Variable detector amplifier stabilization time

Abstract

A mass spectrometer system including a non-transitory computer readable medium is described. The non-transitory computer readable medium includes instructions that, when executed by one or more hardware processors, cause the mass spectrometer to allow an amplifier current to stabilize a time determined by a threshold current between generating a signal due to an ion current from a detector of the mass spectrometer.

Description

[0001] Cross - Reference to Related Applications

[0002] This application claims the priority of U.S. Provisional Application No. 63 / 384,010, filed on November 16, 2022, which is hereby incorporated by reference. Technical Field

[0003] The present invention relates to mass spectrometer systems and methods. Specifically, a mass spectrometer with a detector amplifier having a variable settling time is described. Background Art

[0004] Mass spectrometry is a well - established technique, and mass spectrometers and systems for analyzing a wide variety of samples have been developed. All mass spectrometers include at least three components: an ion source, a mass filter, and a detector. Neutral atoms and molecules are converted into charged gas - phase ions by the ion source, and various methods are used to extract the charged species and accelerate them into an ion beam. The ion beam is sent through a mass filter that separates ions based on the mass - to - charge ratio (m / z). The filtered ions are directed to a detector that generates an ion current for each group of ions. Then, the ion current is amplified by an amplifier.

[0005] The amplifier used to amplify the ion current may require a certain settling time between monitoring different m / z species. Without allowing the amplifier to settle, carry - over ion current from a previous m / z species that impacts the detector can cause an erroneously high ion current to be attributed to a subsequent m / z species. The amplifier settling time can vary between each measurement of an m / z species because the time depends on the intensity or amount of the particular m / z species that generates the ion current. One way to correct for this carry - over effect is to allow the detector to settle for a fixed time. This allows the detector signal to decay to the background noise value without an m / z species impacting the detector and causing an ion current. However, this is not optimal because the fixed time may be too short, resulting in carry - over errors, or the fixed time may be too long, thus extending the measurement time.

[0006] Accordingly, there is an unmet need to optimize the detection of ions by mass spectrometry. Summary of the Invention

[0007] Systems, methods, and products for solving these and other needs are described herein with respect to exemplary, non - limiting specific embodiments. Various alternatives, modifications, and equivalents are also possible.

[0008] According to a first aspect, a system is described. The system includes a mass spectrometer that includes a mass filter and a current amplifier coupled to a detector. The current amplifier includes an amplifier current. The system further includes a non-transitory computer-readable medium coupled to or included with the mass spectrometer, the non-transitory computer-readable medium including instructions. When the instructions are executed by one or more hardware processors, the instructions cause the mass spectrometer to perform the following operations: send an ion beam through the mass filter; set the mass filter to a first mass filter setting so that a first subset of ions from the ion beam is focused onto the detector; generate a first signal proportional to the first subset of ions focused onto the detector; set the mass filter to a second mass filter setting so that a second subset of ions from the ion beam is focused onto the detector; allow the amplifier current to stabilize for a time determined by a threshold current; generate a second signal proportional to the second subset of ions focused onto the detector; and use the first mass filter setting and the second mass filter setting and the corresponding first signal and second signal to generate mass-to-charge ratio versus ion intensity data.

[0009] According to a second aspect, a method of measuring a mass distribution in a sample is described. The method includes: sending an ion beam through a mass filter; setting the mass filter to a first mass filter setting so that a first subset of ions from the ion beam is focused onto a detector; generating a first signal proportional to the first subset of ions focused at the detector; setting the mass filter to a second mass filter setting so that a second subset of ions from the ion beam is focused onto the detector; allowing an amplifier current to stabilize for a second time determined by a threshold; generating a second signal proportional to the second subset of ions focused at the detector; and using the first mass filter setting and the second mass filter setting and the corresponding first signal and second signal to generate mass-to-charge ratio versus ion intensity data.

[0010] According to a third aspect, a non-transitory computer-readable medium including instructions is described, which when executed by one or more hardware processors causes the operations described according to the second aspect to be performed.

[0011] The mass spectrometer system, method, and non-transitory computer-readable medium provide optimized detection using mass spectrometry. For example, it reduces the time to measure several substances in a sample. BRIEF DESCRIPTION OF THE DRAWINGS

[0012] The foregoing and other features and advantages of the present embodiment will be more fully understood from the following detailed description of exemplary embodiments taken in conjunction with the accompanying drawings.

[0013] Figure 1 is a block diagram of a system according to some specific implementations.

[0014] Figure 2 is a graph showing the signal attenuation of a current amplifier over time according to some specific embodiments.

[0015] Figure 3 is a flowchart showing the steps performed according to some specific embodiments to measure the mass distribution in a sample.

[0016] Figure 4 is a graph showing an amplifier and amplifier current according to some specific embodiments.

