Chemical ionization method and ion molecule reactor

Abstract

The invention relates to a method of chemical ionization for ionizing a sample containing an analyte to be ionized. Therein, a reagent volume (2) contains a ligand compound ion formed from a reagent ion and a dopant. Therein, a sample containing the analyte is introduced into the reagent volume (2) and reacts with the ligand compound ion to form an adduct ion and a neutral by-product, wherein the adduct ion comprises the ionized analyte, i.e. the adduct of the reagent ion and the corresponding analyte. Therein, the reagent ion and the dopant provide a binding energy when bound to the ligand compound ion which is higher than the binding energy provided when the reagent ion is bound to the ligand former, wherein the ligand former is present in the reagent volume (2) at least in trace amounts when the sample containing the analyte reacts with the ligand compound ion and forms the adduct ion and the neutral by-product.

Description

Technical Field

[0001] This invention relates to a chemical ionization method, particularly an addition ionization method, for ionizing samples containing an analyte to be ionized. Furthermore, this invention also relates to an ion molecular reactor for ionizing the aforementioned sample containing the analyte to be ionized according to the method of this invention. Background Technology

[0002] Mass spectrometry, as an analytical technique, is widely used in many different technical fields to identify and quantify various substances or compounds of interest in pure samples and complex mixtures. Complex mixtures include not only the aforementioned substances or compounds of interest, but also other substances that do not need to be identified and quantified and are therefore not of interest. Therefore, the various substances and compounds of interest are usually referred to by the comprehensive term "analyte".

[0003] Typically, mass spectrometry involves measuring the mass-to-charge ratio of ionized analytes or analyte ions separately. Therefore, the first step is to ionize the analytes (usually neutral atoms or molecules) in the sample and transfer them to the mass spectrometer. Chemical ionization is particularly advantageous because this technique minimizes analyte fragmentation and preserves the molecular properties and structure of the analyte to a high degree.

[0004] In chemical ionization, ionized analytes are generated within the reaction volume of an ionomolecule reactor by colliding analytes with reactant ions. These reactant ions are typically generated in a reactant ion source, sometimes referred to as primary ions. In a reactant ion source, reactant ions can be generated from reactants in solid, liquid, or gaseous states. During operation, the reactant ion source ionizes reactants into reactant ions, which can be achieved, for example, through electron ionization, electromagnetic radiation such as X-rays or ultraviolet radiation, or radioactive radiation.

[0005] Chemical ionization sources based on adduct ionization also follow a conventional reaction design, where reactant ions combine with analytes to form adduct ions. The optimal sensitivity of such chemical ionization sources is typically achieved under high voltage to maximize the collision frequency between reactant ions and analytes. However, samples usually include not only the analyte but also at least one ligand formation, which often forms ligand ions with the reactant ions. Similarly, trace amounts of ligand formation may be present in the chemical ionization source from which the sample was previously ionized. Therefore, when reactant ions and a sample containing the analyte are introduced into a reaction volume to ionize the analyte, if such ligand formation is present in the reaction volume, then the reaction volume will include not only pure reactant ions but also ligand ions formed by the combination of one or more molecules of the ligand formation with the reactant ions. Each such ligand ion can also react with the analyte to form an adduct ion and some neutral byproduct, wherein the adduct ion consists of the reactant ion of the corresponding analyte and the corresponding aforementioned ligand ion, and the neutral byproduct may be, for example, one or more molecules of the ligand formation. However, in most cases, the probability of a ligand ion colliding with the same analyte to form an adduct ion and a neutral byproduct is different from the probability of a pure reactant ion colliding with a specific analyte to form an adduct ion. Sometimes, this probability difference can even reach one or more orders of magnitude. Therefore, the probability of a specific ligand ion formed from a specific reactant ion and a specific ligand forming a ligand ion colliding with a specific analyte to form an adduct ion and a neutral byproduct is higher than the probability of a corresponding pure reactant ion colliding with the same specific analyte to form an adduct ion. Simultaneously, the probability of a corresponding specific ligand ion formed from a specific reactant ion and a corresponding specific ligand forming a ligand ion colliding with another specific analyte to form an adduct ion and a neutral byproduct is lower than the probability of a corresponding pure reactant ion colliding with the same other specific analyte to form an adduct ion.

[0006] Even a very small change in the partial pressure of ligand-forming compounds within the reaction volume can alter the ratio of pure reactant ions to ligand ions formed from either reactant ions or ligand-forming compounds within that volume. Therefore, a minute change in the partial pressure of ligand-forming compounds within the reaction volume can result in drastically different ionization efficiencies of the chemical ionization source for different analytes. Consequently, a small change in the partial pressure of ligand-forming compounds within the reaction volume may impair the ability of mass spectrometry to quantify or even identify analytes in a sample.

[0007] If iodide ions (I) are used -As a reactant ion, water can act as a ligand formation product. For an example, see the article "Flight Deployment of a High-Resolution Time-of-Flight Chemical Ionization Mass Spectrometer: Observations of Reactive Halogen and Nitrogen Oxide Species" by Ben H. Lee et al., published in the *Journal of Geophysical Research: Atmospheres*, Volume 123, Issue 14, July 27, 2018, pp. 7670-7686. The survey described in this article involved mass spectrometry analysis of analytes present in the atmosphere. It is well known that the water content in the atmosphere varies significantly depending on the air layer and also changes with weather conditions. Therefore, water, as a ligand formation product, can drastically alter the ionization efficiency of chemical ionization sources for different analytes. Furthermore, the article explicitly points out that the sensitivity of iodide ionization to many compounds is affected by the absolute concentration of water vapor in the ion reactor, often changing rapidly under near-dry conditions and more slowly under humid conditions. The article further mentions that this effect can cause numerous problems when evaluating instrument background using dry, ultra-high purity N2, as the sensitivity between the environment and background measurements can change. To address this issue, the article suggests continuously adding 100 sccm of saturated ultra-high purity N2 to the ion reactor. This maintains the water vapor pressure in the ion reactor at least 0.15 Torr (equivalent to measuring relative humidity at approximately 15% relative humidity at 0°C or approximately 60% relative humidity at 20°C), thus reducing the influence of changes in ambient humidity and the variation between the environment and background measurements. Therefore, in this text, the unit "sccm" refers to standard cubic centimeters per minute at a pressure of 101.300 kPa at 298.15 K.

[0008] Therefore, the method described in the above article involves continuously adding ligand-forming compounds to the reaction volume to ensure and maintain a minimum gas partial pressure of ligand-forming compounds within the reaction volume. This minimum gas partial pressure is such that the sensitivity of reactant ions and adduct ionization to many compounds changes slowly when the amount of ligand-forming compounds in the sample changes. This, to some extent, helps improve the quantification results of analytes in samples using mass spectrometry. Nevertheless, accurate and reliable quantification of analytes in samples using mass spectrometry remains very difficult. Summary of the Invention

[0009] The object of this invention is to provide a chemical ionization method, particularly an addition ionization method, and an ion molecular reactor related to the technical field mentioned at the beginning of this document, thereby allowing for more accurate and reliable quantification of analytes in samples by mass spectrometry.

[0010] The present invention is specified by the features of claim 1. According to the invention, a ligand compound ion formed by reactant ions and dopant is present in the reaction volume. Furthermore, a sample containing an analyte can be introduced into the reaction volume and react with the ligand compound ions to form adduct ions and neutral byproducts, wherein the adduct ions comprise ionized analytes, i.e., adducts of the reactant ions and the corresponding analytes. Therefore, the binding energy provided when the reactant ions and dopant bind to the ligand compound ions is higher than the binding energy provided when the reactant ions bind to the ligand formation, wherein when the sample containing the analyte reacts with the ligand compound ions to form the adduct ions and the neutral byproducts, the ligand formation is present in the reaction volume at least in trace amounts.

