System for separating an analyte from a sample

Abstract

A system for isolating an analyte from a sample includes an isolator configured to isolate the analyte from the sample, an analyzer configured to obtain a measurement indicative of an amount of the analyte in the sample, wherein the analyzer is downstream of the isolator, a bypass line configured to provide a first fraction of the sample to the analyzer for measurement without passing through the isolator, and a controller. The controller is configured to receive a measurement obtained by the analyzer on the first fraction of the sample received via the bypass line, the measurement indicating that the first fraction of the sample received via the bypass line includes a threshold amount of the analyte. The controller is configured to control activation of the isolator based on the received measurement. The system is configured to provide a second fraction of the sample to the analyzer without passing through the bypass line, and is configured such that the first fraction of the sample reaches the analyzer before the second fraction of the sample reaches the isolator.

Description

Technical Field

[0001] This disclosure relates to a system for separating analytes from a sample. Background Technology

[0002] A separation process is a method of converting a sample (which may be a mixture of substances) into two or more distinct parts. Various instruments exist configured to perform separation processes. Some separation processes utilize differences in the chemical and / or physical properties (e.g., boiling point, melting point, or other chemical properties) between the components of a mixture. Some separation processes use valves or arrangements of valves that physically divide the sample (e.g., to separate the sample temporally and / or spatially) without relying on the sample's chemical and / or physical properties for differentiation.

[0003] Typically, separation is employed to obtain a portion or subset of the original sample that is relatively rich in the class of interest or analyte. When this occurs, another portion of the sample is also produced that is relatively depleted of the analyte. This additional portion may be waste or may include another class of interest. In some cases, the separation process attempts to completely separate the sample into nearly pure, isolated components, while in others, partial separation is acceptable or desirable.

[0004] Scientific and analytical instruments are typically used to characterize the properties of specific classes of matter or analytes of interest. In such instruments, separation can be employed to enhance the obtained measurement results. If an analyte is present in a relatively small amount in a sample (e.g., only 1% of the total sample), any measurement results obtained based on that relatively small amount of analyte may be obscured by interfering elements in the sample (e.g., measurement artifacts due to the other 99% of the sample). Therefore, separation helps reduce the effects of interference or background noise in scientific and analytical instruments.

[0005] Some separation systems use cryogenic traps to separate analytes from samples. For example, US-7,490,506 describes a detector device positioned upstream of a first cooling section of a conduit assembly to allow control of the residence time of the chemical sample fluid flow in one or more cooling sections of the conduit assembly. US-7,490,506 also describes allowing thermal conditioning of the fluid flow eluted from a first GC column from which complete separation of a chemical mixture is desired in a second GC column.

[0006] US-5,720,798 describes the use of an analyte trap. A detector is mounted on the analyte trap to analyze the headspace of a sample passing through the trap. The detector generates control signals to open and close port valves, enabling an analytical procedure known as “center cutting” or “Dean switching,” in which only a portion of the analyte desorbed from the trap is directed to a gas chromatograph for analysis.

[0007] US-10,115,577 describes isotope ratio mass spectrometry. Isotope ratio mass spectrometry is performed by injecting a sample for analysis into a gas chromatographic column; directing the effluent from the gas chromatographic column to a switching arrangement; selecting a configuration of this switching arrangement such that: in a first mode, the effluent from the gas chromatographic column is provided as input to a peak broadener; and in a second mode, the effluent from the peak broadener is provided to the mass spectrometer used for isotope ratio mass spectrometry analysis, without providing the effluent from the gas chromatographic column as input to the peak broadener.

[0008] While known systems for separating samples perform adequately in many scenarios, some suffer from contamination or discard unacceptable amounts of analyte, which is problematic in analytical instruments such as spectroscopy, mass spectrometry (MS), electrochemical analysis, elemental analysis (EA), and thermal analysis. Furthermore, separation systems can be complex and difficult to configure, involving multiple detectors and analyzers, requiring various interacting components and control circuitry. This can lead to multiple potential failure modes. The purpose of this disclosure is to address these and other issues related to separation systems. Summary of the Invention

[0009] In this context and according to the first aspect, a system according to claim 1 is provided. In the second aspect, a method according to claim 30 is provided. Generally, this disclosure provides a system for separating an analyte from a sample, comprising: a separator configured to separate the analyte from the sample; an analyzer configured to obtain a measurement indicating an amount of the analyte in the sample, wherein the analyzer is downstream of the separator; a bypass line configured to provide a first fraction of the sample to the analyzer for measurement without passing through the separator; and a controller configured to: receive a measurement obtained by the analyzer regarding the first fraction of the sample received via the bypass line, the measurement indicating that the first fraction of the sample received via the bypass line includes a threshold amount of the analyte; and control the activation of the separator based on the received measurement.

