interface unit of the present invention, combined with a mass spectrometry analysis apparatus. In Example 1 and the following paragraphs, the gas (including the mixed gas) containing the sample components and used for ionization is referred to as the carrier gas. In the mixed gas generation unit, the flow rates of argon were controlled at 1.7 L / min and nitrogen at 0.8 L / min, and each gas was introduced separately to generate the carrier gas. The heater temperature in the mixed gas heating mechanism of the mixed gas generation unit was set to 400°C, and the heated carrier gas (argon:nitrogen = 2:1) was discharged at a rate of 2.5 L / min. In the sample supply unit, 0.5 mg of sublimated titanium phthalocyanine oxide powder (manufactured by Tokyo Chemical Industry Co., Ltd.) was placed into a sample cup LF (manufactured by Frontier Lab Co., Ltd.), which served as the sample container. The sample cup LF was rapidly heated to 400°C to vaporize the titanium phthalocyanine oxide, and the sample components were obtained in an atmospheric atmosphere. The ionization region was vented at a rate of 10 L / min to maintain a negative pressure lower than atmospheric pressure, 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 at the interface to ionize the sample components. The generated sample ions were transferred to the mass spectrometer via differential pressure for mass spectrometry analysis. A Shimadzu LCMS-2020 was used as the mass spectrometer. Furthermore, before performing mass spectrometry analysis of the sample components, the heated carrier gas was circulated for 30 minutes to confirm whether the dark discharge changed under this condition compared to the analysis of the sample components. Hereinafter, "stable" refers to a discharge that has not migrated into a form accompanied by luminescence (such as corona discharge, arc discharge, etc.) and can maintain a dark discharge. This definition is used as the criterion for judging the stability of dark discharge. Specifically, the criteria are set as follows: A: The sample composition remained stable for the first 30 minutes before the analysis and remained stable during subsequent analysis. B: The sample composition remained stable for the first 30 minutes, but became unstable during subsequent sample composition measurements. C: Unstable; - No dark discharge occurred.

[0093] [Examples 2 to 8, Comparative Examples 1 to 4] In Example 1, the carrier gas was changed to Figure 15 Mass spectrometry analysis was performed in the same manner as in Example 1, except for the carrier gas described. The flow rate of each carrier gas was set to 2.5 L / min. In the argon and nitrogen mixture, the argon flow rate was set to x L / min and the nitrogen flow rate to y L / min, such that the ratio of x to y was... Figure 15 The ratios shown were used, and x + y = 2.5. The above-mentioned stability of dark discharge was evaluated in experiments conducted in Examples 1 to 8 and Comparative Examples 1 to 4, and the results are summarized in... Figure 15 .Right now, Figure 15 This is a table summarizing the experiments of Examples 1 to 8 and Comparative Examples 1 to 4.

[0094] As demonstrated in Examples 1 to 8 and Comparative Examples 1 to 4, dark discharge occurs when the mass spectrometry is performed using a carrier gas mixture of argon and nitrogen. Furthermore, at a specific ratio, the stability of the dark discharge is good whether only the carrier gas is flowing or when the sample composition is being measured. On the other hand, dark discharge cannot be stably sustained when only argon is used. It was also clarified that no dark discharge occurs when only nitrogen, helium, or hydrogen is used as the carrier gas. According to the present invention, it is possible to replace the expensive and unstable helium with argon, which can be supplied more stably and is relatively inexpensive, for excitation at a low voltage. It is also understood that by using a carrier gas mixed with nitrogen, which is cheaper than argon, a simple and inexpensive mass spectrometry analysis system or method can be provided.

