Hybrid inductively coupled plasma mass spectrometer (ICP-MS) and method

Abstract

A hybrid inductively coupled plasma mass spectrometer (ICP-MS) system is disclosed that enables elemental and molecular analysis of positive and negative polarities within a single instrument. The system includes an ICP torch that generates a plasma with a buffer gas to produce positively and negatively charged ions from a sample. The system has an insert between a sampler and a skimmer of an ICP-MS interface, characterized by having an aperture and a defined geometry forming a reaction chamber. Various embodiments include an insert having a plurality of apertures for pressure regulation, a rotatable disk for regulating the apertures of the insert, a sliding gate between a sampler and a skimmer for pressure control, a circular gate having adjustable radial apertures in a first vacuum stage, and a second vacuum stage for introducing various gases, reagents, bores, etc. And a reaction chamber inlet for dopants or analytes. These innovations provide precise pressure regulation within the reaction chamber, optimizing the functionality of the system in bipolar elemental and molecular mass spectrometry applications.

Description

Technical Field

[0001] The present invention relates generally to mass spectrometry and mass spectrometers, and more particularly to a hybrid system that can be switched to detect positive or negative ions. Background Art

[0002] Inductively coupled plasma mass spectrometry (ICP-MS) is a cornerstone of analytical chemistry, providing unparalleled capabilities in elemental analysis across diverse fields. This sophisticated technique harnesses the power of high-temperature plasma (i.e., ICP) and mass spectrometry to precisely quantify trace elements in samples with sensitivities reaching parts per trillion to parts per quadrillion levels. Since its inception, ICP-MS has become an indispensable tool in a variety of scientific disciplines, including environmental monitoring, semiconductor testing, clinical and biomedical applications, pharmaceuticals, geology, forensics, and more.

[0003] The significance of ICP-MS lies in its ability to provide highly sensitive, accurate, and simultaneous multi-element analysis in a variety of sample types. By using a high-temperature inductively coupled plasma (ICP) as an ionization source, ICP-MS generates ions from the elements in the sample, which are then separated, identified, and quantified based on their mass-to-charge ratio. This technique can detect and quantify elements across the entire periodic table (from alkali metals to rare earth elements) with extremely high accuracy and speed.

[0004] Furthermore, ICP-MS offers unparalleled versatility, allowing for analysis of a wide variety of sample matrices. Its ability to handle complex matrices makes it invaluable in fields such as environmental analysis, where trace element determination in soil and water samples is crucial for understanding environmental contamination and human health risks. ICP-MS plays a vital role in water testing due to its exceptional sensitivity and ability to detect a wide range of elements at trace levels. Water quality assessment is crucial for protecting public health and ensuring environmental sustainability, and ICP-MS enables comprehensive analysis of contaminants such as heavy metals, metalloids, and rare earth elements. Whether monitoring drinking water sources, evaluating wastewater treatment effectiveness, or investigating environmental pollutants, ICP-MS provides accurate and reliable quantification of potentially harmful substances. By identifying contaminants at ultra-low concentrations, ICP-MS enables researchers, environmental agencies, and water treatment agencies to make informed decisions to protect human health and aquatic ecosystems.

[0005] ICP-MS also plays a key role in semiconductor testing, ensuring the quality and reliability of semiconductor materials vital to modern electronics. Its high sensitivity and ability to detect trace elements at extremely low concentrations make it indispensable for identifying impurities that can compromise semiconductor performance. With the semiconductor industry's stringent purity requirements, ICP-MS provides accurate elemental analysis, enabling manufacturers to pinpoint contaminants from various sources, including those originating from the manufacturing process or raw materials. By precisely identifying impurities, ICP-MS helps maintain semiconductor integrity, optimize yields, and ultimately enhance the functionality and lifetime of semiconductor devices, which are crucial to driving today's technological advancements.

[0006] As demand for lithium-ion batteries continues to increase across a variety of applications, including electric vehicles and portable electronics, ensuring their safety, reliability, and performance is crucial. ICP-MS enables precise elemental analysis of lithium and other battery components, identifying impurities that can impact battery efficiency, lifespan, and safety. By detecting trace levels of contaminants, including metals and other impurities, ICP-MS helps researchers and manufacturers optimize battery materials and manufacturing processes, ultimately improving battery performance, durability, and safety standards.

[0007] In clinical applications, ICP-MS has the potential to revolutionize diagnostics and patient care. Its unparalleled sensitivity and ability to detect and quantify a broad range of elements enables precise analysis of biological samples such as blood, urine, and tissue. In clinical laboratories, ICP-MS serves as a vital tool for identifying trace elements and heavy metals that can indicate nutritional deficiencies, metabolic disorders, or toxic exposures. From monitoring essential elements like zinc and iron to detecting toxic metals like lead and mercury, ICP-MS facilitates early disease detection and personalized treatment strategies. Furthermore, its speed and accuracy streamline research efforts to understand the role of elemental imbalances in various diseases, paving the way for innovative therapies and improved patient outcomes.

[0008] In the pharmaceutical industry, ICP-MS is used for quality control, determining trace metal impurities in drug formulations, and monitoring elemental content in biological samples for pharmacokinetic studies. ICP-MS is widely used in geochemical research to analyze trace elements and isotopes in rocks, minerals, soils, and sediments. These analyses provide insights into geological processes, mineral exploration, and environmental geochemistry. Forensic analysts rely on ICP-MS to analyze forensic evidence, such as hair, blood, and soil, for trace elements. This aids criminal investigations by identifying the source of evidence and linking suspects to crime scenes.

[0009] While ICP-MS is a powerful analytical technique, it does have certain limitations. One significant limitation is the potential for spectral interferences, where the mass spectrometer mistakenly identifies ions from interfering species as the target analyte. This can lead to inaccurate quantification and misinterpretation of results, particularly in complex sample matrices containing high levels of background elements (isobaric interferences) and molecules (polyatomic interferences). Mitigating spectral interferences often requires careful and complex method development, such as using collision / reaction cells or high-resolution mass spectrometry to remove interfering ions, or employing mathematical correction algorithms.

[0010] Furthermore, ICP-MS requires specialized instrumentation and skilled operators, and its acquisition and maintenance costs are relatively high compared to other elemental analysis techniques. Besides the need for a high-purity argon gas source and a large chiller to cool the sampling interface, the complexity of the instrument setup increases operating costs, floor space, and technical challenges. Furthermore, the instrument's sensitivity to matrix effects and sample preparation requirements can necessitate extensive method optimization and quality control measures, increasing investment in time and resources.

[0011] Another inherent limitation of ICP-MS is its inability to provide chemical information beyond elemental composition. While it excels at detecting and quantifying elements down to ultratrace levels, it cannot distinguish between the different chemical forms, or oxidation states, of an element present in a sample. This can be problematic when analyzing samples containing different species of the same element, or when speciation information is crucial for understanding biological or environmental processes. However, there are techniques that can be combined with ICP-MS to provide a certain level of molecular information. One such technique is speciation analysis, which aims to determine the chemical forms (speciations) of an element present in a sample. Speciation analysis can be performed by combining liquid chromatography (LC) or gas chromatography (GC) with ICP-MS (LC-ICP-MS or GC-ICP-MS). In LC-ICP-MS or GC-ICP-MS systems, chromatography separates the different chemical species before they enter the ICP-MS instrument. This separation allows the identification and quantification of individual molecules based on their retention time in the chromatographic column. For example, LC-ICP-MS can be used to analyze metal complexes, organometallic compounds, or metalloproteins in biological samples, while GC-ICP-MS can be applied to volatile metal species or metal-containing organic compounds.

[0012] While these techniques provide valuable information, it is worth noting that ICP-MS itself does not directly provide molecular analysis. Instead, it relies on chromatographic separation techniques to separate molecular species before detection. Therefore, while ICP-MS combined with chromatography can provide insights into molecular species containing target elements, it cannot provide direct molecular analysis in the same way as techniques such as mass spectrometry-based methods such as electrospray ionization mass spectrometry (ESI-MS), electron impact gas chromatography mass spectrometry (EI-GC-MS), or matrix-assisted laser desorption / ionization mass spectrometry (MALDI-MS). This inherent limitation is due to the nature of the ionization source used in ICP-MS. ICP, with its high temperature (5000-10000K), essentially breaks down molecules into their constituent ions, stripping away any information about the molecular structure of the sample. As a result, unlike other techniques that maintain molecular integrity and provide insights into molecular composition, ICP-MS focuses primarily on elemental analysis.

[0013] Here, we introduce the first-ever hybrid ICP-MS system with multiple analytical modes. This system, equipped with a novel sampling interface, is capable of analyzing both elemental and molecular samples in both positive and negative modes. In addition to providing complete sample resolution and ionization similar to traditional ICP-MS, this system also offers the ability to softly ionize molecular samples. This soft ionization capability allows for the ionization of fragile molecules without fragmentation, enabling the analysis of intact molecules.