[0011] As previously described, according to the present invention, a sample containing the analyte can be introduced into the reaction volume and react with the ligand compound ions to form adduct ions and neutral byproducts, wherein the adduct ions include the ionized analyte, i.e., the reactant ions and the corresponding adducts of the analyte. Therefore, the analyte to be ionized can be ionized according to the method of the present invention.

[0012] According to the present invention, the presence of the ligand compound ion in the reaction volume is not important before the sample containing the analyte is introduced into the reaction volume and reacts with the ligand compound ion to form the adduct ion and the neutral byproduct; similarly, the presence of the ligand compound ion in the reaction volume is not important either during or after the introduction of the sample containing the analyte into the reaction volume and the reaction with the ligand compound ion to form the adduct ion and the neutral byproduct. However, advantageously, the ligand compound ion is continuously provided in the reaction volume during the introduction of the sample containing the analyte into the reaction volume and the reaction with the ligand compound ion to form the adduct ion and the neutral byproduct. Continuous provision of the ligand ion during the ionization of the sample in the reaction volume allows for stable and reproducible ionization of the sample and analyte in a simple manner.

[0013] According to the invention, the binding energy provided when the reactant ion and the dopant bind to the ligand compound ion is higher than the binding energy provided when the reactant ion binds to the ligand formation. Therefore, the ligand formation is distinct from the dopant. Particularly advantageously, the chemical ionization method includes a preliminary step of selecting at least one of the reactant ion and the dopant so that the binding energy provided when the reactant ion and the dopant bind to the ligand compound ion is higher than the binding energy provided when the reactant ion binds to the ligand formation. Therefore, according to a first preferred variant, the chemical ionization method includes a preliminary step of selecting the dopant so that the binding energy provided when the reactant ion and the dopant bind to the ligand compound ion is higher than the binding energy provided when the reactant ion binds to the ligand formation. However, according to a second preferred variant, the chemical ionization method includes a preliminary step of selecting the reactant ion so that the binding energy provided when the reactant ion and the dopant bind to the ligand compound ion is higher than the binding energy provided when the reactant ion binds to the ligand formation. However, according to a third preferred variant, the chemical ionization method includes a preliminary step of selecting the reactant ions and the dopant such that the binding energy provided when the reactant ions and the dopant bind to the ligand compound ions is higher than the binding energy provided when the reactant ions bind to the ligand forming product. However, the method may also exclude this preliminary step of selecting at least one of the reactant ions and the dopant.

[0014] According to the present invention, when a sample containing the analyte reacts with the ligand compound ions to form adduct ions and neutral byproducts, the ligand formation is present in the reaction volume in at least trace amounts. Therefore, the reason why the ligand formation is present in the reaction volume is not important. For example, the ligand formation may be introduced into the reaction volume while maintaining the reaction volume; or it may be introduced into the reaction volume during the ionization of a previous sample because the ligand formation is part of that previous sample; or it may be introduced into the reaction volume because it is part of a sample being ionized.

[0015] According to the invention, the presence of the ligand compound ions in the reaction volume is also unimportant. According to the first variation, the ligand compound is first provided and then ionized into ligand compound ions, thereby presenting these ligand compound ions in the reaction volume. However, advantageously, reactant ions can be provided, allowing a dopant to react with them to form ligand compound ions containing the reactant ions, thus presenting these ligand compound ions in the reaction volume. The advantage of this is that by providing reactant ions and selecting dopant according to the requirements of the sample and analyte and the ligand formation, the binding energy provided when the reactant ions and the dopant bind to the ligand compound ions can be higher than the binding energy provided when the reactant ions bind to the ligand formation, thus more easily and adaptively providing the ligand compound ions in the reaction volume.

[0016] According to the present invention, an ion molecular reactor for ionizing samples is also provided, wherein the sample comprises an analyte ionized by the chemical ionization method according to the present invention, and particularly, the ion molecular reactor is used in conjunction with a mass spectrometer. The ion molecular reactor includes a reaction volume suitable for chemically ionizing a sample containing an analyte to be ionized, particularly for addition ionization, wherein within the reaction volume, ligand compound ions formed by reactant ions and dopants react with the sample containing the analyte to form adduct ions and neutral byproducts, wherein the adduct ions comprise ionized analytes, i.e., adducts of reactant ions and corresponding analytes. Advantageously, one chamber of the ion molecular reactor is used to define the reaction volume. However, the reaction volume may also be defined by more than one chamber of the ion molecular reactor, or by other means. Regardless of how the reaction volume is defined, the ion molecular reactor includes: at least one sample inlet for introducing a sample containing the analyte into the reaction volume; and at least one reactant inlet for introducing at least one substance into the reaction volume, thereby creating ligand compound ions within the reaction volume. In addition, the ion molecular reactor also includes an outlet for releasing the adducted ions from the reaction volume.

[0017] According to a first preferred variant, the at least one reactant inlet is used to introduce the ligand compound ions and possibly individual reactant ions and dopants into the reaction volume, or to introduce the ligand compound into the reaction volume so as to ionize it into ligand compound ions within the reaction volume. Therefore, in the latter case, the ion molecular reactor advantageously includes a ligand compound ion source for ionizing the ligand compound into ligand compound ions within the reaction volume.

[0018] According to a second preferred variant, the at least one reactant inlet is used to introduce reactants into the reaction volume for ionization into reactant ions within the reaction volume. Therefore, in the second preferred variant, the ion molecular reactor advantageously includes a reactant ion source for ionizing the reactants into reactant ions within the reaction volume. According to a first variant of this second preferred variant, the at least one reactant inlet is also used to introduce the dopant into the reaction volume. However, according to a second variant of this second preferred variant, the at least one reactant inlet is specifically two reactant inlets, wherein a first reactant inlet is used to introduce the reactants into the reaction volume for ionization into reactant ions within the reaction volume, while a second reactant inlet is used to introduce the dopant into the reaction volume.

[0019] According to the third preferred variant, the at least one reactant inlet is specifically two reactant inlets, wherein the first reactant inlet is used to introduce the reactant ions into the reaction volume, and the second reactant inlet is used to introduce the dopant into the reaction volume.

[0020] Therefore, in the second and third variations of this second preferred variant, the at least one reactant inlet is two reactant inlets. Accordingly, to cover the second and third variations of this second preferred variant, it is advantageous to configure the at least one reactant inlet for introducing at least one substance into the reaction volume as multiple reactant inlets, i.e., capable of introducing two substances into the reaction volume so that ligand compound ions are present in the reaction volume.

[0021] Surprisingly, research revealed that when ligand compound ions are present in the reaction volume, and the binding energy provided by the reactant ions and dopants when binding to the ligand compound ions is higher than that provided when the reactant ions bind to the ligand-forming compounds, the dopants will bind to the reactant ions and may even displace the ligand-forming compounds already bound to the reactant ions, thereby occupying the reactant ions. Therefore, it has been found that by providing ligand compound ions in the reaction volume, changes in the partial pressure of ligand-forming compounds in the reaction volume no longer alter the ratio of pure reactant ions to ligand ions, where the ligand ions are formed from either the reactant ions or the ligand-forming compounds present in the reaction volume. Correspondingly, even if the partial pressure of ligand-forming compounds in the reaction volume changes, the ionization efficiency of the chemical ionization source for different analytes remains unchanged. Therefore, more precise and reliable quantification of analytes in samples can be achieved using mass spectrometry.

[0022] Advantageously, the reactant ions can be provided by generating reactant ions within the reaction volume or by introducing reactant ions into the reaction volume. In the latter case, it is advantageous to first generate the reactant ions from a reactant ion source outside the reaction volume and then transfer them into the reaction volume.