[0017] The figures mentioned above are not necessarily drawn to scale, and should be understood as providing a representation of a particular embodiment, and are inherently only conceptual and show the principles involved. The same reference numerals in the figures are used for similar or identical components and features shown in various alternative embodiments. Detailed Description

[0018] In the description of the present invention herein, it should be understood that unless otherwise implicitly or explicitly understood or stated, words in the singular form encompass their plural counterparts, and words in the plural form encompass their singular counterparts. In addition, it should be understood that for any given component or embodiment described herein, any possible candidates or alternatives listed for that component can generally be used alone or in combination with each other, unless otherwise implicitly or explicitly understood or stated. In addition, it should be understood that the figures shown herein are not necessarily drawn to scale, where only some elements may be drawn for the sake of clarity of the present invention. Also, reference numerals may be repeated in the various figures to show corresponding or similar elements. Additionally, it should be understood that any such list of candidates or alternatives is merely exemplary and not restrictive, unless otherwise implicitly or explicitly understood or stated. Further, unless otherwise indicated, the numbers representing the amounts of ingredients, components, reaction conditions, etc. used in the specification and claims should be understood to be modified by the term "about".

[0019] Accordingly, unless indicated to the contrary, the numerical parameters set forth in this specification and the appended claims are approximations that may vary depending upon the desired properties sought to be obtained by the subject matter presented herein. At the very least, and without attempting to limit the application of the doctrine of equivalents to the scope of the claims, each numerical parameter should be construed in light of the number of reported significant digits and by applying ordinary rounding techniques. Although the numerical ranges and parameters setting forth the broad scope of the subject matter presented herein are approximations, the numerical values set forth in the specific examples are reported as precisely as possible. However, any numerical value inherently contains certain errors necessarily resulting from the statistical dispersion found in their corresponding test measurements.

[0020] Figure 1is a block diagram showing some components of a mass spectrometer system 100 according to some specific implementations. The system includes a mass spectrometer 102 and a non-transitory computer-readable medium 110 implemented in a computer system 112.

[0021] The mass spectrometer 102 includes an ion source 103, a mass filter 104, and a detector 106. The detector 106 is coupled to a current amplifier 108. The current amplifier 108 includes an amplifier current.

[0022] Neutral atoms and molecules of a sample are converted into ions by the ion source 103. The ion source 103 includes an inlet or source for the neutral sample material. In some specific implementations, the sample is directly injected with minimal preparation, such as when the sampled ambient or process gas can be filtered to remove particles and / or diluted with an inert (i.e., non-reactive with the substance of interest) gas. In other specific implementations, the sample is sourced from a coupled instrument, such as a chromatographic system (e.g., HPLC, GC). In other specific implementations, the sample is combined to form a matrix, such as for matrix-assisted laser desorption / ionization (MALDI).

[0023] A typical ion source 103 can be an electron ionization (EI) source, a specific type of which is described, for example, in U.S. Patent No. 6,885,010, which is hereby incorporated by reference in its entirety. Other ion sources can be implemented, such as electrospray ionization (ESI), chemical ionization (CI), atmospheric pressure chemical ionization (APCI), and MALDI. Electrodes and ion guides extract ions from the ion source and form these ions into an ion beam that is directed through the mass filter 104.

[0024] The mass filter 104 (sometimes called a mass analyzer) separates or filters ions according to the mass-to-charge ratio (m / z). Most commonly, the ions are positively charged ions (cations), although some specific implementations can use negatively charged ions (anions). The specific mechanism for mass filtering depends on the type of mass filter 104 used. For example, in a magnetic sector mass spectrometer, ions are sent through a magnetic sector flight tube in which the ions are separated according to their m / z ratio in a variable-intensity magnetic field generated by an electromagnet. In a quadrupole mass spectrometer, ions are separated according to their m / z ratio based on a variable electric field provided by the quadrupole.

[0025] The filtered ions are directed to detector 106, which generates an ion current in response to ions striking or focusing on the detection element of detector 106. In some embodiments, detector 106 is a Faraday cup detector. In some other embodiments, detector 106 is a microchannel plate (MCP) detector, also known as a secondary electron multiplier detector. In some embodiments, mass spectrometer 102 includes two or more detectors 106 that can be independently selected for analysis.

[0026] Current amplifier 108 amplifies the ion current. The ion current provided by detector 106 can be extremely small and requires amplification for further processing. For example, in some embodiments, the ion current can be in the range of about 10 -16 amperes to 10 -9 amperes. One way to amplify such signals is to use a transimpedance amplifier. A transimpedance amplifier includes an operational amplifier and a feedback resistor R f connected between the inverting input of the operational amplifier and the output of the operational amplifier. In an ideal situation, the transimpedance amplifier will amplify the amplifier current (I) and convert it into a low-impedance output voltage (V) according to the equation I t :

[0027] V = IR f .