[0014] Compared to conventional electron impact GC-MS (EI-GC-MS), the new hybrid ICP-MS can be combined with a gas chromatograph to significantly expand the applications of GC-MS. This technology also improves the detection limit of MS instruments by many orders of magnitude. This technology utilizes the high abundance of charged and / or electronically excited species and free electrons within the thermal plasma to produce high yields of intact positive and negative molecular ions through soft ionization.

[0015] It's common practice in laboratories to use different mass spectrometers for different sample types. For example, while ICP-MS is used for elemental analysis of samples primarily in solution, LC-MS and GC-MS are designed to analyze samples in the liquid and gas / volatile phases, respectively, with molecular states. Consequently, analytical laboratories may need to maintain several different mass spectrometers or other types of analytical instruments to handle diverse sample types, sample matrices, or analytes for different applications. In such cases, using a mass spectrometer that can combine the features of different mass spectrometers and handle diverse sample types is highly valuable. This reduces costs, the number of operators with different skill sets, the need for diverse technical training, and the system footprint, freeing up valuable laboratory space. The advent of hybrid ICP-MS systems capable of analyzing both elemental and intact molecular ions represents a groundbreaking advancement in analytical chemistry. This innovative technology combines the elemental analysis capabilities of traditional ICP-MS with the molecular analysis capabilities. By integrating these capabilities into a single platform, these hybrid systems offer numerous advantages and open new avenues for research and analysis in various fields.

[0016] A key advantage of a hybrid ICP-MS system is its ability to provide comprehensive chemical characterization by simultaneously analyzing both elemental and molecular ions within a single sample. This holistic approach enables researchers to gain a deeper understanding of sample composition and structure, facilitating more informed decision-making in fields such as pharmaceuticals, environmental science, and materials analysis. By combining multiple ionization modes, a hybrid ICP-MS system offers greater analytical flexibility compared to traditional ICP-MS instruments. Researchers can choose between elemental or molecular analysis modes, depending on the specific requirements of their samples and their research objectives. This versatility enhances the system's utility in a wide range of applications, from trace metal analysis to metabolomics and proteomics studies. Summary of the Invention

[0017] A hybrid inductively coupled plasma mass spectrometer (ICP-MS) system is provided. The system allows both elemental analysis and molecular analysis to be performed in one system. The system includes an ICP torch for generating plasma using a buffer gas (M) to generate positively and negatively charged ions from a sample. The torch is fixed to a torch housing, which is also equipped with a sampling interface. The sampling interface includes a sampler cone having a sampler orifice and is placed in front of the plasma to absorb ions generated by the plasma. A first vacuum stage generated by a roughing pump with a pumping speed generates a first vacuum stage pressure of several Torr behind the sampler cone. A skimmer with an orifice placed behind the sampler orifice is provided to skim and partially absorb the gas and ion flow emitted from the sampler orifice. A second vacuum stage is located behind the skimmer cone mounted on a skimmer holder pumped by a turbomolecular pump, further reducing the pressure to avoid recombination and neutralization of ions. An insert having an insert orifice, geometry, and form factor (shape design, i.e., a cone with a cone angle and aspect ratio) is placed between the sampler cone and the skimmer. The insert is configured to form a reaction chamber between the sampler cone and the insert. The reaction chamber pressure is controlled by the insert orifice and sampler orifice dimensions and the pumping speed of the roughing pump. This allows the pressure in the reaction chamber to be between a few Torr high and tens or hundreds of Torr high. The insert orifice allows ions to pass toward the skimmer orifice. By changing the pressure in the reaction chamber, the ICP-MS mode can be switched from elemental analysis to molecular analysis.

[0018] In elemental mode, the hybrid ICP-MS system is configured to keep the target element ions sampled from the plasma unmodified to enhance the sensitivity and performance of the ICP-MS instrument for elemental analysis and to minimize the formation of any molecular species within the spectrometer stages while maintaining oxide levels below 1-3%.

[0019] In molecular mode, high voltage is generated in the reaction chamber, resulting in the elimination of unwanted positive ions generated by the plasma and preventing them from entering the analytical equipment of the mass spectrometer. In addition, their charge can be used to ionize target analytes in the presence of excited neutral species (metastable states) through charge transfer ion / chemical reactions in the "positive" mode.

[0020] In another embodiment of the system, the insert has one or more holes around its central opening to regulate the pressure within the reaction chamber.

[0021] In another embodiment of the system, a rotatable disk is provided beside the insert to open and partially or completely close the holes of the insert to control the pressure within the reaction chamber.

[0022] In another embodiment of the system, instead of an insert, a sliding gate having a set of openings is provided, which can be slid between the sampler and the skimmer to form a reaction chamber with a desired pressure.

[0023] In another embodiment of the system, a circular gate having one or more radial holes is provided in the first vacuum region to control the reaction chamber pressure. The circular gate is composed of two concentric rings that rotate one above the other to open and close a set of openings in the circular gate, thereby controlling the pressure in the reaction chamber. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] The embodiments of the present invention will be described below with reference to the accompanying drawings, which are provided for illustration and not to limit the scope of the claims, wherein like numerals denote like elements. Figure 1 A conventional ICP system is shown; Figure 2 One embodiment of the present hybrid ICP-MS system is shown having an insert to form a reaction chamber between the sampler cone and the skimmer cone; Figure 3 Another embodiment of the present hybrid ICP-MS system is shown having an insert and channels for introducing reactant gases into the reaction chamber; FIG4 shows another embodiment of the present hybrid ICP-MS system having an insert with a plurality of holes around a central orifice of the insert; Figure 5A Another embodiment of the present hybrid ICP-MS system is shown having a rotatable disk that is placed behind the insert and rotates to close the peripheral opening of the insert; Figure 5B Another embodiment of the present hybrid ICP-MS system is shown having a rotatable disk that is placed behind the insert and rotated to open the peripheral opening of the insert; Figure 6A Another embodiment of the present hybrid ICP-MS system is shown having a sliding gate that is positioned behind the insert and slides to close the peripheral opening of the insert; Figure 6B Another embodiment of the present hybrid ICP-MS system is shown having a sliding gate that is positioned behind the insert and slides to open the peripheral opening of the insert; Figure 7 Another embodiment of the present hybrid ICP-MS system is shown having a circular gate positioned in the first vacuum stage, the circular gate configured to form a reaction chamber between the sampler cone and the skimmer cone; Figure 8Another embodiment of the present hybrid ICP-MS system is shown having an insert and being air cooled; Figure 9 Another embodiment of the present hybrid ICP-MS system is shown having an insert channel for introducing a reaction gas into a reaction chamber, wherein analytes are introduced directly into the reaction chamber using a micro / nano spray; Figure 10A Sample test results are shown; Figure 10B Sample test results are shown; Figure 10C Sample test results are shown; Figure 11 Sample test results are shown; Figure 12 Sample test results are shown; Figure 13A Sample test results are shown; Figure 13B Sample test results are shown; Figure 14A Sample test results are shown, and Figure 14B Sample test results are shown. DETAILED DESCRIPTION

[0025] Figure 1A schematic diagram of an ICP-MS sampling interface and an ICP source is shown, the source comprising an ICP torch 100 housed in a torch housing 101 having an exhaust port 102. In a conventional ICP-MS, a plasma 110 is placed in front of a sampler cone 112. The sample cone 112 has an orifice 115 that draws in ions 116 generated by the plasma 110. The sampler cone is also mounted on a water cooler 120 to cool the sampler 112 and to prevent the orifice, sealing mechanisms (i.e., O-rings and gaskets), or any other heat-sensitive components from being thermally damaged or melted by the high temperatures of the plasma. Typically, a roughing pump 125 is connected to a first vacuum stage 130 to generate a typical pressure of a few Torr behind the sampler. The ion sampling interface 120 is designed to transfer ions from the sampler orifice to one (or more) mass analyzers 199 (which are located in the highest vacuum stage) in the fastest possible manner while minimizing collisions with background gases. This is to avoid any recombination, cluster formation or neutralization of ionic species formed in the plasma and to transfer the target element ions to the mass analyzer exactly as they were formed in the plasma without any changes. Therefore, the skimmer orifice 140 is usually placed just after the sampler orifice 115 to skim and partially aspirate the gas and ion stream emerging from the sampler orifice. The area behind the skimmer cone 145 mounted on the skimmer mounting bracket 152 (i.e., the second vacuum stage 150) is usually pumped by a turbomolecular pump 155 to further reduce the pressure and avoid recombination and neutralization of the ions. The optimal distance x between the two orifices is s 160 is usually based on Mach disk x M The position is determined by the expansion of the supersonic free jet behind the sampler orifice and is calculated according to the following formula: Where D0 is the diameter of the sampler orifice, P0 is the pressure of the plasma (usually atmospheric pressure), and P1 is the pressure in the first vacuum stage behind the sampler orifice. The skimmer orifice is usually placed at x M Before (for example, in x MThe primary skimmer cone is located at 70% or 2 / 3 of the way through the sampler cone to avoid supersonic shock waves forming at or before the skimmer, which could disrupt and disperse the ion beam. In some cases, additional skimmers (such as superskimmers) and orifices are placed after the primary skimmer cone to more slowly reduce the pressure from atmospheric pressure to vacuum, further diluting the gas flow sampled from the plasma. The area behind the additional skimmers is typically evacuated by a turbomolecular pump. Following the skimmer cone, various ICP-MS systems employ extraction lenses, ion optics, ion guides, ion deflectors, photon blockers, or other components to extract, focus, and shape the ion beam and transfer it to the next stage of the MS system for analysis by the mass filter. These components may also be used to prevent photons and neutral species from reaching later stages of the spectrometer, particularly the ion detector. Furthermore, the sampler and skimmer cones are designed so that the vacuum pump can remove gas molecules as quickly as possible to avoid pressure buildup or increase in the various vacuum stages, which could lead to ion scattering, recombination, and neutralization. All of these arrangements in conventional ICP-MS are designed to ensure that the target element ions sampled from the plasma remain unmodified, thereby improving the sensitivity and performance of the ICP-MS instrument for elemental analysis. In particular, the goal of conventional ICP-MS is to minimize the formation of any molecular species within each stage of the spectrometer and to maintain oxide levels below 1-3%.