[0023] Advantageously, the dopant can react with the reactant ions to form ligand compound ions within the reaction volume. This is advantageous when the reactant ions are provided by generating them within the reaction volume or by introducing them into the reaction volume. When reactant ions are introduced into the reaction volume, the dopant reacts with them to form ligand compounds within the reaction volume and / or outside the reaction volume before being introduced. In either case, a ligand compound is ultimately present within the reaction volume.

[0024] Advantageously, the charge of the ligand compound ion is the same as that of the reactant ion. This has the advantage that the ionized analyte is an adduct of the reactant ion and the corresponding analyte, thus providing a known and controllable charge. However, alternatively, the charge of the ligand compound ion may also differ from that of the reactant ion.

[0025] According to the invention, the sample comprises an analyte to be ionized. The analyte is advantageously a substance or compound of interest. Therefore, in an advantageous variation, a specific substance, a specific compound, a class of substances and / or a class of compounds can be identified as of interest, and thus as the analyte to be ionized, before ionizing the sample containing the analyte. This facilitates the optimization of the targeted analysis of the sample. Alternatively, the preliminary step of identifying the analyte to be ionized can be omitted.

[0026] Advantageously, the sample comprises at least trace amounts of the ligand formation. Therefore, the sample advantageously comprises at least trace amounts of the ligand formation and the analyte to be ionized, wherein the ligand formation is different from the analyte to be ionized. Thus, the sample consists not only of the ligand formation but also includes at least one analyte to be ionized.

[0027] When the sample comprises at least trace amounts of ligand formations, preferably, the sample consists of several parts, wherein the several parts refer to atoms or molecules, and the concentration of the ligand formation parts in the total number of sample parts changes at a rate of at least 10% of the initial concentration of the ligand formation parts within one hour, particularly preferably within one minute, and most preferably within one second. However, according to a variation, the concentration of the ligand formation parts in the total number of sample parts does not change at a rate of at least 10% of the initial concentration of the ligand formation parts within one hour.

[0028] In cases where the sample comprises at least trace amounts of a ligand formation, preferably, the sample consists of several parts, wherein each 10,000,000 parts of the sample, particularly preferably each 100,000 parts, and most preferably each 1,000 parts of the sample comprises at least one part of a ligand formation, in particular at least one molecule of the ligand formation, wherein the several parts are atoms or molecules.

[0029] However, alternatively, the sample does not include the ligand formation. In this case, the ligand formation is advantageously present in the reaction volume for other reasons further described above.

[0030] Preferably, the ligand forming compound is one of water, ethanol, benzene, nitric acid, and acetic acid, or other molecules containing an acid, peroxide, alcohol, or ketone group. Particularly preferably, the ligand forming compound is water, because water reacts with the reactant ion, and the amount of water in samples containing the analyte often varies. As mentioned at the beginning of this document, in the case of mass spectrometry analysis of analytes in the atmosphere, especially when the reactant ion is an iodide ion (I... - In the case of ), water can be used as a ligand formation product. On the other hand, if mass spectrometry analysis and quantification of malonic acid or nitric acid are to be performed, acetic acid can be used as a ligand formation product, that is, as the analyte to be ionized.

[0031] Alternatively, the ligand forming compound may be a substance other than water, ethanol, benzene, nitric acid, and acetic acid, and may not be a molecule containing an acid, peroxide, alcohol, or ketone group.

[0032] Preferably, the reactant ion is I. - ,Br - Cl - CF3O - NO3 - Acetate anions, NO + NH4 + Amine cation, acetone cation, ethanol cation, H3O + One of the cations is benzene. The advantage of this is that the reactant ions can be readily and in a controlled manner provided, wherein the reactant ions react well with most analytes to form adduct ions, i.e., adducts of the reactant ions with the corresponding analytes.

[0033] Alternatively, the reactant ion is different from I. - ,Br - Cl - CF3O - NO3 - Acetate anions, NO + NH4 + Amine cation, acetone cation, ethanol cation, H3O + And benzene cations.

[0034] Advantageously, the reactant ion is different from the ion of the ligand forming compound. Thus, for example, in the case where the ligand forming compound is ethanol, the reactant ion is advantageously different from the ethanol cation, and in the case where the ligand forming compound is benzene, the reactant ion is advantageously different from the benzene cation. The advantage of this is that the ligand compound ion can be readily and controllably obtained in the reaction volume.

[0035] However, alternatively, the reactant ions are ligand-forming ions.

[0036] Preferably, the dopant is a molecule. This has the advantage that the dopant, like most ligand forming compounds, can bind to reactant ions. However, alternatively, the dopant is not a molecule. In an example where the dopant is not a molecule, the dopant is a single atom.

[0037] Advantageously, the dopant is different in substance from the reactant ions. Therefore, advantageously, the dopant ions are different from the reactant ions. Accordingly, for example, in the case where the reactant ion is an ethanol cation, the dopant is advantageously different from ethanol. And in the case where the reactant ion is a benzene cation, the dopant is advantageously different from benzene. The advantage of the dopant being different in substance from the reactant ions is that ligand compound ions can be readily and controllably obtained in the reaction volume.

[0038] However, alternatively, the dopant is a substance of reactant ions.

[0039] Particularly advantageously, the dopant can be selected to induce ligand conversion in the adducts of reactant ions and ligand-forming compounds. Therefore, it is advantageous to select the dopant to form ligand compound ions, which are released upon collision with either the reactant ions or the adducts of the ligand-forming compounds. This has the benefit that the presence of ligand compound ions in the reaction volume can be more easily optimized and maintained, even if the partial pressure of the ligand-forming compounds changes within the reaction volume. Thus, changes in the partial pressure of the ligand-forming compounds within the reaction volume do not alter the ratio of pure reactant ions to the ligand ions of either the reactant ions or the ligand ions present in the reaction volume. Correspondingly, the ionization efficiency of the chemical ionization source for different analytes remains constant even if the partial pressure of the ligand-forming compounds changes within the reaction volume. Therefore, more precise and reliable quantification of analytes in the sample can be achieved by mass spectrometry.

[0040] Preferably, the dopant is one of water, ethanol, methanol, benzene, acetone, acetonitrile (ACN), formic acid, lactic acid, and nitric acid, or any other molecule containing an acid, peroxide, alcohol, or ketone group. Therefore, the binding energy provided when the dopant and reactant ions bind to the ligand compound ions is higher than the binding energy provided when the reactant ions bind to the ligand forming compound. Furthermore, when the ligand forming compound is water and the reactant ion is I... -In this case, the dopant is preferably one of acetone, methanol, acetonitrile (ACN), formic acid, lactic acid, and nitric acid, because they have a stronger affinity for iodides than water. However, in this case, the dopant is particularly preferred to be acetone, because acetone reacts with iodides... - The binding energy of this compound is closer to that of water with Iodide than that of any of the following: methanol, acetonitrile (ACN), formic acid, lactic acid, and nitric acid with iodides. - The binding energy. If the ligand forming product is benzene or ethanol and the reactant ion is I... - The dopant is advantageously one of water, methanol, acetone, acetonitrile, formic acid, lactic acid, and nitric acid, because they bind to iodides more strongly than ethanol or benzene.

[0041] However, the dopant is alternatively different from water, ethanol, methanol, benzene, acetone, acetonitrile (ACN), formic acid, lactic acid, and nitric acid.