[0028] A transimpedance amplifier configured to operate with a small or extremely small I in the picoampere to femtoampere range typically operates with a large feedback resistor R 9 in the range of 10 14 ohms to 10 f ohms. Such large resistors exhibit self-capacitance, which causes the amplifier current to decay slowly when the source such as the ion current is removed. In practice, the noise signal is improved by shunting R f with a small capacitor in the range of 0.05 pF to 0.1 pF, although this added small capacitor is not always required or used. There may also be some capacitance due to parts that are part of the amplifier or connected to the amplifier. Thus, there is an equivalent capacitance C * that takes into account all the capacitance-generating elements associated with current amplifier 108. Therefore, the amplifier current (I) and decay time (t) after removing the ion current Ic can be described by equation II:

[0029] t = R f C * ln(I c / I).

[0030] Figure 2 is a natural logarithm graph of the predicted decay of the amplifier current (I). This graph uses 3x10-12 C of farad * and 10 -10 R of ohm f The estimated value. The capacitance is estimated by observing the retention current and by considering other factors such as the components and types of the mass spectrometer. In some specific embodiments, C * is determined according to the equivalent circuit analysis of the current amplifier 108. In some specific embodiments, C * is calculated by measuring the signal attenuation relative to time and solving for C in Equation II * . R f C is the RC time constant of the current amplifier 108. If Ic is known, the time t to reach the target amplifier current can be determined.

[0031] The amplifier current is a variable current and can include the ion current from the detector 106, the background current from the detector 106, the background current from the amplifier 108, and the decay current, such as the decay current described above by Equation II. Thus, in response to different ions generating an ion current at the detector 106, a low amplifier current considered as background noise when no ions impinge on the detector 106, and the decay current between these values, the amplifier current can have different and large values. The magnitude of the ion current is proportional to the number of ions impinging on the detector 106. The level of the background noise can depend on the components in the detector 106 and factors such as temperature and electrical insulation.

[0032] In some specific embodiments, the current amplifier includes a known amplifier current decay profile. Although other decay profiles are envisioned (such as a decay profile including two or more exponential decay time constants), in some specific embodiments, the current amplifier 108 has an RC equivalent circuit, and the known decay profile corresponds to the RC equivalent circuit current decay profile such as described above with reference to Equation II. In some specific embodiments, the resistor R of the RC circuit f is between 10 9 ohms and 10 11 ohms. In some specific embodiments, the equivalent capacitor C of the RC circuit * is between 10 -13 farads and 10 -11 farads.

[0033] Return Figure 1, System 100 includes computer system 112. Computer system 112 includes sub-components such as hardware processor 114, memory 116, and input / output (I / O) device 118. Hardware processor 114 may include more than one device, such as a CPU and a microprocessor. Hardware processor 114 executes commands stored in memory 116. Memory 116 may include a dynamic storage device such as random access memory (RAM), a static memory such as read-only memory (ROM). Memory 116 also includes non-transitory computer-readable medium 110. In some embodiments, at least some of the sub-components may be physically combined into a single unit different from mass spectrometer 102. In some embodiments, at least some of the sub-components are physically integrated with mass spectrometer 102.

[0034] Non-transitory computer-readable medium 110 refers to any non-transitory medium that stores data and instructions that cause mass spectrometer system 100 to operate in a specific manner. Such non-transitory media may include non-volatile media and / or volatile media. Non-volatile media includes, for example, optical discs or magnetic disks. Volatile media includes dynamic memories such as RAM. Common forms of storage media include, for example, floppy disks, flexible disks, hard disks, solid state drives, magnetic tapes, or any other magnetic data storage media, CD-ROMs, any other optical data storage media, any physical medium with a pattern of holes, RAM, PROM, and EPROM, flash EPROM, NVRAM, any other memory chip or cartridge, content addressable memory (CAM), and ternary content addressable memory (TCAM). The non-transitory computer-readable medium may be read into one of the other memories included in memory 116 for storage or execution by hardware processor 114.

[0035] I / O device 118 may include devices for outputting information, such as monitors, printers, or indicator lights and alarms. The I / O device may also include devices for inputting commands, such as keyboards or other keys and buttons, mice or other cursor control devices, and microphones for voice commands. The I / O device may also include a communication interface for two-way communication with a local network, a remote server, or the cloud. Two-way communication may include wireless and / or hardwired connections.

[0036] The various components in the mass spectrometer 102 and the computer system 112 are coupled to each other so that they can operate as a system. For example, one or more components can be electrically coupled by wires and contacts. One or more components can also be wirelessly coupled. The coupling can be direct or through other components, such as a bus within the computer system 112, which can also be coupled to the mass spectrometer 102, such as through a microcontroller in the mass spectrometer 102. In addition, central power, such as from a main power supply or a battery, can be distributed throughout the system 100 via a network to power the various components. Local individual power supplies can also be used for any of the mass spectrometer 102 and the computer system 112 or components therein.

