Method for analyzing samples containing high M / Z cutoffs

Abstract

In one aspect, a method of performing mass spectrometry analysis of a sample, for example a food-based sample, is disclosed that includes ionizing the sample to generate a plurality of ions, introducing the plurality of ions into a mass filter configured to provide a high M / Z cutoff greater than a maximum m / z ratio of ions associated with one or more analytes of interest in the sample and to allow passage of analyte ions while blocking passage of ions having m / z ratios greater than the high M / Z cutoff, and performing mass analysis of the ions passing through the mass filter. In a related aspect, a mass spectrometer is disclosed that includes an atmospheric pressure ion source, a first mass filter, a user interface, and a controller.

Description

Technical Field

[0001] (Related Application) This application claims priority to U.S. Provisional Application No. 63 / 166,158, filed March 25, 2021, entitled "Method For Analyzing Samples Including A High M / Z Cutoff," which is incorporated herein by reference in its entirety.

[0002] The present teachings generally relate to mass spectrometry methods and systems for the analysis of samples, and more specifically to such methods and systems that can be employed for the analysis of food-based and tissue samples.

Background Art

[0003] The analysis of food-based samples is increasing in importance, particularly in relation to the detection of pesticides and other harmful chemicals. Such analysis typically requires the processing of samples with reagents to extract the chemical of interest (the analyte) from the sample under investigation. One common approach for the processing of food samples is an extraction method known under the acronym QuECheRS (Quick, Easy, Cheap, Effective, Rugged, and Safe). This extraction method is typically employed for the detection of pesticide residues in food samples. While effective in extracting pesticide residues from food samples, the QuEChERS approach can result in a very complex matrix that leads to rapid contamination of the mass spectrometer system employed to detect the pesticide residues.

[0004] For example, when a triple quadrupole mass spectrometer is employed for such analysis, such charge buildup and performance degradation can be exacerbated in systems that employ low inlet ion energies for the first mass analyzer (e.g., Q1). Contamination of the mass analyzer requires periodic cleaning of the system, which can negatively impact the workflow for the analysis of samples and add to the cost of operating the system.

[0005] Therefore, there is a need for improved mass spectrometry methods for the analysis of samples, particularly food-based samples. [Overview of the project] [Means for solving the problem]

[0006] In one aspect, a method for performing mass spectroscopic analysis of a sample is disclosed, comprising ionizing the sample to generate a plurality of ions, introducing the plurality of ions into a mass filter positioned upstream of a mass spectrometer, the mass filter being configured to provide a high M / Z cutoff greater than the maximum M / Z ratio of ions associated with one or more analytes of interest in the sample, allowing the passage of analyte ions while blocking the passage of ions having an M / Z ratio greater than the high M / Z cutoff, and performing mass spectrometry of the ions passing through the mass filter, the high M / Z cutoff being selected to reduce contamination of the downstream mass spectrometer.

[0007] Various types of mass spectrometers can be employed. For example, but not limited to, the mass spectrometer may be a quadrupole mass spectrometer (e.g., a triple quadrupole mass spectrometer), a time-of-flight (TOF) mass spectrometer, an ion trap, or a combination thereof.

[0008] In some embodiments, at least some of the ions passing through the mass filter are subjected to fragmentation, for example, in a collision cell located downstream of the mass filter, generating multiple product ions. The product ions can then be subjected to mass spectrometry, for example, using a quadrupole and / or time-of-flight (TOF) mass spectrometer, to generate their mass spectra. In some such embodiments, the step of performing mass spectrometry may include monitoring one or more multiple reaction monitoring (MRM) migrations of at least one of the analyte ions using a triple quadrupole mass spectrometer.

[0009] For example, in some embodiments, the high M / Z cutoff can be set to about 700, or about 900, or about 1,000, but other cutoff values ​​may also be employed, for example, depending on the M / Z ratio of the pollutant ions.

[0010] In some embodiments, the sample under study may be a food-based sample. For example, but not limited to, in some such embodiments, such a food-based sample may be any other sample matrix comprising any beverage such as tea or coffee and crops such as arugula, lettuce, carrots, or edible materials. In some embodiments, the sample under study may be a tissue sample.

[0011] In some embodiments, the band-pass window of the mass filter can be selected to allow target ions to pass through the mass filter. For example, in some embodiments, the band-pass window of the mass filter can be selected to be in the range of about 20 to about 1,250, for example, about 50 to 900, or any other suitable range for a particular application.

[0012] In some embodiments, the sample is processed prior to its ionization. For example, the processing of a food-based sample may be carried out to extract, for example, a certain analyte of interest, such as one or more pesticides. In some embodiments, a processing method known as QuEChERS is employed, but any other suitable processing technique may also be used. In some embodiments, a tissue sample may be processed to form a homogenate tissue matrix.

[0013] Various mass filters can be employed in the practice of this teaching. For example, in some embodiments, the mass filter can include a multipole ion guide. In some such embodiments, the multipole ion guide can include a quadrupole rod set extending from a proximal end to a distal end, the four rods of the quadrupole rod set being positioned relative to one another such that they provide an inlet at the proximal end for receiving ions and an outlet at the distal end through which ions exit the quadrupole rod set. The quadrupole rod set can include a first pair of rods and a second pair of rods, each rod being spaced from and extending along a central longitudinal axis, and a plurality of auxiliary electrodes inserted between the rods of the quadrupole rod set such that the auxiliary electrodes are separated from each other by the rods of the quadrupole rod set, and each of the auxiliary electrodes is adjacent to a single rod of the first pair of rods and a single rod of the second pair of rods.

[0014] A power source is coupled to a multipole ion guide and is operable to i) supply a first RF voltage to a first pair of rods at a first frequency and first phase, ii) supply a second RF voltage to a second pair of rods at a second frequency equal to the first frequency and a second phase opposite to the first phase, and iii) supply an auxiliary electrical signal to each of the auxiliary electrodes, the auxiliary electrical signals applied to each of the auxiliary electrodes being substantially the same, at least one auxiliary RF voltage source is operable to supply an RF voltage to the auxiliary electrodes, and an auxiliary DC voltage source is operable to supply a DC voltage to the auxiliary electrodes to prevent the transmission of ions having an m / z ratio greater than the cutoff. In some such embodiments, the DC voltage can be supplied to the auxiliary electrodes such that the DC voltage supplied across the two pairs of auxiliary electrodes has opposite polarity and can be offset symmetrically with respect to a reference, e.g., a DC offset supplied to the ion guide.

[0015] In a related aspect, a method for performing mass spectroscopic analysis of a sample is disclosed, which includes ionizing the sample to generate a plurality of ions, introducing the plurality of ions into a mass filter, the mass filter being configured to provide a high M / Z cutoff greater than the maximum M / Z ratio of ions associated with one or more analytes of interest in the sample, allowing the passage of analyte ions while blocking the passage of ions having an M / Z ratio greater than the high M / Z cutoff, and performing mass spectrometry of the ions passing through the mass filter.

[0016] In a related aspect, a mass spectrometer is disclosed, which comprises an atmospheric pressure ion source configured to receive a sample, ionize the sample, and generate a plurality of ions; a first mass filter positioned downstream of the ion source to receive at least a portion of the plurality of ions; a user interface for receiving information from a user about one or more m / z ratios of interest or a range of m / z ratios; and a controller communicating with the user interface and the first mass filter to receive information from the user interface about the m / z ratios of interest or a range of m / z ratios. Based on the information received from the user interface, the controller determines the maximum m / z ratio of interest for mass spectrometry and adjusts the band-pass window of the first mass filter so that the band-pass window has a high M / Z cutoff greater than the maximum m / z ratio.

[0017] In some embodiments, the high M / Z cutoff is set to a value within the range of approximately 10 to approximately 500 m / z, which is a distance from the maximum m / Z ratio.

[0018] In some embodiments, a mass filter and a first mass spectrometer positioned downstream of the mass filter are arranged in two separate chambers maintained at different pressures, where the pressure in the chamber in which the first mass filter is located (also referred to herein as the “first chamber”) exceeds the pressure in the chamber in which the mass spectrometer is located (also referred to herein as the “second chamber”). For example, the pressure in the first chamber exceeds the pressure in the second chamber by at least about 2 times, or at least about 5 times, or at least about 10 times, or at least about 20 times, or at least about 100 times. As an example, in some embodiments, the operating pressure in the first chamber can be in the range of about 2 to about 20 mTorr, and the operating pressure in the second chamber can be 5 × 10⁻⁶ mTorr. -5 It can be less than Torr.

[0019] In some embodiments, a second mass spectrometer can be positioned downstream of a first mass spectrometer. In some such embodiments of the mass spectrometer described above, the first mass filter and either the first or second mass spectrometer may comprise a plurality of rods arranged in a quadrupole configuration. The RF and DC voltages applied to the quadrupole rods can be selected so that the first mass filter exhibits a desired bandpass window, and the downstream mass spectrometer allows the passage of ions with a desired m / z ratio while blocking the passage of other ions. For example, a controller can communicate with at least one RF voltage source, and at least one DC voltage source can apply control signals to these voltage sources to set the bandpass window of the first mass filter and the transmission window of the first mass spectrometer.

[0020] In some embodiments, the frequency of the applied RF voltage can be, for example, in the range of about 100 kHz to about 10 MHz, and the amplitude of the RF voltage (zero / peak amplitude) can be, for example, in the range of about 0 volts to about 6,000 volts. For example, a DC voltage may be used as the DC decomposition voltage to ensure the passage of ions having a desired m / z ratio. For example, the DC voltage can be in the range of about 5 volts to about 5,000 volts.

[0021] The controller can communicate with the first and / or second mass spectrometers to allow the passage of at least one m / z ratio associated with ions received from the first mass filter. The controller can also be configured to shift the m / z values ​​of the first and / or second mass spectrometers to allow the passage of ions with different m / z ratios received from the first mass filter.

