analyzer system

Abstract

An analyzer system (110) is disclosed that includes at least one mass analyzer (112) having at least one electrospray ion source nozzle (114), at least one liquid supply (116) configured to provide at least one liquid having at least one analyte, at least one gas supply (118) configured to provide at least one gas, and at least one dopant gas supply (120) configured to provide at least one chemical dopant gas having at least one chemical dopant (122) to the analyte provided by the liquid supply (116), the liquid supply (116) and the gas supply (118) being coupled to the mass analyzer (112) via the electrospray ion source nozzle (114), and the dopant gas supply (120) being connected to the gas supply (118).

Description

[Technical field]

[0001] Technical Field The present invention relates to an analyzer system, a multiplexed analyzer system, the use of the analyzer system, and a method for analyzing at least one analyte. These devices and methods can be applied to measure the molecular weight or molecular weight to charge ratio of an analyte or a fragment of said analyte for the purpose of analyzing, i.e. identifying and quantifying, said analyte. In particular, these devices and methods can be applied to the analysis of biomolecules, such as small biomolecules. However, other applications are also feasible. [Background technology]

[0002] Background technology ESI (electrospray ionization) is a technique used in mass spectrometry to produce ions using electrospray, which is the application of a high voltage to a liquid to generate an aerosol. A liquid containing one or more analytes of interest can be dispersed into a fine aerosol by electrospray.

[0003] Improving the signal-to-noise ratio in mass spectrometry systems with electrospray ion sources before or during ionization is a chemical reaction that can enhance the electrospray process. Dopant This can be accomplished or facilitated by the addition of, typically as an additive to the solvent or chromatographic eluent, respectively (pre-column) or by the use of a T-piece mixer (post-column).

[0004] Li et al., Anal. Chem. 2014, 86, 331-335, describe chemical vapor-assisted electrospray ionization to enhance the signal of analytes in electrospray ionization mass spectrometry. Specifically, a chemical vapor-assisted electrospray ionization (ESI) technique is reported to improve the detection sensitivity of ESI mass spectrometry (MS). The technique involves introducing a chemical vapor into the sheath gas around the nano-ESI spray tip or through a tube with an outlet located near the spray tip. Various chemical vapors have been tested and shown to have different degrees of influence on the signal intensity of the analytes. The use of benzyl alcohol vapor in ESI has been shown to increase the signal intensity of standard peptides by up to four-fold. When this technique was coupled with capillary liquid chromatography tandem MS (LC-MS / MS), the number of unique peptides identified in acid hydrolysates of alpha casein increased by 45%, and the number of peptides and proteins identified in tryptic digests of E. coli cell lysates increased by 13% and 14%, respectively, with improved average match scores. The technique was also able to increase analyte signals by up to three-fold for some small molecules, such as phenylephrine. The increased analyte signals observed in the chemical vapor-assisted ESI process are associated with improved ionization efficiency in ESI. This method can be easily implemented at minimal cost into existing ESI mass spectrometers to improve detection sensitivity.

[0005] Badu-Tawiah et al., Analyst, 2017, 142, 2152-2160, describe a configurable multimode housed electrospray ionization for protein folding and unfolding on the millisecond time scale. Specifically, a configurable housed electrospray (ES) ion source that can operate in three unique modes (type I, II, and III) and was applied to control the charge state of proteins for subsequent online characterization by mass spectrometry is described. Using this device, proteins prepared in 100% water were highly charged after exposure to hydrochloric acid vapor. For myoglobin, a shift to a higher charge state occurred faster than the heme cofactor could escape from the unfolding protein. This effect was reflected in the detection of a highly charged holo-myoglobin intermediate (+26), suggesting that the modification process occurred on a millisecond time scale (type I mode). By introducing a cavity into the accommodated ES emitter (type II mode), increased protein denaturation was observed and only apo-myoglobin ions were detected.

[0006] Similarly, US Patent Publication No. 2016 / 0329198 describes an apparatus comprising an electrospray emitter comprising a sample capillary extending from a sample inlet to a sample outlet, and an element comprising a conduit arranged coaxially around the electrospray emitter, thereby forming a chamber extending between the conduit and the sample capillary and terminating at a gas outlet. The element may in some instances further comprise a carrier gas inlet in communication with the chamber, and a working gas inlet in communication with the chamber, the chamber being configured to provide a path for fluid flow from the carrier gas inlet and the working gas inlet to the gas outlet. Methods of use of the apparatus are also disclosed therein. In some instances, methods and apparatus for contained electrospray for use in, for example, mass spectrometry and / or droplet reactions are discussed therein.

[0007] Despite the advantages achieved by the above-mentioned devices, some technical challenges still exist. Pre-column implementations generally limit the deployment of chromatographic methods and / or chromatographic assays by affecting the column's lifetime and changing the elution characteristics of the solvents used, such as methanol, acetonitrile, and / or water. Thus, there may be serious effects on the performance and lifetime of the column. When electrospray ionization techniques are combined with liquid chromatography (LC), such as high performance liquid chromatography (HPLC) or ultra-high performance liquid chromatography (UHPLC), post-column implementations are typically not feasible, especially due to their adverse effects on separation and analytical peak shape signal overlap. This effect may be even more aggravated, especially in liquid chromatography techniques that typically use low flow rates, such as the microliter / min range or nanoliter / min range. Such liquid chromatography techniques may specifically include capillary liquid chromatography techniques (cLC, capillary LC, CapLC) and / or nanoscale liquid chromatography techniques (NanoLC). Due to excessive peak broadening, post-column implementations generally introduce undesirable hold-up volumes that are generally not feasible for use at such low flow rates. Furthermore, the incorporation of post-column connections into the liquid chromatography flow path, such as by T-piece capillary connectors, can be problematic. Dopant By adding Dopant of downstream liquid chromatography flow paths for assays susceptible to negative Dopant Concerns about clearance and general carryover arise, especially in the case of fully integrated random access automated chromatography and / or mass spectrometry clinical analyzers where chromatographic conditions and analytes of interest change frequently. Summary of the Invention [Problem to be solved by the invention]

[0008] Problem to be solved It would therefore be desirable to provide an analyzer system, a multiplexed analyzer system, uses of the analyzer system, and methods for analyzing at least one analyte that at least partially address the above-mentioned technical challenges. In particular, it would be desirable to increase the signal-to-noise ratio of the analyte signal acquired by the analyzer system. [Means for solving the problem]

[0009] overview This problem is addressed by an analyzer system, a multiplexed analyzer system, the use of the analyzer system and a method for analyzing at least one analyte with the features of the independent claims. Advantageous embodiments, which may be realized alone or in any combination, are listed in the dependent claims as well as in the entire specification.

[0010] When used below, the terms "have", "comprise" or "include", or any grammatical variants thereof, are used in a non-exclusive manner. These terms may therefore refer both to the situation where, apart from the features introduced by these terms, no further features are present in the entity described in this context, and to the situation where one or more further features are present. As an example, the expressions "A has B", "A comprises B" and "A includes B" may refer both to the situation where, apart from B, no other elements are present in A (i.e., the situation where A consists solely and exclusively of B), and to the situation where, apart from B, one or more further elements are present in the entity A, such as element C, elements C and D, or further elements.

[0011] Furthermore, it should be noted that the terms "at least one" or "one or more," or similar expressions, indicating that a feature or element may be present only once or more than once, are typically used only once when introducing each feature or element. In the following, in most cases, when referring to each feature or element, the expressions "at least one" or "one or more" will not be repeated, despite the fact that each feature or element may be present only once or more than once.

[0012] Furthermore, when used hereinafter, the terms "preferably", "more preferably", "particularly", "more particularly", "particularly", "more particularly" or similar terms are used in relation to optional features without limiting the possibility of alternatives. Features introduced by these terms are therefore optional features and do not in any way limit the scope of the claims. The invention may be implemented using alternative features, as would be understood by a person skilled in the art. Similarly, features introduced by "in an embodiment of the invention" or similar expressions are intended to be optional features and do not entail any limitations on alternative embodiments of the invention, any limitations on the scope of the invention, or any limitations on the possibility of combining features introduced in such a manner with other optional or non-optional features of the invention.

[0013] In a first aspect of the present invention, an analyzer system is disclosed. The analyzer system comprises at least one mass analyzer having at least one electrospray ion source nozzle. Further, the analyzer system comprises at least one liquid supply. The liquid supply is configured to provide at least one liquid having at least one analyte. Further, the analyzer system comprises at least one gas supply. The gas supply is configured to provide at least one gas. Further, the analyzer system comprises at least one Dopant Equipped with a gas supply section. Dopant The gas supply section is equipped with at least one chemical Dopant At least one chemical Dopant and configured to provide a gas to the analyte provided by the liquid supply. The liquid supply and the gas supply are coupled to the mass analyzer through an electrospray ion source nozzle; Dopant The gas supply is connected to a gas supply.

[0014] As used herein, the term "analyzer system" is a broad term and should be given its common and ordinary meaning to one of ordinary skill in the art and should not be limited to a specific or special meaning. The term specifically includes, but is not limited to: , may refer to any system configured to perform at least one analytical measurement with at least one sample or at least one component of the sample. As a result of, or as part of, the measurement, the analyzer system may generate at least one measurement result characteristic of the sample and / or at least one component, in particular at least one measurement result related to the analyte. In particular, analyte-related information about the analyzed sample may be derived or derivable from the analytical measurement. The information may be, for example, information about the presence, absence, concentration, or amount of the analyte present in the sample. In particular, the analyzer system may be configured to detect the analyte in the sample. In particular, the analyzer system may be an in vitro diagnostic analyzer. As used herein, the term "in vitro diagnostic analyzer" is a broad term and should be given its common and ordinary meaning to those skilled in the art and should not be limited to a special or special meaning. The term may in particular, but not limited to, refer to any analyzer system configured to perform at least one analytical measurement with at least one sample or at least one component of the sample obtained from a human or animal body. In particular, the sample may be or include blood, tissue, or components thereof. Additionally, the sample may be or include other bodily fluids or excretions or components thereof. In particular, the sample may include hair, urine, or feces. In vitro diagnostic analyzers may be configured to detect disease or other conditions, and may be configured to monitor overall health to aid in the cure, treatment, or prevention of disease.