[0037] In addition to communicating and receiving commands locally to operate the system 100, in some specific embodiments, the I / O device 118 can be connected to a larger system, such as a control or monitoring system of a manufacturing plant. For example, the system 100 can be included in a Process Analytical Technology (PAT) system, such as for monitoring a bioreactor. In such specific embodiments, for example, the I / O device 118 can receive data and instructions from other process monitoring devices (e.g., temperature sensors or pH meters or instructions to make measurements), or the I / O device 118 can send instructions to the PAT system, such as instructions to add nutrients or heat to the bioreactor. As another example of a specific embodiment, the system 100 can be part of a gas flare monitoring system, in which the I / O device 118 can send signals or instructions, such as an alarm signal or an instruction to close a valve to the gas flare monitoring system.

[0038] The non-transitory computer-readable medium 110 includes instructions executable by one or more hardware processors 114. For example, the processor 114 can send electrical signals or data to a microcontroller or other device to cause the mass spectrometer 102 to perform a sequence of events as indicated by the instructions. The instructions include causing the mass spectrometer 102 to perform as Figure 3 depicted in

[0039] Instruction 202 is to send an ion beam through the mass filter 104. It should be understood that, for effectiveness, previous instructions, such as providing a sample to the ion source 103 and providing an ionization current to ionize the sample, are also sent to the ion source 103. While steps 204, 206, 210, and 212 are being performed, the ion beam is continuously sent through the mass filter 104. In some specific embodiments, instruction 202, or a previous or subsequent instruction (such as immediately before or immediately after), includes monitoring an amplifier output signal, such as a steady current or a background current (background noise).

[0040] Instruction 204 sets the mass filter 104 to a setting such as a first mass filter setting. This mass filter setting focuses a subset of the ions from the ion beam, such as a first ion subset, onto the detector 106. This causes an ion current, such as a first ion current, to be generated.

[0041] Instruction 206 generates a signal such as a first signal that is proportional to a subset of the ions (e.g., the first subset) focused onto the detector 106. The ion current (e.g., the first ion current) is amplified by the current amplifier 108 to provide the signal (e.g., the first signal). For example, in a particular implementation using a transimpedance amplifier, the first signal can be a voltage output generated by the first ion current. In some particular implementations, instruction 206 is immediately followed by instruction 214 discussed below. In some particular implementations, instruction 206 includes instructions to start collecting data and to stop collecting data, thereby causing the amplifier current to be sampled between the start instruction and the stop instruction. In some particular implementations, the generated signal is the average of the sampled amplifier current between the time of the start instruction and the stop instruction. In another particular implementation, the instruction to start collecting data or the instruction to stop collecting data causes a physical element such as a switch between the detector 106 and the current amplifier 108 to open or close. Such a physical element connects the detector 106 to the current amplifier 108 and collects data, and disconnects the detector 106 from the current amplifier 108 to stop data collection.

[0042] Instruction 208 sets the mass filter to another, next, or second mass filter setting. This next mass filter setting focuses the next (such as a second) subset of the ions from the ion beam onto the detector 106. This causes another, next, or second ion current to be generated.

[0043] Instruction 210 allows time for the amplifier current to stabilize for a first time period determined, for example, by a threshold current. For example, the amplifier current decays from the first ion current according to the circuit design that determines its decay characteristics. Instruction 210 can be implemented by determining the expected time for the amplifier to reach the threshold current. For example, using the RC decay depicted by Figure 2 if the first ion current is 1x10 -12 amperes (210a), and the threshold is 1x10 -15(210b), the instruction 210 is to wait for approximately 0.2 seconds (210c) before proceeding to the next step. Thus, instead of directly monitoring or using the amplifier current, a decay model of the current is used to determine the time required to achieve a desired threshold of the amplifier current. In some specific implementations, the amplifier current actually never reaches the threshold current, such as when the threshold current is much lower than the background noise level of the amplifier current. In some specific implementations, before setting the mass filter to the first mass filter setting, the amplifier current is allowed to stabilize to the background noise level.

[0044] The instruction 212 is to generate another, next, or second signal corresponding to the next (such as the second) sub-integration ratio of the ions focused on the detector 106. The ion current (e.g., the second ion current) is amplified by the current amplifier 108 to provide this next signal (e.g., the second signal). In some specific implementations, the instruction 212 includes instructions to start collecting data and stop collecting data as previously described for the instruction 206. In some specific implementations, the generated signal is the average of the sampled amplifier current between the start instruction and the stop instruction. In another specific implementation, starting to collect data or stopping to collect data causes the actuation of a physical element such as a switch, as previously described for the instruction 206. In some specific implementations, the instruction 212 is immediately followed by the instruction 214 discussed below.

[0045] The instruction 214 is to generate m / z versus ion intensity data using the mass filter settings (such as the first mass filter setting and the second mass filter setting) and the corresponding generated signals (such as the first signal and the second signal). The mass filter settings identify specific substances from the sample associated with their m / z, and the generated signals are proportional to the ion current and thus the concentration of the specific substances, or are derived from the ion current and thus the concentration. In some specific implementations, the m / z versus ion intensity data is output as the substance concentration of the sample. In some specific implementations, the m / z ion intensity data is sent to a process monitoring system. For example, the system 100 can be used as a gas analyzer for flare gas analysis or for monitoring a bioreactor, such as for monitoring hydrocarbons (e.g., methane), sulfur dioxide, carbon dioxide, carbon monoxide, amines, and nitrogen oxides.