[0022] In a related aspect, a method for performing a mass spectroscopic measurement using a mass spectrometer having a mass filter is disclosed, which includes performing mass spectrometry on a sample to determine a range of m / z ratios associated with one or more compounds of interest in the sample, identifying the maximum m / z ratio associated with that range of m / z ratios, and adjusting the band-pass window of the mass filter to exhibit a high M / Z cutoff greater than the maximum m / z ratio. Following the adjustment of the band-pass window of the mass filter, mass spectrometry of another portion of the sample can be performed using the mass filter with the adjusted band-pass window.

[0023] In a related aspect, a mass spectrometer system is disclosed, which comprises an atmospheric pressure ion source configured to receive a sample, ionize the sample, and generate a plurality of ions, and a first mass filter positioned downstream of the ion source to receive at least a portion of the plurality of ions, wherein the first mass filter is configured to allow passage of ions having an m / z ratio within a bandpass window. The system can further include a user interface for receiving, for each of a plurality of measurement periods, a target m / z ratio or a range of target m / z ratios for mass analysis during that measurement period.

[0024] The controller communicates with the user interface and the first mass filter, and for each of the measurement periods, the controller is configured to determine a maximum m / z ratio and adjust the bandpass window of the first mass filter to exhibit a high M / Z cutoff greater than the maximum m / z ratio with respect to that measurement period, and the first mass filter exhibits different high M / Z cutoffs for at least two different measurement periods.

[0025] In a related aspect, a mass spectrometer is disclosed, which comprises an atmospheric pressure ion source configured to receive a sample, ionize the sample, and generate a plurality of ions, and a first mass filter positioned downstream of the ion source to receive at least a portion of the plurality of ions, wherein the first mass filter is configured to allow passage of ions having an m / z ratio within a bandpass window. The mass spectrometer can further include a user interface for receiving a maximum m / z ratio of interest from a user, and the controller adjusts the bandpass window of the first mass filter such that the bandpass window has a high M / Z cutoff greater than the maximum m / z ratio of interest. In some embodiments, the controller can set the high M / Z cutoff to be at least about 10 amu greater than the maximum m / z ratio of interest.

[0026] In some embodiments, the mass spectrometry system and method according to this teaching may be used for the following anthelmintics, namely, in particular 1-(2,4-dichlorophenyl)-2-imidazole (imazalil metabolite); 1-4 (chlorophenylurea); 1-naphthaleneacetamide (1-NAD); 2,3,5-trimetacarb; 2,4-dichlorobenzophenone; 2,4-dimethylaniline (2,4-xylide); 2,6-dichlorobenzamide; 2-hydroxypropoxycarbazone; 6-chlor-3-phenylpyridazine-4-ol; acephate; acephate Nosyl; Acetamiprid; Acetamiprid-N-desmethyl; Acibenzoral-S-methyl; Azacitidine; Aranicarb; Aldicarb; Aldicarb sulfoxide; Aldicarb sulfone (Aldoxycarb); Aldimorph; Alidichlor; Alloxidim-sodium; Ametoctrazine; Ametrin-1; Amidithione; Aminocarb; Amisulbrom; Amitraz; Amitrol; Ancimidor; Anilazine; Anilofos; Aramite; Apsone; Ashram; Atidathion; Atrazine-desethyl; Atrazine-desisopropyl; Atra Zin; avermectin; azaconazole 1; azadirachtin; azamethiphos; azinphos-methyl; adiprothrin; azoxystrobin; Barban; venalaxyl; benziocarb; benfuracarb; benodanil; benomyl; bensulfuron-methyl; bentazon-methyl; bentiavaricarb; bentiavaricarb-isopropyl; benzoximate; benzoylprop-ethyl; benzthiazulon; BIPC (chlorbafame); bispiribac-sodium; boscalid (nicobifen); bromconazole; BTS44596; bufencarb; Bupirimate; Buprofezin; Butamiphos; Butocarboxime; Butoxycarboxime-sulfoxide; Butoxycarboxime; Buturon; Kazusaphos; Carbaryl; Carbendazim, Carbetamide; Carbofuran-1; Carbofuran-3-hydroxy; Carboxone; Carpropamide; Chlorantraniliprole; Chlorbromulone; Chlorethoxyphos; Chlorfluazurone; Chlorflurenol-methyl; Chloridazone; Chlorixrone; Chlorprofam; Chlorsulfuron; Chlorthiamide; Chlorthiophos; Chlortolurone; Chromafenozide;One or more of cinidon-ethyl, cinosulfuron, and clethodim can be employed to detect them. It should be understood that the uses of the present teachings are not limited to the detection and / or analysis of the chemical species and / or compound examples provided above. Rather, the present teachings can be employed to detect and / or analyze any chemical species or component present in a sample, such as a food-based sample.;

[0027] In a related aspect, a method of performing mass spectrometric analysis of a sample is disclosed, which comprises ionizing the sample to generate a plurality of ions and introducing the plurality of ions into a mass filter, the mass filter being configured to provide a high M / Z cutoff greater than the maximum m / z ratio of the ions and to allow passage of analyte ions associated with one or more target analytes in the sample while blocking passage of ions having an m / z ratio greater than the high M / Z cutoff, and performing mass spectrometry of the ions passing through the mass filter.

[0028] In a related aspect, a mass spectrometer is disclosed, which comprises an atmospheric pressure ion source configured to receive a sample, ionize the sample, and generate a plurality of ions, a first mass filter positioned downstream of the ion source to receive at least a portion of the plurality of ions, a user interface for receiving information from a user regarding one or more target m / z ratios or ranges of m / z ratios, and a controller in communication with the user interface and the first mass analyzer for receiving information from the user interface regarding the target m / z ratios or ranges of m / z ratios, the controller determining a maximum target m / z ratio for mass spectrometry based on the information received from the user interface and adjusting the bandpass window of the first mass analyzer such that the bandpass window has a high M / Z cutoff greater than the maximum m / z ratio.

[0029] In some embodiments of the mass spectrometers described above, the high M / Z cutoff is separated from the maximum m / z ratio by a value within the range of about 10 to about 500 amu.

[0030] In some embodiments, the first mass filter is placed inside a depressurization chamber. In some such cases, the depressurization chamber is maintained at a pressure in the range of about 2 mTorr to about 20 mTorr.

[0031] In some embodiments, the first mass filter comprises a plurality of rods arranged in a quadrupole configuration. The mass spectrometer may further include a second mass filter positioned downstream of the first mass filter to receive ions transmitted through the first mass filter, the second mass filter having a band-pass window that defines a range of m / z ratios that can be transmitted through it. A controller can communicate with the second mass filter and adjust its band-pass window to allow the passage of m / z ratios associated with ions received from the first mass filter. The controller may also be configured to shift the band-pass window of the second mass filter to allow the passage of ions having different m / z ratios received from the first mass filter.

[0032] In a related aspect, a method is disclosed for performing a mass spectroscopic measurement using a mass spectrometer having a mass filter, which includes performing mass spectrometry on a sample to determine a range of m / z ratios associated with one or more compounds of interest in the sample, identifying the maximum m / z ratio associated with the range of m / z ratios, and adjusting the band-pass window of the mass filter to exhibit a high M / Z cutoff greater than the maximum m / z ratio. The method may further include performing mass spectrometry on the sample using the band-pass window of the adjusted mass filter.

[0033] In a related aspect, a mass spectrometer system is disclosed, which comprises an atmospheric pressure ion source configured to receive a sample, ionize the sample, and generate a plurality of ions, and a first mass filter positioned downstream of the ion source to receive at least a portion of the plurality of ions, the first mass filter configured to allow the passage of ions having an m / z ratio within a band-pass window. A user interface receives a target m / z ratio or range of target m / z ratios for mass spectrometry during each of a plurality of measurement periods, and a controller is configured to communicate with the user interface and the first mass filter and, for each of the measurement periods, adjust the band-pass window of the first mass filter to show a maximum m / z ratio greater than the maximum m / z ratio with respect to that measurement period, the first mass filter showing different high m / z cutoffs with respect to at least two different measurement periods.

[0034] In a related aspect, a mass spectrometer is disclosed, which comprises an atmospheric pressure ion source configured to receive a sample, ionize the sample, and generate a plurality of ions, and a first mass filter positioned downstream of the ion source to receive at least a portion of the plurality of ions, the first mass filter being configured to allow the passage of ions having an m / z ratio within a band-pass window. A user interface receives the maximum m / z ratio of interest from the user, and a controller communicating with the user interface and the first mass spectrometer receives the maximum m / z ratio of interest and adjusts the band-pass window so that it has a high M / Z cutoff greater than the maximum m / z ratio.

[0035] In a related aspect, a method for performing mass spectroscopic analysis of a sample is disclosed, which includes ionizing the sample to generate a plurality of ions, introducing the plurality of ions into a mass filter positioned upstream of a mass spectrometer, the mass filter comprising a plurality of rods to which an RF and / or DC voltage can be applied to provide a high M / Z cutoff greater than the maximum m / Z ratio of ions associated with one or more analytes of interest in the sample, thus allowing the passage of those analyte ions, while at least some of the ions having an m / Z ratio greater than the high M / Z cutoff are deposited on one or more of the rods of the mass filter, thus preventing the passage of high m / Z ions to a downstream mass spectrometer, and performing mass analysis of the ions that have passed through the mass filter.

[0036] In a related aspect, a method for performing mass spectroscopic analysis of a sample is disclosed, which includes ionizing the sample to generate a plurality of ions and introducing the plurality of ions into a mass filter positioned upstream of a mass spectrometer, the mass filter comprising a plurality of rods to which an RF and / or DC voltage can be applied to provide a high M / Z cutoff greater than the maximum m / Z ratio of ions associated with one or more analytes of interest in the sample, thus allowing the passage of those analyte ions, while at least a portion of the ions having an m / Z ratio greater than the high M / Z cutoff are deposited on one or more of the rods, thus preventing the passage of high m / Z ions to a downstream mass spectrometer, and performing mass analysis of the ions passing through the mass filter.

[0037] In a related aspect, a method for performing mass spectroscopic analysis of a sample is disclosed, which involves introducing a plurality of ions into a mass filter positioned upstream of a mass spectrometer, the mass filter being maintained at a higher pressure than the mass spectrometer, and the mass filter being configured to provide a high M / Z cutoff greater than the maximum M / Z ratio of ions associated with one or more analytes of interest in the sample, allowing the passage of analyte ions while blocking the passage of ions having an M / Z ratio greater than the high M / Z cutoff, and delivering the ions passing through the mass filter to the mass spectrometer in order to perform the mass analysis.