[0015] As mentioned above, the analyzer system comprises at least one mass analyzer. As used herein, the term "mass analyzer" is a broad term and should be given its common and ordinary meaning to those skilled in the art and should not be limited to a special or special meaning. The term may specifically refer to, but is not limited to, any analysis technique configured to measure the mass-to-charge ratio of ions. The measurement results may specifically be presented as a mass spectrum, e.g., a plot of intensity as a function of mass-to-charge ratio. As mentioned above, the mass analyzer comprises at least one electrospray ion source nozzle, which may be further described in more detail below. Furthermore, the mass analyzer may comprise at least one mass analyzer and at least one detector. The electrospray ion source nozzle, the mass analyzer, and the detector may be disposed in the ionization chamber. The mass analyzer may be configured to sort and separate ions according to their mass-to-charge ratio. The mass analyzer may comprise one or more ion optical components, such as skimmers, focusing lenses, or electromagnetic elements such as multipoles. The ion optics may be configured to transport ions to a region within the ionization chamber in which the mass analyzer is located.

[0016] As used herein, the term "electrospray ion source nozzle" is a broad term and should be given its common and ordinary meaning to those skilled in the art and should not be limited to a special or special meaning. The term may specifically refer to, but is not limited to, any device configured to disperse a liquid into a fine aerosol by using electricity. The electrospray ion source nozzle may comprise at least one capillary. The capillary may illustratively be made of at least one metal, such as glass and / or stainless steel. The capillary may have an inner diameter of 0.05 mm to 0.5 mm, preferably 0.1 mm to 0.3 mm. Other dimensions may be feasible. The electrospray ion source nozzle may be configured to apply a high voltage to an outer surface of the capillary. The outer surface may have electrical contacts for applying the high voltage. Illustratively, the electrical contacts may be a conductive coating on the outer surface of the capillary. The conductive coating may illustratively be a gold film, specifically a sputtered gold film. The high voltage may be in the range of 0.1 kV to 10 kV, particularly 0.5 kV to 7 kV. The electrospray ion source nozzle may be configured to generate an electric field that disperses the liquid into an aerosol. The aerosol may include electrically charged droplets.

[0017] As used herein, the term "liquid supply" is a broad term and should be given its general and ordinary meaning to those skilled in the art and should not be limited to a special or special meaning. The term may specifically refer to, but is not limited to, any device configured to provide at least one liquid. Specifically, the liquid supply may provide a liquid and include at least one storage element, such as a flask or container, configured to specifically store the liquid. Additionally or alternatively, the liquid supply may include at least one tube, such as at least one hose. The tube may be configured to transport the liquid to a desired location or to transport the liquid to another element. Specifically, the electrospray ion source nozzle may include at least one capillary. For further details, see the above description. As described above, the liquid supply and the gas supply are coupled to the mass analyzer via the electrospray ion source nozzle. Specifically, the liquid supply may include at least one tube, which may be connected or connectable to the capillary of the electrospray ion source nozzle. The liquid supply may be configured to provide liquid to the capillary of the electrospray ion source nozzle, in particular via a tube. In particular, the liquid supply may comprise at least one liquid supply dosing device, such as a liquid supply syringe pump, which may be configured to dosing a flow of liquid having at least one analyte to the capillary of the electrospray ion source nozzle. The liquid supply dosing device, in particular the liquid supply syringe pump, may be configured to dosing a flow of liquid having at least one analyte to the capillary of the electrospray ion source nozzle at a flow rate in the range of 1 nl / min to 50 μL / min.

[0018] Specifically, the analyzer system may include at least one liquid chromatography device. As used herein, the term "liquid chromatography device" is a broad term and should be given its general and ordinary meaning to those skilled in the art and should not be limited to a specific or special meaning. The term may specifically refer to, but is not limited to, any device configured to separate components of a mixture from one another. The mixture may be dissolved in a fluid, which may be called a mobile phase. The mobile phase may be configured to carry the mixture through a system, such as a column, capillary, plate, or sheet, having a material, which may be called a stationary phase. Different components of the mixture have different affinities for the stationary phase. Depending on the interaction with the stationary phase, different components of the mixture may move at different speeds in the mobile phase, which may result in the separation of the different components from one another. The liquid chromatography device may be selected from the group consisting of a nano-liquid chromatography device, a micro-liquid chromatography device, a high-performance liquid chromatography device, and a high-performance liquid chromatography device. However, other types of liquid chromatography devices may be feasible. In particular, the liquid supply may correspond to the liquid chromatography device. Furthermore, as an alternative, the liquid supply may be coupled or may be coupleable to the liquid chromatography device, such as via at least one tube. Thus, the liquid chromatography device may be configured to provide liquid to the liquid supply.

[0019] As used herein, the term "liquid" is a broad term and should be given its general and ordinary meaning to those skilled in the art, and should not be limited to a special or special meaning. The term may specifically refer to, but is not limited to, any substance having a liquid state of aggregation. Specifically, the liquid may be a nearly incompressible fluid that conforms to the shape of its container but maintains at least a nearly constant volume regardless of pressure. The liquid may specifically be selected from the group consisting of water, particularly deionized water, organic solvents, buffers. Furthermore, the liquid may include at least one test substance as described above. As used herein, the term "test substance" is a broad term and should be given its general and ordinary meaning to those skilled in the art, and should not be limited to a special or special meaning. The term may specifically refer to any chemical or biological substance or species, such as, but not limited to, a molecule or chemical compound to be detected and / or measured. Specifically, the presence, concentration, and / or amount of the analyte in the sample may be detected or measured. Specifically, the analyte may be a biological molecule or macromolecule. The analyte may specifically be a steroid or a metabolite thereof, in particular estradiol. Furthermore, the analyte may be selected from the group consisting of therapeutically active substances, in particular antibiotics, in particular anesthetics, peptides, proteins, endogenous metabolites, in particular nucleotides, lipids, in particular phospholipids, in particular ceramides, in particular diacylglycerides, in particular triacylglycerides, in particular related compounds including fatty acids, toxins, toxic compounds, exogenous compounds, sugars, in particular monosaccharides, in particular disaccharides, in particular oligosaccharides, in particular polysaccharides, in particular related compounds thereof. The analyte may also be a metabolite of the aforementioned compounds. However, other analytes may also be feasible.

[0020] As used herein, the term "gas supply" is a broad term and should be given its general and ordinary meaning to those skilled in the art and should not be limited to a specific or special meaning. The term may specifically refer to, but is not limited to, any device configured to provide at least one gas. Specifically, the gas supply may provide gas and include at least one storage element, such as a flask or container, configured to specifically store the gas. Furthermore, specifically, the gas supply may include at least one gas generator. Additionally or alternatively, the gas supply may include at least one tube, such as at least one hose. The tube may be configured to transport the gas to a desired location or to transport the gas to another element. Specifically, as described above, the electrospray ion source nozzle may include at least one capillary. For further details, see the description above. As described above, the liquid supply and the gas supply are coupled to the mass analyzer via the electrospray ion source nozzle. The gas supply may include at least one tube, which may lead to the end or tip of the capillary or to a region near the end or tip of the capillary. Specifically, the gas supply may include at least one gas supply dosing device, such as a gas supply syringe pump, configured to administer a flow of gas through the tube. As used herein, the term "gas" is a broad term and should be given its general and ordinary meaning to those skilled in the art and should not be limited to a specific or special meaning. The term may specifically refer to, but is not limited to, any substance that has a gaseous state of aggregation. Particles of gas may move freely at large distances from one another and may uniformly fill the available space.

[0021] Specifically, the gas supply may be a nebulizer gas supply. The nebulizer gas supply may be configured to provide at least one nebulizer gas. The nebulizer gas may be configured to nebulize the liquid provided by the liquid supply. Specifically, the nebulizer gas may be configured to assist in dispersing the liquid into a fine aerosol. Furthermore, the nebulizer gas may be configured to assist in moving the fine aerosol from the capillary towards the mass analyzer. Specifically, the nebulizer gas may include at least one inert gas, specifically at least one of nitrogen, argon, and helium. Furthermore, the nebulizer gas may include a mixture of at least one of nitrogen, argon, and helium with oxygen. Further, specifically, the nebulizer gas may include compressed zero-grade air without oil. The nebulizer gas supply may also be referred to as a sheath gas supply.

[0022] Further, optionally, the analyzer system may include at least one heated gas supply. The heated gas supply may be configured to provide at least one heated gas to the electrospray ion source nozzle. The heated gas may be at a temperature greater than a temperature of an environment of the heated gas supply. The heating gas may have a temperature in the range of 20°C to 800°C, particularly 25°C to 700°C. In particular, the heating gas may include at least one inert gas, particularly at least one of nitrogen, argon, and helium. Furthermore, the heating gas may include a mixture of at least one of nitrogen, argon, and helium with oxygen. Furthermore, in particular, the heating gas may include compressed zero-grade air without oil. Furthermore, the heating gas may be compressed air without oil. Furthermore, other types of gas may be feasible. The heating gas supply may provide the heating gas and may include at least one storage element, such as a flask or a container, configured to store the gas. Furthermore, in addition to or instead of this, the heating gas supply may include at least one tube, such as at least one hose. Furthermore, the heating gas supply may include at least one heating element. In particular, the heating element may be configured to heat the gas by natural or forced convection, vortex and / or circulation of the gas. The heating element may be configured to heat the gas to a desired temperature. In particular, the heated gas supply may comprise at least one pipeline, and the heating element may be configured to directly or indirectly heat the gas in the pipeline, which may be stationary or circulating. The heating element may be configured to be in direct contact with the gas or to heat the gas through a protective tube. The heating element may in particular be selected from the group consisting of: ring radiator, flange radiator. Also, other embodiments may be feasible.