[0042] Preferably, the sample comprises several parts, wherein the several parts are atoms or molecules; the dopant comprises several parts, wherein the several parts are atoms or molecules, wherein, in the reaction volume, at least one dopant is provided in every 10,000,000 parts of sample, particularly preferably every 1,000,000 parts, more preferably every 100,000 parts, even more preferably every 1,000 parts, and most preferably every 100 parts of sample, because ligand compound ions are present in the reaction volume. Therefore, advantageously, the amount of dopant provided as a dopant or already provided in the form of ligand compound ions in the reaction volume is preferably controlled to contain at least one dopant in every 10,000,000 parts, particularly preferably every 1,000,000 parts, more preferably every 100,000 parts, and most preferably every 100 parts of sample introduced into the reaction volume. In particular, preferably, during the chemical ionization method according to the invention, the amount of dopant provided as a dopant or already provided in the form of ligand compound ions in the reaction volume is always controlled to be at least one part of the dopant per 10,000,000 parts, particularly preferably per 1,000,000 parts, more preferably per 100,000 parts, even more preferably per 1,000 parts, and most preferably per 100 parts of the sample present in the reaction volume. In all these variations, the amount of dopant in the reaction volume is preferably controlled to be no more than one part per part of the sample in the reaction volume.

[0043] Advantageously, the binding energy provided when the reactant ion binds to the dopant is lower than the binding energy provided when the reactant ion binds to any analyte. This allows the analyte to induce a ligand conversion between the reactant ion and the dopant adduct, i.e., the ligand compound ion. This ensures effective ionization of the analyte.

[0044] Therefore, in a preferred variant, the chemical ionization method includes a preliminary step of selecting dopants such that the binding energy provided by the dopants and reactant ions when they bind to ligand compound ions is lower than the binding energy provided by the reactant ions when they bind to the analyte. This is particularly advantageous if a specific substance, a specific compound, a class of substances and / or a class of compounds is identified as the analyte of interest before ionizing a sample containing the analyte to be ionized.

[0045] However, alternatively, the initial step of selecting dopant can be omitted, such that the binding energy provided by the dopant and reactant ions when they bind to the ligand compound ions is lower than the binding energy provided by the reactant ions when they bind to the analyte.

[0046] Preferably, the gas pressure in the reaction volume is maintained between 1 mbar and 1,000 mbar, particularly preferably between 10 mbar and 1,000 mbar, and most preferably between 20 mbar and 1,000 mbar. This maximizes the collision frequency between reactant ions and analytes in the reaction volume.

[0047] In a preferred variation, the gas pressure in the reaction volume is maintained between 1 mbar and 500 mbar, particularly preferably between 10 mbar and 500 mbar, and most preferably between 20 mbar and 500 mbar. This optimizes the collision frequency between reactant ions and analytes in the reaction volume and further reduces the probability of reactant ions binding to ligand-forming compounds.

[0048] In another preferred variation, the gas pressure in the reaction volume is maintained between 1 mbar and 100 mbar, particularly preferably between 10 mbar and 100 mbar, and most preferably between 20 mbar and 100 mbar. This optimizes the collision frequency between reactant ions and analytes in the reaction volume and further reduces the probability of reactant ions binding to ligands.

[0049] However, alternatively, the gas pressure in the reaction volume is not maintained within either of the aforementioned ranges.

[0050] Preferably, during the execution of this chemical ionization method, the temperature in the reaction volume is maintained within a bandwidth of 10°C, particularly preferably within a bandwidth of 5°C, and most preferably within a bandwidth of 10°C. This has the advantage that the ratio of pure reactant ions to ligand compound ions in the reaction volume remains stable, thereby making the ionization efficiency of the chemical ionization source more constant for different analytes, and thus enabling more accurate and reliable quantification of analytes in the sample by mass spectrometry. Therefore, it is necessary to advantageously maintain the corresponding bandwidth of the desired temperature. Thus, the ionization efficiency of the analyte can be optimized by selecting the desired temperature, and at the same time, the temperature can be maintained within the corresponding bandwidth of the desired temperature, thereby making the ionization efficiency of the chemical ionization source even more constant for different analytes.

[0051] However, alternatively, the temperature in the reaction volume is not always maintained within a bandwidth of 10°C.

[0052] During the chemical ionization process, regardless of whether the temperature in the reaction volume is maintained within a bandwidth of 2°C or 1°C, it is advantageous to maintain the temperature below 200°C. This allows for the maintenance of dissociation of the cleavage and adducts at an acceptable level, and allows the analyte to include even low-volatility compounds. If the analyte is known, intended, or accepted to include low-volatility compounds, the temperature in the reaction volume is advantageously maintained at at least 40°C to ionize the low-volatility compounds with optimal ionization efficiency.

[0053] In a preferred variation, the temperature within the reaction volume is maintained below 40°C. This has the advantage of keeping the splitting and dissociation of the adduct at a low level. This is particularly advantageous when the analyte does not contain low-volatility compounds.

[0054] In both cases, the temperature within the reaction volume is preferably maintained above 0°C. This has the advantage of preventing the equipment from freezing.

[0055] In a preferred variation, the temperature in the reaction volume is maintained between 15°C and 100°C, particularly preferably between 25°C and 100°C, and most preferably between 40°C and 100°C. This has the advantage of optimizing the ionization efficiency of the analyte while also keeping the analyte splitting and adduct dissociation at low levels.

[0056] Alternatively, unlike these variations, the temperature within the reaction volume may not be maintained within the aforementioned limits. Therefore, the temperature within the reaction volume may be 0°C or lower, or 200°C or higher.

[0057] Advantageously, the chemical ionization method according to the invention can be used for mass spectrometry analysis of analytes in samples containing analytes. Therefore, in the method for mass spectrometry analysis of analytes contained in a sample containing analytes, the sample containing the analytes can be ionized by the chemical ionization method according to the invention, and the resulting ions can be transferred to a mass spectrometer for mass spectrometry analysis. Therefore, advantageously, the analyte to be mass spectrometrically analyzed is the analyte to be ionized mentioned in the above-described chemical ionization method according to the invention.

[0058] The advantage of this method of mass spectrometry analysis of samples containing analytes is that it allows for accurate and reliable quantitative analysis of the analytes in the samples using mass spectrometry.

[0059] Advantageously, before performing mass spectrometry analysis, the resulting ions can be separated in a drift chamber based on their mobility to facilitate mass spectrometry analysis of the analytes. This improves the analytical results for the analytes in the sample. However, alternatively, methods for mass spectrometry analysis of analytes do not require such separation of the resulting ions based on their mobility.

[0060] Advantageously, the chemical ionization source includes an ion molecular reactor according to the invention for ionizing a sample containing an analyte according to the chemical ionization method of the invention, wherein the chemical ionization source includes a reactant ion source for ionizing reactants into reactant ions or a ligand compound ion source for ionizing ligand compounds into ligand compound ions, thereby presenting ligand compound ions in the reaction volume.

[0061] Advantageously, the chemical ionization source includes a control unit for controlling the chemical ionization source and adapting it for performing the chemical ionization method according to the invention. However, alternatively, the chemical ionization source may not include this control unit.

[0062] In cases where the chemical ionization source includes a reactant ion source, the reactant ion source is advantageously a laser ablation ion source, an electron ion source, an electrospray ion source, an ultraviolet ion source, a spark discharge ion source, an inductively coupled plasma ion source, or a microwave-induced plasma ion source. This ensures a reliable supply of reactant ions. However, alternatively, the reactant ion source may not be one of these types.

[0063] In cases where the chemical ionization ion source includes a ligand compound ion source, this ligand compound ion source is advantageously based on a soft ionization method to reduce the fragmentation of the ligand compound during ionization into ligand compound ions. Therefore, the ligand compound ion source is advantageously an electrospray ion source or a matrix-assisted laser desorption / sorption ionization (MALDI) source. However, alternatively, this ligand compound ion source differs from these types of ion sources.

[0064] In the chemical ionization method employed by a chemical ionization source, if it is necessary to maintain a gas pressure within one of the aforementioned ranges in the reaction volume, then the chemical ionization source advantageously includes a device for achieving and maintaining the gas pressure within the reaction volume within the corresponding range. Since the aforementioned pressure range is lower than the Earth's atmospheric pressure, the device for achieving and maintaining the gas pressure within the reaction volume can advantageously be a vacuum pump or at least a connector connecting the chemical ionization source to a vacuum system, which is readily available in scientific laboratories. However, the chemical ionization source may also exclude the aforementioned device for achieving and maintaining the gas pressure within the reaction volume within the corresponding range.