[0026] As mentioned above, ICP-MS relies on a high-temperature inductively coupled plasma (ICP) source to generate a high yield of atomic ions for elemental analysis. Atomization and ionization processes occur within the ICP source, producing a certain abundance of atomic cations. The high-temperature plasma in the ICP-MS source is the result of introducing AC power into the plasma gas within the ICP torch. The frequency of the power is typically in the radio frequency range (e.g., 27.12 MHz or 40.68 MHz), but microwave frequencies (e.g., 2.45 GHz) have also been used. Argon (Ar) is the most common gas used for this purpose. Helium (He), nitrogen (N2), air, and other gases (monoatomic or diatomic) have also been used. The success of the ICP plasma source is due to its high temperature, which produces a high yield of positive ions. For elemental analysis, this is an ideal source for generating high yields of target positive atomic ions. However, this source is not suitable for generating negative ions or analyzing molecules. This, in turn, limits the application of ICP-MS in obtaining a complete profile of the elemental and molecular species in a given sample.

[0027] When Ar is used as the plasma gas, undesirable ions and species such as Ar cations (Ar + ), argon neutral metastable state (Ar * ) and argon metastable cations (Ar +* ), as well as diatomic and triatomic cations such as ArO + and ArH + (See Figure 1 ). The presence of high yields of these species can interfere with the detection of target ions and limit the ion transmission efficiency of the MS equipment, thereby limiting the proper detection of the desired ions. This is why conventional ICP-MS systems typically use a method or device to prevent these species from reaching the mass spectrometer and later stages of the ion detector. It is understood that in an ICP plasma source, the net charge is zero (i.e., global charge neutrality). Therefore, an equal amount of negative species must be present relative to the positively charged species. Although there may be a certain level of negative atomic and molecular species in the plasma, the large number of free electrons (e - ) is the main reason for maintaining charge balance.

[0028] The plasma discharge within the ICP torch, using a selected buffer gas (M), produces positively and negatively charged ions. In most cases, a noble gas is used as the buffer gas. Argon is the most common gas, while helium and other gases are also used in some cases. In both cases, due to the low electron affinity of the noble gas, the abundance of positively charged ions is much greater than that of negatively charged ions.

[0029] The present invention introduces a hybrid ICP-MS that is capable of performing both elemental and molecular analysis in various operating modes. The hybrid ICP-MS is equipped with technology, equipment and techniques that utilize some of the materials generated by the plasma to produce high yields of positively and negatively charged ions. There are two main advantages: first, the unwanted positive ions generated by the plasma are eliminated and prevented from entering the analytical equipment of the mass spectrometer. In addition, their charge can be used to ionize the target analyte in a "positive" mode through charge transfer ion / chemical reactions. Second, the presence of excited neutral species (metastable states) and free electrons can be an excellent source for generating target negative ions.

[0030] In this paper, we introduce a new ICP-MS interface that, for the first time, enables users to switch between multiple operating modes as needed for elemental analysis, molecular analysis, and background interference removal. These new capabilities provide users with additional control over system operation and open the door to the design and development of new analytical methods with higher precision and selectivity than was previously possible. It also provides the ability to directly identify and quantify molecules and compounds.

[0031] Figure 2A first embodiment of the invention is shown in which an insert 200 is mounted between the sampler 112 and the skimmer orifice 140. The insert 200 may be circular, square, asymmetric or any arbitrary shape or form factor. The insert has at least one orifice 210 to allow ions 216 to pass through towards the skimmer orifice. This will form a reaction chamber 220 between the sampler 112 and the insert 200 where the pressure is higher than the pressure within the first stage 130 of the vacuum chamber pumped by the roughing pump 125. The reaction chamber is not pumped directly by any vacuum pump. Instead, it is pumped through one or more of its orifices which will result in a higher pressure behind the sampler and within the reaction chamber. Depending on the size of the orifices in the insert and sampler and the pumping speed of the roughing pump, the pressure within the reaction chamber may range from a few torr to tens or hundreds of torr. For example, for a sampler using a pumping speed of 30-50 m / s 3 / hr with a sampling orifice of about 1 mm and a vacuum pump with an insert orifice of 2-5 mm, the pressure inside the reaction chamber can be between 20-200 Torr. This is higher than the typical pressure of 1 to 3 Torr inside the first vacuum stage of a typical ICP-MS system. The geometry and form factor of the insert and the resulting reaction chamber are configured to provide the required conditions. Depending on the pressure inside the reaction chamber, a supersonic free jet can be formed and emanate from the rear of the sampler orifice, which jet can reach the orifice of the insert. Therefore, preferably, the insert has a tapered geometry to avoid the formation of normal shock waves on its orifice (see Figure 2 ). The angle of the cone is determined based on the Mach number of the free jet. For example, the cone angle can be between 20 and 80 degrees. The geometry of the insert can also be flat, or it can have a concave shape, depending on the extent or presence of supersonic expansion and the gas flow pattern within the reaction chamber. The concave shape can also help focus the flow pattern towards the insert orifice and avoid any recirculation or dead zones within the reaction chamber, which could cause memory effects or contamination. As another example, the geometry of the insert around the orifice area can be designed to avoid interfering with the gas flow and ions traveling around the central axis between the sampler and skimmer cones. In this case, the edges of the insert orifice are preferably sharp to minimize the interaction of ions with the insert orifice. In addition, it is preferred to use a smaller cone angle on the insert around the orifice to minimize the formation of normal or bow shocks on the orifice. For example, the cone angle can be between 40-60 degrees or less.

[0032] Because the pressure in the reaction chamber is high, ions and other substances sampled from the plasma may be modified by various reactions. By providing an appropriate level of higher pressure in the reaction chamber, the mean free path will be short enough to allow any given ion / molecule reaction to proceed completely. The analyte is introduced into the reaction chamber directly or through any heated spray chamber, evaporator, thermal desorption device or other sample introduction method (depending on the sample type), allowing the analyte to ionize in both negatively and positively charged states via gas phase ion chemistry. In this case, the plasma power may be significantly reduced (for example, to 300-500W) so that the plasma can be used to desolvate the sample rather than completely decompose it. In the case where the user prefers to perform elemental analysis similar to a conventional ICP-MS system, the insert can be removed, or the pressure in the reaction chamber can be changed as described below. Thus, the user can choose between various operating modes for elemental and molecular analysis. These are unique aspects of the present invention.

[0033] The insert can be mounted on the interface body below the sampler cone. To this end, a threaded insert can be used to secure the insert in place. Alternatively, the insert can be attached to the interface using screws. A quick-connect feature can be implemented in the insert design to allow the insert to be quickly assembled or removed from its position without the use of any screws or fasteners. Sealing components, such as O-rings, gaskets, or washers, can be used to properly seal the area within the reaction chamber from the first vacuum stage or atmosphere to enable more reliable pressurization of the reaction chamber. When using rubber O-rings, the temperature of the interface and insert should preferably be kept below 100°C to avoid damage to the O-rings. To this end, the interface can be water- or air-cooled to improve heat transfer rates. Alternatively, metal or graphite gaskets can be used for this purpose, which can withstand higher temperatures. The roughness of the sealing surface should be kept below 1.6 μm, more preferably 0.8 μm. Given the relatively low pressures within the reaction chamber and the first stage of the mass spectrometer (compared to the pressure ratio of atmospheric pressure to the first vacuum stage), sealing components may not be required between the insert and the interface body.