[0023] Illustratively, the analyzer system may include a nebulizer gas supply and a heating gas supply, the nebulizer gas supply corresponding to the gas supply described above. Dopant The gas supply may be connected to a nebulizer gas supply. Further illustratively, the analyzer system may include a nebulizer gas supply and a heating gas supply, the heating gas supply corresponding to the gas supply described above. Thus, DopantThe gas supply may be connected to a heating gas supply. Further illustratively, the analyzer system may only include a nebulizer gas supply and not a heating gas supply, with the nebulizer gas supply corresponding to the gas supply described above.

[0024] As used herein, " Dopant The term "gas supply" is a broad term and should be given its common and ordinary meaning to one of ordinary skill in the art and should not be limited to a specific or special meaning. The term specifically refers to, but is not limited to, at least one chemical Dopant It may refer to any device configured to provide a gas. Dopant The gas supply section is Dopant The gas supply is configured to supply a chemical Dopant or chemical Dopant The method may include at least one storage element, such as a flask or container, configured to store at least one ingredient of the chemistry. Dopant Or Chemistry Dopant The raw material is in gas form. Dopant It may be stored in the gas supply. Dopant Or Chemistry Dopant The raw materials are in solid or liquid form. Dopant It may be stored in the gas supply. Dopant Further details regarding embodiments of the gas supply are described in more detail below.

[0025] As used herein, "chemical Dopant The term "gas" is a broad term and should be given its common and ordinary meaning to one of ordinary skill in the art and should not be limited to a specific or special meaning. The term specifically refers to, but is not limited to, at least one chemical Dopant It may refer to any gas, including chemical Dopant may be configured to enhance the signal to noise ratio of measurements made with the analyzer system by enhancing the signal of the analyte, suppressing background signals, etc. DopantThe gas may be configured to assist in the protonation or deprotonation of the analyte. Dopant The gas may contain at least a component that can be subsequently deprotonated or protonated. Dopant The gas may be ammonia. The nia may be configured to protonate the analyte. Dopant At least one source for the formation of the gas may be selected from the group consisting of ammonium carbonate, ammonium fluoride, ammonium acetate, and ammonium methanate. Dopant The at least one source for the formation of the gas may include other compounds capable of dissociating into or releasing ammonia gas.

[0026] As mentioned above, Dopant The gas supply unit is connected to the gas supply unit. Dopant The gas supply may be connected to a nebulizer gas supply or a heating gas supply. In particular, the analyzer system may include at least one supply line, such as at least one tube. The supply line may be configured to connect at least one container of the gas supply to the electrospray ion source nozzle, in particular to the capillary. Dopant The gas supply may in particular be connected to a supply line of the gas supply. More particularly, Dopant The gas supply unit includes at least one Dopant At least one gas supply tube, etc. Dopant A gas supply line may be provided. Dopant The gas supply line may be connected to a supply line of a gas supply. Dopant The gas supply line may be connected to the supply line of the gas supply via at least one connecting element, such as via at least one valve or via at least one T-piece. Further, the supply line of the gas supply may be connected to the supply line of the gas supply via at least one connecting element, such as via at least one valve or via at least one T-piece. Dopant The gas supply may include at least one inlet that may be configured to deliver gas to the gas supply. Further, the supply line of the gas supply may include: Dopant At least one outlet may be provided that may be configured to transfer gas from the gas supply to the supply line of the gas supply. There may be several other options. Dopant The gas supply line is Dopant From gas supply to gas supply Dopant at least one syringe pump configured to administer the flow of gas; Dopant A gas dosing device may be provided. Dopant The gas administration device is Dopant It may be integrated into the gas supply line. Dopant The gas dosing device may be integrated into the outlet of the gas supply line. Dopant The gas dosing device is Dopant The concentration of may be adapted to match the gradient of the liquid chromatography device. Dopant The gas dosing device is Dopant The concentration of may be adapted to vary with ionization efficiency.

[0027] Specifically, the gas supply unit and Dopant A gas supply unit may be sequentially arranged. More specifically, the gas supply unit, Dopant The gas supply and the liquid supply may be arranged in sequence. Dopant A gas supply and, optionally, a liquid supply may also be connected to the supply line of the gas supply. As used herein, the term "sequential arrangement" is a broad term and should be given its general and ordinary meaning to those skilled in the art and should not be limited to a specific or special meaning. This term may specifically refer to, but is not limited to, a serial arrangement without any branching. Thus, specifically, a gas supply and a liquid supply are connected in such a way that a single flow path is formed. Dopant Connected in series with the gas supply unit or connected to the gas supply unit Dopant There may be a series connection of a gas supply and a liquid supply.

[0028] Dopant The gas supply section is DopantAt least one gas-containing Dopant A gas flask may be provided. Dopant The term "gas flask" is a broad term and should be given its common and ordinary meaning to one of ordinary skill in the art and should not be limited to a specific or special meaning. The term specifically refers to, but is not limited to, a gas, particularly a chemical Dopant It may refer to any flask that may be configured to store and provide a gas. Dopant The gas flask is Dopant It may also be called a gas flask bottle. The flask may specifically be a pressure-stable bottle. Furthermore, the flask may specifically be made of glass. Specifically, Dopant Gas flask, chemistry Dopant as a pressurized gas. Dopant Gasfu The LASCO may be connected or connectable to a gas supply, in particular a nebulizer gas supply or a heating gas supply. Dopant The gas flask may be connected or connectable to a gas supply via at least one connecting element, such as at least one T-piece, in particular at least one gas supply tube of the gas supply; Dopant At least one tube connected or connectable to the gas flask may be connected or connectable to each other via at least one T-piece. Dopant The gas supply may comprise at least one flow regulating element, such as at least one valve. The flow regulating element, particularly the valve, regulates the flow of chemicals to the gas supply. Dopant The valve may be configured to regulate the flow of the gas. The valve may be referred to as a gas regulating valve.

[0029] moreover, DopantThe gas supply may comprise at least one headspace gas extraction device. As used herein, the term "headspace gas extraction device" is a broad term and should be given its general and ordinary meaning to those skilled in the art and should not be limited to a specific or special meaning. The term may specifically, but not exclusively, refer to any container configured to provide a gas, in particular a sealed or sealable container. In particular, the container may be configured to receive at least one substance, in particular at least one volatile substance, that may be in a gaseous state or may be made to be in a gaseous state, as will be further described in more detail below. The gas may be available in the headspace of the container, for example in the upper region of the container, and may be removed from the headspace and transferred to another device. In particular, the headspace gas extraction device may be used to extract a gas from a chemical Dopant It may be configured to provide a gas.

[0030] The headspace gas extraction device may be connected or connectable to a gas supply. In particular, the analyzer system may comprise at least one supply line. The supply line may be configured to supply gas from the gas supply to the headspace gas extraction device. Furthermore, the analyzer system may comprise at least one further supply line for supplying gas from the headspace gas extraction device to the gas supply. The supply line and the further supply line may in particular be or include one or more tubes. The supply line may be referred to as an inlet and the further supply line may be referred to as an outlet.

[0031] The headspace gas extraction device is specifically Dopant or a chemical solution of at least one of Dopant The liquid may be configured to receive at least one solution of Dopant The solution may specifically be a volatile solution. The headspace gas extraction device extracts chemicals in the form of gas from the gas headspace. DopantThe headspace gas extraction device may be configured to extract the gas from the gas supply chemically, for example via a further supply line as described above. Dopant It may be configured to collide with

[0032] Further, the headspace gas extraction apparatus may comprise at least one reaction vessel. As used herein, the term "reaction vessel" is a broad term and should be given its general and ordinary meaning to those skilled in the art and should not be limited to a specific or special meaning. The term may specifically, but not exclusively, refer to any apparatus configured to receive and hold at least one substance, particularly at least one liquid substance, and to allow reaction within the apparatus, such as within at least one interior space of the apparatus. The at least one substance, particularly at least one liquid substance, may be configured to undergo a chemical reaction with at least one further substance. Thus, a chemical reaction may be performed by a reaction vessel. Dopant The gas may be generated in situ by reaction, in particular by reaction of at least one substance, in particular at least one ammonia salt, with a solution, in particular a solution of sodium hydroxide or potassium hydroxide. The reaction vessel may have any shape. In particular, the reaction vessel is , may be configured to receive at least one ammonium salt. Further, the headspace gas extraction device may comprise at least one reaction vessel feed to the reaction vessel. The reaction vessel feed may specifically comprise at least one reaction vessel feed line or at least one reaction vessel tube. The reaction vessel feed may be configured to provide at least one reaction liquid to the reaction vessel. The ammonium salt may be configured to chemically react with the reaction liquid. The ammonia salt may be selected from the group consisting of ammonium sulfate, ammonium nitrate, ammonium methanoate, ammonium acetate, ammonium carbonate. However, other types of ammonia salts may be feasible. Further, the reaction liquid may be selected from the group consisting of a solution of sodium hydroxide, a solution of potassium hydroxide. However, other reaction liquids may be feasible. The concentration of the reaction liquid may be in the range of 0.1 mol / l to 20 mol / l, specifically 0.5 mol / l to 15 mol / l, more specifically 1 mol / l to 11 mol / l. Specifically, a lower concentration of the reaction liquid may improve operator safety. More specifically, a higher concentration may increase gas output.