[0065] In the chemical ionization method employed by a chemical ionization source, where the temperature within the reaction volume is consistently maintained within a bandwidth of 2°C or 1°C, and / or where the temperature is consistently maintained within one of the aforementioned temperature ranges, the chemical ionization source advantageously includes a device for bringing the temperature within the reaction volume to and maintaining it within the corresponding bandwidth and / or range. For example, the device for bringing the temperature within the reaction volume to and maintaining it within the corresponding bandwidth and / or range may be a temperature control unit connected to a temperature sensor and a heater for heating the reaction volume to bring the temperature within the reaction volume to and maintain it within the corresponding bandwidth and / or range. However, the chemical ionization source may also be used without such a device for bringing the temperature within the reaction volume to and maintaining it within the corresponding bandwidth and / or range.

[0066] Advantageously, the mass spectrometer is used to perform mass spectrometry analysis on the analyte contained in a sample containing the analyte, wherein the mass spectrometer includes a chemical ionization ion source for ionizing the sample containing the analyte into result ions, wherein the mass spectrometer further includes a mass spectrometer analyzer for performing mass spectrometry analysis on the result ions in order to perform mass spectrometry analysis on the analyte, wherein the mass spectrometer analyzer is fluidly coupled to the chemical ionization ion source for receiving the result ions.

[0067] Advantageously, the mass spectrometer includes a control unit adapted to control the mass spectrometer and to control the mass spectrometer to perform a method for mass spectrometric analysis of the analyte contained in a sample containing the analyte. However, alternatively, the mass spectrometer may not include this control unit.

[0068] Advantageously, the mass spectrometer includes an anion mobility separation unit fluidly coupled between a chemical ionization ion source and a mass spectrometer, for separating the result ions received from the chemical ionization ion source according to their mobility before mass spectrometric analysis of the result ions. This improves the analytical performance of analytes in the sample. Alternatively, however, the mass spectrometer may not include this anion mobility separation unit.

[0069] Other advantageous embodiments and combinations of features can be found in the detailed description below and throughout the claims. Attached Figure Description

[0070] The following figures are used to explain the above embodiments.

[0071] Figure 1 This is a simplified schematic diagram of an ion molecular reactor according to the present invention for ionizing a sample containing an analyte according to the method of the present invention, the ion molecular reactor being used in conjunction with a mass spectrometer;

[0072] Figure 2 This is a simplified schematic diagram of a chemical ionization source, which includes... Figure 1 The ion molecular reactor shown is used for ionizing a sample containing an analyte according to the method of the present invention.

[0073] Figure 3 This is a simplified schematic diagram of a variant of a chemical ionization source, which includes... Figure 1 The ion molecular reactor shown is used for ionizing a sample containing an analyte according to the method of the present invention.

[0074] Figure 4 This is a simplified schematic diagram of a mass spectrometer used for mass spectrometry analysis of samples containing analytes. The mass spectrometer includes... Figure 2 The chemical ionization source shown;

[0075] Figure 5a , 5b 5c is a calculation graph showing the effect of changes in the gaseous partial pressure (pH2O) of water in the ion molecular reactor (IMR), i.e., the reaction volume, at a temperature of 25°C on the reaction of iodide ions (I₂O). - ) and the reactant ions (I - ) and water (I(H2O)) - I(H2O)2- and I(H2O)3 - Changes in the ratio of ligand ions formed;

[0076] Figure 6 and Figure 5a The curves shown are identical and were calculated under the condition of a total gas pressure of 50 mbar in the reaction volume at 25°C. That is, they show the amount of nitric acid, acrylic acid and formic acid in the laboratory air measured in different gas partial pressures of water in the reaction volume at 25°C and 50 mbar. This amount is normalized to the amount of nitric acid, acrylic acid and formic acid measured under completely dry conditions where the gas partial pressure of water in the reaction volume is 0.

[0077] Figure 7a , 7b The measurement diagram illustrates the chemical ionization method according to the invention using acetone as a dopant at a total gas pressure of 50 mbar and a temperature of 25°C within the reaction volume.

[0078] Figure 8a , 8b The measurement diagram illustrates the chemical ionization method according to the invention using methanol as a dopant at a total gas pressure of 50 mbar and a temperature of 25°C within the reaction volume.

[0079] Figure 9a , 9b The measurement diagram illustrates the chemical ionization method according to the invention using acetonitrile (ACN) as a dopant at a total gas pressure of 50 mbar and a temperature of 25°C within the reaction volume; and

[0080] Figure 10 Showing with Figure 6 The same two pictures, in which Figure 10 The data points in the figure below are shown as filled dots, which additionally show the amounts of nitric acid, formic acid, and acrylic acid in laboratory air measured under the same conditions, but by the chemical ionization method according to the invention.

[0081] In the accompanying drawings, the same elements are shown using the same reference numerals. Detailed Implementation

[0082] Figure 1 This is a simplified schematic diagram of an ion molecular reactor 1 according to the present invention for ionizing a sample containing an analyte according to the method of the present invention, and the ion molecular reactor is particularly associated with a mass spectrometer 100 (see...). Figure 4This is used in conjunction with the ion molecular reactor 1. The ion molecular reactor 1 includes a reaction volume 2, which is defined by a chamber 3 within the ion molecular reactor 1. The reaction volume 2 is suitable for the adduct ionization of a sample containing an analyte to be ionized; this adduct ionization is also a form of chemical ionization. Within the reaction volume 2, ligand compound ions formed by reactant ions and dopants can react with the sample containing the analyte to form adduct ions and neutral byproducts. These adduct ions include the ionized analyte, i.e., adducts of reactant ions and the corresponding analyte.

[0083] The ion molecular reactor 1 includes a sample inlet 4 for introducing a sample containing an analyte into a reaction volume 2, and two reactant inlets 5 and 6. The first reactant inlet 5 introduces reactant ions into the reaction volume 2, while the second reactant inlet 6 introduces a dopant into the reaction volume 2 to form a ligand compound ion with the reactant ions in the reaction volume 2, thereby ensuring the presence of ligand compound ions in the reaction volume 2. Therefore, the ion molecular reactor 1 includes two reactant inlets 5 and 6 for introducing at least one substance into the reaction volume 2, ensuring the presence of ligand compound ions in the reaction volume 2. Furthermore, the ion molecular reactor 1 includes an outlet 7 for releasing adducted ions from the reaction volume 2. When the ion molecular reactor 1 is used with a mass spectrometer 100, it also enables the transfer of adducted ions from the reaction volume 2 to the mass spectrometer analyzer 101 of the mass spectrometer 100.

[0084] Figure 2 A simplified schematic diagram of a chemical ionization source 50 is shown, which includes... Figure 1 The ionization molecular reactor 1 shown is used for ionizing a sample containing an analyte according to the method of the present invention. The chemical ionization ion source 50 further includes a reactant ion source 51 for ionizing the reactant into reactant ions. This reactant ion source 51 is an ultraviolet ion source and is fluidly coupled to a first reactant inlet 5 of the ionization molecular reactor 1, which introduces reactant ions from the reactant ion source 51 into the reaction volume 2. The chemical ionization ion source 50 also includes a dopant library 52 fluidly coupled to a second reactant inlet 6 of the ionization molecular reactor 1, which introduces dopants into the reaction volume 2 to ensure the presence of ligand compound ions in the reaction volume 2.

[0085] Furthermore, the chemical ionization source 50 includes a device 55 for bringing the reaction volume to and maintaining a desired temperature within a required bandwidth. This device 55 is a temperature control unit, which includes a temperature sensor for sensing the temperature within the reaction volume 2 and a heater for heating the reaction volume 2 to bring the temperature within the reaction volume to and maintain it within the corresponding bandwidth and range.