[0034] To avoid overheating of the insert, which could lead to oxidation, melting, or thermal damage, the insert can be made of a material with high thermal conductivity, a high melting point, and good to excellent corrosion and oxidation resistance. Some examples include aluminum, nickel, copper, stainless steel, molybdenum, brass, and their various alloys or compositions. The surface of the insert can be plated with gold, silver, or platinum to improve corrosion resistance and inhibit oxidation, or coated with a ceramic or thermal barrier coating such as alumina, yttria-stabilized zirconia, yttria, or a combination of these materials. Ceramics such as alumina, boron nitride, and silicon nitride can be used for the insert, as they have relatively high thermal conductivity, very high melting points, excellent corrosion resistance, and good thermal shock properties. In some cases, it is beneficial to keep the temperature of the insert and the reaction chamber walls as high as possible (as long as the properties of the materials used for these components allow and as long as this does not cause thermal damage, oxidation, or corrosion) to avoid deposition and memory effects. This can be achieved by limiting the rate of heat transfer from these components to the surroundings to keep as much of the heat absorbed from the plasma as possible within these components.

[0035] Typically, the insert can be electrically grounded through the interface body. However, the insert can also be electrically isolated from the interface by using some ceramic or plastic spacer between the insert and the interface body. In this case, a positive or negative voltage can be applied to the insert to focus ions exiting the insert as they travel toward the skimmer orifice and to extract ions emerging from the sampler orifice to improve ion transmission.

[0036] Alternatively, the insert may be mounted, assembled or screwed onto the sampler cone to form the reaction chamber together with the sampler cone. In this way, both the insert and the sampler cone may be more easily accessible and disassembled for cleaning, maintenance and repair purposes.

[0037] Figure 3 A second embodiment of the present invention is shown in which a channel 300 is implemented within an interface body 320 to enable the introduction of a target gas, reagent, dopant, or sample (i.e., analyte) 340 into the reaction chamber. Portions of this channel can be implemented within a sampler cone or insert. For example, a gas, reagent, dopant, or sample can be introduced into the reaction chamber through an opening in the interface body. These gases can then enter the reaction chamber directly or pass through a set of one or more openings and channels within the sampler cone or insert before entering the reaction chamber. The plasma heat absorbed by the sampler cone or insert or interface body can be used to ensure that the gas, reagent, dopant, or sample introduced into the reaction chamber does not condense as it passes through the channel. The heat can also be used to evaporate or desolvate any liquid or unevaporated material within the channel. The heat can also help keep the channel, sampler cone, and insert clean by evaporating and degassing any material deposited on their surfaces, thereby providing a self-cleaning interface and reaction chamber to minimize memory effects and contamination problems.

[0038] The flow rate of gas introduced into the reaction chamber can be precisely controlled using a mass flow controller, precision valve, or pressure controller. To minimize sample or reagent loss within the reaction chamber, the aforementioned channel can be designed to introduce the sample or reagent directly in front of the insert orifice. Furthermore, to better mix all gaseous species and increase homogeneity and reaction rate within the reaction chamber, a swirling flow pattern can be induced within the reaction chamber by introducing the gas or sample tangentially through one or a set of openings distributed around the reaction chamber. This improves mixing of gases and ions from the plasma with materials introduced into the reaction chamber through the channel.

[0039] In this case, the pressure and temperature of the reaction chamber can be further controlled and adjusted by introducing various gases or samples into the reaction chamber while controlling the flow rate. This will create a situation in the reaction chamber that is suitable for soft ionization of the sample. In an exothermic reaction, the ionization energy of the analyte (An) introduced into the reaction chamber must be less than the ionization energy of the buffer gas M (such as argon) so that the charge transfer reaction can release energy (exothermic reaction). The energy released is proportional to the difference in ionization energies of the reactant partners and is generally dissipated throughout the structure of the analyte molecule. The small amount of dissipated energy is unlikely to be strong enough to destroy any bonds of the charged analyte. In some cases, the structure of the positively or negatively charged analyte is unstable; therefore, it will spontaneously fragment.

[0040] In most cases, when Ar is used as a buffer gas, Ar + 、ArO + 、ArH + and Ar2 + The presence of Ar is highly dominant in the mass spectra. In addition, the glow discharge produced by these species within the mass spectrometer is clearly visible. * and the presence of free electrons (e-). Note that any other buffer gas, whether monatomic or diatomic, can be used in this manner and will produce a variety of ionic, neutral, and metastable species that can be used within the reaction chamber. Here, we utilize the positively charged Ar species within the reaction chamber to ionize the target analyte via soft charge transfer to produce high yields of intact target analyte molecular ions. This new technique allows for unprecedented high yields of intact molecular ions, which are not possible with other ICP-MS systems. In this context, the following reactions can be considered: Charge transfer: M ± +An→An ± +M+δE In the presence of analyte in the reaction chamber, it is expected that the buffer ions (M + ) to the positive charge transfer ratio M- More dominant.

[0041] Free electrons are considered the most abundant charged species in thermal plasma sources. Many studies have shown that these electrons have energies less than 10 eV, more commonly around 1 eV. This makes them suitable for attachment to any molecule or atom with a negative electron affinity. Electron attachment reactions typically proceed rapidly with high reaction cross-sections. The presence of free electrons and analyte atoms or molecules within the reaction chamber allows for efficient electron attachment. These reactions consume very little energy, making them highly unlikely to cause fragmentation. Electron attachment: e - +An→An - +M+δE

[0042] In addition, due to the plasma discharge in the ICP torch, metastable species are formed, which is evident from the glow discharge behind the sampler interface and at different points in the mass spectrometer. The most controlled ionization process known is Penning ionization, in which the energy of the metastable state is transferred to the reactant partner. If the ionization energy of the reactant partner is less than the excitation energy of the metastable species, all of this energy will be transferred to the reactant partner, resulting in efficient ionization of the reactant molecules (Penning ionization) and the generation of free electrons. This is a selective ionization process because the metastable state is well understood and the energy of the excited state is well classified from the ionization energy of the reactants. Therefore, appropriate reactions can be designed to allow Penning ionization to proceed with high selectivity. In these types of exothermic reactions, the amount of energy dissipated is simply equal to the difference between the energy of the excited electron (metastable energy level) and the ionization energy of the reactant molecule. This is not a significant amount that leads to fragmentation. Therefore, the intact target molecule can be ionized in high abundance, which is of great significance, especially in quantitative analysis. Energy transfer via Penning ionization: M + +An→An + +M+e - +δE

[0043] The free electrons generated by the above reactions can also be used to form complete negatively charged ions via electron attachment reactions: Electron attachment: e - +An→An - +M+δE

[0044] Figure 4A Another embodiment of the present invention is shown. In this case, in addition to the central orifice 410, an opening 420 or opening is implemented in the insert 400, such as Figure 4B As shown, Figure 4BA top view of one example of an insert design is shown. The openings can have any shape and form factor. For example, they can be circular, arcuate slots and annular openings, distributed symmetrically or asymmetrically around a center. The number and area of ​​these openings and apertures are adjusted to achieve the pressure level required for elemental and molecular analysis within the reaction chamber. As a result, if no analytes, gases, reagents or dopants are introduced into the reaction chamber, the pressure within the reaction chamber can be equal to or slightly higher than the pressure of the first stage. In this way, the ion beam 416 consists primarily of elemental ions formed within the plasma, which can pass through the reaction chamber without significant collisions or recombination. This mode of operation is similar to conventional ICP-MS systems, where the level of oxides (typically characterized based on the ratio of cerium oxide ions to cerium ions) can be maintained below 1-3%, which is common practice in the art. In this case, the distance between the sampler orifice and the skimmer orifice is maintained at x according to the above formula M As a result, by introducing and regulating the gas flow into the reaction chamber to adjust the pressure within the reaction chamber, users will be able to rapidly switch between elemental and molecular analysis modes, providing the first-ever hybrid ICP-MS.

[0045] Figure 5A and Figure 5B Another embodiment of the present invention is shown in which a rotatable disk 530 is implemented within the interface. The rotatable disk has one or more openings. When the opening of the rotatable disk is aligned 532 with the opening or openings of the insert 500, the reaction chamber 520 will not be pressurized, thereby providing an elemental analysis mode ( Figure 5B When the openings are misaligned 531, the reaction chamber will be pressurized, which will result in modification of the ion beam or the creation of new analyte ions (molecular, positive or negative molecular or elemental ions) through the above-mentioned gas phase reactions ( Figure 5A ). The rotatable disk can be moved using a motor, an actuator, pneumatically, manually or via any other method to switch between various analysis modes. For example, an electric servo motor can be implemented in the interface, which can rotate the rotatable disk through a set of gears. In another case, the rotatable disk can be connected to a handle that extends outside the interface and is accessible outside the vacuum chamber. Therefore, the handle can be moved manually or by a linear pneumatic actuator to rotate the disk. Sealing components such as O-rings, gaskets or washers can be used between the rotating disk, the interface body and the insert to separate the space in the reaction chamber from the first stage seal of the mass spectrometer so that the gas and analyte can be kept at the required pressure level in the reaction chamber. From a sealing point of view, it may be more convenient to implement a mechanism for rotating the disk inside the vacuum chamber. Otherwise, additional sealing components will be required to avoid atmospheric leakage from outside the vacuum chamber.