[0033] Furthermore, the analyzer system may comprise at least one pump, in particular at least one syringe pump, more particularly at least one motorized syringe pump. The reaction vessel supply may comprise at least one pump, in particular at least one syringe pump. The pump may be configured to transport the reaction fluid and to dispense a flow of the reaction fluid into the reaction vessel. Furthermore, the analyzer system may comprise at least one three-way valve. The three-way valve may be configured to selectively connect the syringe pump to the reaction vessel and to the gas supply. During the reaction, the syringe pump may be connected to the reaction vessel and the chemical Dopant After the reaction, the syringe pump may be connected to a gas supply to allow the chemical DopantThe analyzer system may be configured to provide gas to the gas supply. Further, the analyzer system may include at least one pressure regulating valve. The pressure regulating valve may refer to a valve configured to control the pressure of a fluid or gas to a desired value. The pressure regulating valve may specifically be an integral device with a pressure setting, a restrictor, and / or a pressure sensor. Specifically, the pressure regulating valve may be a pressure reducing regulator. The pressure reducing regulator may be a control valve configured to reduce the input pressure of the fluid or gas to a desired value at its output. Further, specifically, the pressure regulating valve may be a back pressure regulator. The back pressure regulator may be a control valve configured to open and allow flow when the inlet pressure exceeds a set value to maintain a set pressure at its inlet side. The pressure regulating valve may connect the syringe pump to the gas supply. The headspace gas extraction device may be connected to the syringe pump via at least one three-way valve. The syringe pump may be configured to control the amount of chemicals in the reaction. Dopant It may be configured to be filled with a gas.

[0034] In addition, chemistry Dopant may be provided as a solid or liquid substance and the headspace gas extraction device may be configured to impinge gas from the gas supply on the solid or liquid substance. Dopant Gas is DopantThe gas may be released from a solution or from a compliant solid or liquid, for example by release of physically bound or adsorbed gases that evaporate, or by chemical decomposition of a precursor chemical. The solid substance may in particular be selected from the group consisting of ammonium methanoate, ammonium acetate, ammonium carbonate. However, other types of solid substances may also be feasible. The headspace gas extraction device may in particular comprise at least one gas heating unit. The gas heating unit may be configured to heat the gas provided by the gas supply before the gas impinges on the solid substance. The gas heating unit may in particular be configured to heat the gas provided by the gas supply to a temperature in the range of 50°C to 500°C, in particular in the range of 100°C to 400°C. The gas heating unit may be configured to heat the gas by natural or forced convection, vortex, and / or circulation of the gas. The gas heating unit may be configured to heat the gas to a desired temperature. In particular, the headspace gas extraction device may comprise at least one pipeline, the gas heating unit being configured to heat the gas provided by the gas supply to a temperature in the range of 50°C to 500°C, in particular in the range of 100°C to 400°C. The gas heating unit may be configured to directly or indirectly heat the gas in the pipeline, which may be stationary or circulating. The gas heating unit may be configured to be in direct contact with the gas or to heat the gas through a protective tube. The gas heating unit may in particular be selected from the group consisting of a ring radiator, a flange radiator. Other embodiments may also be feasible. Additionally or alternatively, the vessel may comprise at least one vessel heating element. The vessel heating element may be configured to heat the reaction vessel.

[0035] Furthermore, the headspace gas extraction device may comprise at least one laser ablation device. The laser ablation device may be configured to ablate solid material. As used herein, the term "laser ablation device" is a broad term and should be given its general and ordinary meaning to those skilled in the art and should not be limited to a special or special meaning. The term may specifically, but not exclusively, refer to any device configured to remove material from a surface, particularly a solid surface, by irradiating the surface with a laser beam. In particular, the material may be heated and evaporated or sublimated by absorption of the laser energy. However, further, the material may be converted into plasma. In particular, the laser ablation device may comprise a pulsed laser. However, other embodiments may also be feasible.

[0036] Also, Dopant Other embodiments of the gas supply may be possible. Dopant The gas supply may include at least one bubbling extractor. The bubbling extractor extracts chemicals from the solution. Dopant The term "bubbling extractor" as used herein is a broad term and should be given its common and ordinary meaning to one of ordinary skill in the art and should not be limited to a specific or special meaning. The term may specifically refer to, but is not limited to, any vessel configured to provide a liquid, particularly a sealed or sealable vessel. The liquid may be a chemical Dopant The bubbling extractor may be connected or connectable to a gas supply, as described above. In particular, as described above, the analyzer system may include at least one supply line. The supply line may be configured to supply gas from the gas supply to the bubbling extractor, in particular to a liquid provided by a vessel of the bubbling extractor. In this way, a chemical Dopant can be put into a gaseous state.

[0037] In particular, the analyzer system may further comprise at least one storage tank, in particular at least one storage pressure tank. The term "storage pressure tank" may refer to any container configured to hold a gas or liquid at a pressure different from the pressure of the surrounding atmosphere. The storage pressure tank may be used to store chemicals in the form of gases. Dopant The analyzer system may be configured to store a gas including a chemical compound in the form of a gas. The storage pressure tank may be connected or connectable to a tube of a gas supply, in particular a nebulizer gas supply. Furthermore, the analyzer system may comprise at least one dosing gas regulator. The dosing gas regulator may be configured to connect the gas supply to the storage pressure tank. Furthermore, the analyzer system may be configured to store a chemical compound in the form of a gas. Dopant The compressor may comprise at least one compressor unit configured to compress a gas, including: a compressor unit configured to compress a gas, the compressor unit being ...

[0038] Additionally, the analyzer system may include at least one reservoir pressure tank syringe pump, specifically at least one motorized reservoir pressure tank syringe pump. Dopant The gas supply, particularly the reaction vessel, or the headspace gas extraction device, is provided with at least one valve, particularly Typically, the syringe pump is connected or connectable to a reservoir pressure tank via at least one three-way valve. Dopant During the production of gas, chemical DopantThe reservoir pressure tank syringe pump may be configured to be filled with a gas. Furthermore, the valve may be configured to connect the reservoir pressure tank syringe pump to a gas supply, in particular a nebulizer gas supply, in particular after filling. In particular, the valve may be configured to connect the reservoir pressure tank syringe pump to a tube of the gas supply, in particular a nebulizer gas supply. More particularly, the valve may be configured to connect the reservoir pressure tank syringe pump to a pressure regulating valve connected to a tube of the gas supply. The reservoir pressure tank syringe pump may be configured to connect a pressure regulating valve connected to a tube of the gas supply. Dopant The syringe pump may be configured to compress the gas to an operating pressure, specifically a preset operating pressure. Further, the reservoir pressure tank syringe pump may be configured to provide a chemical pressure regulator to a gas supply, specifically a nebulizer gas supply, more specifically a pressure regulator connected to a tube of the gas supply. Dopant It may be configured to provide a steady supply of gas.

[0039] Furthermore, the analyzer system may comprise at least one refilling device, in particular at least one automatic refilling device. The refilling device may be configured, in particular continuously, to fill or refill the gas supply, in particular the headspace gas extraction device or the reaction vessel, with at least one substance. The substance may be, in particular, a chemical Dopant It may be a gaseous precursor or a chemical in liquid or solid form. Dopant Chemicals, even in liquid or solid form Dopant In particular, the replenishment apparatus may include at least one replenishment apparatus storage tank. The replenishment apparatus storage tank may include a storage tank for storing a precursor or chemical in liquid or solid form. Dopant The replenishment device may be configured to store at least one substance such as a replenishment device storage tank. Furthermore, the replenishment device may comprise at least one replenishment device pump, which may be specifically configured to transfer the substance from the replenishment device storage tank to the gas supply. Furthermore, the replenishment device may comprise at least one valve or at least one restricting capillary tube, which may be specifically configured to dose or regulate the flow of the substance to the gas supply. Thus, the replenishment device may be configured to store at least one chemical, e.g., a replenishment device storage tank, a replenishment device pump ... DopantThe headspace gas extraction device may be configured to permanently transfer material to the gas supply in order to keep the concentration of the gas constant. Dopant The pressure of the gas can be compensated by the replenishment device, in particular by the replenishment device pump. Thus, the liquid level in the headspace gas extraction device can be constant, but at the same time, the chemical Dopant of unused solution may be available.

[0040] The analyzer system specifically includes at least two Dopant At least two gas supplies may be provided. Dopant The gas supply section has at least two chemical Dopant At least two chemical Dopant The analyzer system may be configured to provide a gas. The analyzer system may further include at least one mixer. The mixer may include at least two chemical Dopant The mixing device may be configured to create a mixture of gases. Dopant The analyzer system may be configured to create a mixture of the gas and the further gas. Further, the analyzer system may include at least one dosing device. The dosing device may include Dopant The mixing device may be configured to dispense the gas. The dosing device and the mixing device may be separate components. Alternatively, however, the dosing device and the mixing device may be designed as an integral unit. The mixing device and / or the dosing device may comprise at least one component selected from the group consisting of a microsolenoid, in particular a 2 / 2-way microsolenoid, a 3 / 2-way microsolenoid, a membrane pump, a microdosing pump. Other components may also be feasible.