[0086] Furthermore, the chemical ionization source 50 includes a device 56 for achieving and maintaining the gas pressure within the reaction volume within a desired range. Since the required pressure range in the chemical ionization source 50 is lower than the atmospheric pressure of Earth, and since the chemical ionization source 50 is intended for use on the ground, the aforementioned device for achieving and maintaining the gas pressure within the reaction volume can simply be a vacuum pump.

[0087] exist Figure 3 In the variant shown, the chemical ionization source 50 includes a ligand compound ion source 54 instead of a reactant ion source 51. In this case, the ligand compound formed by the reactants and dopants is ionized into ligand compound ions by the ligand compound ion source 54. Therefore, in this case, the ion molecular reactor 1 includes only one reactant inlet 8, which is fluidly coupled to the ligand compound ion source 54 and used to introduce ligand compound ions from the ligand compound ion source 54 into the reaction volume 2 so that ligand compound ions are present in the reaction volume 2.

[0088] exist Figure 2 and Figure 3 In both cases shown, the chemical ionization source 50 further includes a control unit 53, which is adapted to control the chemical ionization source 50 and perform the chemical ionization method according to the present invention.

[0089] Figure 4 This is a simplified schematic diagram of a mass spectrometer 100 used for mass spectrometric analysis of analytes contained in a sample. The mass spectrometer 100 includes... Figure 2 The chemical ionization source 50 shown is used to ionize a sample containing the analyte into result ions. The mass spectrometer 100 also includes a mass spectrometer 101 for mass spectrometric analysis of the result ions to perform mass spectrometric analysis of the analyte. In this embodiment, the mass spectrometer 101 is a time-of-flight mass spectrometer. However, the mass spectrometer 101 could also be any other type of mass spectrometer, such as a quadrupole mass spectrometer. Figure 4 In the mass spectrometer 100 shown, the mass spectrometer 101 is fluidly coupled to a chemical ionization source 50 for receiving result ions. Therefore, the mass spectrometer 100 is used to perform mass spectrometric analysis on analytes contained in a sample containing analytes, wherein the sample containing analytes can be ionized according to the method of the present invention, and the result ions are transferred to the mass spectrometer 101 for mass spectrometric analysis, thereby performing mass spectrometric analysis on the analytes.

[0090] The mass spectrometer 100 also includes an ion mobility separation unit 102, which is fluidly coupled between the chemical ionization ion source 50 and the mass spectrometer 101, and is used to separate the result ions received by the chemical ionization ion source 50 according to their mobility before the mass spectrometer 101 performs mass spectrometry analysis on the result ions. Therefore, in the method of mass spectrometry analysis of analytes contained in a sample containing analytes, the result ions are separated according to their mobility in the ion mobility separation unit 102 before the mass spectrometry analysis is performed by the mass spectrometer 101. To allow the result ions to pass through the ion mobility separation unit 102 in a pulsed manner, the mass spectrometer 100 includes an ion trap 104, which is disposed downstream of the chemical ionization ion source 50 and upstream of the ion mobility separation unit 102. In the ion trap 104, the result ions received by the chemical ionization ion source 50 are collected and released in a pulsed manner, allowing them to pass through the ion mobility separation unit 102, thereby separating them according to their mobility.

[0091] For completeness, the mass spectrometer 100 described herein includes a control unit 103 adapted to control the mass spectrometer 100 and to control the mass spectrometer 100 to perform the methods described herein. Figure 4 In the diagram, the control unit 103 is schematically shown as a square in the mass spectrometer 100. However, the control unit 103 can also be a separate computer connected to other parts of the mass spectrometer 100. Therefore, the control unit 103 can directly control the chemical ionization source 50, or it can control the control unit 53 of the chemical ionization source 50. Since the control unit 103 suitable for controlling a mass spectrometer is well known in the art, this document will not discuss it further. Figure 4 The control unit 103 of the mass spectrometer 100 shown will not be described in detail.

[0092] Figure 5a , 5b 5c is a calculation graph showing the effect of changes in the partial pressure of water (pH2O) in the gaseous volume of the ionotropic reactor (IMR) at 25°C on the concentration of iodide ions (I₂O) as reactants. - ) and the reactant ions (I - ) and water (I(H2O)) - I(H2O)2 - and I(H2O)3 - The change in the ratio between ligand ions produced by the reaction. Therefore, the partial pressure of water in the reaction volume is expressed in mbar on the x-axis, while the reactant ions (I) -The quantities of ligand ions are expressed on the y-axis as their fraction of the total iodide in the reaction volume. For this purpose, the Y-axis is labeled "Fractional Reactant Ions," while the X-axis represents the partial pressure of water in the reaction volume.

[0093] Figure 5a The schematic diagram shown is calculated with a total gas pressure of 50 mbar in the reaction volume. Therefore, the partial pressure of water on the x-axis ranges from 0 mbar to 1.4 mbar, accounting for 0 to 2.8% of the total gas pressure in the reaction volume. Figure 5b The schematic diagram shown is calculated with a total gas pressure of 150 mbar in the reaction volume. Therefore, the partial pressure of water on the x-axis ranges from 0 mbar to 4.2 mbar, which also represents 0 to 2.8% of the total gas pressure in the reaction volume. Figure 5c The schematic diagram shown is calculated with a total gas pressure of 500 mbar within the reaction volume. Therefore, the partial pressure of water on the x-axis ranges from 0 mbar to 14 mbar, which also represents 0 to 2.8% of the total gas pressure in the reaction volume.

[0094] Figure 5a , 5b The schematic diagram shown in Figure 5c uses iodide ions (I - Taking reactant ions as an example, the presence of water as a ligand formation in the reaction volume is used to illustrate the effect of the presence of water as a ligand formation on the purity of reactant ions (I). - ) and different types of ligand ions formed from reactant ions and ligand formations (I(H2O) respectively) - I(H2O)2 - and I(H2O)3 - How much does the ratio affect the concentration of reactant ions? As shown in the figure, when the sample includes different amounts of water as ligand formations, this ratio changes significantly with the water content. Pure reactant ions (I... - ) and different types of ligand ions (I(H2O) respectively) - I(H2O)2 - and I(H2O)3 - The probability of a ligand ion reacting with an analyte to generate reactant ions and analyte adduct ions differs. Furthermore, if the ion is a ligand ion, in addition to reactant ions and analyte adduct ions, neutral byproducts may also be generated. Therefore, the ionization efficiency of existing chemical ion sources varies significantly for different analytes depending on the amount of ligand-forming compounds in the sample.

[0095] from Figure 5a , 5bAs can be seen from 5c, when the total gas pressure in the reaction volume is 50 mbar and the partial pressure of water in the reaction volume is between 0.2 mbar and 0.4 mbar, the change in ligand ions is minimal, especially for pure reactant ions (I0). - ) and the first ligand ion I(H2O) - The ratio change is minimal. Therefore, existing technology tells us that the reaction volume must meet the above conditions to improve the quantification results of analytes contained in the sample after mass spectrometry analysis. This can be achieved by keeping the total gas pressure within the reaction volume sufficiently low, while continuously adding ligand-forming substances to the reaction volume to reach and maintain the minimum partial pressure of ligand formation. This minimum partial pressure falls within a range where the sensitivity of reactant ions and adduct ionization to many compounds changes slowly when the amount of ligand formation in the sample changes.