[0046] Figure 6A and Figure 6BAnother embodiment of the present invention is shown. In this case, instead of implementing an insert to form the reaction chamber, a sliding gate 600 having an orifice 620 is implemented that can be manually or automatically actuated and moved to slide between the sampler orifice and the skimmer orifice to form the reaction chamber 630 ( Figure 6A ), or the sliding gate 621 is removed to prevent the formation of the reaction chamber 640. Sealing components such as O-rings, gaskets or washers are used to prevent and control gas leakage between the reaction chamber, the first stage of the spectrometer and the atmosphere. To this end, the gate can be moved electronically or pneumatically or manually. Thus, the user will be able to switch between the conventional ICP-MS elemental analysis mode and the molecular analysis mode again as required. The orifice of the gate allows the product ions in the reaction chamber to reach the skimmer orifice. The distance between the sampler orifice and the skimmer orifice is similarly determined according to the Mach disk x M The position of (as provided by the above formula) is determined to ensure optimal operation in elemental analysis mode.

[0047] Figure 7 Another embodiment of the invention is shown in which a circular gate 700 is implemented instead of an insert or a sliding gate. The circular gate can have one or several radial openings (not shown) to achieve the desired pressure level within the reaction chamber 720 and avoid over-pressurizing the vacuum level after the skimmer orifice by pushing excess gas through the skimmer orifice. For example, the circular gate can be composed of two cylindrical parts. Each of the two parts can have one or several openings or openings distributed radially around its central axis. One of the parts can be stationary and the other part can be rotated relative to the stationary part using a mechanism. Figure 5A and Figure 5B Similar to the design shown, as the moving part rotates, its apertures or openings can align with those of the stationary part, depressurizing the reaction chamber. Otherwise, if the moving part completely or partially covers and blocks the apertures and openings of the stationary part, the reaction chamber will be pressurized. In this way, for the elemental analysis mode of operation, the gate can be opened, allowing the vacuum pump to fully evacuate the first vacuum stage behind the sampler orifice to the several torr typical in conventional ICP-MS.

[0048] Figure 8 Another embodiment of the present invention is shown, where the new interface has an air cooling system 800 for air cooling, rather than the water cooling system common in conventional ICP-MS. To facilitate maintenance and repair, a gate valve can be implemented in the port behind the skimmer cone to allow access to the sampler cone, insert, and skimmer cone without breaking vacuum. In this way, the gate valve can be closed to maintain vacuum outside the skimmer and avoid any problems with the vacuum pumps (i.e., roughing pumps and turbomolecular pumps) due to high pressure or unnecessary exposure of sensitive components within the mass spectrometer to the atmosphere and contamination when servicing the port. Once the gate is closed, the sampler cone, insert, and skimmer cone can be easily removed for cleaning or replacement. This will also reduce instrument downtime.

[0049] In all of these embodiments, several sample introduction systems (depending on the sample type and the desired analysis mode) can be used to introduce the analyte into the ICP-MS system through the syringe tube of the ICP torch or through a channel implemented in the reaction chamber interface. In the case of elemental analysis, it is generally desirable to run the plasma at a higher power (e.g., between 700-1600W) to completely decompose the sample and ionize the elements, avoiding higher levels of oxides and molecular species. In this case, the sample can be introduced by the ICP torch. For the soft ionization of molecular samples, the sample can be introduced into the ICP-MS system by a plasma torch with a lower power (e.g., 300-500W) or higher than the optimal carrier gas flow rate to avoid decomposing the target molecule by providing a cooler plasma. In this way, the plasma will typically act as an evaporator, desolvator, or thermal desorption system, and the soft ionization process will primarily occur within the reaction chamber.

[0050] Alternatively, it may be more desirable to introduce the sample in gaseous, solid (e.g. fine solid aerosol) or liquid (e.g. nano or micro spray or fine aerosol) state directly into the reaction chamber. This would provide a more efficient and less aggressive scenario for the soft ionization of fragile molecules. Figure 9 An embodiment of the present invention is shown in which the sample is introduced into the reaction chamber via a microspray or nanospray 900. In this case, the temperature within the reaction chamber is high enough to allow desolvation, evaporation, or thermal desorption of the spray. In other cases, the sample can be introduced into the reaction chamber via an ICP torch, through a channel, or directly into the reaction chamber, by electrospray ionization (ESI), or from a gas chromatograph (GC), or a liquid chromatograph (LC), a laser ablation system (LA), or any other sample introduction method.

[0051] After the skimmer orifice, the mass spectrometer may have various components and electrical equipment to extract, form and focus the ion beam emerging from the skimmer orifice. For example, one or several radio frequency only ion guides may be used after the skimmer for this purpose, in combination with an ion lens. Alternatively, one or several ion lenses may be used to focus the ion beam and transfer it to the mass analyzer. In order to prevent any photons or neutral species from reaching the later stages of the mass spectrometer, an ion deflector or photon limiter may be used after the skimmer. To analyze the ions, the mass spectrometer may have a single quadrupole, triple quadrupole, sector field, ion transport, ion trap, Fourier transform ion cyclotron resonance mass spectrometer or time of flight architecture. In any case, due to the unique ability of the present invention in generating positive and negative ions, the hybrid ICP-MS system can analyze ions in both positive and negative modes. Likewise, the ion detector is equipped with a bipolar function to detect both positive and negative ions. To this end, various ion detector types can be used, such as continuous dynodes, discrete dynodes, Faraday cups, multi-channel plate detectors (MCPs), dual-mode detectors, avalanche dynodes, etc. This is unprecedented in the art, as conventional ICP-MS systems are only capable of and configured to analyze positive ions. It should be mentioned that, as described above, the analyte can be introduced into any other area of ​​the mass spectrometer instead of using a reaction chamber, which allows ion chemistry to be performed using ions and metastable species and electrons generated in the plasma or reaction chamber (e.g., ion guides, collision / reaction cells, etc.).

[0052] Another capability of the hybrid ICP-MS system is that it can eliminate background interferences from argon species. As mentioned above, argon (Ar) is the most commonly used gas in ICP-MS. Therefore, a high abundance of argon cations (Ar + ), argon neutral metastable state (Ar * ), argon metastable cation (Ar *+ ) and other argon diatomic and triatomic cations, such as ArO + and ArH + These substances have many negative effects on the detection of certain target element ions. For example: potassium ( 39 K) and calcium ( 40 Ca) is a very important element in many scientific disciplines. However, 38 ArH + (39) and 40 Ar + (40) The presence of such high abundance obscures the correct detection of these target atoms. 41 Calcium is very important in medical diagnosis. 41 Ca + However, even with high-resolution equipment, 40 ArH +The presence of will also hinder the detection of this isotope. Another isobaric interference is 40 ArO + (56) and the main isotopes of iron ( 56 Fe + ).

[0053] Some of the most troublesome interferences come from the argon ICP source, which generates a certain abundance of argon ions and molecular species. The most significant elements subject to isobaric and polyatomic interferences from the plasma gas species include iron (Fe), calcium (Ca), potassium (K), and selenium (Se).

[0054] Calcium is the third most abundant metal and the fifth most abundant element in the Earth's crust. It has many different applications, making accurate analysis of trace and ultra-trace levels of calcium very important. While ICP-MS is the most powerful technique for elemental analysis, the most abundant isotope of calcium is 40 Ca is completely consumed by the plasma gas 40 As a result, accurate and sensitive detection and isotopic analysis of calcium using ICP-MS presents significant challenges.

[0055] Potassium is used in various fields such as agriculture, medicine, and food industry. 41 Potassium also has some new applications in pharmaceutical synthesis, life sciences, and biology. Analyzing potassium at ppb-ppt levels as a contaminant on and within semiconductor components is also important. Mining potassium fertilizers has significant environmental impacts, so there is a need to monitor and track potassium fertilizer levels in the environment, mining trails, and abandoned mines (by analyzing natural potassium radionuclides, such as 40 K) as part of a water treatment program for mining companies. These applications emphasize the importance of accurate potassium measurement and speciation in various samples. Similar to calcium, 40 Ar ions interfere with the most abundant potassium isotope 39 K, which is caused by the large amount of argon ions generated in the plasma 40 The tail of the Ar peak forms in the mass spectrum 39 K peak, resulting in low accuracy in analyzing this element. 38 ArH species also interfere 39 K. Another isotope of potassium 4 1K was also 40 Covered by ArH species.

[0056] For iron, the most abundant isotope is 56 Fe, whose mass is the same as that from the plasma 40 Ar 16Iron is the same substance as O. Obviously, iron has many applications across various industries and is widely used in steel production, manufacturing, the automotive industry and transportation, civil engineering and construction. In the body, iron is responsible for the transport, supply and storage of oxygen and contributes to metabolism, the immune system and cognitive function. 56 Due to the interference of Fe, the analysis of iron is difficult and requires complicated procedures and instruments.