[0038] In some embodiments, the mass filter includes at least one set of multipolar rods configured to guide ions through the mass filter, and at least one set of rods positioned to capture at least a portion of ions having an m / z ratio greater than the m / z cutoff.

[0039] In a related aspect, a method for performing mass spectroscopic analysis of a sample is disclosed, which includes ionizing the sample to generate multiple ions, introducing the multiple ions into the orifice of a mass spectrometer, and mass filtering the ions by capturing ions having an m / z ratio greater than a high M / Z cutoff and allowing lower m / z ions to pass to a downstream mass spectrometer. Mass filtration of ions can be performed by transmitting the ions through a mass filter having multiple electrodes (also referred to herein as sacrificial electrodes or rods) such that ions having an m / z ratio greater than the M / Z cutoff are captured by at least one of the sacrificial electrodes of the mass filter. The method may further include delivering ions having an m / z ratio below a high M / Z cutoff to a downstream mass spectrometer for its mass analysis. In some embodiments, the mass filter is located in a chamber maintained at a higher pressure than the chamber in which the downstream mass spectrometer is positioned. Various mass spectrometers can be employed. Some examples of such mass spectrometers include, but are not limited to, time-of-flight (TOF) mass spectrometers, quadrupole mass spectrometers, ion traps, and combinations thereof.

[0040] A further understanding of the various aspects of this instruction can be obtained by referring to the detailed explanation below, along with the associated diagrams briefly described below. The present invention provides, for example, the following: (Item 1) A mass spectrometer, wherein the mass spectrometer is An atmospheric pressure ion source configured to receive a sample, ionize the sample, and generate multiple ions, A first mass filter positioned downstream of the ion source to receive at least a portion of the plurality of ions, A user interface for receiving information from the user regarding one or more m / z ratios of interest or ranges of m / z ratios, A controller that communicates with the user interface and the first mass spectrometer in order to receive information regarding the aforementioned m / z ratio of interest or the range of the m / z ratio from the user interface. Equipped with, A mass spectrometer comprising a controller that determines the maximum m / z ratio of interest for mass spectrometry based on information received from the user interface, and adjusts the band-pass window of the first mass spectrometer so that the band-pass window has a high M / Z cutoff greater than the maximum m / z ratio. (Item 2) The high M / Z cutoff is set to a value within the range of approximately 10 to approximately 500, and is set to a mass spectrometer as described in item 1. (Item 3) The first mass filter is located in a reduced pressure chamber, and the mass spectrometer is as described in any one of items 1-2. (Item 4) The mass spectrometer described in item 4, wherein the depressurization chamber is maintained at a pressure in the range of approximately 2 mTorr to approximately 20 mTorr. (Item 5) The first mass filter comprises a plurality of rods arranged in a quadrupole configuration, as described in any one of items 1-4 of the mass spectrometer. (Item 6) A mass spectrometer according to any one of items 1-5, further comprising a second mass filter positioned downstream of the first mass filter to receive ions transmitted through the first mass filter, wherein the second mass filter has a band-pass window that defines a range of m / z ratios that can be transmitted through the second mass filter. (Item 7) The mass spectrometer according to item 6, wherein the controller communicates with the second mass filter and adjusts the band-pass window of the second mass filter to allow the passage of a certain m / z ratio associated with ions received from the first mass filter. (Item 8) The mass spectrometer according to item 7, wherein the controller is configured to shift the band-pass window of the second mass filter to allow the passage of ions having different m / z ratios received from the first mass filter. (Item 9) A method for performing mass spectrometry analysis of a sample, wherein the method is: Ionizing the sample and generating multiple ions, The method involves introducing the plurality of ions into a mass filter located upstream of a mass spectrometer, wherein the mass filter is configured to allow the passage of analyte ions by providing a high M / Z cutoff greater than the maximum M / Z ratio of ions associated with one or more analytes of interest in the sample, while blocking the passage of ions having an M / Z ratio greater than the high M / Z cutoff. The mass spectrometry of ions passing through the aforementioned mass filter is performed. Includes, The high M / Z cutoff is selected to reduce contamination of the downstream mass spectrometer. (Item 10) The aforementioned sample comprises a food-based sample, Optionally, the aforementioned food-based sample may be provided with tea. Optionally, the food-based sample may include arugula. Optionally, the processing of the food-based sample may include utilizing the QuEChERS extraction method, as described in item 9. (Item 11) The aforementioned sample comprises a tissue sample, The method according to item 9, wherein the tissue sample optionally comprises liver tissue homogenate. (Item 12) The step of performing the mass spectrometry includes introducing the ions that have passed through the mass filter into the downstream mass spectrometer, The method according to any one of items 9-11, wherein the mass spectrometer optionally comprises a plurality of rods arranged in a multipolar configuration. (Item 13) The high M / Z cutoff is selected to reduce contamination of the multipole rod, as described in any one of items 9-12. (Item 14) The step of performing the mass spectrometry includes causing fragmentation of at least some of the ions passing through the mass spectrometer, thereby generating a plurality of generated ions. Optionally, the method according to any one of items 9-13, further comprising generating a mass spectrum of the generated ions. (Item 15) The step of performing the mass spectrometry includes monitoring the migration of at least one of the analyte ions to MRM, Optionally, the method according to any one of items 9-14, wherein the step of performing the mass spectrometry includes using a quadrupole mass spectrometer. (Item 16) The aforementioned high M / Z cutoff is approximately 700. Optionally, the high M / Z cutoff is approximately 1,000, as described in any one of items 9-15. (Item 17) The method according to any one of items 9-16, wherein the mass filter is configured to provide a bandpass window for ion transmission. (Item 18) The method described in item 17, wherein the aforementioned bandpass window extends from approximately 20 amu to approximately 1,250 amu. (Item 19) The method according to any one of items 9-18, further comprising treating the sample prior to the step of ionizing the sample. (Item 20) The method according to any one of items 9-19, wherein the one or more analytes of interest comprises at least one pesticide. [Brief explanation of the drawing]

[0041] [Figure 1] Figure 1 is a flowchart illustrating the various steps of an embodiment of the method for performing mass spectroscopy according to this instruction. [Figure 2] Figure 2 is another flowchart illustrating various steps of another embodiment of the method for performing mass spectroscopy measurements according to this teaching. [Figure 3] Figures 3 and 4 show suitable mass filters for use in a system according to one embodiment of this teaching. [Figure 4] Figures 3 and 4 show suitable mass filters for use in a system according to one embodiment of this teaching. [Figure 5A] Figure 5A is a partial view of a mass spectrometer in which a mass filter according to one embodiment of this teaching is incorporated. [Figure 5B] Figures 5B and 5C show schematic examples of the bandpass window of the mass filter according to the embodiment depicted in Figure 5A, where the bandpass window includes two or more m / z ratios at once for transmission. [Figure 5C] Figures 5B and 5C show schematic examples of the bandpass window of the mass filter according to the embodiment depicted in Figure 5A, where the bandpass window includes two or more m / z ratios at once for transmission. [Figure 6] Figure 6 schematically depicts a mass spectrometer into which the system described in this instruction will be incorporated. [Figure 7]Figure 7 schematically illustrates examples of controller and / or analyzer implementations used in systems and mass spectrometers according to various embodiments of this instruction. [Figure 8] Figure 8 shows MRM charge data acquired on a triple quadrupole system after injection of a 30 mL food-based sample matrix. [Figure 9] Figures 9A and 9B show digital photographs of the debris pattern on the Q1 rod assembly after injection of 30 mL of food-based matrix. [Figure 10] Figure 10 shows the mass spectrum of a food-based sample and the mass spectrum of the same sample obtained by filtering out all charged species in the Q0 mass filter, except for ions with an m / z ratio in the range of 250–400 (which are then introduced into the Q1 analyzer). [Figure 11] Figure 11 shows the signal intensity for reserpine ions measured initially and then in 10 mL increments up to 100 mL of total matrix, using the band-pass window of Figure 10. [Figure 12] Figures 12A and 12B show digital photographs of the Q1 rod assembly, and Figures 12C and 12D show a pair of Q0T bars after the injection of 100 mL of food-based matrix into the mass spectrometer, indicating that despite the injection of 100 mL of food-based matrix, no substantial accumulation of debris was observed on the Q1 rod, while a large amount of debris was deposited on the Q0T bar. [Figure 13] Figure 13 shows the mass spectrum of a food-based sample and the sample mass spectrum obtained when the bandpass of the Q0 mass filter is set to an m / z window in the range of 400 to 850, and the mass spectrum of any ion having an m / z ratio within this range is obtained. [Figure 14] Figure 14 shows an overlay of multiple intensity measurements for reserpine ions obtained using 0–100 mL of food-based matrix sprayed into a quantitative analyzer when the Q0 mass filter band-pass setting is configured as shown in Figure 13. [Figure 15]Figures 15A and 15B show photographs of the Q1 rod, and Figures 15C and 15D show photographs of the Q0T bar, illustrating that a large amount of debris is deposited on the Q0T bar, significantly reducing the amount of debris on the Q1 rod compared to a control experiment without T-bar filtration. [Figure 16] Figures 16A and 16B show digital photographs of a pair of Q1 rods after injection of 40 mL of tea / arugula matrix using a band-pass window set to transmit all ions with m / z greater than 720, demonstrating the presence of large deposits on the Q1 rods similar to the original baseline data obtained without using a T-bar. [Figure 17A] Figures 17A and 17B show mass spectrometry data representing the Q1 scan (upper frame) for the tea / arugula matrix and the Asteroid scan (lower frame) for the same matrix. [Figure 17B] Figures 17A and 17B show mass spectrometry data representing the Q1 scan (upper frame) for the tea / arugula matrix and the Asteroid scan (lower frame) for the same matrix. [Figure 18] Figure 18 shows the mass spectra of a food-based sample and the sample when a Q0T bar is used to set the mass filtration window and exclude ions with an m / z ratio greater than 900. [Figure 19] Figures 19A, 19B, 19C, and 19D show the changes in TIC and Q1 peak width over a 5-minute charging experiment after injecting a 100 mL matrix using the band-pass filter shown in Figure 18. [Figure 20] Figures 20A and 20B show digital photographs of the Q0T bar and Q1 rod, respectively. [Figure 21] Figure 21 shows the mass spectra of rat liver homogenate matrices for two modes of Q1 scanning with and without Q0 filtration. [Figure 22] Figures 22A, 22B, and 22C show the Q1 charge data after injection of a 40 mL rat liver homogenate sample matrix without the use of a Q0 mass filter. [Figure 23-1]Figures 23A, 23B, and 23C show the Q1 charge data after injection of a 40 mL rat liver homogenate sample matrix using Q0 mass filtration with a Q0 value of 400 m / z. [Figure 23-2] Figures 23A, 23B, and 23C show the Q1 charge data after injection of a 40 mL rat liver homogenate sample matrix using Q0 mass filtration with a Q0 value of 400 m / z. [Figure 24A] Figures 24A and 24B show an overlay of Q1 data for 59 m / z obtained after injection of 10 mL each of rat liver homogenate matrix. [Figure 24B] Figures 24A and 24B show an overlay of Q1 data for 59 m / z obtained after injection of 10 mL each of rat liver homogenate matrix. [Figure 25] Figures 25A, 25B, 25C, and 25D show digital photographs of the debris pattern deposited on a pair of poles of the Q1 rod of a triple quadrupole mass spectrometer after injection of 40 mL of rat liver homogenate. Figures 25A and 25B show that a substantial debris pattern was deposited when high-mass filtration with the T-bar was not employed, while Figures 25C and 25D show that there was no visible debris deposit when the T-bar was set to filter ions with an m / z ratio greater than 400. [Modes for carrying out the invention]