[0046] Figure 4 showing a reference amplifier current curve according to a specific implementation Figure 3Some of the steps shown in. The curve diagram shows the amplifier current relative to time, with the instruction shown when the instruction appears along the time axis. Before the instruction 202 to send the ion beam through the mass filter 104, the current amplifier 108 is turned on, and the amplifier current stabilizes at the background noise level 402 indicated by the dashed line. Initially, when the ion beam is turned on or generated, only background noise is detected because no ions are focused on the detector 106 yet. The instruction 204 to set the mass filter 104 to a setting such as the first mass filter setting causes a first subset of ions to be focused on the detector 106, and the amplifier current surges upward until the amplifier current reaches a steady state due to the first ion current 404, with some background noise superimposed. Then the instruction 206 to generate the first signal is given. The instruction 206 lasts for a certain time interval within the time period when the detector 108 is generating the first ion current 404. The instruction 206 can be shorter than the entire time when the first ion current 404 is being generated and is bounded by the previously described start collecting data and stop collecting data instructions. The instruction 206 retrieves the ion current amplified by the amplifier (such as) to generate a voltage value, which can then be further converted into the concentration of ions. When the mass spectrometer 102 receives the instruction 208 to set the mass filter to another, next, or second mass filter setting, the amplifier current caused by the first ion current decays along 406 and can reach the background noise level 402. In an alternative specific implementation, the amplifier current does not reach the background noise level because when the amplifier current caused by the first ion current decays along 406, the amplifier current caused by the next (such as second) subset of ions focused on the detector 106 rises along 410 until the amplifier current reaches a steady state due to the second ion current 412. That is, in this alternative specific implementation, the amplifier current can start to rise and relax downward to the background noise level 402 between the steady states 404 and 412.

[0047] In Figure 4Also shown is a calculated decay curve 408, which is hidden under the current decay 406, except where it is shown to be below the background noise level 402. Instruction 210 allows the amplifier current to stabilize below the threshold current 414 by waiting for the time it takes for the calculated decay curve 408 to intersect the threshold current 414. After this time, an instruction 212 to generate a second signal is sent. Similar additional instructions are sent, such as an instruction 208' to set the mass filter 104 to the next (e.g., third) mass filter setting and an instruction 210' to allow the amplifier current to stabilize below the threshold 414. The threshold current 414 can be selected at any level 402, such as below, equal to, or above the background noise level 402. In some embodiments, the threshold current 414 is different between measurements of the ion current, such that there are multiple threshold currents 414, such as a first threshold after generating a first ion current, a second threshold after generating a second ion current, a third threshold after generating a third ion current, and so on.

[0048] It should be noted that, as Figure 4 depicted, the time associated with instruction 210 (such as a first time) is longer than the time associated with instruction 210' (such as a second time). The reason for this is that the first ion current 404 is higher than the second ion current 412, and thus the amplifier current takes longer to decay from the first ion current 404 than from the second ion current 412.

[0049] In some specific embodiments, the instructions include a mass filter command sequence, where the first mass filter setting and the second mass filter setting are set according to the mass filter command sequence. For example, the first mass filter command sends an instruction 204 that sets the mass filter 104 to the first filter setting, and the second mass filter command sends an instruction 208 that sets the mass filter 104 to the second mass filter setting. The sequence may include additional mass filter commands, such as a third mass filter setting, a fourth mass filter setting, a fifth mass filter setting, etc., and each mass filter setting provides a corresponding instruction for setting the third mass filter setting, the fourth mass filter setting, the fifth mass filter setting, etc. In some specific embodiments, the mass filter command sequence includes between 2 and 100 (e.g., between 2 and 50, between 5 and 20) mass filter commands. This is depicted by the arrow connecting instruction 212 and instruction 208, which iterates instructions 208, 210, and 212 until the mass filter command sequence has been executed. Thus, in some specific embodiments, the instructions cause the mass spectrometer 102 to: set the mass filter to the third mass filter setting, thereby focusing a third subset of ions from the ion beam onto the detector; allow the amplifier current to stabilize for a time determined by a threshold current; generate a third signal proportional to the third subset of ions focused at the detector; and use the third mass filter setting and the corresponding third signal to generate mass-to-charge ratio versus ion intensity data.