[0057] Selenium (Se) is another element whose most abundant isotope is 80 Se is removed by the plasma 40 Ar 40 Selenium is a semiconductor widely used in electronics, including photovoltaic cells, light sensors, copiers, and power supplies. Selenium is also a biologically essential trace element. However, excessive amounts of selenium (>400-800 μg / day) can lead to toxicity. Selenoproteins and enzymes are involved in antioxidant activity and in preventing oxidative damage to DNA, which helps prevent cancer and other diseases. As a result, selenium has been widely used as a label to facilitate the identification and determination of selenium-containing substances in complex sample mixtures.

[0058] Another element that is subject to significant interference from argon species is arsenic (As). Due to its toxicity and potential impacts on human health and the environment, the analysis of arsenic using ICP-MS is of paramount importance. Arsenic contamination in water, soil, and food poses a significant risk, as long-term exposure can lead to serious health problems, including cancer, skin lesions, and cardiovascular disease. However, due to the high ionization energy of arsenic and its potential to cause toxicity, the presence of arsenic in water, soil, and food can be a significant risk. 40 Ar 35 Polyatomic interference of Cl+ molecules, analysis of arsenic using ICP-MS ( 75 As + ) with difficulty.

[0059] In addition to these interferences, the presence of these species also causes other negative effects. For example, when occupied by these unwanted species, the potential well depth of the ion guide reaches the space charge limit, thereby restricting the transmission of target elements and reducing the sensitivity of the MS equipment. In addition, it is known that neutral Ar * The presence of will limit the performance of MS equipment.

[0060] The hybrid ICP-MS system of the present invention has the ability to completely eliminate the aforementioned Ar interference by introducing suitable reagents or dopants into the reaction chamber, which can react with and neutralize Ar species through various mechanisms. In the following sections, examples of the new method using the hybrid ICP-MS system are provided, demonstrating its ability to analyze elemental and molecular samples in both positive and negative modes, as well as its ability to completely remove argon interference from mass spectra. Example 1 of Soft Ionization Molecular Analysis Using Hybrid ICP-MS

[0061] Figure 10A The background mass spectrum using Ar as buffer gas is shown. + and ArH + There is also the presence of Ar dimer ions (Ar2 + ), which is a typical background of ICP plasma source. In addition, argon metastable neutral (Ar * ) usually exist in high abundance along with free electrons.

[0062] A small amount of acetone vapor is then introduced into the reaction chamber through the introduction channel. Figure 10B The mass spectra of the protonated acetone ion and the protonated acetone dimer are shown. The acetone dimer ion is formed as a result of the secondary reaction of the protonated acetone with the neutral acetone molecule (see Figure 10C ). The formation mechanism of protonated acetone dimers is believed to be caused by the formation of protonated bridges between molecules, as shown below. These types of molecules are believed to be very fragile and require very little energy to fragment. The presence of high counts of protonated acetone dimers clearly indicates that soft ionization is occurring in the reaction chamber. It is worth noting that all ions associated with argon contribute to this process by providing charge through ion / molecule reactions to form acetone ions. This is also of great significance in eliminating background Ar ions that are not needed in the normal operation of ICP-MS. The technique of forming molecular ions in ICP-MS by soft ionization without fragmenting them is an innovative aspect of the present invention.

[0063] This process can also occur within other stages of the mass spectrometer, where ion chemistry can be performed using ions and metastable species and electrons generated in plasma or reaction chambers (e.g., ion guides, collision / reaction cells, etc.), as described above. Example 2 of Soft Ionization Molecular Analysis Using Hybrid ICP-MS

[0064] Figure 11 The formation of intact positive molecular ions is shown via a charge transfer reaction from the buffer ions to the analyte (perfluorodecalin, PFD, in this case) within the reaction chamber. Energy from neutral metastable molecules is another viable source of intact positive ions via Penning ionization. In this example, the intact target molecule is largely detectable along with some fragments.

[0065] In GC-MS, an electron impact ionization (EI) source is typically used to generate ions. To produce positive ions, the energy of the electron impact beam is maintained at greater than 70 eV to improve ionization efficiency. This amount of energy is typically dissipated throughout the molecule's structure and in many cases results in fragmentation of the target molecule. In the case of PFD, complete molecular ions are typically not detected in GC-MS due to severe fragmentation. This example clearly demonstrates the ability of a hybrid ICP-MS system to generate complete molecular ions and can open the door to new applications. Example 3 of Negative Mode Soft Ionization Molecular Analysis Using Hybrid ICP-MS

[0066] Figure 12 This figure shows the formation of intact negative molecular ions from a PFD when introduced into the reaction chamber of a hybrid ICP-MS system. The formation of intact negative ions is due to the direct generation of low-energy free electrons from the plasma discharge of the buffer gas (here, argon). These free electrons readily attach to analyte molecules via electron attachment. Another possible electron attachment pathway may involve free electrons generated by the reaction of neutral metastable species with the analyte. Both free electron sources are believed to form intact negative ions. Example 4 of Removing Argon Interference in Elemental Analysis Using Hybrid ICP-MS

[0067] Numerous attempts have been made to reduce or even eliminate unwanted species generated by ICP sources before they reach the MS instrument. In particular, argon species, which interfere with the accurate determination of elements such as calcium, potassium, selenium, arsenic, and iron, have been the subject of much research and complex method development. Here, we disclose a novel technique that allows the injection of suitable dopants into the reaction chamber to completely neutralize and eliminate argon cations and their cluster ions, including argon metastable neutrals.

[0068] Ar has a doublet ground state with an energy difference of 0.2 eV ( 2 P 1 / 2 , 2 P 3 / 2 The ionization energies of these two states are 15.4 and 15.6 eV, respectively. It has the highest ionization energy after He, Ne, and F. Therefore, charge transfer is possible when reacting with any dopant.

[0069] The metastable energy state of Ar has a long lifetime (t 1 / 2 =45s), the energies of the two spin states are 11.4 and 11.6 eV respectively. Through the Penning ionization process, any reagent with an ionization energy lower than this energy can be easily ionized by Ar * Ionization. Ar *Reactions with reagents with higher ionization energies than metastable argon may share the energy of the excited electronic states; therefore, Ar is likely to lose some of its energy, with the excited electrons occupying lower energy states, which are often short-lived states. It either decays spontaneously to a lower energy state or loses further energy in subsequent collisions.

[0070] ArO + The ionization energy of Ar appears to be higher than that of methane (CH4) [IE = 12.6 eV], as the reaction between these two species proceeds very efficiently via charge transfer. On the other hand, Ar has a low affinity for oxygen, making oxygen ion transfer a favorable pathway for the reaction. This is particularly evident in the reaction of this ion with CO and N2.

[0071] ArH+ is formed in high abundance from the plasma source. Given that the proton affinity of Ar is very low (≈369.2 kJ / mol), it can be easily proton transferred to any reagent with a higher proton affinity (which includes most, if not all, reagents). This is very evident in the reactions reported here. For example, the proton affinities of some reagents are as follows: PA(N2) = 493.8 kJ / mol; PA(CO) = 426.2 kJ / mol; PA(CO2) = 540.5 kJ / mol; PA(CH4) = 543.5 kJ / mol. Note that proton transfer reactions are generally short-range. This means that if the proton transfer reaction is exothermic, the reaction will proceed with a high reaction cross section.

[0072] Ar2 + The high efficiency of charge transfer to such a wide range of reagents, including N2, O2, Kr, Xe, CO, CO2, NO, NO2, N2O, CS2, SO2, and SF6, has been experimentally observed using a variety of different methods. This is likely due to the high ionization energy of this ion, which has been reported to be 14.5-15.0 eV.

[0073] The following is the elimination of Ar with N2 + 、Aro + 、ArH + 、Ar2 + and Ar * Some chemical reaction mechanisms: Charge transfer: Mass transfer: Proton transfer: Quick quenching: Ar * +N2→N2+Ar+δ Charge transfer:

[0074] Figure 13ABackground ions generated by an argon ICP source are shown. + and ArH + Clearly visible in high abundance. Ar2 + In this example, we did not observe ArO + .

[0075] Figure 13B The spectrum is shown after N2 has been injected into the reaction chamber. We can clearly see the destruction of Ar ions and their associated species. Clump 37 appears to be a contaminant that appeared during the N2 injection.