[0010] One advantage of such systems is that the separation of sample types (e.g., solids, liquids, or gases) can be performed at improved timing due to the bypass line, regardless of sample size. The arrangement disclosed herein provides a system with reduced need for manual optimization of the trapping timing. Furthermore, such systems ensure that the separation timing does not need to be readjusted when the sample size changes, as the bypass line described herein can be used to continuously monitor the presence of the analyte in any sample. Therefore, the systems described herein increase automation, leave less margin for error, and thereby improve the accuracy of measurements. Moreover, a single analyzer can be used to obtain measurements for controlling the separator and to provide analytical measurements, thus eliminating the need for additional upstream detectors. This provides a system that can be manufactured and configured quickly, easily, and cost-effectively.

[0011] The specific analyte of interest is N2, and the timing for its separation is crucial. Because N2 is abundant in the atmosphere, it can cause particular problems by entering the system through small leaks. Therefore, improving the separation timing is highly advantageous when measuring N2. However, interfering peaks are a common problem, and the system described herein can also advantageously separate CO2, CO, SO2, and H2, or various gas mixtures such as CO2 and He. Furthermore, it is also possible to separate SF6, CH4, and NO. x (x = 1, 2 or 0.5), Ar and / or O2. This invention is not limited to gases, but can also separate other forms of matter, such as liquids, solids, slurries and suspensions.

[0012] The system disclosed herein is particularly advantageous in the context of isotope ratio measurements or any other scenario requiring precise control of the sample. Small fractions of the sample received via the bypass (e.g., 1% or 2%) are sufficient to estimate the concentration and activate the separator (especially when using IRMS, due to its high sensitivity), meaning that most samples can be used for accurate measurements, such as isotope ratio measurements. The bypass line described herein helps avoid the loss of the first few seconds of peak arrival in the separator. For example, in isotope ratio mass spectrometry (IRMS) measurements, integration over the entire peak is important for accurate isotope ratio measurements (to prevent fractional separation), therefore the bypass line described herein helps ensure accurate IRMS measurements due to the efficient separation of the sample.

[0013] Throughout this disclosure, the phrase "a portion of the sample" refers to a subset of the sample that has been divided by a separator controlled based on measurements obtained using a bypass line. In contrast, other means of dividing the sample, such as a splitter, are disclosed that are not controlled by a controller in this manner. Throughout this disclosure, these other means of dividing the sample are described as dividing the sample into "fractions of the sample." Thus, in the system of this disclosure, the sample is divided into first and second (or more) fractions. The first fraction of the sample is provided to the analyzer via a bypass line to provide measurements for generating control signals, and the second fraction (or additional fractions) is separated by a separator controlled by such control signals. The separator, controlled by such control signals, causes the second fraction (or multiple fractions) of the sample to be separated into distinct portions (e.g., a first portion and a second portion).

[0014] This disclosure provides several benefits, including: automation of the signal readback-based capture process; capture of sample peaks of different sizes and durations with equal efficiency; a cost-effective, reliable, and relatively inexpensive system because it uses a single analyzer for two purposes; and enhanced ability to separate samples with difficult-to-detect peak tails by using peak height from the monitoring stream to determine the capture time endpoint. These and other advantages of the system described herein will be apparent to those skilled in the art based on the content of this disclosure. Attached Figure Description

[0015] The present disclosure will now be described by way of example with reference to the accompanying drawings, in which:

[0016] Figure 1 A system for separating analytes from a sample according to a first embodiment is schematically shown;

[0017] Figure 2 The elemental analyzer-isotope ratio mass spectrometry (EA-IRMS) setup is illustrated schematically.

[0018] Figure 3 The chromatograms of N2 and CO2 are shown.