[0096] Figure 6 The above figure shows the relationship with Figure 5a The same curve was calculated at a temperature of 25°C and a total atmospheric pressure of 50 mbar within the reaction volume. This is to illustrate the change in the sensitivity of addition ionization to reactant ions in existing chemical ionization methods. Figure 6 The figure below shows the amounts of nitric acid, acrylic acid, and formic acid in laboratory air measured at different gas partial pressures of water in the reaction volume at 25°C and 50 mbar total atmospheric pressure. These amounts were normalized to those measured under completely dry conditions where the gas partial pressure of water in the reaction volume was 0. The measurements were performed using mass spectrometry, where the analytes nitric acid, acrylic acid, and formic acid in the laboratory air sample can be determined using existing chemical ionization methods with iodide ions (I0.05). - The water is ionized. To simulate different amounts of water as ligand formation in the sample, water vapor can be introduced into the reaction volume to create different partial pressures of water gas in the reaction volume.

[0097] from Figure 6As shown in the figure below, in the reaction volume with a water partial pressure of 0 to 0.4 mbar, the sensitivity of nitric acid ionized by the existing chemical ionization method increased by 100%. Simultaneously, in the reaction volume with a water partial pressure of 0 to 0.4 mbar, the sensitivity of ionized acrylic acid decreased by approximately 70%, and this decrease further increased with increasing water partial pressure. Furthermore, in the reaction volume with a water partial pressure of 0 to 0.2 mbar, the sensitivity of ionized formic acid increased by approximately 70%, then decreased with further increases in water partial pressure. Moreover, when the water partial pressure in the reaction volume increased to just over 1 mbar, its sensitivity even fell below that at 0 mbar.

[0098] Figure 7a , 7b The diagram illustrates the chemical ionization method according to the invention at a total gas pressure of 50 mbar and a temperature of 25°C within reaction volume 2. In this example, iodide ions (I... - Similarly, water is a ligand former, while other reactant ions are present. To simulate different amounts of ligand formers in the sample, water vapor can be introduced into reaction volume 2 to create different partial pressures of water gas within it. Unlike existing techniques, to ensure the presence of ligand compound ions in reaction volume 2, a dopant is additionally introduced. This dopant can react with the reactant ions to form ligand compound ions.

[0099] exist Figure 7a and 7b In the example shown, the dopant is acetone. Therefore, the graphs show the curves measured after introducing different amounts of dopant (in sccm) into the reaction volume. Similarly, the partial pressure of water within the reaction volume is shown on the x-axis in these three graphs. Figure 7a In the above figure, the measured pure reactant ions (I - The quantity is displayed on the y-axis in arbitrary units. Figure 7a In the middle figure, the first ligand ion I(H2O) was measured. - The quantity is displayed on the y-axis in the same arbitrary units. And... Figure 7a In the figure below, the number of ligand compound ions formed by the dopant acetone is shown on the y-axis in the same arbitrary units.

[0100] from Figure 7a It can be seen that as the amount of dopant acetone in reaction volume 2 increases, the ratio of ligand ions to ligand compound ions shifts in a direction that favors ligand compound ions.

[0101] exist Figure 7bThe diagram illustrates the sampling of nitric acid (top), formic acid (middle), and acrylic acid (bottom) from laboratory air using mass spectrometry. This was also conducted under different gas partial pressures of water within reaction volume 2, and with varying amounts of dopants introduced into reaction volume 2. Therefore, in Figure 7b In all three graphs shown, the y-axis is normalized to the amount of acid measured when the water is dry, that is, when the partial pressure of water is 0.

[0102] from Figure 7b It can be seen that if iodide ions (I - When acetone is used as a reactant ion and nitric acid as a dopant, the ionization efficiency of nitric acid, formic acid, and acrylic acid in the chemical ionization method according to the present invention is less dependent on water as a variable ligand formation in the sample. This effect occurs because acetone reacts with iodide ions (I... - The binding energy provided by the combination is slightly higher than that of water and iodide ions (I). - The binding energy provided during bonding.

[0103] Figure 8a and 8b Schematic diagram and Figure 7a and 7b They are the same, meaning they were measured under essentially the same conditions. However, in Figure 8a and 8b In this method, methanol is used as the dopant instead of acetone. It can be seen that, in the chemical ionization method according to the present invention, if methanol is used as the dopant, the dependence of the ionization efficiency of nitric acid, formic acid, and acrylic acid on water as a variable ligand formation in the sample is further reduced. This effect occurs because methanol reacts with iodide ions (I... - The binding energy provided by the combination is higher than that of acetone and iodide ions (I). - The binding energy provided by ions is also higher than that between water and iodide ions (I). - The binding energy provided during bonding.

[0104] Figure 9a and 9b Schematic diagram and Figure 7a and 7b as well as Figure 8a and 8b They are the same, and were measured under essentially the same conditions. However, in Figure 9a and 9b In this study, acetonitrile (ACN) was used as the dopant, rather than acetone or methanol. It can be seen that the ionization efficiency of nitric acid and formic acid depends on water as a variable ligand formation in the sample in roughly the same way as when methanol is used as the dopant (see [reference needed]). Figure 8bHowever, in the chemical ionization method according to the present invention, if acetonitrile (ACN) is used as a dopant, the ionization efficiency of acrylic acid is further reduced in dependence on water as a variable ligand formation in the sample. This effect occurs because acetonitrile (ACN) reacts with iodide ions (I... - The binding energy provided by the combination is higher than that of methanol and iodide ions (I). - The binding energy provided by acetone when it binds to iodide ions (I-) is higher than that provided by acetone when it binds to iodide ions (I-), and it is also higher than that provided by water when it binds to iodide ions (I-). - The binding energy provided during bonding.

[0105] Figure 10 The two figures shown are Figure 6 Same. However, in Figure 10 In the figure below, the data points are shown as filled dots, which additionally indicate the amounts of nitric acid, formic acid, and acrylic acid in laboratory air measured under the same conditions, but by the chemical ionization method according to the invention. In this additional measurement figure, 30 sccm of acetonitrile (ACN) is introduced as a dopant into reaction volume 2 to ensure the presence of ligand compound ions in reaction volume 2.

[0106] from Figure 10 As shown in the figure below, the chemical ionization method according to the present invention allows for more precise and reliable quantification of analytes in samples using mass spectrometry. The sensitivity for ionizing nitric acid, formic acid, and acrylic acid no longer changes 100% with variations in water content in the sample. Instead, the sensitivity decreases to 20% or even lower with changes in water content.

[0107] This invention is not limited to the examples shown in the figures. For example, this invention is not limited to the use of iodide ions (I... - ) as reactant ions. I - ,Br - Cl - CF3O - NO3 - Acetate anions, NO + NH4 + Amine cation, acetone cation, ethanol cation, H3O +Any of the benzene ions can be used as reactant ions. Alternatively, the invention may not be limited to the aforementioned reactant ions and may use other reactant ions. Furthermore, the dopant is not limited to acetone, methanol, and acetonitrile (ACN). The dopant can be any of water, ethanol, methanol, benzene, acetone, acetonitrile (ACN), formic acid, lactic acid, and nitric acid. Alternatively, the invention may not be limited to the aforementioned dopant and may use any other dopant. Furthermore, the ligand forming agent is not required to be water as in the example shown in the figure. The ligand forming agent can be any of water, ethanol, benzene, nitric acid, and acetic acid. Furthermore, the invention may not be limited to the aforementioned ligand forming agents and may use any other ligand forming agent. Importantly for the invention, the binding energy provided when the reactant ions and dopant bind to the ligand compound ions is higher than the binding energy provided when the reactant ions bind to the ligand forming agent. The chemical ionization method according to the invention is particularly advantageous if at least trace amounts of the ligand forming agent are present in the sample, and the amount of the ligand forming agent may vary in a single measurement or in two or more measurements and will be quantitatively compared subsequently. Therefore, the chemical ionization method according to the invention is particularly advantageous when the sample consists of several parts, and when each 10,000,000 parts of the sample includes at least one ligand forming compound, particularly at least one molecule of the ligand forming compound. Furthermore, the chemical ionization method according to the invention is also advantageous when the sample consists of several parts, wherein the several parts refer to atoms or molecules, and the concentration of the ligand forming compound in the total number of parts of the sample changes at a rate of at least 10% of the initial concentration of the ligand forming compound within one hour, one minute, or even one second.