[0050] In some specific embodiments, the mass filter 104 takes some time to stabilize. For example, the electromagnet used in a magnetic sector mass spectrometer may take a significant amount of time to stabilize to a stable magnetic field (e.g., within 0.01% of the target magnetic field). In such specific embodiments, the mass filter 104 is allowed to stabilize before any ion current is amplified by the current amplifier 108 to provide a signal. In some specific embodiments, the mass filter 104 set to the first mass filter setting is allowed to stabilize before generating the first signal; the mass filter 104 set to the second mass filter setting is allowed to stabilize before generating the second signal; and the mass filter 104 set to the third mass filter setting is allowed to stabilize before generating the third signal.

[0051] In some specific embodiments, the threshold current is equal to or lower than one standard deviation of the amplifier current. That is, the amplifier current varies due to background noise equal to three standard deviations of the signal. In some specific embodiments, the threshold current is equal to or lower than 0.1 standard deviation of the amplifier current. In some specific embodiments, the threshold is equal to or lower than 3 standard deviations of the amplifier current.

[0052] The threshold current can also be selected to be above the background noise level (3 standard deviations). For example, while this may allow some trapped ion current into the subsequent or next ion current, it will also shorten the analysis time because the time for the amplifier current to stabilize to the threshold current will be shorter. Thus, there is a balance between shortening the measurement of many different m / z species and the precision of the measurement, and this balance is taken into account.

[0053] In some embodiments, the threshold current is selected by the user or by another machine or system connected to system 100. The threshold can be selected by the user using I / O devices such as a keyboard and a monitor.

[0054] In some embodiments, the time for the amplifier current to stabilize (such as the first time or the second time) is between 0.01 seconds and 1 second. The time delay here corresponds to the time between generating subsequent signals for each mass filter setting. For example, the time delay between generating the first signal and generating the second signal. In some embodiments, the mass filter 104 takes longer to stabilize than the current amplifier 108. In such instances, the time delay is significant simply due to the stabilization of the mass filter 104. For example, when the magnetic field of a magnetic sector mass spectrometer is switched to the next mass filter setting, the field may take 0.1 seconds to 0.2 seconds to stabilize. If the ion current is low due to a previous measurement, the time calculated for the amplifier current to decay below the threshold current may be less than the time taken for the magnetic field to stabilize. In such instances, the next signal can be generated immediately.

[0055] In some embodiments, the mass spectrometer is a magnetic sector mass spectrometer, the mass filter includes a magnetic sector flight tube, the first mass filter setting is the first magnetic field, and the second mass filter setting is the second magnetic field. In some embodiments, the mass spectrometer is a quadrupole mass spectrometer, the mass filter includes a quadrupole mass filter, the first mass filter setting causes a first quadrupole electric field, and the second mass filter setting causes a second quadrupole electric field setting.

[0056] Embodiments are shown for calculating the time delay between two ion currents due to different ion beams associated with two different masses using an RC equivalent circuit. This shows that for a 30 ms RC time constant, the reading at mass 30.5 has stabilized. Thus, system 100 can select 30 ms or longer to ensure that the measurement of mass 30.5 will not have any trapped current from mass 28.

[0057] Table: Experiments showing different RC time constants 。

[0058]

[0059] The following numbered paragraphs 1 through 21 provide various examples of the embodiments disclosed herein.

[0060] Paragraph 1. A system (100) comprising: a mass spectrometer (102) including a mass filter (104) and a current amplifier (108) coupled to a detector (106), wherein the current amplifier (108) includes an amplifier current; and a non-transitory computer-readable medium (110) coupled to or included with the mass spectrometer (102), the non-transitory computer-readable medium (110) including instructions that, when executed by one or more hardware processors (112), cause the mass spectrometer (102) to: send (202) an ion beam through the mass filter 104; set (204) the mass filter to a first mass filter setting to focus a first subset of ions from the ion beam onto the detector; generate (206) a first signal proportional to the first subset of ions focused onto the detector; set (208) the mass filter to a second mass filter setting to focus a second subset of ions from the ion beam onto the detector; allow (210) the amplifier current to persist for a first time determined by a threshold current; generate (212) a second signal proportional to the second subset of ions focused onto the detector; and generate (214) mass-to-charge ratio versus ion intensity data using the first and second mass filter settings and the corresponding first and second signals.

[0061] Paragraph 2. The system of paragraph 1, wherein the instructions include a mass filter command sequence, and wherein the first and second mass filter settings are set according to the mass filter command sequence.

[0062] Paragraph 3. The system of paragraph 1 or paragraph 2, wherein: a first ion current is generated by the first subset of ions focused onto the detector and the first ion current is amplified by the current amplifier to provide the first signal; and a second ion current is generated by the second subset of ions focused onto the detector and the second ion current is amplified by the current amplifier to provide the second signal.

[0063] Paragraph 4. The system of any one of paragraphs 1 through 3, the system further comprising allowing the mass filter 104 set to the first mass filter setting to stabilize before generating the first signal and allowing the mass filter 104 set to the second mass filter setting to stabilize before generating the second signal.