[0019] Figure 4 The diagram shows the CO2 peak derived from EA, d 13 A graph showing the change of C value over capture time;

[0020] Figure 5 The N2 background in IRMS signals without trapping is shown;

[0021] Figure 6 The N2 background in the captured IRMS signal is shown;

[0022] Figure 7A system for separating analytes from a sample according to a second embodiment is schematically shown;

[0023] Figure 8 A system for separating analytes from a sample according to a third embodiment is schematically shown;

[0024] Figure 9 A diagram illustrating the selectivity of sector field IRMS by considering EA analysis using gas chromatography (GC) separation is shown;

[0025] Figure 10 A shunt is schematically illustrated for use in any of the embodiments described herein; and

[0026] Figure 11 A system for separating analytes from a sample according to a fourth embodiment is schematically shown. Detailed Implementation

[0027] exist Figure 1 The image shows a system 100 for separating analytes from a sample according to a first embodiment. System 100 includes a plurality of conduits 101-105 through which the sample passes when separated by system 100. The system includes a separator 130 for separating analytes from the sample and an analyzer 140 for measuring the sample. The system also includes a controller 150 capable of controlling the separator 130 and receiving measurement results from the analyzer 140.

[0028] Specifically, the system includes a first conduit 101 that receives a sample from a sample source (not depicted). The first conduit 101 guides the sample to a second conduit 102 and a third conduit 103. The third conduit 103 delivers a first fraction of the sample directly to the analyzer 140 without passing through the separator 130, while the second conduit 102 delivers a second fraction of the sample to the separator 130.

[0029] Two additional conduits are connected to separator 130. A fourth conduit 104 delivers a portion of the sample produced from separator 130 to analyzer 140. A fifth conduit 105 can be used to deliver another portion of the sample produced from separator 130 elsewhere. For example, the fifth conduit 105 can be used to discard certain items that are not intended to be delivered to analyzer 140.

[0030] In use, the sample passes through the first conduit 101, and the first fraction of the sample is delivered to the analyzer 140 for measurement via the third conduit 103 without passing through the separator 130. Therefore, the third conduit 103 acts as a bypass line, allowing the analyzer 140 to measure and monitor the flow. The analyzer 140 performs a measurement on the first fraction of the sample, which provides an indication of how much of a particular analyte is present in the sample received via the third conduit 103. This measurement result is transmitted to the controller 150, as indicated by the arrow between the analyzer 140 and the controller 150. The controller 150 uses the received measurement result to control the operation of the separator 130, as indicated by the arrow between the controller 150 and the separator 130. For example, the controller 150 can activate or deactivate the separator 130. Furthermore, the controller can adjust the activation level of the separator 130 based on the measurement result received from the analyzer 140 (e.g., to change the separator 130 from a state of maximum or minimum activation to a state of partial activation).

[0031] As the first fraction of the sample passes through the first conduit 101 and enters the third conduit 103, the second fraction of the sample is directly delivered to the separator 130 via the second conduit 102. Generally, the system described herein may include a splitter located upstream of the separator, analyzer, and bypass line. This splitter may be configured to split the sample into a first fraction and a second fraction. Various splitting devices may be used.

[0032] When activated, separator 130 is used to perform a second-stage separation of the sample into two parts. The activation of separator 130, and thus the number and composition of the two parts, are controlled by controller 150. Separator 130 can be deactivated when certain control signals are received from controller 150.

[0033] The fourth conduit 104 delivers a portion of the sample produced from the separator 130 to the analyzer 140 for measurement. The fifth conduit 105 delivers another portion of the sample produced from the separator 130 for disposal, storage elsewhere, or delivery for analysis elsewhere. In any case, the fifth conduit 105 removes a portion of the sample produced from the separator 130 from the system 100.

[0034] Figure 1 System 100 can be used in a variety of ways for advantageous effects. For example, using a third conduit 103 as a bypass line allows for measurements of a relatively small amount of sample to generate a control signal. This control signal can be used to provide precise control of the operation of separator 130 using a single analyzer 140, without the need for an additional upstream analyzer (which may also be referred to herein as a detector) to provide the control signal.