[0041] Additionally, the analyzer system may include at least one temperature controller, which controls the temperature of the gas provided by the gas supply, Dopant Chemistry provided by Gas Supply Department DopantThe analyzer system may be configured to control the temperature of one of the gases, the liquid supply ... Specifically, the liquid provided by the liquid supply unit may correspond to an eluent provided by the liquid chromatography device. Dopant Chemistry provided by Gas Supply Department Dopant Increasing the temperature of the gas and / or the temperature of the liquid provided by the liquid supply may increase signal-enhancing or noise-suppressing reactions, in particular increasing the protonation or deprotonation of the analyte. In particular, the temperature controller and / or the further temperature controller may be configured for one or more of measuring the temperature of the gas or liquid, adjusting the temperature of the gas or liquid. The temperature controller may comprise at least one component selected from the group consisting of a tubular heater, a flow heater, a ceramic cross-sectional heater, a threaded heater, and a heating flange. Additionally, the temperature controller may comprise at least one temperature sensor, such as a thermocouple or a resistance temperature sensor, configured to determine the temperature of the gas.

[0042] In a further aspect of the present invention, a multiplexed analyzer system is disclosed.

[0043] As used herein, the term "multiplexed analyzer system" is a broad term and should be given its general and ordinary meaning to those skilled in the art, and should not be limited to a specific or special meaning. The term may specifically, but not exclusively, refer to any analyzer system configured to perform multiple analytical measurements on multiple samples, the execution of the multiple analytical measurements being performed sequentially and / or interleaved in time. Illustratively, one first step of analytically measuring a first sample and one second step of analytically measuring a second sample may be performed in parallel. The first step and the second step may specifically correspond to different types of steps of an analytical measurement. However, the first step and the second step may also correspond to the same type of steps of an analytical measurement.

[0044] The multiplexed analyzer system comprises at least one mass analyzer having at least one electrospray ion source nozzle. Further, the multiplexed analyzer system comprises at least two, preferably at least three, liquid supplies. The liquid supplies are configured to provide at least one liquid having at least one analyte. Further, the multiplexed analyzer system comprises at least one gas supply. The gas supply is configured to provide at least one gas. The gas supply is coupled to the mass analyzer via the electrospray ion source nozzle. Further, the multiplexed analyzer system comprises at least one Dopant Equipped with a gas supply section. Dopant The gas supply section is equipped with at least one chemical Dopant At least one chemical Dopant It is configured to provide a gas to a test substance provided by one of the two liquid supplies. DopantThe gas supply is connected to the gas supply. The liquid supply can be alternately coupled to the mass analyzer via the electrospray ion source nozzle. In particular, each of the liquid supplies may have at least one liquid supply line, such as at least one liquid supply tube, which may be connected or connectable to the capillary of the electrospray ion source nozzle. Furthermore, each of the liquid supply lines may have at least one liquid supply valve. The liquid supply valve may have or comprise at least one locking piece, which may be movable to at least two different positions. In a first position, the locking piece may be arranged in the liquid supply valve such that a connection between a portion of the liquid supply line and a further portion of the liquid supply line appears. Thus, a connection between the liquid supply and the capillary of the electrospray ion source nozzle may appear. Furthermore, in a second position, the locking piece may be arranged in the liquid supply valve such that a portion of the liquid supply line and a further portion of the liquid supply line are decoupled from each other. Thus, the liquid supply and the capillary of the electrospray ion source nozzle may be decoupled from each other.

[0045] Specifically, the multiplexed analyzer system comprises at least two Dopant Gas supply, preferred Or at least three Dopant At least two gas supplies may be provided. Dopant The gas supply may in turn be coupleable to the mass spectrometer via an electrospray ion source nozzle. Dopant The gas supply unit is Dopant A gas supply line may be provided. Dopant Each of the gas supplies is Dopant Each of the gas supply lines may include: Dopant Each of the gas supplies may include Dopant At least one gas supply line may be connected or connectable to the gas supply line. Dopant At least one gas supply tube, etc. Dopant Each of the gas supply lines may include DopantThe gas supply line may lead to the end or tip of the capillary. Dopant Each of the gas supply lines has at least one Dopant Each may have a gas supply valve. Dopant The gas supply valve may have or be equipped with at least one locking piece that may be movable to at least two different positions. In a first position, the locking piece: Dopant Gas supply lines and further Dopant So that the connection between the gas supply line appears, Dopant It may be disposed in the gas supply valve. Dopant The connection between the gas supply and the electrospray ion source nozzle can be revealed. Furthermore, in the second position, the locking piece is Dopant Gas supply lines and further Dopant So that it can be disconnected from the gas supply line, Dopant It may be disposed in the gas supply valve. Dopant The gas supply and the electrospray ion source nozzle may be decoupled from each other.

[0046] A mass spectrometer, a liquid supply unit, a gas supply unit, and Dopant With regard to the gas supply, reference may be made to the above description. Furthermore, the multiplexed analyzer system may comprise analyzer system components such as a mixing device, a dosing device, and / or a temperature control device, with reference to the above description for these components.

[0047] In a further aspect of the present invention, the use of an analyzer system as described above or as further described in more detail below for detecting at least one steroid or a metabolite thereof, in particular estradiol, is disclosed.

[0048] In a further aspect of the present invention, a method for analyzing at least one analyte is disclosed.

[0049] The method specifically includes the following steps, which may be performed in a given order. However, it should be noted that different orders are also possible. Furthermore, it is also possible to perform one or more of the method steps once or repeatedly. Furthermore, it is also possible to perform two or more of the method steps simultaneously or in a time-overlapping manner. The method may include further method steps not listed.

[0050] The method comprises the following steps: a) providing at least one analyzer system as described above or further described in more detail below; b) providing a liquid having an analyte and providing a gas to an electrospray ion source nozzle; c) Chemical via gas supply Dopant Chemistry with Dopant providing a gas to assist in protonating or deprotonating the analyte; d) performing at least one measurement with a mass spectrometer; Includes.

[0051] For further details, definitions or options of the method steps, reference may be made to the analyzer system as described above or in more detail below.

[0052] The method and apparatus according to the present invention provide a number of advantages over known methods and apparatus.

[0053] In particular, the sensitivity of the negative mode of electrospray ionization may be increased. Furthermore, the introduction of post-column peak dispersion volumes may be avoided. Furthermore, the method for analyzing at least one analyte and the analyzer system itself may be made less complex. Furthermore, the method for analyzing at least one analyte and the analyzer system may be made less complex, in particular for chemical analysis. Dopant The basic nature of may make it primarily robust to acidic contamination such as formic acid.

[0054] The nebulizer gas may be a gas that can simultaneously increase the signal of the analyte of interest during electrospray ionization or other ambient pressure ionization techniques, suppress background signals, or enhance the signal-to-noise ratio by both of the aforementioned modes of operation. Dopant And it can be doped. Dopant Gas may be supplied from a pressurized gas bottle or extracted from solution by headspace extraction or Dopant from a compliant solid or liquid, either by direct bubbling extraction of gas from solution, or by release of physically bound / adsorbed gases that evaporate, or by chemical decomposition of precursor chemicals by heat introduced, for example, by heated gas, direct heating by a heating element, or by laser energy coupled to a surface. Dopant It may be produced in situ by the release of gas. Dopant An example of a source of gas may be ammonia, for example as a pressurized gas or in solution, or its salts, particularly carbonates, fluorides, formates, acetates, which are decomposed by heating or decomposition methods as described above. Some embodiments of the present invention may largely eliminate the need for pressurized gas containers by replacing them with on-site generation units, avoiding safety and regulatory concerns. Chemicals in gaseous form, for example by utilizing ammonia gas, may be used to generate gaseous forms of ammonia. Dopant Application of , due to its volatility, can shorten cycle times.

[0055] In summary, without excluding further possible embodiments, the following embodiments can be envisaged:

[0056] Embodiment 1: At least one mass spectrometer having at least one electrospray ion source nozzle; at least one liquid supply configured to provide at least one liquid having at least one test substance; at least one gas supply configured to provide at least one gas; At least one chemistry Dopant At least one chemical Dopantat least one configured to provide a gas to a test substance provided by the liquid supply; Dopant Gas supply unit and Equipped with the liquid supply and the gas supply are coupled to the mass analyzer via an electrospray ion source nozzle; Dopant The gas supply is connected to the gas supply of the analyzer system.

[0057] Embodiment 2: An analyzer system according to embodiment 1, wherein the gas supply is a nebulizer gas supply configured to provide at least one nebulizer gas, the nebulizer gas configured to nebulize a liquid provided by the liquid supply.

[0058] Embodiment 3: Dopant 3. An analyzer system according to embodiment 2, wherein the gas supply is connected to a nebulizer gas supply.

[0059] Embodiment 4: An analyzer system according to embodiment 2 or 3, wherein the nebulizer gas comprises at least one inert gas, in particular at least one of nitrogen, argon, helium.

[0060] Embodiment 5: An analyzer system according to any one of embodiments 1 to 4, wherein the heated gas supply further comprises at least one heated gas supply configured to provide at least one heated gas to the electrospray ion source nozzle.

[0061] Embodiment 6: Dopant 6. An analyzer system according to embodiment 5, wherein the gas supply is connected to a heated gas supply.

[0062] Embodiment 7: An analyzer system according to embodiment 5 or 6, wherein the heating gas comprises at least one inert gas, in particular at least one of nitrogen, argon, helium.

[0063] Embodiment 8: Chemistry DopantThe analyzer system according to any one of embodiments 1 to 7, wherein the gas is ammonia.

[0064] Embodiment 9: Chemistry Dopant The analyzer system according to embodiments 1-8, wherein the at least one raw material for the formation of the gas is selected from the group consisting of ammonium carbonate, ammonium fluoride, ammonium acetate, ammonium methanate.

[0065] Embodiment 10: An analyzer system according to any one of embodiments 1 to 9, comprising at least one liquid chromatography device, the liquid supply being coupled to the liquid chromatography device.