[0095] [Example 9] An ion introduction device equipped with the mixed gas generation section, sample supply section and interface section of the present invention was combined with a mass spectrometry analysis device to conduct a mass spectrometry analysis experiment demonstrating the heating effect of the carrier gas. [Example 9-1] In the mixed gas generation section, the flow rates of argon are controlled at 0.5 L / min and nitrogen at 2.0 L / min, and each gas is introduced separately to generate a mixed gas. The mixed gas is not heated and is discharged from the mixed gas generation section at room temperature as a carrier gas. The discharge rate is the sum of the flow rates of each component gas, i.e., 2.5 L / min. In the sample supply section, a ceramic heater is installed on a heating plate, and a sample cup LF is placed there. 0.5 mg of sublimed titanium phthalocyanine powder is placed in the sample cup LF as the sample. The temperature of the ceramic heater is set to increase from room temperature to 400 °C in 2 minutes (heating rate 200 °C / min) to obtain the sample composition. The ionization region is vented at a flow rate of approximately 10 L / min, and the carrier gas containing the sample composition is introduced into the ionization region. A voltage is applied to the needle electrode in the ionization region located at the interface to excite the argon gas in the carrier gas containing the sample composition. The excitation voltage is set to 2.2 kV. The generated sample ions are introduced into a mass spectrometer for analysis. The mass spectrometer used was a Shimadzu LCMS-9030 (an upgraded version of the 9050). The mass spectrometer settings were as follows: Positive ion mode, m / z range 10–1500. The mass spectrometer was calibrated before the experiment to confirm that the device was in good working order. Figure 16 This is a graph representing the experimental results of Example 9-1. In this experiment, impurity components appeared as impurity peaks, while the parent peak of titanium phthalocyanine was relatively low (low sensitivity).

[0096] [Example 9-2] In Example 9-1, the mass spectrometry analysis experiment was performed under the same conditions as in Example 9-1, except that the mixed gas was heated to a set temperature of 400°C by a heater in the mixed gas generation unit and discharged as a carrier gas from the mixed gas generation unit. In the sample supply unit, the sample was placed and rapidly heated as in Example 9-1 to obtain the sample composition. A carrier gas containing the sample composition was introduced into the ionization region. The argon excitation conditions in the ionization region and the mass spectrometry analysis apparatus were set to the same conditions as in Example 9-1. The mass spectrometry analysis apparatus was calibrated before the experiment, as in Example 9-1, to ensure the apparatus was in good working order. Figure 17 This is a graph showing the experimental results of Example 9-2. In this experiment, it was observed that by contacting with the heated carrier gas, highly volatile impurities were eliminated, and only the peak of titanium phthalocyanine, a non-volatile component, was strongly detected. That is, the sensitivity (S / N ratio) of the mass spectrometry analysis was improved.

[0097] [Example 10] In Example 5, mass spectrometry analysis 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. The peak from aspartic acid (m / z = 134.1) was well detected. Furthermore, the dark discharge stability was A. [Example 11] In Example 5, mass spectrometry analysis 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. The peak from glycine (m / z = 76.1) was well detected. Furthermore, the dark discharge stability was A.

[0098] [Example 12] In Example 5, as a sample, a glass rod was immersed in (R)-(+) limonene (Fujifilm and Koden Chemical), causing the (R)-(+) limonene to adhere to the glass rod. In the sample supply section, the (R)-(+) limonene attached to the glass rod was brought close to the carrier gas discharged from the mixed gas generation section, allowing the vaporized (R)-(+) limonene to be introduced into the ionization region through the gas inlet. Otherwise, mass spectrometry analysis was performed in the same manner as in Example 5. The peak from (R)-(+) limonene (m / z = 137.2) was well detected. Furthermore, the dark discharge stability was A.

[0099] [Example 13] In Example 12, as a sample, a glass rod was immersed in a 0.01% acetonitrile solution of caffeine (Tokyo Chemical Industries) to allow the caffeine to adhere to the glass rod. Otherwise, mass spectrometry analysis was performed in the same manner as in Example 12. The peak from caffeine (m / z = 195.2) was well detected. Furthermore, the stability of dark discharge was A. [Example 14] In Example 12, cholesterol (Tokyo Chemical Industries) was attached to a glass rod as a sample, and mass spectrometry analysis was performed in the same manner as in Example 12. The peak (m / z = 369.4) from cholesterol (M−H2O+1) was well detected. Furthermore, the stability of dark discharge was A.