[0042] This disclosure generally relates to methods and systems for performing mass spectrometry, wherein the mass filter is configured to exhibit a band-pass window characterized by a high M / Z cutoff, which allows for the removal of undesirable ions that could otherwise cause contamination of downstream components (e.g., downstream mass spectrometers) and allows the passage of target ions of interest to the downstream components. In many embodiments, the methods according to this teaching are employed to analyze food-based samples, but other samples such as tissue samples can also be analyzed. Food-based samples have been observed to cause performance degradation of mass spectrometers, such as triple quadrupole mass spectrometers, within a short period after introduction of, for example, 30–45 mL of food-based matrix.

[0043] The terms “about” and “approximately” are used herein synonymously to indicate a variation that falls within 15% or 10% of a numerical value in either direction. Furthermore, as used herein, the term “substantially” refers to a qualitative condition indicating the whole or nearly whole range or degree of a characteristic or property of interest, where the variation is, where applicable, up to 15% or 10% from the perfect state.

[0044] The term “food-based sample” means, as used herein, a sample containing one or more edible ingredients / components, and in many cases, all ingredients and / or components of a food-based sample are edible.

[0045] It was unexpectedly discovered that in many cases, ions with a large m / z ratio (e.g., an m / z ratio greater than 700) were the primary cause of such performance degradation. This finding was unforeseen because the mass spectra of food-based samples typically show, for example, numerous low-mass peaks and very few high-mass peaks. Furthermore, it was unexpectedly discovered that the accumulation of such ions on the rods of the first mass spectrometer was primarily responsible for the degradation of the spectrometer's performance.

[0046] The various embodiments discussed below disclose a mass spectrometry method for the analysis of a sample, e.g., a food-based or tissue sample, wherein a mass filter having a high M / Z cutoff above the highest m / Z of the analyte of interest is employed, for example, upstream of the first mass spectrometer, to reduce (preferably prevent) contamination of the spectrometer's mass spectrometer by matrix components of the sample being processed, while enabling detection of the analyte of interest. For example, as will be discussed in more detail below, in some such embodiments, the high M / Z cutoff is set to about m / Z 400, or about m / Z 700, or about m / Z 900, or about m / Z 1,000, which can reduce, preferably prevent, contamination caused by matrix components. As will be discussed below, in many embodiments, the use of such a high M / Z cutoff can result in an extension of the cleaning interval for the mass spectrometer by at least three times.

[0047] Referring to the flowchart in Figure 1, in one embodiment of the method according to this teaching, a sample, e.g., a food-based or tissue sample, is ionized to generate a number of ions (Step 1), at least some of the ions are introduced into a mass filter, which is configured to allow the passage of those ions by providing an M / Z cutoff greater than the maximum M / Z ratio associated with one or more analytes of interest in the sample, e.g., a food-based sample, while blocking the passage of ions with an M / Z ratio greater than the threshold, e.g., contaminants with an M / Z ratio greater than the cutoff (Step 2). Subsequently, mass spectrometry of the ions passed through the mass filter is performed (Step 3).

[0048] For example, in some embodiments, ions passing through a mass filter operate at a pressure lower than the pressure maintained by the upstream mass filter and are introduced into another downstream mass spectrometer configured to detect target ions of interest, e.g., ions having a desired m / z ratio. In some embodiments, the M / Z cutoff can be set based on the expected m / z ratio of the analyte of interest and the expected m / z ratio of ions associated with one or more contaminants in the sample.

[0049] For example, in some embodiments, without limitation, the M / Z cutoff can be set to about m / z 700 or higher, for example, about m / z 720 or about m / z 1,000. For example, in some embodiments, in which the food-based sample may include tea and / or arugula, the M / Z cutoff can be set to 700 or 1,000. With respect to other sample matrices, the M / Z cutoff can be selected to be slightly higher than the maximum m / z for the ion of interest, for example, about 10 to about 50.

[0050] Referring to Figure 2, in some embodiments, mass spectrometry of the sample of interest is performed via mass spectrometry of a portion of the sample to determine the range of m / z ratios associated with one or more compounds of interest present in the sample (Step 1). The largest m / z ratio in the range of m / z ratios is identified (Step 2), and the band-pass window of the mass filter is adjusted so that it exhibits an M / Z cutoff greater than the largest m / z ratio associated with the analyte ion of interest (Step 3). Subsequently, mass spectrometry of another portion of the sample is performed using the band-pass window of the adjusted mass filter (Step 4). As an example, in some embodiments, such mass spectrometry can be performed using a triple quadrupole mass spectrometer in which the mass filter is positioned upstream of the first mass spectrometer of the system.

[0051] Various mass filters and mass spectrometers can be employed to implement the methods for mass spectrometry of samples, particularly food-based and tissue samples, according to this teaching. For example, as will be discussed in more detail below, a mass filter may include multiple rods arranged in a multi-pole configuration, and RF and / or DC voltages may be applied to the multiple rods not only to confine ions radially but also to filter out ions of interest. In some such embodiments, multiple auxiliary electrodes may be inserted between the quadrupole rods, and the auxiliary electrodes are separated from each other by one of the quadrupole rods. Furthermore, in some embodiments, the mass filter may be incorporated within a triple quadrupole mass spectrometer or a hybrid quadrupole / time-of-flight mass spectrometer.

[0052] The implementation of the method for performing mass spectroscopy measurements according to this instruction is not limited to the mass filters discussed above. Rather, a variety of mass filters can be employed in the practice of this instruction. Some examples of suitable mass filters, but not limited to, other suitable techniques known in the art, include devices including a T-bar along with a multi-pole (e.g., quadrupole) arrangement of multiple rods, such as the devices discussed below; electrofiltration devices; and devices for bending ion paths at an angle sufficient to eliminate high m / z ratios above the target threshold.

[0053] As an example, in some embodiments, a mass filter described in U.S. Patent No. 10,741,378 ("Patent No. 378"), titled "RF / DC Filter to Enhance Mass Spectrometer Robustness" (which is incorporated herein by reference as a whole), may be employed. In short, Figures 2 and 3 of Patent No. 378, reproduced herein as Figures 3 and 4, illustrate an ion guide 120 including a set of four rods 130a,b extending from a proximal inlet end located adjacent to an inlet orifice to a distal outlet end located adjacent to an outlet opening.

[0054] Rods 130a and 130b are arranged according to a quadrupole configuration to form a quadrupole rod set 130 that encloses a space from which ions can travel from the inlet end to the outlet end. As in the previous embodiment, each of the rods 130 can be electrically coupled to an RF power source (not shown in Figures 3 and 4) such that the rods on both sides of the central axis form a rod pair together, and substantially the same RF signal is applied to them, such that the phase of the RF signal applied to one rod set is opposite to the phase of the respective RF signals applied to the other rod set. A DC offset voltage can also be applied to the rods of the quadrupole rod set.

[0055] Continuing with reference to Figures 3 and 4, the ion guide 120 also includes a plurality of auxiliary electrodes 140 scattered between the rods of the quadrupole rods of the quadrupole rod assembly 130. Each of the auxiliary electrodes 140 can be coupled to an RF and / or DC power source to provide them with auxiliary electrical signals to control the transmission of ions through the ion guide 120. For example, in some embodiments, a DC voltage equal to the DC offset voltage applied to the rods of the quadrupole rod assembly can be applied to the auxiliary electrodes. Further details regarding various aspects of such mass filters employing auxiliary electrodes can be found in the published international application WO / 2020 / 039371, entitled "RF / DC cutoff to reduce contamination and enhance robustness of mass spectrometry systems" (which is incorporated herein by reference in its entirety).

[0056] In some embodiments, a mass filter may be employed that has a band-pass window in a mass / charge (m / z) ratio domain containing multiple m / z ratios, which are transferred to a downstream mass filter. In many embodiments, the band-pass window of the downstream mass filter is configured to allow the passage of one m / z ratio at a time. By configuring the band-pass window of the upstream mass filter to allow the transport of ions across multiple m / z ratios, as will be discussed in more detail below, faster analysis of multiple ions with different m / z ratios can be achieved.