[0076] The following are used to eliminate Ar + 、ArO + 、ArH + and Ar * Other examples of ionic chemical mechanisms: In the reaction with CO: Charge transfer: O + Transfer: Proton transfer: Quick quenching: Charge transfer:

[0077] In the case of CO In the reaction of 2:

[0078] In the reaction with CH4: Charge transfer: Charge transfer: Proton transfer: Quick quenching: Charge transfer: Example 5: Interference-free Analysis of Calcium and Potassium Using Hybrid ICP-MS

[0079] It is understood that chemistry is driven entirely by electron interactions, while radioactivity is caused purely by nucleus interactions and does not contribute to chemical kinetics. Therefore, it can be concluded that the ion chemistry processes of radioisotopes will be similar to those of stable isotopes. Mass spectrometers that can detect very low concentrations of pure state radioisotopes will have a major impact on our understanding in many scientific fields. Low levels of radioisotopes can be good candidates for isotope labeling in living tissues while minimizing the effects of chemical and radioactive toxicity. For this reason, it is preferable that the selected elements are already part of the anatomy of a living body (e.g., C, N, O, H, Ca, K, Na, P, Cl, Fe, Zn, Co, I, Se, V, etc.) so that they do not produce significant adverse effects via chemical reactions. In this way, the presence of rare radioisotopes of existing elements in living tissues will be unique and easy to track. There are mainly two categories of radioisotopes for this purpose: stable trace isotopes (minimum population) or short-lived synthetic radioisotopes. The presence of these two isotopes in living tissues will be unique and very easy to detect by mass spectrometers.

[0080] Generally, stable trace isotopes will have a long lifetime. They will radioactively decay into other elements with relatively long lifetimes. On the other hand, short-lived synthetic radioisotopes with half-lives of a few hours or days can cause interference problems when decaying into other elements. Here, we disclose a method for eliminating this problem using a hybrid ICP-MS system.

[0081] Calcium (Ca) and potassium (K) are two major elements in living organisms. Calcium is one of the most abundant elements in the human body and plays an important role in the formation of bones and teeth, controlling muscle growth, and maintaining blood pressure. Monitoring calcium atoms has a high value in diagnostic medicine. Therefore, it is clear that detecting pure state calcium atoms is very important for maintaining and monitoring human health. Potassium is another important element in the human body.

[0082] Here, we introduce a method for analyzing calcium and potassium based on their most abundant isotopes without any interference using a hybrid ICP-MS. Since the ICP source produces high abundance of 40 Ar + and 38 ArH + , which is a challenge for traditional platforms. The presence of these unwanted ions hinders accurate and convenient detection of 40 Ca and 39 K isotopes and results in higher detection limits for these elements than for other elements in the periodic table.

[0083] Figure 14A and Figure 14BIt is shown that when 0.1 μg / mL of this compound is injected into the ICP source and nitrogen is introduced into the reaction chamber at a flow rate of 0.1-2 L / min to eliminate argon ion species, in addition to its corresponding isotope, 40 Ca and 39 The unprecedented detection of K at its original mass. The pressure inside the reaction chamber is also between 20-200 Torr. Detecting these ions at their original mass has always been one of the biggest challenges for traditional ICP-MS equipment, among which Ar + The presence of and its related substances overlaps with the detection of these ions, so without any special arrangement or complex equipment in the mass spectrometer, it is almost impossible to detect these high target elements in pure form. Example 6: Interference-free Analysis of Various Isotopes of Calcium and Potassium Using Hybrid ICP-MS

[0084] The following are some other reaction mechanisms using a hybrid ICP-MS system, by which interferences can be removed or avoided, allowing for the high-precision analysis of other calcium and potassium isotopes. These reactions are possible by introducing the various reagents upstream of the mass spectrometer (i.e., mass analyzer), where the pressure is high enough to efficiently carry out these ion chemistries. This is another unique aspect of this hybrid ICP-MS compared to existing tandem ICP-MS systems with collision / reaction cells. Simultaneously, the reagents can also be introduced into the collision cell of the tandem mass spectrometer along with the collision gas.

[0085] 41 Ca is a trace isotope of calcium with a half-life of (t 1 / 2 =10 5 y). This element can be used as a candidate for isotope labeling. This isotope is generated by electron capture (ε - ) decays to 41 Although there is no Ar in living tissue, ICP-MS 40 ArH + 、 41 Ar + and 41 The presence of K (abundance of 6.7% and present in living tissues) causes 41 Here, we introduce methods that can detect Ca without interference by eliminating the aforementioned isotopes through ion chemistry using a reaction chamber. 41 Ca + .

[0086] Analysis by reaction with SF6 41 Ca to avoid 41 Interference from K: Mass transfer: No response: Mass transfer: Mass transfer:

[0087] By analysis with NO2 41 Ca to avoid 41 Interference of K: Mass transfer: No response: Charge transfer: Proton transfer:

[0088] also, 45 Ca and 47 Ca is a synthetic isotope of calcium that has important applications in nuclear medicine. - The emission decays to 45 Sc& 47 Sc, whose 1 / 2 lifetimes are 162.6 days and 4.5 days respectively. Therefore, it is very necessary to develop a method to distinguish these two Ca isotopes and the isotopes they decay into (i.e., Sc isotopes).

[0089] Analysis of Ca by reaction with NH3: No response: Mass transfer:

[0090] Analysis of Ca by reaction with D2O: No response: Mass transfer:

[0091] In conclusion, the hybrid ICP-MS mass spectrometer can detect Ca and K in pure form, which greatly improves the level of nuclear diagnostic medicine.

[0092] Let me give you another example. 40 K is a rare 39 K isotope, which is an ideal candidate for isotope labeling, has a half-life of t 1 / 2 =1.2x10 9 y, decays via electron capture to 40 Ar.

[0093] Reaction with SF6: No response: Mass transfer:

[0094] Reaction with NO2: No response: Charge transfer:

Claims

1. A hybrid inductively coupled plasma mass spectrometer (ICP-MS) system for elemental and molecular analysis under positive and negative polarity, the system comprising: a) an inductively coupled plasma (ICP) source having at least one inlet for receiving a background gas and an analyte and at least partially ionizing the background gas and generating plasma and plasma species, the plasma species comprising positive and negative ions, metastable ions and neutral particles, and molecules of the background gas, and free electrons; b) Mass spectrometer (MS) c) an interface having an interface body and a sampler cone, the sampler cone having a sampler orifice and positioned in front of the plasma to draw in ions and plasma species; d) a first vacuum stage behind the sampler cone to create a first vacuum stage pressure of several Torr behind the sampler cone using a first pump having a pumping speed; e) a skimmer positioned a predetermined distance behind the sampler orifice, wherein the skimmer has a central orifice for skimming and partially aspirating a stream of plasma material emerging from the sampler orifice; f) a second vacuum stage behind the skimmer cone to create a second vacuum level pressure behind the skimmer using a second pump to further reduce pressure and avoid recombination and neutralization of the ions; g) an insert having an insert orifice, a geometry, and a form factor, positioned between the sampler cone and the skimmer, wherein the insert orifice allows passage of plasma material toward the skimmer orifice; wherein the insert is configured to form a reaction chamber (region) between the sampler cone and the insert, wherein the pressure of the reaction chamber and its temperature are controlled by the size and form factor of the insert orifice, the size of the sampler orifice and the pumping speed of the first pump, thereby allowing the pressure of the reaction chamber to be between a few Torr and tens or hundreds of Torr, or atmospheric pressure; h) one or more channels configured within the interface body, or in the sampler cone, or in the insert, to introduce gases, reagents, dopants, samples, or analytes into the reaction chamber, thereby allowing the analytes to be ionized via gas-phase ion chemistry and in negatively and positively charged states, Thus, the analytes in the present hybrid ICP-MS system can be introduced into the ICP torch or the reaction chamber or both, and by adjusting the pressure and temperature of the reaction chamber, the reaction chamber of the hybrid ICP / MS switches between elemental analysis and molecular analysis modes and allows soft ionization of the sample.

2. The system of claim 1 , wherein the insert has a plurality of holes around the insert orifice, wherein the plurality of holes are circular, arc-shaped, and annular, symmetrically or asymmetrically distributed around the insert orifice, and wherein their number and opening area are configured to obtain a predetermined reaction chamber pressure.

3. The system of claim 1 , further comprising a rotatable disk with one or more holes, the rotatable disk being positioned below or above the insert and configured to open and close the plurality of holes of the insert upon rotation, wherein the rotatable disk can be switched between various analysis modes using a motor, an actuator, pneumatically, manually, or via any other method, Thus when the plurality of apertures are open the reaction chamber is not pressurized, thereby providing an elemental analysis mode, and when the plurality of apertures are fully or partially closed the reaction chamber is pressurized, thereby providing a molecular analysis mode.

4. The system of claim 1 , wherein the insert is mounted on the interface body below the sampler cone, or is mounted, assembled or screwed onto the sampler cone to form the reaction chamber together with the sampler cone, wherein both the insert and the sampler cone are accessible and removable for cleaning, maintenance and repair purposes.

5. The system according to claim 1, further having a gate valve implemented in the interface after the skimmer cone to enable access to the sampler cone, the insert and the skimmer cone without breaking the vacuum, wherein once the gate valve is closed to maintain the vacuum outside the skimmer and avoid any problems with the vacuum pump due to high pressure or unnecessary exposure of sensitive components within the mass spectrometer to the atmosphere and contamination when servicing the interface, the sampler cone, the insert and the skimmer cone can be easily removed for cleaning purposes or replacement, which will also reduce instrument downtime.