[0066] Embodiment 11: An analyzer system according to embodiment 10, wherein the liquid chromatography device is selected from the group consisting of a nano liquid chromatography device, a micro liquid chromatography device, a high performance liquid chromatography device, and a high performance liquid chromatography device.

[0067] Embodiment 12: The analyzer system according to any one of embodiments 1 to 11, wherein the test substance is a steroid or a metabolite thereof, in particular estradiol.

[0068] Embodiment 13: An analyzer system according to any one of embodiments 1 to 12, which is an in vitro diagnostic analyzer.

[0069] Embodiment 14: Dopant The gas supply section is Dopant At least one containing Dopant Equipped with a gas flask, Dopant The analyzer system according to any one of embodiments 1 to 13, wherein the gas flask is connected to a gas supply.

[0070] Embodiment 15: Dopant The gas flask is connected to a gas supply via at least one T-piece; Dopant The gas supply further comprises at least one valve, the valve providing a chemical to the gas supply. Dopant16. The analyzer system according to embodiment 15, configured to adjust the flow rate of

[0071] Embodiment 16: Dopant Gas flask, chemistry Dopant 16. The analyzer system according to embodiment 14 or 15, comprising as a pressurized gas.

[0072] Embodiment 17: Dopant The gas supply includes at least one headspace gas extraction device, the headspace gas extraction device extracting chemicals in the form of gases. Dopant and the headspace gas extraction device is connected to a gas supply. Analyzer system.

[0073] Embodiment 18: An analyzer system according to embodiment 17, comprising at least one supply line for supplying gas from the gas supply to the headspace gas extraction device, and further comprising at least one further supply line for supplying gas from the headspace gas extraction device to the gas supply.

[0074] Embodiment 19: The headspace gas extraction device is Dopant The headspace gas extraction device extracts chemicals in the form of gas from the gas headspace. Dopant 19. The analyzer system according to any one of embodiments 17 or 18, configured to extract:

[0075] 20. The headspace gas extraction device is configured to extract gas from a gas supply Dopant 20. The analyzer system according to embodiment 19, configured to collide with

[0076] Embodiment 21: An analyzer system according to any one of embodiments 17 to 20, wherein the headspace gas extraction device comprises at least one reaction vessel, the reaction vessel being configured to receive at least one ammonium salt, and the headspace gas extraction device further comprises at least one reaction vessel supply to the reaction vessel, the reaction vessel supply being configured to provide at least one reaction liquid to the reaction vessel.

[0077] Embodiment 22: An analyzer system according to embodiment 21, wherein the reaction vessel supply comprises at least one pump, the pump configured to administer a flow of reaction fluid into the reaction vessel.

[0078] Embodiment 23: The analyzer system according to embodiment 21 or 22, wherein the ammonium salt is selected from the group consisting of ammonium sulfate, ammonium nitrate, ammonium methanate, ammonium acetate, and ammonium carbonate.

[0079] Embodiment 24: The analyzer system according to any one of embodiments 21 to 23, wherein the reaction liquid is selected from the group consisting of a solution of sodium hydroxide, potassium hydroxide.

[0080] Embodiment 25: The method further comprises at least one syringe pump, in particular at least one electrically operated syringe pump, and at least one three-way valve, which is configured to selectively connect the syringe pump to the reaction vessel and the gas supply, and during the reaction, the syringe pump is connected to the reaction vessel and the chemical Dopant The syringe pump is connected to a gas supply to fill the reaction chamber with gas. Dopant An analyzer system according to any one of embodiments 21-24, configured to provide gas to a gas supply.

[0081] Embodiment 26: The analyzer system according to embodiment 25, further comprising at least one pressure regulating valve, the pressure regulating valve connecting the syringe pump to a gas supply.

[0082]

[0041] Embodiment 27: The headspace gas extraction device is connected to a syringe pump via at least one three-way valve, and the syringe pump is adapted to pump chemicals during the reaction. Dopant 27. The analyzer system according to embodiment 25 or 26, configured to be filled with gas.

[0083] Embodiment 28: Chemistry Dopant The analyzer system according to any one of embodiments 7 to 27, wherein the is provided as a solid material.

[0084] Embodiment 29: A headspace gas extraction device is provided to collide solid material with gas from a gas supply. 29. An analyzer system according to embodiment 28, configured as follows:

[0085] Embodiment 30: An analyzer system according to embodiment 28 or 29, wherein the headspace gas extraction device comprises at least one gas heating unit configured to heat the gas provided by the gas supply, in particular before the gas impinges on the solid material.

[0086] Embodiment 31: An analyzer system according to any one of embodiments 28 to 30, wherein the headspace gas extraction device comprises at least one laser ablation device, the laser ablation device configured to ablate solid material.

[0087] Embodiment 32: The analyzer system according to any one of embodiments 28 to 31, wherein the solid material is selected from the group consisting of ammonium methanoate, ammonium acetate, and ammonium carbonate.

[0088] Embodiment 33: The method further comprises at least one storage tank, in particular at least one storage pressure tank, which stores chemicals in gas form. Dopant 33. The analyzer system according to any one of embodiments 16 to 32, configured to store a gas comprising:

[0089] Embodiment 34: Chemistry of gas forms Dopant34. The analyzer system according to embodiment 33, further comprising at least one compressor unit configured to compress a gas comprising:

[0090] Embodiment 35: An analyzer system according to embodiment 33 or 34, further comprising at least one dosing gas regulator, the dosing gas regulator configured to connect the gas supply to the storage tank.

[0091] Embodiment 36: An analyzer system according to any one of embodiments 1 to 35, wherein the liquid supply comprises at least one liquid supply syringe pump configured to administer a flow of liquid having at least one test substance to the liquid supply.

[0092] Embodiment 37: At least two chemistries Dopant At least two chemical Dopant At least two configured to provide a gas Dopant At least two chemical Dopant An analyzer system according to any one of embodiments 1 to 36, further comprising at least one mixer configured to create a mixture of gases.

[0093] Embodiment 38: The method further comprises at least one administration device, the administration device comprising: Dopant An analyzer system according to any one of embodiments 1 to 37, configured to administer a gas.

[0094] Embodiment 39: At least one mass spectrometer having at least one electrospray ion source nozzle; at least two, preferably at least three, liquid supplies configured to provide at least one liquid having at least one test substance; at least one gas supply configured to provide at least one gas and coupled to the mass analyzer via the electrospray ion source nozzle; At least one chemistry Dopant At least one chemical DopantAt least one gas supply is connected to the gas supply and configured to supply gas to the test substance provided by one of the two liquid supplies. Dopant Gas supply unit and Equipped with The liquid supply is in turn coupled to a mass spectrometer via an electrospray ion source nozzle. Possible, multiplexed analyzer systems.

[0095] Embodiment 40: At least two Dopant Gas supply, preferably at least three Dopant Equipped with a gas supply, two Dopant 40. A multiplexed analyzer system according to embodiment 39, wherein the gas supplies are alternately coupleable to the mass analyzer via the electrospray ion source nozzle.

[0096] Embodiment 41: Use of an analyzer system according to any one of the preceding embodiments relating to the analyzer system for detecting at least one steroid or a metabolite thereof, in particular estradiol.

[0097] Embodiment 42: A method for analyzing at least one analyte, comprising: a) providing at least one analyzer system according to any one of the preceding embodiments relating to an analyzer system; b) providing a liquid having an analyte and providing a gas to an electrospray ion source nozzle; c) Chemical via gas supply Dopant Chemistry with Dopant providing a gas to assist in protonating or deprotonating the analyte; d) performing at least one measurement with a mass spectrometer; The method includes:

[0098] BRIEF DESCRIPTION OF THE DRAWINGS Further optional features and embodiments are disclosed in more detail in the following description of the embodiments, preferably in conjunction with the dependent claims, where each optional feature may be realized in an independent manner or in any possible combination, as understood by a person skilled in the art. The scope of the present invention is not limited by the preferred embodiments. The embodiments are illustrated diagrammatically in the figures, where the same reference numbers in these figures refer to the same or functionally equivalent elements. [Brief description of the drawings]

[0099] [Figure 1A] 1 illustrates an exemplary embodiment of an analyzer system according to the present invention. [Figure 1B] 1 illustrates an exemplary embodiment of an analyzer system according to the present invention. [Figure 1C] 1 illustrates an exemplary embodiment of an analyzer system according to the present invention. [Diagram 2] 1 shows chromatograms illustrating a proof-of-concept experiment. [Diagram 3] 1 shows chromatograms illustrating further proof-of-concept experiments. [Figure 4] 1 illustrates an exemplary embodiment of a multiplexed analyzer system according to the present invention. [Diagram 5] 1 illustrates diagrammatically a method for analyzing at least one sample in a multiplexing system according to the present invention; DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0100] Detailed Description of the Embodiments 1A-1C show an exemplary embodiment of an analyzer system 110 according to the present invention. The analyzer system 110 comprises at least one mass analyzer 112 having at least one electrospray ion source nozzle 114. Furthermore, the analyzer system 110 comprises at least one liquid supply 116. The liquid supply 116 is configured to provide at least one liquid having at least one analyte. Furthermore, the analyzer system comprises at least one gas supply 118. The gas supply 118 is configured to provide at least one gas. Furthermore, the analyzer system 110 comprises at least one Dopant A gas supply unit 120 is provided. Dopant The gas supply 120 includes at least one chemical Dopant At least one chemistry with 122 Dopant Gas to liquid The liquid supply 116 and the gas supply 118 are coupled to the mass analyzer 112 via the electrospray ion source nozzle 114, Dopant The gas supply 120 is connected to the gas supply 118 .