[0057] For example, referring to Figure 5A, the mass filter Q0 includes four sets of rods Q0A, Q0B, Q0C, and Q0D, which are positioned in series with respect to each other in a quadrupole configuration, providing a pathway through which ions received via the inlet 14 of the mass filter Q0 can propagate to its outlet 16 from the mass filter Q0. In this embodiment, the Q0 mass filter receives ions from an upstream ion guide Qjet, which includes four rods 10 (only two of which are visible) arranged in a quadrupole configuration.

[0058] The RF voltage source 12 (or a separate RF voltage source) and the DC voltage source 20 apply RF and DC voltages to the rods of the mass filter Q0 to provide radial focusing of ions and establish a bandpass window (i.e., a transmission window) for the passage of ions through the mass filter Q0.

[0059] In other words, ions with an m / z ratio that falls within the band-pass window of the mass filter Q0 can pass through the mass filter Q0, while the transmission of ions with an m / z ratio that falls outside the band-pass window is substantially reduced, and preferably blocked. In this embodiment, as will be discussed in more detail below, an RF voltage (signal) is applied to the first, second, and fourth sets Q0A, Q0B, and Q0D of the rod, while an RF voltage and a decomposed DC voltage (to set the band-pass window of the mass filter Q0) are applied to the third set Q0C of the rod.

[0060] In some such embodiments, the band-pass window of the mass filter Q0 (e.g., a quadrupole mass filter) can be configured to include the mass of the next precursor to be monitored, in addition to the mass of the precursor ion of interest. This is illustrated schematically in Figures 5B and 5C. In this example, initially, the mass filter Q0 is configured to have a band-pass window (BP1) that allows the transmission of ions with m / z ratios of m1 and m2, and the mass spectrometer Q1 is configured to allow the transmission of ions with m / z ratio of m1. When the transmission window of the mass spectrometer Q1 is shifted to the next mass of interest, i.e., the ion with m / z ratio of m2, the band-pass window of the mass filter Q0 is adjusted to allow the transmission of ions with m / z ratios of m2 and m3 (this adjusted band-pass window is designated herein as BP2).

[0061] In many embodiments, such adjustment of the band-pass window of the mass filter Q0 can be accomplished by first increasing the RF voltage applied to the mass filter Q0, and then adjusting the decomposed DC component. This results in an initial increase in the band-pass window of the mass filter Q0, which can include both m2 and m3 without interrupting the flow of m2 ions into the downstream mass spectrometer Q1. Following the change in the RF voltage of the mass filter Q0, the DC decomposed voltage applied to the mass filter Q0 is adjusted to adjust its band-pass window to a desired width.

[0062] In many such embodiments, the mass spectrometer Q1 is operated to select ions with an m / z ratio of m3 while the DC decomposition voltage applied to the mass filter Q0 is adjusted. Subsequently, the band-pass window of the mass filter Q0 can be adjusted to include the m / z ratios of m3 and m4 (i.e., the band-pass window designated as BP3). In this example, this is followed by adjusting the band-pass window of the mass filter Q0 to include m4 and m5 (see the band-pass window designated as BP4).

[0063] In this embodiment, the RF and DC voltage sources 12 and 20 are operated under the control of a controller 22 to control the application of RF and DC voltages to the mass filter Q0 and the mass spectrometer Q1 located downstream of the mass filter Q0, in order to set and adjust the band-pass window of the mass filter Q0 and the transmission window of the mass spectrometer Q1. More specifically, the controller 22 can be programmed to control the RF and DC voltage sources so that the RF and DC voltages applied to the rods of the mass filter Q0 and the mass spectrometer Q1 provide a desired band-pass window for the mass filter Q0 and also allow the transmission of ions having a desired m / z ratio through the mass spectrometer Q1. Furthermore, the controller 22 can also update the band-pass window of the mass filter Q0 to the next band-pass window, adjust the RF and / or DC voltages applied to the mass spectrometer Q1, and switch the transmission of ions through the mass spectrometer Q1 from one m / z ratio to another.

[0064] For example, at the start of a measurement cycle, the controller 22 can set the band-pass window of the mass filter Q0 and the transmission window of the mass spectrometer Q1 such that the band-pass window of the mass filter Q0 includes several m / z ratios of interest, and the transmission window of the mass spectrometer Q1 includes one of those m / z ratios. After a pre-set period (e.g., the time required for the mass spectrometer Q1 to process ions having a m / z ratio of interest), the controller 22 switches the transmission window of the mass spectrometer Q1 to the next m / z ratio of interest that is already within the band-pass window of the mass filter Q0, and further shifts the band-pass window of the mass filter Q0 to include the new m / z ratio of interest in addition to the m / z ratios being processed by the mass spectrometer Q1 (e.g., based on a predetermined list of m / z ratios of interest previously provided to the controller).

[0065] In some embodiments, the controller 22 can be configured to shift the transmission bandwidth of the mass filter Q0 and the transmission window of the mass spectrometer Q1 substantially simultaneously. In other embodiments, the controller 22 can be configured to shift the transmission bandwidth of the mass filter Q0 before shifting the transmission window of the mass spectrometer Q1 to the next m / z ratio of interest. For example, referring again to Figure 5B, while the mass spectrometer Q1 is monitoring ions with m / z m2, the controller 22 can shift the transmission bandwidth of the mass filter Q0 to include ions with m / z ratios m2 and m3 (i.e., from BP1 to BP2). The controller 22 can then shift the transmission window of the mass spectrometer Q1 to include the m / z ratio m3 while ions with m / z ratio m3 are equilibrated in the mass filter Q0 (e.g., via collisional cooling).

[0066] In the example above, it is explained that the controller 22 shifts the transmission bandwidth of the mass filter Q0 and the transmission window of the mass spectrometer Q1 in the direction of increasing the m / z ratio. However, the teaching is not limited thereto, and in some embodiments, the controller 22 can be configured to shift the transmission bandwidth pass of the mass filter Q0 and the transmission window of the mass spectrometer Q1 in the direction of decreasing the m / z ratio.

[0067] This instruction can be incorporated into various different mass spectrometers. As an example, Figure 6 schematically depicts a mass spectrometer 100 that includes an ion source 102 for generating multiple ions. Various ion sources can be employed in the practice of this instruction. Some examples of suitable ion sources, but not limited to, include, among others, electrospray ionization devices, nebulizer-assisted electrospray devices, chemical ionization devices, nebulizer-assisted atomization devices, chemical ionization devices, matrix-assisted laser desorption / ionization (MALDI) ion sources, photoionization devices, laser ionization devices, thermospray ionization devices, inductively coupled plasma (ICP) ion sources, sonic spray ionization devices, glow discharge ion sources, atmospheric pressure chemical ionization (APCI) sources, and electron shock ion sources.

[0068] The generated ions pass through the opening 104a of the car template 104 and the orifice 106a of the orifice plate 106 located downstream of the car template 104, the orifice plate 106 being separated from the car template 104 so that a gas curtain chamber is formed between the orifice plate 106 and the car template 104. A curtain gas source (not shown) can provide a curtain gas flow (e.g., nitrogen) between the car template 104 and the orifice plate 106, helping to keep the downstream section of the mass spectrometer clean by clustering and exhausting larger neutral particles. The curtain chamber can be maintained at a high pressure (e.g., above atmospheric pressure), while the downstream section of the mass spectrometer can be maintained at one or more selected pressures via exhaust through one or more vacuum pumps (not shown).

[0069] In this embodiment, ions passing through the orifices 104a and 106a of the car template 104 and orifice plate 106 are received by the ion optical system QJet, which comprises four rods 108 (two of which are visible in this figure) arranged in a quadrupole configuration to form an ion beam for transmission to the downstream components of the mass spectrometer 100. When in use, the ion optical system QJet can employ a combination of gas dynamics and radio frequency fields to capture and focus the ions received through the openings of the orifice plate 106.

[0070] The ion beam exits the ion optical system Qjet and is focused through lens IQ0 into a subsequent differential pressure pumped vacuum stage, which may include an additional ion guide (Q0) containing a mass filter. In some embodiments, the pressure of the mass filter Q0 can be maintained in the range of, for example, about 2 mTorr to about 20 mTorr.

[0071] The mass filter Q0 includes four rods 110 (two of which are visible in this figure), which are arranged according to a quadrupole configuration and provide a passage between them that extends from an inlet 110a into which ions can enter the passage to an outlet 110b into which ions can exit the passage. As described above, in this embodiment, the mass filter Q0 receives ions exiting the ion optical system Qjet via the ion lens IQ0.

[0072] The RF voltage source 200 applies an RF voltage to the rods 110 of the mass filter Q0 to generate an electromagnetic field within the passage that can provide radial confinement of ions as they pass through the passage. In this embodiment, the RF voltage applied to one pair of rods has the same amplitude and opposite phase to the RF voltage applied to the other pair of rods.

[0073] Furthermore, the DC voltage source 202 can apply a resolved DC voltage to at least one of the rods 110 of the mass filter Q0 to set the band-pass window of the mass filter. In particular, in many embodiments, the resolved DC voltage can be selected to ensure that the band-pass window of the mass filter will exhibit a high M / Z cutoff greater than a desired threshold (e.g., 700 or 1,000 in some embodiments). Alternatively, the DC voltage source can be used to apply a DC potential to an additional T-bar electrode between the Q0 quadrupole rods. The DC potential can be used to establish a high M / Z cutoff within the mass filter. In some embodiments, the high M / Z cutoff is fixed as a value higher than the highest target m / z, and therefore, the mass filter setting does not need to be changed during subsequent mass spectrometry steps.

[0074] A controller 204 communicating with RF and DC voltage sources can control these voltage sources to apply the required RF and DC voltages to the rod or auxiliary electrode. For example, in some embodiments, information regarding desired characteristics of the mass filter, such as a high M / Z cutoff value, can be provided to the controller, which can then use this information to calculate the RF and DC voltages required to achieve the desired characteristics of the mass filter. In many embodiments, the RF frequency can be in the range of about 100 kHz to about 10 MHz, and the RF amplitude (zero / peak) can be in the range of, for example, about 0 to about 6,000 volts.