6. The system of claim 1, wherein the sampling interface is water-cooled or air-cooled to cool the sampler cone and prevent the orifice and sealing mechanism thereof from being thermally damaged or melted due to high temperature of plasma.

7. The system of claim 1, wherein the sampler orifice is between 0.5 and 3 mm, the insert orifice is between 0.1 and 5 mm and the pumping speed is 30-50 m / s. 3 / hr, resulting in a pressure in the reaction chamber between 2 and 760 Torr.

8. The system according to claim 1, wherein the pumping speed is between 10 and 100 m / s. 3 / hr to adjust the pressure of the reaction chamber.

9. The system of claim 1 , wherein the insert is electrically isolated from the interface, and wherein a positive or negative voltage is applied to the insert to focus ions exiting the insert as they travel toward the skimmer orifice and to extract ions exiting the sampler orifice to improve ion transmission.

10. The system of claim 1, wherein the one or more channels are configured to be tangential to the reaction chamber through one or a group of holes distributed around the reaction chamber to generate a swirling flow for better mixing of substances and improving homogeneity and reaction rate within the reaction chamber.

11. The system of claim 1 , wherein the insert is made of aluminum, nickel, copper, stainless steel, molybdenum, brass, or alloys or combinations thereof, wherein the material has high thermal conductivity, high melting point, and high corrosion and oxidation resistance to prevent the insert from overheating, which may result in oxidation, melting, or thermal damage.

12. The system of claim 1, wherein the surface of the insert is plated with gold, silver, or platinum to improve corrosion resistance and inhibit oxidation, or coated with a ceramic or thermal barrier coating.

13. A hybrid inductively coupled plasma mass spectrometer (ICP-MS) system for elemental and molecular analysis under positive and negative polarity, the system comprising: a) an inductively coupled plasma (ICP) source having at least one inlet for receiving a background gas and an analyte and at least partially ionizing the background gas and generating plasma and plasma species, the plasma species comprising positive and negative ions, metastable ions and neutral particles, and molecules of the background gas, and free electrons; b) Mass spectrometer (MS) c) an interface having an interface body and a sampler cone, the sampler cone having a sampler orifice and positioned in front of the plasma to draw in ions and plasma species; d) a first vacuum stage behind the sampler cone to produce a first vacuum stage pressure of a few Torr or less behind the sampler cone using a first pump having a pumping speed; e) a skimmer positioned a predetermined distance behind the sampler orifice, wherein the skimmer has a central orifice for skimming and partially aspirating a stream of plasma material emerging from the sampler orifice; f) a second vacuum stage behind the skimmer cone to create a second vacuum level pressure behind the skimmer using a second pump to further reduce pressure and avoid recombination and neutralization of the ions; g) a slide gate having one or more orifices that are manually or automatically actuated and moved to slide between the sampler orifice and the skimmer orifice to form a reaction chamber (region) between the sampler cone and the slide gate, wherein the reaction chamber is characterized by a reaction chamber pressure that is controlled by the one or more orifices of the slide gate and the sampler orifice and the pumping speed of the first pump, thereby allowing the reaction chamber pressure to be between a few Torr and tens or hundreds of Torr, or atmospheric pressure; h) one or more channels configured within the interface body, or within the sampler cone, to introduce gases, reagents, dopants, samples, or analytes into the reaction chamber, thereby allowing the analytes to be ionized in negatively and positively charged states via gas phase ion chemistry, Thus, the analytes in the present hybrid ICP-MS system can be introduced into the ICP torch or the reaction chamber or both, and by adjusting the reaction chamber pressure and temperature, the reaction chamber of the hybrid ICP / MS switches between elemental analysis and molecular analysis modes and allows soft ionization of samples.

14. A hybrid inductively coupled plasma mass spectrometer (ICP-MS) system for elemental and molecular analysis under positive and negative polarity, the system comprising: a) an inductively coupled plasma (ICP) source having at least one inlet for receiving a background gas and an analyte and at least partially ionizing the background gas and generating plasma and plasma species, the plasma species comprising positive and negative ions, metastable ions and neutral particles, and molecules of the background gas, and free electrons; b) Mass spectrometer (MS) c) an interface having an interface body and a sampler cone, the sampler cone having a sampler orifice and positioned in front of the plasma to draw in ions and plasma species; d) a first vacuum stage behind the sampler cone to produce a first vacuum stage pressure of a few Torr or less behind the sampler cone using a first pump having a pumping speed; e) a skimmer positioned a predetermined distance behind the sampler orifice, wherein the skimmer has a central orifice for skimming and partially aspirating a stream of plasma material emerging from the sampler orifice; f) a second vacuum stage behind the skimmer cone to create a second vacuum level pressure behind the skimmer using a second pump to further reduce pressure and avoid recombination and neutralization of the ions; g) a circular gate comprising a first cylindrical part and a second cylindrical part, wherein the first cylindrical part has one or more holes and is stationary, and the second cylindrical part is rotatable, wherein a reaction chamber (region) is formed behind the sampler cone by rotating the second cylindrical part to open and close the one or more holes of the first part, so that the pressure in the reaction chamber is between a few Torr and tens or hundreds of Torr, or atmospheric pressure; h) one or more channels configured within the interface body, or within the sampler cone, for introducing gases, reagents, dopants, samples, or analytes into the reaction chamber, thereby allowing the analytes to be ionized in negatively and positively charged states via gas phase ion chemistry, Thus, the analytes in the present hybrid ICP-MS system can be introduced into the ICP torch or the reaction chamber or both, and by adjusting the pressure and temperature of the reaction chamber, the reaction chamber of the hybrid ICP / MS switches between elemental analysis and molecular analysis modes and allows soft ionization of samples.

15. A soft ionization method for elemental and molecular analysis using a hybrid inductively coupled plasma mass spectrometer (ICP-MS) system with an ICP-MS interface under positive and negative polarity, the method comprising the following steps: a) generating a plasma and plasma species in an inductively coupled plasma (ICP) source having at least one inlet for receiving a background gas and an analyte, the plasma species comprising positive and negative ions, metastable ions and neutral particles, molecules of the background gas, and free electrons; b) forming a reaction chamber or zone between said sampler cone and said skimmer, wherein said reaction chamber is characterized by a predetermined reaction chamber pressure and temperature; c) introducing a gas, reagent, dopant, sample, analyte, fine solid aerosol, or nano- or micro-spray into the reaction chamber; d) controlling the reaction chamber pressure and temperature to switch between elemental analysis and molecular analysis modes, The sample is thereby introduced directly into the reaction chamber, providing conditions for soft ionization of fragile molecules.

16. The method of claim 15, wherein in order to switch between elemental analysis and molecular analysis modes, a) operating a plasma torch for elemental analysis at high power in the range of 700-1600 W to completely decompose the sample and ionize the elements and avoid higher levels of oxides and molecular species, and introducing the sample through an ICP torch and soft ionizing the molecular sample, or b) operating the plasma torch at a lower power in the range of 300-500 W, or injecting a higher than optimal carrier gas flow rate to avoid decomposing the target molecules by providing a cooler plasma, in this way the plasma will typically act as an evaporator, desolvation or thermal desorption system, and the soft ionization process will mainly occur within the reaction chamber.

17. The method of claim 15, wherein a reagent gas is injected into the reaction chamber to neutralize the primary argon ions and metastable states generated by the ICP source, wherein the reagent gas is selected from the group consisting of nitrogen, helium, oxygen, nitrous oxide, acetone, SF6, nitric oxide, nitrogen dioxide, methane, krypton, xenon, carbon monoxide, carbon dioxide, carbon disulfide, and sulfur dioxide to neutralize Ar. + 、ArH + 、ArO + 、ArCl + or Ar2 + , thus enabling interference-free analysis of elements that are individually interfered with by argon background ions, including but not limited to calcium, potassium, iron, arsenic or selenium.

18. The method of claim 15, wherein the reaction chamber pressure and temperature are controlled by providing an insert having an insert orifice, geometry, and form factor placed between a sampler cone and a skimmer of an ICP-MS interface, wherein the insert orifice allows plasma species to pass toward the skimmer orifice.

19. The method of claim 15, wherein the reaction chamber pressure and temperature are controlled by providing an insert having a central insert orifice and a plurality of peripheral holes that can be opened, partially closed, or fully closed by a rotatable disk.

20. The method of claim 15, wherein the reaction chamber pressure and temperature are configured to allow a sample or analyte introduced directly into the reaction chamber to undergo a soft ionization process by charge transfer, proton transfer, oxygen transfer, electron attachment, Penning ionization, chemical ionization, or adduct formation, wherein the sample or analyte reacts with the positive and negative ions, metastable ions and neutral particles generated by the inductively coupled plasma (ICP) source, molecules of the background gas, and free electrons to form new ions that can be analyzed by the mass spectrometer.

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