[0064] Segment 5. The system according to any one of segments 1 to 4, wherein the instruction further causes the mass spectrometer to: set the mass filter to a third mass filter setting so as to focus a third subset of ions from the ion beam onto the detector; allow the amplifier current to stabilize for a second time determined by the threshold current; generate a third signal proportional to the third subset of ions focused at the detector; and use the third mass filter setting and the corresponding third signal to generate mass-to-charge ratio versus ion intensity data.

[0065] Segment 6. The system according to segment 5, the system further comprising allowing the mass filter set to the second mass filter setting to stabilize before generating the third signal.

[0066] Segment 7. The system according to any one of segments 1 to 6, wherein the mass-to-charge ratio versus ion intensity data is output as a substance concentration.

[0067] Segment 8. The system according to any one of segments 1 to 7, wherein the mass-to-charge ratio versus ion intensity data is sent to a process monitoring system.

[0068] Segment 9. The system according to any one of segments 1 to 8, wherein the current amplifier includes a known amplifier current decay profile.

[0069] Segment 10. The system according to any one of segments 1 to 9, wherein the current amplifier has an RC equivalent circuit, and the known decay profile corresponds to the RC equivalent circuit current decay profile.

[0070] Segment 11. The system according to segment 10, wherein the equivalent resistor of the RC circuit is between 10 9 ohms and 10 11 ohms.

[0071] Segment 12. The system according to segment 10 or 11, wherein the equivalent capacitor of the RC circuit is between 10 -13 farads and 10 -11 farads.

[0072] Segment 13. The system according to any one of segments 1 to 12, wherein the threshold current is equal to or lower than one standard deviation of the amplifier current.

[0073] Segment 14. The system according to any one of segments 1 to 13, wherein the threshold current is selected by the user.

[0074] Segment 15. The system according to any one of segments 1 to 14, wherein the first time is between 0.01 seconds and 1 second, and for the system according to segment 5, wherein the second time is between 0.01 seconds and 1 second.

[0075] Segment 16. The system according to any one of segments 1 to 15, the system further comprising allowing the amplifier current to reach the background current before setting the mass filter to the first mass filter setting.

[0076] Segment 17. The system according to any one of segments 1 to 16, wherein the mass spectrometer is a magnetic sector mass spectrometer, the mass filter comprises a magnetic sector flight tube, the first mass filter setting is a first magnetic field, and the second mass filter setting is a second magnetic field.

[0077] Segment 18. The system according to any one of segments 1 to 17, wherein the mass spectrometer is a quadrupole mass spectrometer, the mass filter comprises a quadrupole mass filter, the first mass filter setting is a first quadrupole electric field, and the second mass filter setting is a second quadrupole electric field setting.

[0078] Segment 19. A method for measuring a mass distribution in a sample, the method comprising: sending an ion beam through a mass filter; setting the mass filter to a first mass filter setting such that a first subset of ions from the ion beam is focused onto a detector; generating a first signal proportional to the first subset of ions focused at the detector; setting the mass filter to a second mass filter setting such that a second subset of ions from the ion beam is focused onto the detector; allowing the amplifier current to stabilize for a first time determined by a threshold current; generating a second signal proportional to the second subset of ions focused at the detector; and using the first mass filter setting and the second mass filter setting and the corresponding first signal and second signal to generate mass-to-charge ratio versus ion intensity data.

[0079] Segment 20. The method according to segment 21, the method further comprising: setting the mass filter to a third mass filter setting such that a third subset of ions from the ion beam is focused onto the detector; allowing the amplifier current to persist for a second time determined by the threshold current; generating a third signal proportional to the third subset of ions focused at the detector; using the third magnetic field and the corresponding third signal to generate mass-to-charge ratio versus ion intensity data.

[0080] Segment 21. A non-transitory computer-readable medium, the non-transitory computer-readable medium comprising instructions that, when executed by one or more hardware processors, cause the performance of the operations according to segment 19 or 20.

[0081] Using the knowledge obtained from this disclosure, those skilled in the art will recognize that various changes can be made to the disclosed devices and methods without departing from the scope of this disclosure in the process of obtaining these and other advantages. Thus, it should be understood that the features described herein are susceptible to modification, variation, change, or substitution. For example, all combinations of elements and / or steps that perform substantially the same function in substantially the same manner to achieve the same result are explicitly contemplated to be within the scope of the embodiments described herein. Substitution of elements from one described embodiment to another is also fully contemplated and considered. The specific embodiments illustrated and described herein are for illustrative purposes only and do not limit the embodiments set forth in the appended claims. Other embodiments will be apparent to those skilled in the art. It should be understood that the foregoing description is provided for clarity only and is merely exemplary. The spirit and scope of this disclosure are not limited to the specific implementations and examples above, but are covered by the following claims. All disclosures and patent applications cited above are incorporated by reference in their entirety for all purposes to the same extent as if each individual disclosure or patent application were specifically and individually designated to be incorporated by reference in such manner.