[0075] Continuing to refer to Figure 6, in some embodiments, a graphical user interface (GUI) 206 is operably coupled to a controller 204, and the GUI allows the user to input a target focus m / z ratio or a range of target focus m / z ratios. For example, the GUI may present one or more graphical elements, such as an input window 206a, which allows the user to input information about a specific focus m / z or range of focus m / z ratios.

[0076] A graphical user interface can transmit this information to the controller. In some such embodiments, the controller is programmed to apply one or more control signals to the RF and / or DC voltage sources to identify the maximum target m / z ratio and set the band-pass window of the mass filter to have a high M / Z cutoff greater than the maximum m / z ratio identified by the controller. For example, in some embodiments, the controller can set the high M / Z cutoff to a value greater than the maximum target m / z ratio by at least 10%, or at least 20%, or at least 30%, or at least 40%, or at least 50%.

[0077] GUI206 can be implemented in various different ways. Furthermore, in some embodiments, GUI206 can present various methods for inputting data based on a specific way in which the mass spectrometer is being operated. For example, in one operating mode, the operator can operate a triple quadrupole mass spectrometer with a first quadrupole mass spectrometer set to a specific m / z ratio, for example, in multiple reaction monitoring mode (MRM), and the second quadrupole, which functions as a mass spectrometer, is also set to a specific m / z ratio corresponding to the fragmented ion of interest generated in the collision cell via the fragmentation of multiple precursor ions. In such an operating mode, the user can input a series of Q1 / Q3 mass pairs into GUI206, and the controller 204 can determine the highest target m / z ratio and configure the mass filter to show an M / Z cutoff at a value higher than the identified maximum target m / z ratio. The M / Z cutoff value could be, for example, 75 m / z higher, 150 m / z higher, or any value higher than the maximum target m / z ratio. By using this approach, a fixed high M / Z cutoff is used for all transitions.

[0078] In another operating mode similar to the previous one, the user can input a series of Q1 / Q3 mass pairs, but instead of the controller defining the high M / Z cutoff of the mass filter positioned upstream of the mass spectrometer, the user can specify a value for the high M / Z cutoff. For example, for food-based analysis, the high M / Z cutoff might be a value of approximately m / z 900, but the high M / Z cutoff may differ for other samples. The user can also specify values ​​lower than some of the Q1 values. With respect to these MRM transitions, the software and / or firmware will recognize that the specified cutoff will filter out the signal for some MRM transitions, and specifically, turn off the T-bar potential only with respect to those MRM transitions with higher Q1 m / z. Using this approach, a fixed high M / Z cutoff is used for all transitions with m / z lower than the cutoff.

[0079] In yet another operating mode, the user can input a series of Q1 / Q3 mass pairs into GUI206, and the software and / or firmware will consider the Q1 value for each pair and set conditions for the upstream mass filter to provide a high M / Z cutoff for the Q1 m / z value, where the cutoff offset for the Q1 m / z value can be, for example, higher than 75 m / z, higher than 150 m / z, etc. The user can also specify the desired offset for each pair.

[0080] As discussed above, it has been found that such high M / Z cutoffs can prevent certain contaminant ions from reaching downstream components of the mass spectrometer (such as the downstream mass spectrometer Q1). More specifically, as a result of the high M / Z cutoff of the Q0 mass filter, ions with an M / Z ratio greater than the cutoff will acquire unstable orbits as they pass through the Q0 mass filter and therefore will be deposited on one or more rods of the Q0 mass filter. Consequently, such ions will not reach the downstream Q1 mass spectrometer. However, as explained above in relation to Figures 3 and 4, if a Q0 T-bar is used, ions with an M / Z value greater than the cutoff will be deposited on the T-bar rather than on the Q0 rods.

[0081] It was unexpectedly discovered that the deposition of contaminant ions on either the Q0 mass filter or the T-bar rods would not adversely affect the passage of target ions through the Q0 mass filter. While not limited to any particular theory, this phenomenon can be explained by the understanding that the Q0 mass filter is typically operated within a milliliter pressure range, where the collision frequencies of ions with background neutral species are relatively high, thereby reducing the radial oscillations of ions transmitted through the filter. In other words, the Q0 mass filter operates in a collision focusing regime. Such radial confinement of the transmitted ions makes them less susceptible to contamination of the Q0 rods or T-bars.

[0082] The mass filter Q0 delivers ions to the downstream mass spectrometer Q1 via an ion lens IQ1 and a short, thick lens ST1 that functions as a Brubaker lens. In this embodiment, the mass spectrometer Q1 includes four rods 112 (two of which are visible in this figure), which are arranged according to a quadrupole configuration, to which RF and DC voltages can be applied to select the m / z ratio of interest for mass spectrometry.

[0083] The RF voltage source 200 can apply an RF voltage to the rods of the Q1 mass filter to cause radial confinement of ions passing through the mass filter, and the DC voltage source 202 can apply a resolved DC voltage to the rods of the Q1 mass spectrometer to set the bandpass of the mass spectrometer so as to allow the passage of ions having a target m / z or m / z within the target window, while blocking the passage of ions with other m / z ratios.

[0084] The controller 204 can control the RF and DC voltages generated by the RF and DC voltage sources. In particular, the controller can change the bandpass of the mass filter and sweep the amplitude of the DC resolved voltage so that ions with different m / z ratios can pass through the mass filter and be subjected to mass analysis by downstream components of a mass spectrometer incorporating the mass filter Q0 and mass spectrometer Q1.

[0085] The Q1 mass spectrometer operates at a lower pressure than the Q0 mass filter. For example, the pressure of the Q0 mass filter can exceed the pressure of the Q1 mass spectrometer by at least 10 times, or at least 20 times, or at least 30 times, or at least 40 times, or at least 50 times, or at least 60 times, or at least 70 times, or at least 80 times, or at least 90 times, or at least 100 times. For example, the Q1 mass spectrometer operates at approximately 5e -5 It can operate at pressures below Torr or about 120 times lower than the typical operating pressure of the Q0 mass filter. Such reduced pressures result in significantly fewer collisions between ions and background neutral species, thereby leading to a larger radial oscillation range of ions passing through the Q1 mass spectrometer. This, in turn, may make the ions more susceptible to the effects of charged debris deposited on the rods of the Q1 mass spectrometer, where applicable. For example, quadrupole mass spectrometers typically operate with high Mathieu a- and q-parameters and a narrow transmission window, e.g., about 1 amu.

[0086] Such operating parameters for a quadrupole mass spectrometer may require precise settings of both RF and DC voltages. Narrowband passage of ions through a quadrupole mass spectrometer can result in relatively high radial amplitude of transmitted ions and a clear distinction between stable and unstable ions. As a result, any charged material deposited on the rods of the Q1 mass spectrometer can "blur" the boundary between stable and unstable ions by causing time variations in one or both of the RF and DC fields experienced by ions passing through the mass spectrometer, which can then degrade the performance of the mass spectrometer.

[0087] More specifically, in this embodiment, the quadrupole rod set of the second mass spectrometer Q1 can be operated as a transmission RF / DC quadrupole mass spectrometer for selecting ions having a desired m / z ratio. For example, the quadrupole rod set of the mass filter Q1 can be provided with an RF / DC voltage suitable for operation in mass resolution mode. For instance, the parameters of the applied RF and DC voltages can be selected so that the mass spectrometer Q1 establishes a transmission window for the selected m / z ratio, and therefore those ions can traverse the mass spectrometer Q1 largely without interruption. However, ions with m / z ratios falling outside the window may not achieve stable trajectories within the quadrupole and may be prevented from traversing the quadrupole rod set of the mass spectrometer Q1. It should be understood that this mode of operation is only one possible mode of operation for the mass spectrometer Q1.

[0088] Those skilled in the art will understand that the energy of ions introduced into a quadrupole mass spectrometer is typically low to ensure that the ions are subjected to sufficient cycling within the quadrupole field as they traverse the spectrometer. For example, typical ion energies can be about 0.5 to 3 eV, and such low-energy ions can be adversely affected by debris accumulation and charge at the quadrupole inlet.

[0089] In this embodiment, ions selected by the mass spectrometer Q1 are focused into the impact cell Q2 via a short-thick lens ST2 and an ion lens IQ2. In this embodiment, the impact cell Q2 includes a pressurized compartment which can be maintained at a pressure in the range of, for example, about 1 milliliter to about 20 milliliters, although other pressures may be used for this or other purposes. A suitable impact gas (e.g., nitrogen, argon, helium, etc.) can be provided via a gas inlet (not shown) to cause fragmentation of at least some of the ions received by the impact cell Q2.

[0090] In this embodiment, the collision cell Q2 is arranged in a quadrupole configuration and includes four rods Q2a to which an RF voltage can be applied to provide radial confinement of ions received by the collision cell Q2. Furthermore, in this embodiment, a pair of short-bulb lenses Q2b and Q2c focus the generated ions, which are generated via the fragmentation of at least some of the precursor ions, into the orifice of the exit ion lens IQ3, through which the generated ions exit the collision cell. It will be apparent to those skilled in the art that other embodiments may be used (for example, without the short-bulb lenses Q2b and Q2c). The collision cell, Q2 may also include a higher-order multipole or ring guide.

[0091] The generated ions produced by the collision cell Q2 are received by the downstream quadrupole mass spectrometer Q3 via ion lens IQ3 and short-thick lens ST3, which function to focus the generated ions into the quadrupole mass spectrometer Q3. In this embodiment, the downstream analyzer is a quadrupole mass spectrometer, but in other embodiments, it may be a different type of mass spectrometer, such as a time-of-flight (TOF) mass spectrometer or an ion trap.

[0092] The quadrupole mass spectrometer Q3 includes four rods 114 arranged in a quadrupole configuration relative to each other to provide mass spectrometry of the generated ions, to which RF and / or DC voltages can be applied in a manner known in the art. Ions passing through the mass spectrometer Q3 pass through ion lenses 116 and 118 and are received and detected by a downstream detector 122, which generates an ion detection signal in response to the incident ions. Communicating with the detector 122, the analyzer 124 receives and processes the ion detection signal to generate a mass spectrum of the generated ions, thereby enabling monitoring of MRM transitions by fixing Q1 to the target precursor m / z, fragmenting the precursor ions in Q2, and fixing Q3 to the target daughter m / z.