[0100] In the detailed description of the present invention above, an ion introduction device and an ion introduction method for introducing ions into a mass spectrometry analysis apparatus have been described, but 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 and apparatus for generating ions in an atmospheric atmosphere, and can also be applied to fields other than mass spectrometry analysis. Figure Labels

[0101] 100… Mixed gas generation section, 11… Mixed gas generation mechanism, 111… Argon inlet path, 112… Nitrogen inlet path, 113… Mixed gas outlet path, 114… Mixed gas, 12… Gas heating mechanism, 121… Mixed gas flow path, 122… Heater, 123… Mixed gas, 200… Sample supply section, 21… Sample, 211… Sample container, 212… Sample stage, 213… Heating plate, 22… Atmospheric atmosphere, 23… Sample composition contains mixed gas, 300… Interface section, 31… Ionization region, 31a (interface section) recess, 32… Exhaust port, 33… Voltage unit, 34… Discharge electrode, 34a… Discharge electrode front end, 35… Sample component containing mixed gas inlet path, 36a… Upper hinge, 36b… Lower hinge, 38… Interface opening and closing direction, 41a… Upper part of coated component, 41b… Lower part of coated component, 500… Sample container exchange mechanism, 51a… Sample container, 51b… Sample container, 51c… Sample container, 52… Sample container arrangement direction, 53… Sample supply and discharge direction, 600… Mass spectrometer, 60a… (Mass spectrometer) recess, 61… Ion transfer port of mass spectrometer, 62… Outer wall surface of mass spectrometer, 63… Outer side surface of mass spectrometer, 900… Ionization unit, 91… Substrate.

Claims

1. An ion introduction device for introducing ions into a mass spectrometry analysis apparatus, characterized in that, The ion implantation device includes a mixed gas generation unit, a sample supply unit, and an interface unit. The mixed gas generating unit mixes argon and nitrogen to generate a mixed gas. The sample supply unit is located in an atmospheric environment. A sample is disposed in the sample supply section, and the mixed gas discharged from the mixed gas generation section comes into contact with the sample to form a mixed gas containing the sample components. The interface section has an exhaust port that communicates with an external exhaust system, and it is in close contact with one side of the mass spectrometer to form an ionization region. The ionization region is maintained at a negative pressure below atmospheric pressure by the external exhaust system. In the ionization region, a mixed gas containing sample components is introduced from the sample supply section, and the mixed gas containing sample components is excited by dark discharge to generate sample ions. The sample ions are introduced from the ionization region into the mass spectrometer via the ion transfer port of the mass spectrometer.

2. The iontophoresis device as described in claim 1, characterized in that: A discharge electrode is provided in the ionization region. The discharge electrode is disposed between the mixed gas inlet containing the sample components (from the sample supply section) and the ion transfer port. Dark discharge is generated between the discharge electrode and the ion transfer port to generate sample ions from the sample components in the mixed gas containing the sample components.

3. The iontophoresis device as described in claim 2, characterized in that: Except for the front end, the discharge electrode is covered by an insulator.

4. The iontophoresis device as described in claim 2, characterized in that: The voltage applied between the discharge electrode and the ion transfer port is above 1.8 kV and below 3.0 kV.

5. The iontophoresis device as described in claim 1, characterized in that: In the mixed gas generating section, the volume percentage of argon in the generated mixed gas is 2% or more and 67% or less, preferably 17% or more and 25% or less.

6. The iontophoresis device as described in claim 1, characterized in that: The gas mixture generating unit also includes a mechanism for heating the gas mixture.

7. The iontophoresis device as described in claim 1, characterized in that: The sample supply unit also includes a mechanism for heating the sample.

8. The iontophoresis device as described in claim 1, characterized in that: The sample supply unit is equipped with a sample container exchange mechanism, which can hold multiple sample containers containing samples.