[0101] As shown in Figures 1A and 1B, the electrospray ion source nozzle 114 may include at least one capillary 124. The capillary 124 may illustratively be made of at least one metal, such as glass and / or stainless steel. The electrospray ion source nozzle 114 may be configured to apply a high voltage to an outer surface 126 of the capillary 124. In particular, the liquid supply 116 may be or may correspond to a liquid chromatography device 128. The capillary 124 of the electrospray ion source nozzle 114 may be or may be connectable to the liquid supply 116, in particular the liquid chromatography device 128, via at least one tube or the like, as shown diagrammatically by arrow 130.

[0102] 1A and 1B, the gas supply 118 may include at least one storage element 132, such as a container 134 configured to provide and store a gas. Additionally, the gas supply 118 may include at least one tube 136, such as at least one hose 138. Specifically, the gas supply 118 may include at least one tube 136, which may lead to an end 140 of the capillary 124.

[0103] In particular, the gas supply may be a nebulizer gas supply 142. The nebulizer gas supply 142 may be configured to provide at least one nebulizer gas. The nebulizer gas may be configured to atomize the liquid provided by the liquid supply 116. In particular, the nebulizer gas 142 may include at least one inert gas, in particular nitrogen. Furthermore, the analyzer system may comprise at least one further gas supply 144. The further gas supply may be a heating gas supply 146. The heating gas supply 146 may be configured to provide at least one heating gas to the electrospray ion source nozzle 114. In particular, the heating gas may include at least one inert gas, in particular nitrogen. The heating gas supply 146 may comprise at least one further storage element 148, such as a further container 150, configured to provide and store gas. Additionally, the heated gas supply 146 may include at least one additional tube 152, such as at least one additional hose 154. Specifically, the heated gas supply 146 may include at least one additional tube 152, which may lead to the end 140 of the capillary 124. Illustratively, as shown in FIG. 1A, the analyzer system 110 may include a nebulizer gas supply 142 and a heated gas supply 146. Additionally, as shown in FIG. 1A, Dopant The gas supply 120 may be connected to a nebulizer gas supply 142 .

[0104] Specifically, as shown in FIG. 1A, DopantThe gas supply 120 may comprise at least one headspace gas extractor 156. The headspace gas extractor 156 may in particular comprise at least one container 158. The container 158 may be configured to receive at least one substance that may be in a gaseous state or may be made to be in a gaseous state, in particular at least one volatile substance. The headspace gas extractor 156 may in particular comprise a chemical Dopant 122. Dopant The solution 160 of 122 may specifically be a volatile solution 162. The headspace gas extractor 156 extracts chemicals in the form of gas from the gas headspace 164. Dopant 122.

[0105] The headspace gas extraction device 156 may be connected or connectable to the gas supply 118, in particular the nebulizer gas supply 142. In particular, the analyzer system 110 may comprise at least one supply line 166 for supplying gas from the gas supply 118, in particular the nebulizer gas supply 142, to the headspace gas extraction device 156. Furthermore, the analyzer system 110 may comprise at least one further supply line 168 for supplying gas from the headspace gas extraction device 156 to the gas supply 118, in particular the nebulizer gas supply 142. The supply line 166 may be referred to as an inlet 170 and the further supply line 168 may be referred to as an outlet 172.

[0106] Chemistry involving nebulizer gas Dopant may meet with the eluate provided by the liquid chromatography device 128 at the end 140 of the capillary 124, resulting in homogeneous mixing with the eluate. Dopant 122 may be configured to assist in deprotonation in negative mode of electrospray ionization or protonation in positive mode of electrospray ionization.

[0107] Alternatively, as shown in FIG. Dopant The gas supply unit 120 is a chemical DopantAt least one gas containing gas 122 Dopant A gas flask 174 may be provided. Dopant The gas flask 174 may specifically be a pressure-stabilized bottle 176. Dopant Gas flask 174 is used to store chemicals as pressurized gas. Dopant 122. Dopant The gas flask 174 may be connected or connectable to the gas supply 118, particularly the nebulizer gas supply 142. Specifically, Dopant The gas flask 174 may be connected or connectable to the gas supply 118 via at least one T-piece 178. Specifically, Dopant The gas flask 174 may be connected to at least one tube 180, which may be connected to the tube 136 of the gas supply 118 via a T-piece 178. Dopant The gas supply 120 may include at least one gas flow regulator 182, specifically at least one valve 184. The gas flow regulator 182 regulates the flow of chemicals to the gas supply 118, specifically the tube 136 of the gas supply 118. Dopant The T-piece may be configured to regulate the flow of the chemical Dopant The gas may be configured to mix with the nebulizer gas.

[0108] 1C shows a detailed view of an exemplary embodiment of an analyzer system 110 according to the present invention. Shown is an electrospray ion source nozzle 114 having at least one capillary 124. Additionally, a heating gas supply 146 is shown. Dopant The mixture of chemical and heating gas may be externally transferred to the electrospray ion source nozzle 114 as illustrated by bar 186 which meets the ion spray at point 188. The outlet of the heating gas supply 146 may be disposed at an angle α of 20° to 80°, specifically 30° to 70°, more specifically 45°, relative to the capillary 124. Dopant The mixture of gas and heated gas can result in an optimized electrospray ionization process.

[0109] Figure 2 shows a chromatogram illustrating a proof-of-concept experiment. The analyte estradiol was directly infused into the mass spectrometer using a syringe pump. The numbered parts of the chromatogram represent different parts of the experiment and are explained below. In the chromatogram, the intensity I is shown as a function of time t.

[0110] At region 1 of the chromatogram, the syringe pump was turned on and the injection of the test substance estradiol was started. An increase in the signal was observed, which after a few seconds reached a stable plateau. The intensity level of the plateau was about 1400.

[0111] At portion 2 of the chromatogram, the syringe pump was turned off and an immediate decrease in signal was observed as analyte was no longer being injected. A pressure-stabilized bottle containing a solution of ammonium hydroxide was connected to the mass spectrometer.

[0112] At part 3 of the chromatogram, when the syringe pump was turned on again, an increase in the signal was observed, which after a few seconds stabilized and reached a plateau of intensity of about 13,000. Dopant This equates to roughly a 9-fold signal enhancement by using

[0113] At portion 4 of the chromatogram, the syringe pump was turned off and an immediate decrease in signal was observed as analyte was no longer being injected.

[0114] At site 5 of the chromatogram, the pressure-stabilized bottle containing the ammonium hydroxide solution was disconnected from the mass spectrometer and the syringe pump was turned on again. An increase in signal was observed, which stabilized after a few seconds and reached a plateau of intensity around 1600. The experiment showed comparable results to site 1.

[0115] At portion 6 of the chromatogram, the syringe pump was turned on again and an increase in signal was observed. Because the syringe pump had emptied, the signal was not able to reach a stable plateau. Therefore, the syringe pump was turned off and manually refilled.

[0116] At site 7 of the chromatogram, the syringe pump was turned on again and an increase in signal was observed, which stabilized after a few seconds and reached a plateau of intensity of about 14000. The experimental results may be comparable to site 3.

[0117] Figure 3 shows chromatograms illustrating further proof-of-concept experiments. To investigate signal enhancement for liquid chromatography-mass spectrometry based assays, Agilent The 1290 Infinity HPLC system was connected to an Agilent 6495 Triple Quadrupole. The chromatograms show counts per second cps as a function of retention time t.

[0118] Chromatogram 190 shows an injection of 100 pg / mL estradiol calibrant dissolved in neat solvent, performed with eluent A containing LC / MS grade deionized water and eluent B containing 0.2 mmol / L ammonium fluoride in methanol. Neat solvent may refer to LC / MS grade standard solvent, specifically neat such that signal effects, particularly matrix effects on the signal, are avoided or at least greatly reduced. This mobile phase composition is representative of state of the art estradiol assays. Estradiol peak 192 eluted with a retention time of 28 seconds and had an area value of 59. To generate chromatogram 194, Dopant The addition of gaseous ammonium hydroxide as a chromatographic detector was utilized. The mobile phase consisted of LC / MS grade water in eluent A and methanol in eluent B. The retention time of estradiol was 28 seconds with an area value of 495, which represents approximately an 8-fold signal enhancement compared to the state-of-the-art estradiol assay.

[0119] FIG. 4 illustrates an exemplary embodiment of a multiplexed analyzer system 196 in accordance with the present invention.

[0120] The multiplexed analyzer system 196 comprises at least one mass analyzer 112 having at least one electrospray ion source nozzle 114. Furthermore, the multiplexed analyzer system 196 comprises at least two, preferably at least three, liquid supplies 116. In the embodiment according to FIG. 4, the multiplexed analyzer system 196 may comprise at least four liquid supplies 116. In particular, three of the four liquid supplies 116 are high-temperature The liquid supply 116 may be a high pressure liquid chromatography (HPLC) device 198, and one of the four liquid supplies 116 may be a high performance liquid chromatography device 200. The liquid supplies 116 may be alternately coupled to the mass spectrometer 112 via the electrospray ion source nozzle 114. In particular, each of the liquid supplies 116 may have at least one liquid supply line 214 that may be connected or connectable to the capillary 124 of the electrospray ion source nozzle 114. Furthermore, each of the liquid supply lines 214 may have at least one liquid supply valve 216. The liquid supply valve 216 may have or comprise at least one locking piece that may be movable to at least two different positions. In a first position, the locking piece may be disposed in the liquid supply valve 216 such that a connection between a portion 218 of the liquid supply line 214 and a further portion 220 of the liquid supply line 214 appears. Thus, a connection between the liquid supply 116 and the capillary 124 of the electrospray ion source nozzle 114 can appear. Furthermore, in the second position, the locking piece may be arranged in the liquid supply valve 216 such that the portion 218 of the liquid supply line 214 and the further portion 220 of the liquid supply line 214 are decoupled from each other. Thus, the liquid supply 116 and the capillary 124 of the electrospray ion source nozzle 114 may be decoupled from each other. The liquid supplies 116 may be alternately coupleable to the vessels 202 that provide at least one sample. In particular, the liquid supplies 116 may each be alternately coupleable to the vessels 202 via at least one valve 222.