[0093] As is known in the art, the analyzer 124 and controller 204 can be implemented in hardware / firmware and / or software using techniques known in the art, as provided by this teaching. For example, the analyzer 124 may include a processor, one or more random access memory (RAM) modules, one or more permanent memory modules, and at least one communication bus to enable communication between these and other components. As an example, Figure 7 schematically depicts an example of an implementation 700 of either the analyzer or the controller, which includes a processor 701, random access memory (RAM) 702, permanent memory 703 (e.g., ROM), a communication module 705, and a communication bus 704 connecting the processor to these components. In some embodiments, instructions for controlling RF and / or DC voltage sources, and / or instructions for analyzing detection signals by the detector of the mass spectrometer according to this teaching, may be stored in permanent memory and, during runtime to be executed, transferred by the processor to the RAM modules.

[0094] The following examples are provided for further illustration of various aspects of this teaching and are not necessarily provided to demonstrate the best way to practice this teaching and / or the best results that may be obtained. [Examples]

[0095] A series of experiments were conducted to determine the cause of performance degradation in mass spectrometers when used to analyze food-based samples. Surprisingly, as discussed above and illustrated below, it was found that heavier ions, such as those with an m / z ratio greater than approximately 700, rather than lighter ions, were the primary cause of performance degradation. Furthermore, it was found that the deposition of charged ions in the first mass spectrometer, positioned after one or more mass filters, can lead to the charging of the mass spectrometer rods, which in turn can degrade the performance of the mass spectrometer. As discussed above, placing a mass filter with a high M / Z cutoff upstream of the first mass spectrometer is advantageous in that it can prevent such contaminating ions from passing into the first mass spectrometer.

[0096] The sample matrix contained extracts of black tea and arugula. The stock tea was prepared by adding 10 mL of LC / MS-grade deionized water to 4 g of tea. The sample was homogenized by shaking for 30 seconds, and then 10 mL of LC / MS-grade acetonitrile was added. The sample was vortexed for 10 minutes, and a salt mixture comprising 4 g of magnesium sulfate, 1 g of sodium chloride, 1 g of trisodium citrate dihydrate, and 0.5 g of disodium hydrogen citrate sesquihydrate was added. The sample was vortexed for 10 minutes, and then centrifuged at 3,500 rpm for 5 minutes. The acetonitrile layer was removed and pooled for parallel samples prepared in the same manner.

[0097] A similar procedure was used to prepare arugula stock using 10 g of starting material. A mixed solution was prepared by combining 56 mL of tea extract and 56 mL of arugula extract, and adding 28 mL of water and 0.14 mL of formic acid. The mixed solution was diluted 50-fold with water in a 1:1 acetonitrile:0.1% formic acid mixture and filtered through a Whatman glass microfiber filter (grade 696). (Example 1)

[0098] A similar triple quadrupole mass spectrometer, as depicted in Figure 6 above, was used in a series of experiments with tea and arugula extracts to characterize signal degradation due to contamination and the m / z range of charged species that produced enough quadrupole analyzer deposits to degrade performance.

[0099] The experiment involved injecting 10 mL each of a mixed extract of tea and arugula matrix, followed by baseline testing of the mass spectrometer's performance. The baseline testing included charging tests performed in MRM and Q1 modes, monitoring signal fluctuations and changes in Q1 peak width. Figure 8 shows the MRM charging data obtained on the aforementioned triple quadrupole system after injection of 30 mL of sample matrix. The charging tests involved operating the spectrometer in negative ion mode for 5 minutes prior to switching to positive ion mode, tracking signal stability. This experiment was performed without the use of a Q0 mass filter.

[0100] As shown in Figure 8, the substantial charge of Q1 was observed on the system after the injection of 30 mL of food-based matrix, initially showing an increasing trend followed by a decreasing trend in the signal. Over the course of the 5-minute experiment, the Q1 FWHM changed by more than 10% (not shown in this figure). It will be obvious to those skilled in the art that the example in Figure 8 demonstrates a serious charge effect that would impair the performance of the mass spectrometer.

[0101] Figures 9A and 9B show digital photographs of a pair of excellent debris patterns on a pair of Q1 rods after injection of 30 mL of food-based matrix. A considerable debris pattern was visible on one pair of Q1 rods, while the other pair was relatively clean (not shown). (Example 2)

[0102] A series of additional experiments were conducted using a Q0 mass filter, which consisted of a T-bar electrode similar to the mass filter discussed in connection with Figure 3-4, while injecting the same food-based matrix into the mass spectrometer to establish a mass window associated with contaminant ions.

[0103] In the first experiment, the RF and DC voltages applied to the T-bar and Q0 assembly were set to filter out all charged species within the Q0 region, except for ions with an m / z ratio in the range of approximately 250–400 (then introduced into the Q1 mass spectrometer), as indicated by the gray traces depicted in Figure 10. This m / z window was selected after analyzing a list of 1,033 typical pesticide MRM migrations. The average m / z value from the list was 312, with minimums and maximums of 85 and 890.5, respectively. The 250–400 m / z window would contain 583 (56%) of the 1,033 MRM migrations typically monitored for pesticides above 5500.

[0104] From the Q1 scan in Figure 10, the total ion current measured with or without an upstream mass filter establishing a bandpass window of m / z 250-400 was approximately 4 × 10⁻¹⁶ when scanning the range of 100-1,000 m / z using a mass spectrometer. 9 cps to 7x10 8 The signal strength decreased to cps. When using a mass filter, it was possible to inject 100 mL of matrix without significantly increasing the charge of the mass spectrometer. Figure 11 shows the signal intensity traces with respect to the reference (reserpine ions) obtained after each 10 mL matrix injection. The total signal loss was less than 2 times.

[0105] Figures 12A and 12B show digital photographs of the Q1 rod assembly, indicating that despite the injection of 100 mL of food-based matrix, no significant debris accumulation was visible on the Q1 rod. Figures 12C and 12D show a pair of Q0T bars after the injection of 100 mL of matrix, showing a large amount of debris deposited on the surface within the inlet region. These results suggest that the large amount of debris causing the Q1 charge originates from charged species with m / z ratios outside the range of m / z 250–400.

[0106] In the second experimental set, the bandpass of the Q0 mass filter was set to a new m / z window extending in the range of 400–800, and mass spectra of ions with any m / z ratio within this range were obtained, as shown in the gray trace depicted in Figure 13. The TIC was approximately 4 × 10⁻⁶ as a result of the T-bar window. 9 cps to 1.7 × 10 9 It descended to cps (not visible in this figure).

[0107] By using a T-bar that limits the m / z range to 400-800, it was possible to spray 100 mL of food-based matrix without significant charge problems. Again, Figure 14 shows an overlay of intensity data obtained with respect to the reserpine criterion after injection of each 10 mL of matrix. The total signal reduction was less than 2x.

[0108] Figures 15A and 15B show photographs of the Q1 rods, and Figures 15C and 15D show photographs of the Q0T bar, illustrating that a large amount of debris accumulated on the Q0T bar, significantly reducing the amount of debris on the Q1 rods compared to a control experiment without T-bar filtration. A small amount of deposit was visible on one pair of Q1 rods, but the amount of deposit was far less than what was observed after only 30 mL of matrix when the T-bar was not filtered. The gain in robustness was more than 3x, despite a reduction of less than 3x in the total number of ions reaching the mass spectrometer. These results suggest that TIC is not simply a matter of the effects of contamination, but that certain types of debris are likely to be more harmful than others.

[0109] Previous results indicate that the food-based matrix contains charged contamination debris with m / z ratios outside the typical m / z range of 250–800. To confirm the mass range for these debris, additional experiments were performed, in which the DC potential applied to the T-bar was turned off and the Q0 RF potential was increased to provide a low m / z cutoff at approximately 720 m / z. Under these conditions, considerable charge was observed on the system after injection of 40 mL of the food-based matrix. The Q1 peak width changed by more than 10% over the course of the 5-minute charging experiment.

[0110] Figures 16A and 16B show digital photographs of a pair of Q1 rods, demonstrating the presence of large sediments similar to the original baseline data obtained without the use of a T-bar (see Figures 9A and 9B).

[0111] The above data shows that 1) when analyzing food-based matrices such as tea and arugula extracts, charged debris most involved in causing Q1 charging has an m / z ratio greater than approximately 720, and 2) when high m / z charged species are filtered out prior to the Q1 analyzer, instrument robustness is significantly improved, for example, by more than three times in the above experiment.

[0112] Additional experiments were conducted using a tea / arugula matrix to characterize a range of large charged species with very high m / z. In the first set of experiments, as shown in Figure 17A, the Q0 RF potential was set to 1,560 V, the T-bar was turned off, and it is clear that the Q0 RF level resulted in a low m / z cutoff.

[0113] While an elevated background was visible in the Q1 scan, no extreme peak indications were present in the region where the m / z ratio was above approximately 1,000. The mass spectrometer on this triple quadrupole instrument is limited to m / z 2,000; therefore, a custom scan was used to attempt to characterize the magnitude of ion currents with m / z ratios greater than 2,000.

[0114] The Q1 mass spectrometer was set to open, and the instrument was operated in MS / MS mode with the precursor mass set to 2,000. This resulted in a low M / Z cutoff in Q1, around 1,500 m / z. The collision energy was then optimized to maximize the signal measured in Q3, which required an energy of approximately 70 eV. Under these conditions, numerous peaks corresponding to fragments from larger charged cluster species were observed in the Q3 region, as shown in Figure 17B.

[0115] Many of the freed peaks in the asteroid scanning (e.g., ions with large m / z ratios outside the upper mass limit of MS) ​​correspond to endemic species from the food-based matrix, which were also observed in the Q1 scanning (Figure 17A).

[0116] In the aforementioned Asteroid scan (e.g., ions with large m / z ratios outside the upper mass limit of MS) ​​in conjunction with an uncontaminated matrix, it is estimated that approximately 4% of the ion currents related to reserpine were captured within large clusters. For the food-based matrices tested here, Asteroid contents are thought to be much higher, with the TIC from the Asteroid scan being 12% of the TIC from the Q1 scan. This suggests that these food-based matrices can create unbalanced ion currents contained within very large m / z clusters or droplets, contributing to mass spectrometer contamination.