9. The iontophoresis device as described in claim 8, characterized in that: The sample container exchange mechanism can continuously and automatically replace multiple sample containers.

10. The iontophoresis device as claimed in claim 1, characterized in that: The ionization region maintains a higher pressure than the mass spectrometer, and the gas flow passes through the mixed gas generation section, the sample supply section, and the ionization region before flowing into the mass spectrometer.

11. A mass spectrometry analysis system for ionizing a sample and introducing it into a mass spectrometry analysis device for mass analysis, characterized in that, The mass spectrometry analysis system includes a mixed gas generation unit, a sample supply unit, and an interface unit. The mixed gas generating unit mixes argon and nitrogen to generate a mixed gas. The sample supply unit is located in an atmospheric environment. A sample is disposed in the sample supply section, and the mixed gas discharged from the mixed gas generation section comes into contact with the sample to form a mixed gas containing the sample components. The interface section has an exhaust port that communicates with an external exhaust system, and it is in close contact with one side of the mass spectrometer to form an ionization region. The ionization region is maintained at a negative pressure below atmospheric pressure by the external exhaust system. In the ionization region, a mixed gas containing sample components is introduced from the sample supply section, and the mixed gas containing sample components is excited by dark discharge to generate sample ions. The sample ions are introduced from the ionization region into the mass spectrometer via the ion transfer port of the mass spectrometer for mass analysis.

12. An ion introduction method for introducing ions into a mass spectrometry analyzer, characterized in that, Includes the following steps: The steps for mixing argon and nitrogen to generate a mixed gas; The step of releasing the mixed gas into the atmospheric atmosphere; The step of bringing a sample placed in an atmospheric atmosphere into contact with the mixed gas to form a mixed gas containing the sample components; The step of introducing the mixed gas containing the sample components into the ionization region, which is maintained at a negative pressure below atmospheric pressure by an external exhaust system; The step of generating sample ions by exciting the mixed gas containing the sample components through dark discharge in the ionization region; The step of introducing the sample ions from the ionization region into the mass spectrometry analysis device.

13. The iontophoresis method as described in claim 12, characterized in that: After the step of generating the mixed gas, the method further includes a step of heating the mixed gas.

14. The iontophoresis method as described in claim 12, characterized in that: In the step of forming the mixed gas containing the sample components, the sample disposed in an atmospheric atmosphere is heated.

15. The iontophoresis method as described in claim 12, characterized in that: The step of forming the mixed gas containing the sample components includes a sample replacement step: replacing the sample that has been in contact with the mixed gas and the sample that has not been in contact with the mixed gas in an atmospheric atmosphere.

16. The iontophoresis method as described in claim 15, characterized in that: The sample replacement step uses a mechanism that can automatically replace multiple samples to replace the sample that has completed the contact treatment with the sample to be treated.

17. An ionization apparatus for ionizing a sample, characterized in that, The ionization device includes a mixed gas generation unit, a sample supply unit, and an interface unit. The mixed gas generating unit mixes argon and nitrogen to generate a mixed gas. The sample supply unit is located in an atmospheric environment. A sample is disposed in the sample supply section, and the mixed gas discharged from the mixed gas generation section comes into contact with the sample to form a mixed gas containing the sample components. The interface section has an ionization region, and the mixed gas containing the sample components is introduced into the ionization region from the sample supply section. In the ionization region, the mixed gas containing the sample components is excited by dark discharge to generate sample ions.

18. An ionization method for ionizing a sample, characterized in that, Includes the following steps: The steps for mixing argon and nitrogen to generate a mixed gas; The step of releasing the mixed gas into the atmospheric atmosphere; The step of bringing a sample placed in an atmospheric atmosphere into contact with the mixed gas to form a mixed gas containing the sample components; The step of introducing the mixed gas containing the sample components into the ionization region; The step of generating sample ions by exciting the mixed gas containing the sample components through dark discharge in the ionization region.

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