Claims

1. A system (100), the system comprising: A mass spectrometer (102), the mass spectrometer including a mass filter (104) and a current amplifier (108) coupled to a detector (106), wherein the current amplifier (108) includes an amplifier current; and A non-transitory computer-readable medium (110), the non-transitory computer-readable medium coupled to or included with the mass spectrometer (102), the non-transitory computer-readable medium (110) including instructions that, when executed by one or more hardware processors (112), cause the mass spectrometer (102) to: Send an ion beam through the mass filter (104); Set the mass filter (104) to a first mass filter setting such that a first subset of ions from the ion beam is focused onto the detector (106); Generate a first signal proportional to the first subset of ions focused onto the detector (106); Set the mass filter (104) to a second mass filter setting such that a second subset of ions from the ion beam is focused onto the detector (106); Allow the amplifier current to stabilize for a first time determined by a threshold current; Generate a second signal proportional to the second subset of ions focused onto the detector (106); Use the first mass filter setting and the second mass filter setting and the corresponding first signal and second signal to generate mass-to-charge ratio versus ion intensity data.

2. The system of claim 1, wherein the instructions include a mass filter command sequence, and wherein the first mass filter setting and the second mass filter setting are set according to the mass filter command sequence.

3. The system of claim 1, wherein: A first ion current is generated by the first subset of ions focused onto the detector, and the first ion current is amplified by the current amplifier to provide the first signal; And A second ion current is generated by the second subset of ions focused onto the detector, and the second ion current is amplified by the current amplifier to provide the second signal.

4. The system of claim 1, the system further comprising allowing the mass filter (104) set to the first mass filter setting to stabilize before generating the first signal, and allowing the mass filter 104 set to the second mass filter setting to stabilize before generating the second signal.

5. The system of claim 1, wherein the instructions further cause the mass spectrometer to: Set the mass filter to a third mass filter setting such that a third subset of ions from the ion beam is focused onto the detector; Allow the amplifier current to stabilize for a second time determined by the threshold current; Generate a third signal proportional to the third subset of ions focused at the detector; and Use the third mass filter setting and the corresponding third signal to generate mass-to-charge ratio versus ion intensity data.

6. The system according to claim 5, the system further comprising allowing the mass filter set to the second mass filter setting to stabilize before generating the third signal.

7. The system according to claim 1, wherein the mass-to-charge ratio versus ion intensity data is output as a substance concentration.

8. The system according to claim 1, wherein the mass-to-charge ratio versus ion intensity data is sent to a process monitoring system.

9. The system according to claim 1, wherein the current amplifier includes a known amplifier current decay profile.

10. The system according to claim 9, wherein the current amplifier has an RC equivalent circuit, and the known amplifier current decay profile corresponds to the RC equivalent circuit current decay profile.

11. The system according to claim 10, wherein the equivalent resistor of the RC circuit is between 10 9 ohms and 10 11 ohms.

12. The system according to claim 10, wherein the equivalent capacitor of the RC circuit is between 10 -13 farads and 10 -11 farads.

13. The system according to claim 1, wherein the threshold current is equal to or lower than one standard deviation of the amplifier current.

14. The system according to claim 1, wherein the threshold current is selected by a user.

15. The system according to claim 1, wherein the first time is between 0.01 seconds and 1 second.

16. The system according to claim 1, the system further comprising allowing the amplifier current to stabilize to a background current before setting the mass filter to the first mass filter setting.

17. The system according to claim 1, wherein the mass spectrometer is a magnetic sector mass spectrometer, the mass filter includes a magnetic sector flight tube, the first mass filter setting is a first magnetic field, and the second mass filter setting is a second magnetic field.

18. The system according to claim 1, wherein the mass spectrometer is a quadrupole mass spectrometer, the mass filter includes a quadrupole mass filter, the first mass filter setting is a first quadrupole electric field, and the second mass filter setting is a second quadrupole electric field setting.

19. A method of measuring a mass distribution in a sample, the method comprising: sending an ion beam through a mass filter; setting the mass filter to a first mass filter setting so as to focus a first subset of ions from the ion beam onto a detector; generating a first signal proportional to the first subset of ions focused at the detector; setting the mass filter to a second mass filter setting so as to focus a second subset of ions from the ion beam onto the detector; allowing an amplifier current to stabilize for a first time determined by a threshold current; generating a second signal proportional to the second subset of ions focused at the detector; and using the first mass filter setting and the second mass filter setting and the corresponding first signal and second signal to generate mass-to-charge ratio versus ion intensity data.

20. The method according to claim 19, the method further comprising: setting the mass filter to a third mass filter setting so as to focus a third subset of ions from the ion beam onto the detector; allowing the amplifier current to stabilize for a second time determined by the threshold current; generating a third signal proportional to the third subset of ions focused at the detector; Generate mass-to-charge ratio versus ion intensity data using the third mass filter setting and the corresponding third signal.

21. A non-transitory computer-readable medium comprising instructions that, when executed by one or more hardware processors, cause performance of the operations of claim 19.

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