[0108] Furthermore, the chemical ionization method according to the invention is particularly advantageous when the sample consists of several parts, wherein these parts are atoms or molecules, and during the execution of the chemical ionization method according to the invention, the amount of dopant provided as a dopant or already provided in the form of ligand compound ions in the reaction volume is always controlled to contain at least one dopant per 10,000,000 parts of the sample in the reaction volume, for example, per 10,000 parts of the sample or even per 100 parts of the sample. Figure 10The figure below shows a measurement graph obtained by the chemical ionization method according to the present invention. The total gas pressure within the reaction volume is 50 mbar, the temperature is maintained at 25°C, and the temperature bandwidth is 1°C. This was chosen because these parameters are ideal for measurement results obtained by prior art chemical ionization methods, as also shown in the figure. In the chemical ionization method according to the present invention, the total gas pressure within the reaction volume can be set higher or lower. In the examples, the total gas pressures within the reaction volume are 10 mbar, 30 mbar, 100 mbar, 250 mbar, 500 mbar, 750 mbar, and 900 mbar. Furthermore, the temperature within the reaction volume can also be chosen to be higher or lower. In the examples, the temperatures within the reaction volume are 16°C, 20°C, 30°C, 50°C, 70°C, 100°C, 150°C, and 170°C.

[0109] In summary, it should be noted that, based on the provided chemical ionization methods, particularly addition ionization methods, and ion molecular reactors related to the technical field mentioned at the beginning of this paper, more accurate and reliable quantification of analytes in samples can be achieved by mass spectrometry.

Claims

1. A chemical ionization method for ionizing a sample containing an analyte to be ionized. in, The reaction volume (2) contains ligand compound ions formed by reactant ions and dopants; The sample containing the analyte is introduced into the reaction volume (2) and reacts with the ligand compound ions to form adduct ions and neutral byproducts, wherein the adduct ions comprise ionized analytes, which are adducts of the reactant ions and the corresponding analytes; and Wherein, the binding energy provided when the reactant ion and the dopant combine to form the ligand compound ion is higher than the binding energy provided when the reactant ion combines with the ligand formation, wherein the binding energy provided when the reactant ion combines with the dopant is lower than the binding energy provided when the reactant ion combines with any of the analytes to be analyzed, wherein when the sample containing the analyte reacts with the ligand compound ion to form the adduct ion and the neutral byproduct, the ligand formation exists in the reaction volume (2) in at least trace amounts.

2. The chemical ionization method according to claim 1, wherein, The sample contains at least trace amounts of the ligand formation.

3. The chemical ionization method according to claim 2, wherein, The sample consists of several parts, and each 10,000,000 parts of the sample includes at least one part of the ligand formation, wherein the several parts are atoms or molecules.

4. The chemical ionization method according to claim 3, wherein, Each 100,000 of the samples includes at least one of the ligand formations.

5. The chemical ionization method according to claim 3, wherein, Each 1,000 of the samples includes at least one of the ligand formations.

6. The chemical ionization method according to claim 3, wherein, Each 10,000,000 portions of the sample includes at least one molecule of the ligand formation.

7. The chemical ionization method according to claim 3, wherein, Each 100,000 portions of the sample includes at least one molecule of the ligand formation.

8. The chemical ionization method according to claim 3, wherein, Each 1,000 portions of the sample includes at least one molecule of the ligand formation.

9. The chemical ionization method according to any one of claims 1 to 8, wherein, The ligand forming compound is one of water, ethanol, benzene, nitric acid, and acetic acid, or any other molecule containing an acid, peroxide, alcohol, or ketone group.

10. The chemical ionization method according to any one of claims 1 to 8, wherein, The reactant ion is I. - ,Br - Cl - CF3O - NO3 - Acetate anions, NO + NH4 + Amine cation, acetone cation, ethanol cation, H3O + One of the phenyl cations.

11. The chemical ionization method according to any one of claims 1 to 8, wherein, The dopant is a molecule.

12. The chemical ionization method according to any one of claims 1 to 8, wherein, The dopant is one of water, ethanol, methanol, benzene, acetone, acetonitrile, formic acid, lactic acid, nitric acid, or any other molecule containing an acid, peroxide, alcohol, or ketone group; wherein the binding energy provided when the dopant and the reactant ion combine to form the ligand compound ion is higher than the binding energy provided when the reactant ion combines with the ligand formation.

13. The chemical ionization method according to any one of claims 1 to 8, wherein, In the reaction volume (2), the gas pressure is maintained between 1 mbar and 1,000 mbar.

14. The chemical ionization method according to claim 13, wherein, The air pressure was maintained between 10 mbar and 1,000 mbar.

15. The chemical ionization method according to claim 13, wherein, The air pressure is maintained between 20 mbar and 1,000 mbar.

16. The chemical ionization method according to any one of claims 1 to 8, wherein, During the chemical ionization process, the temperature in the reaction volume (2) is maintained within a bandwidth of 2°C.

17. The chemical ionization method according to any one of claims 1 to 8, wherein, During the chemical ionization process, the temperature in the reaction volume (2) is maintained within a bandwidth of 1°C.

18. The chemical ionization method according to any one of claims 1 to 8, wherein, The temperature in the reaction volume (2) is always maintained within the range of 15°C to 100°C.

19. The chemical ionization method according to any one of claims 1 to 8, wherein, The temperature in the reaction volume (2) is always maintained within the range of 25°C to 100°C.

20. The chemical ionization method according to any one of claims 1 to 8, wherein, The temperature in the reaction volume (2) is always maintained within the range of 40°C to 100°C.

21. A method for mass spectrometric analysis of said analyte contained in a sample containing an analyte, comprising: The sample containing the analyte is ionized by the chemical ionization method according to any one of claims 1 to 20; The resulting ions are transferred to the mass spectrometer (101); And mass spectrometry analysis is performed by the mass spectrometer (101) to perform mass spectrometry analysis on the analyte.

22. A chemically ionized ion source (50), comprising: Ion molecular reactor (1), the ion molecular reactor comprising: A reaction volume (2) is provided for chemically ionizing the sample containing the analyte to be ionized; wherein, within the reaction volume (2), ligand compound ions formed by reactant ions and dopants react with the sample containing the analyte to form adduct ions and neutral byproducts, wherein the adduct ions comprising the ionized analyte are adducts of the reactant ions and the corresponding analyte; At least one sample inlet (4) is used to introduce the sample containing the analyte into the reaction volume (2). At least one reactant inlet (5, 6) is provided for introducing at least one substance into the reaction volume (2) so that the ligand compound ions are present in the reaction volume (2); Outlet (7), which is used to release the adduct ions from the reaction volume (2); and The control unit is configured to control the chemical ionization ion source to ionize a sample containing an analyte according to any one of claims 1 to 20, wherein the chemical ionization ion source (50) further includes a reactant ion source (51) for ionizing reactants into reactant ions, or a ligand compound ion source (54) for ionizing ligand compounds into ligand compound ions so that ligand compound ions are present in the reaction volume (2).

23. A mass spectrometer (100) for performing mass spectrometric analysis of said analyte contained in a sample containing an analyte according to the method of claim 21; wherein, The mass spectrometer (100) includes a chemical ionization ion source (50) according to claim 22, which is used to ionize the sample containing the analyte into result ions; wherein the mass spectrometer (100) further includes a mass spectrometer (101) for performing mass spectrometry analysis on the result ions to perform mass spectrometry analysis on the analyte, wherein the mass spectrometer (101) is fluidly coupled to the chemical ionization ion source (50) to receive the result ions.

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