[0117] The pesticides that would typically be monitored for food-based matrices on triple quadrupole spectrometers such as the Sciex 5500 series contain 1,033 MRMs and have a Q1 m / z range of 85 to 890.5. Of these compounds, only 18 have an m / z ratio of approximately 720, and therefore the window experiment described in Figures 13-15 shows that a large amount of charged debris arises from an m / z window larger than the m / z range required for 98.3% of the pesticides. These results indicate that 1) food-based matrices contaminate triple quadrupole instruments faster than other common sample matrices, and 2) Q1 charge is the primary cause of degradation in spectrometer performance.

[0118] Furthermore, by using the maximum pesticide m / z of 890.5, the example described above proposes a novel approach for pesticide analysis by including a mass filter with an m / z cutoff greater than the maximum target m / z (in this case, m / z 890.5). Figure 18 shows an additional example where the Q0T bar was used as a mass filter to exclude all ions with m / z greater than 900. It was possible to spray 100 mL of food-based matrix with virtually no charge.

[0119] Figures 19A-19D show the changes in TIC and Q1 peak width over a 5-minute charging experiment after injecting 100 mL of matrix using the bandpass filter shown in Figure 18, indicating that the reserpin signal and Q1 peak shape remained constant after injecting 100 mL of matrix.

[0120] Figures 20A and 20B show digital photographs of the Q0 T-bar and Q1 rod, respectively. Again, a large amount of debris accumulated on the T-bar, while no large debris accumulation was present on the Q1 mass spectrometer. (Example 3)

[0121] In another series of experiments, rat liver homogenate matrix was injected in 10 mL increments into a triple quadrupole mass spectrometer, followed by baseline testing of the mass spectrometer's performance, which involved charge testing performed in MRM and Q1 modes to monitor signal variability and changes in Q1 peak width.

[0122] More specifically, rat liver homogenate was prepared by mixing 1 part rat liver tissue with 10 parts PBS (phosphate buffer solution). The homogenate was precipitated according to 1 part tissue homogenate (3.5 mL of homogenate and 10.5 mL of methanol) with 3 parts methanol, and the resulting precipitate was vortexed and centrifuged. The supernatant was removed and dried. It was then reconstituted with 5 mM ammonium formate in 15 mL of 80:20 mobile phase A:B (vortexed and sonicated for reconstitution), 0.1% formic acid. The reconstituted precipitate was filtered through 0.45 micron and 0.2 micron cellulose. The final dilution factor was 4.2 times.

[0123] Figure 21 shows the Q1 scan acquired when injecting a rat liver homogenate matrix. The mass spectrum marked as Trace 1 presents the mass spectrum acquired without using the Q0 mass filter. The mass spectrum marked as Trace 2 was acquired with the RF and DC voltages applied to the T-bar and Q0 assembly set to filter out all charged species in the Q0 region except for ions with an m / z ratio of less than 400 (then introduced into the Q1 mass spectrometer). This m / z window was selected based on user input where all analytes of interest had an m / z ratio of 314 or lower.

[0124] Figures 22A–C show Q1 charge data obtained on a Sciex6500 triple quadrupole system after injection of 40 mL of sample matrix without the use of a Q0 mass filter. This charge test involved operating the spectrometer in negative ion mode for 10 minutes prior to switching to positive ion mode and tracking signal stability. Figure 22A shows data for m / z ratios above 500 and illustrates that minimal Q1 charge was observed.

[0125] Figure 22B shows data for m / z 175, where the signal begins to increase over the course of the 10-minute process, indicating severe charging. Figure 22C shows data for m / z 59, illustrating complete signal loss, which may be attributable to Q1 charging. These results indicate that, without a T-bar, after injecting 40 mL of matrix, the system experienced severe charging for m / z ratios below 300.

[0126] Figures 23A-C show Q1 charge data obtained using the aforementioned triple quadrupole system after injecting 40 mL of sample matrix with Q0 mass filter filtration above m / z 400. More specifically, Figure 23A shows charge data for m / z ratios above 500, illustrating the minimum charge. Figures 23B and 23C show charge data for m / z 175 and 59, respectively. These results demonstrate that, by using T-bar filtration above m / z 400, a minimum charge exists for any m / z ratio after injecting 40 mL of matrix.

[0127] Figures 24A and 24B show overlays of Q1 data for m / z 59 obtained after each 10 mL of matrix injection. The overlay shown in Figure 24A corresponds to data acquired when the mass spectrometer is operated without filtration with the T-bar. The peak width from baseline (prior to the start of the experiment), shown in Trace A, begins to narrow after each injection. Trace B shows the peak width after the injection of 40 mL of matrix, illustrating that the Q1 FWHM has changed by more than 26% from baseline. The overlay shown in Figure 24B shows the results when the T-bar is operated and m / z ratios greater than 400 are filtered. The peak width shows very minimal change after each 10 mL injection, which is clearly evident in the charged data.

[0128] Figures 25A–D show digital photographs of the debris pattern deposited on the poles of one pair of Q1 rods after injection of 40 mL of rat liver homogenate matrix. Figures 25A and 25B show that a considerable debris pattern was visible on one pair of Q1 rods where no T-bar was used. In contrast, as shown in Figures 25C and 25D, no visible debris deposits were present on the Q1 rods when the T-bar was set to filter out anything above m / z 400.

[0129] Those skilled in the art will understand that various modifications can be made to the above embodiments without departing from the scope of this teaching.

Claims

1. A mass spectrometer, wherein the mass spectrometer is An atmospheric pressure ion source configured to receive a sample and generate multiple ions by ionizing the sample, A first mass filter positioned downstream of the ion source to receive at least a portion of the plurality of ions, A user interface for receiving information from the user regarding one or more m / z ratios of interest or the range of m / z ratios of interest, A controller that communicates with the user interface and the first mass filter in order to receive the information relating to the m / z ratio of interest or the range of the m / z ratio of interest from the user interface. Equipped with, A mass spectrometer comprising a controller that determines the maximum m / z ratio of interest for mass spectrometry based on the information received from the user interface, and adjusts the band-pass window of the first mass filter, the band-pass window being adjusted to have a high m / z cutoff greater than the maximum m / z ratio.

2. The mass spectrometer according to claim 1, wherein the high m / z cutoff is set to a value in the range of about 10 to about 500, and is set to a value in the range of the maximum m / z ratio.

3. The mass spectrometer according to any one of claims 1 to 2, wherein the first mass filter is located in a reduced pressure chamber.

4. The mass spectrometer according to claim 3, wherein the depressurization chamber is maintained at a pressure in the range of about 2 mTorr to about 20 mTorr.

5. The mass spectrometer according to any one of claims 1 to 4, wherein the first mass filter comprises a plurality of rods arranged in a quadrupole configuration.

6. The mass spectrometer according to any one of claims 1 to 5, further comprising a second mass filter positioned downstream of the first mass filter to receive ions transmitted through the first mass filter, wherein the second mass filter has a band-pass window that defines a range of m / z ratios that can be transmitted through the second mass filter.

7. The mass spectrometer according to claim 6, wherein the controller communicates with the second mass filter to adjust the band-pass window of the second mass filter to allow the passage of a certain m / z ratio associated with ions received from the first mass filter.

8. The mass spectrometer according to claim 7, wherein the controller is configured to shift the band-pass window of the second mass filter to allow the passage of ions having different m / z ratios received from the first mass filter.

9. A method for performing mass spectrometry analysis of a sample, wherein the method is: Receiving information from the user regarding one or more m / z ratios of interest or the range of m / z ratios of interest, Based on the information received from the user, the maximum m / z ratio of ions associated with one or more analytes of interest in the sample is determined, Adjusting the bandpass window of a mass filter located upstream of the mass spectrometer to allow the passage of ions associated with the analyte of interest, while blocking the passage of ions having an m / z ratio greater than the maximum m / z ratio and above a high m / z cutoff; By ionizing the aforementioned sample, multiple ions are generated, Introducing the plurality of ions into the mass filter, Performing mass spectrometry on ions passing through the aforementioned mass filter Includes, The high m / z cutoff is selected to reduce contamination of the mass spectrometer.

10. The aforementioned sample includes a food-based sample, Optionally, the food-based sample may include tea. Optionally, the food-based sample may contain arugula. The method according to claim 9, wherein the processing of the food-based sample optionally includes using the QuEChERS extraction method.

11. The aforementioned sample includes a tissue sample, The method according to claim 9, wherein the tissue sample optionally includes liver tissue homogenate.

12. The step of performing the mass spectrometry includes introducing the ions that have passed through the mass filter into the mass spectrometer, The method according to any one of claims 9 to 11, wherein the mass spectrometer optionally comprises a plurality of rods arranged in a multipolar configuration.

13. The method according to claim 12, wherein the high m / z cutoff is selected to reduce contamination of the plurality of rods.

14. The step of performing the mass spectrometry includes generating a plurality of generated ions by causing fragmentation of at least some of the ions passing through the mass spectrometer, The method according to any one of claims 9 to 13, optionally further comprising generating mass spectra of the plurality of generated ions.

15. The step of performing the mass spectrometry includes monitoring the migration of at least one of the analyte ions to one or more MRMs, The method according to any one of claims 9 to 14, wherein the step of performing the mass spectrometry optionally includes using a quadrupole mass spectrometer.

16. The aforementioned high m / z cutoff is approximately 700. The method according to any one of claims 9 to 15, wherein the high m / z cutoff is optionally about 1,000.

17. The method according to any one of claims 9 to 16, wherein the mass filter is configured to provide a bandpass window for ion transmission.

18. The method according to claim 17, wherein the bandpass window extends from about 20 amu to about 1,250 amu.

19. The method according to any one of claims 9 to 18, further comprising processing the sample prior to the step of ionizing the sample.

20. The method according to any one of claims 9 to 19, wherein the one or more analytes of interest comprises at least one pesticide.

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