[0121] Additionally, the multiplexed analyzer system 196 includes at least one gas supply 118 configured to provide at least one gas, such as nitrogen. The gas supply 118 is coupled to the mass analyzer 112 via the electrospray ion source nozzle 114. Additionally, the multiplexed analyzer system 196 includes at least one Dopant The gas supply 120 is connected to the multiplexed analyzer system 196. Specifically, the multiplexed analyzer system 196 includes at least three DopantA gas supply unit 120 may be provided. At least three Dopant The gas supply 120 may be alternately connectable to the gas supply 118. Specifically, Dopant Each of the gas supply units 120 includes: Dopant Each of the gas supply lines 224 may be provided. Dopant Each of the gas supplies 120 includes a further Dopant At least one gas supply line 226 may be connected or connectable to the gas supply line 226. Dopant Each of the gas supply lines 224 may include Dopant The gas supply line 226 may communicate with the end 140 of the capillary 124. Dopant Each of the gas supply lines 224 has at least one Dopant Each may have a gas supply valve 228 . Dopant The gas supply valve 228 may have or be equipped with at least one locking piece that may be movable to at least two different positions. In a first position, the locking piece: Dopant Gas supply line 224 and further Dopant 2 so that the connection between the gas supply line 226 appears. Dopant may be disposed in the gas supply valve 228. Dopant The connection between the gas supply 120 and the electrospray ion source nozzle 114 can be revealed. Furthermore, in the second position, the locking piece Dopant Gas supply line 224 and further Dopant To allow the gas supply line 226 to be disconnected, Dopant may be disposed in the gas supply valve 228. Dopant The gas supply 120 and the electrospray ion source nozzle 114 may be decoupled from each other. Additionally, the multiplexed analyzer system 196 may include at least one controller 204. The controller 204 controls the liquid supply valve 216, the valve 222, Dopant The gas supply valve 228 may be configured to control at least one of the gas supply valves 228. Additionally, optionally, the multiplexed analyzer system 196 may include a heated gas supply 146.

[0122] A method for analyzing at least one sample with a multiplexing system 196 is shown generally in FIG.

[0123] The three high pressure liquid chromatography (HPLC) streams 206 and one high performance liquid chromatography stream 208 may be multiplexed and alternately directed to the mass analyzer 112, which may be kept in a random access measurement mode at all times. The mass spectra 210 may be acquired one after the other in a time period t. The time period t may be illustratively 36 seconds. In this manner, mass spectrometry data 212 may be collected. The liquid chromatography mass spectrometry cycle may specifically include three phases, namely an equilibration phase A, a detection phase B, and a wash phase C, as shown in the box on the right. One of the HPLC streams 206 may be in the equilibration phase, while one of the remaining HPLC streams 206 may be in the detection phase and one of the remaining HPLC streams 206 may be in the wash phase, or vice versa. Chemistry Dopant Gas may be specifically and selectively supplied only during detection phase B.

[0124] A challenge for mass spectrometer detectors can be rapid switching of mobile phases with changes in pH, buffers, and organic content. Dopant The addition of facilitates random access since buffer and / or pH changes only need to occur post-column at the electrospray ion source nozzle, rather than requiring buffer and pH exchange for the entire flow path of the HPLC system, thus allowing for more rapid switching and equilibration of mass spectrometry conditions and enabling robust high throughput analysis. [Explanation of symbols]

[0125] 110 Analyzer System 112 Mass spectrometer 114 Electrospray Ion Source Nozzle 116 Liquid supply section 118 Gas Supply Section 120 DopantGas Supply Unit 122 Chemistry Dopant 124 Capillary 126 Exterior 128 Liquid Chromatography Equipment 130 Arrow 132 Storage elements 134 Container 136 Tubes 138 Horse 140 End 142 Nebulizer gas supply unit 144 Further Gas Supply Section 146 Heating gas supply section 148 Further Storage Elements 150 More Containers 152 More Tubes 154 More Hose 156 Headspace Gas Extraction Device 158 Container 160 solution 162 Volatile Solutions 164 Gas headspace 166 Supply Line 168 More Supply Lines 170 Entrance 172 Exit 174 Dopant Gas Flask 176 Pressure Stabilizing Bottle 178 T-piece 180 tubes 182 Flow rate adjustment section 184 Valve 186 Bar 188 points 190 Chromatograms 192 Peak 194 Chromatogram 196 Multiplexed Analyzer System 198 High Pressure Liquid Chromatography Equipment 200 High-performance liquid chromatography equipment 202 Container 204 Controller 206 High Pressure Liquid Chromatography Streams 208 High Performance Liquid Chromatography Streams 210 Mass Spectrum 212 Mass Spectrometry Data 214 Liquid supply line 216 Liquid supply valve 218 parts 220 Further Parts 222 Valve 224 Dopant Gas supply lines 226 Further Dopant Gas supply lines 228 Dopant Gas supply valve

Claims

1. at least one mass analyzer (112) having at least one electrospray ion source nozzle (114); at least one liquid supply (116) configured to provide at least one liquid having at least one analyte; at least one gas supply (118) configured to provide at least one gas; at least one dopant gas supply (120) configured to provide at least one chemical dopant gas having at least one chemical dopant (122) to the analyte provided by the liquid supply (116); Equipped with the liquid supply (116) and the gas supply (118) are coupled to the mass analyzer (112) via the electrospray ion source nozzle (114), and the dopant gas supply (120) is connected to the gas supply (118); The gas supply (118) is a nebulizer gas supply (142), the nebulizer gas supply (142) configured to provide at least one nebulizer gas, the nebulizer gas configured to atomize the liquid provided by the liquid supply (116), and the nebulizer gas supply (142) and the dopant gas supply (120) are arranged sequentially in the analyzer system (110).

2. The analyzer system of claim 1 , further comprising at least one heated gas supply configured to provide at least one heated gas to the electrospray ion source nozzle.

3. The analyzer system of claim 1 , wherein the analyte is a steroid or a metabolite thereof.

4. 2. The analyzer system of claim 1, wherein the dopant gas supply comprises at least one dopant gas flask containing the chemical dopant, the dopant gas flask being connected to the gas supply.

5. 2. The analyzer system of claim 1, wherein the dopant gas supply comprises at least one headspace gas extractor configured to provide a gas containing the chemical dopant in gaseous form, the headspace gas extractor connected to the gas supply.

6. 6. The analyzer system of claim 5, wherein the headspace gas extractor (156) contains a solution of the chemical dopant (122), the headspace gas extractor (156) is configured to extract the chemical dopant (122) in gas form from a gas headspace (164), and the headspace gas extractor (156) is configured to impinge the gas from the gas supply (118) on the chemical dopant (122).

7. 6. The analyzer system of claim 5, wherein the headspace gas extraction apparatus comprises at least one reaction vessel, the reaction vessel configured to receive at least one ammonium salt, and the headspace gas extraction apparatus further comprises at least one reaction vessel feed to the reaction vessel, the reaction vessel feed configured to provide at least one reaction liquid to the reaction vessel.

8. 6. The analyzer system of claim 5, wherein the chemical dopant is provided as a solid material, and the headspace gas extractor is configured to collide the solid material with the gas of the gas supply.

9. 10. The analyzer system of claim 8, wherein the headspace gas extraction device comprises at least one gas heating unit configured to heat the gas provided by the gas supply before the gas impinges on the solid material.

10. The analyzer system of claim 8 , wherein the headspace gas extraction device comprises at least one laser ablation device, the laser ablation device configured to ablate the solid material.

11. at least one mass analyzer (112) having at least one electrospray ion source nozzle (114); at least two liquid supplies (116) configured to provide at least one liquid having at least one analyte; at least one gas supply (118) configured to provide at least one gas and coupled to the mass analyzer (112) through the electrospray ion source nozzle (114); at least one dopant gas supply (120) configured to provide at least one chemical dopant gas having at least one chemical dopant (122) to the test material provided by one of the two liquid supplies (116), the dopant gas supply (120) being connected to the gas supply (118); Equipped with the liquid supply is in turn connectable to the mass analyzer (112) via the electrospray ion source nozzle (114); The gas supply (118) is a nebulizer gas supply (142), the nebulizer gas supply (142) configured to provide at least one nebulizer gas, the nebulizer gas configured to atomize the liquid provided by the liquid supply (116), and the nebulizer gas supply (142) and the dopant gas supply (120) are arranged in series in a multiplexed analyzer system (196).

12. 12. The multiplexed analyzer system of claim 11, comprising at least two dopant gas supplies alternately coupleable to the mass analyzer via the electrospray ion source nozzle.

13. Use of an analyzer system (110) according to any one of claims 1 to 10 for detecting at least one steroid or a metabolite thereof, in particular estradiol.

14. 1. A method for analyzing at least one analyte, comprising: a) providing at least one analyzer system (110) according to any one of claims 1 to 10; b) providing the liquid having the analyte and providing the gas to the electrospray ion source nozzle (114); c) providing the chemical dopant gas having the chemical dopant (122) via the gas supply (118) to assist in protonating or deprotonating the analyte; d) performing at least one measurement with said mass spectrometer (112); A method comprising:

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