[0035] In some instruments, it may be important to analyze the peak leading edge of an analyte or to ensure that all analytes are analyzed without introducing unnecessary background measurements. Therefore, in such cases, it is advantageous to ensure that separation begins as soon as feasible, so as to ensure that the analyte is separated from the sample once it is present in the stream received at analyzer 140. The bypass line of this disclosure can help ensure that separator 130 is activated as soon as a specific measurement is received from analyzer 140. In such cases, system 100 can be configured such that the first fraction of the sample arrives at analyzer 140 before the second fraction of the sample arrives at separator 130. In this way, a control signal that causes separator 130 to be rapidly activated can be provided using a possibly small amount of sample received at analyzer 140 via third conduit 103. For example, once a small amount of analyte is detected in the first fraction of the sample, controller 150 can induce activation of separator 130 based on the measurement received from analyzer 140 or multiple measurements. Without a bypass line, the analyte will pass through the deactivated separator 130 and then be analyzed by the analyzer 140, during which time some analytes will be unnecessarily lost.

[0036] Therefore, in general, the system described herein can be configured to provide the second fraction of the sample to the analyzer without bypassing the bypass line. The system can be configured such that the second fraction of the sample passes through a separator (and is divided into different portions by the separator). In such systems, it is advantageous to ensure that the first fraction of the sample arrives at the analyzer before the second fraction of the sample reaches the separator, thereby allowing for accurate timing of the activation and / or deactivation of the separator. This can be achieved, for example, by providing a long delay line (such as a long conduit) (e.g., by ensuring that conduit 102 is sufficiently long).

[0037] Furthermore, some types of separators 130 may introduce measurement errors, and therefore it may be advantageous to ensure that separation is stopped immediately once a measurement is performed. For example, it may be desirable to stop separation to prevent the sample from being contaminated by separator 130. Thus, once a satisfactory measurement result has been obtained by analyzer 140 (e.g., a measurement result with acceptable statistical significance, or a measurement result for an acceptable high proportion of a specific analyte peak), controller 150 may deactivate separator 130 to prevent further separation based on the measurement result (or multiple measurement results) received from analyzer 140. Alternatively, in some scenarios, the composition of the sample changes over time, and it may be desirable to analyze the sample only within a specific time window. System 100 allows this to be achieved. For example, if the measurement result indicates that the composition of the sample has changed over time (e.g., indicating that it is being contaminated), measurement and separation may be stopped to prevent further changes in the composition of the sample from affecting the resulting measurement results.

[0038] therefore, Figure 1 System 100 uses an analyzer 140 to perform the function of generating control signals for separator 130 and obtaining measurement results for the analyte. System 100 can be used to ensure that the timing of separator activation and / or deactivation is automatically adapted to the specific analyte of interest without the need for an additional detector. Furthermore, Figure 1 System 100 can reduce contamination without requiring additional detectors.

[0039] Generally, a controller can be configured to: receive multiple measurements of a first fraction of a sample obtained by the analyzer at different times; and control the activation of the separator based on each of the received measurements. For example, the controller described herein can be configured to activate the separator at a first time and deactivate it at a second time. The controller can be configured to activate the separator based on a first received measurement indicating that the first fraction of the sample includes at least a lower threshold amount of analyte; and the controller can be configured to deactivate the separator based on a second received measurement received after the first received measurement, indicating that the first fraction of the sample includes an amount of analyte less than or equal to an upper threshold amount. Thus, precise activation and deactivation of the separator can be achieved, enabling the separation of analytes while reducing the risk of contamination. Controlling the activation of the separator can include activating the separator, deactivating the separator, or changing the degree of activation of the separator (e.g., changing the separator from fully activated / deactivated to partially activated, or changing the activation from partially activated to fully activated / deactivated). In the case of a cryogenic trap, controlling the activation of the cryogenic trap may involve raising a conduit (e.g., a fitting) from liquid N2 (or any other substance suitable for cooling) or lowering the conduit (e.g., a fitting) into it, or changing the height of the conduit within the cooling substance.

[0040] It should be understood that... Figure 1 The system can be modified in several ways. For example, the fifth catheter 105 is optional and can be omitted. In some cases, temporary separation of the sample is advantageous, and it is not necessary to discard waste or transport a portion of the sample elsewhere. Alternatively, Figure 1 System 100 includes only one analyzer 140, but additional analyzers can be placed downstream of the fifth conduit 105. Therefore, a cascaded arrangement of separators can be provided, each separator controlled by a controller based on measurements received via a corresponding bypass line. This arrangement in... Figure 11 As shown in the diagram, this will be described in further detail below.

[0041] The conduits 101-105 of system 100 can be any structure suitable for conveying a sample or at least a fraction or portion of a sample between different components of the system. For example, conduits 101-105 can be tubes, pipes, channels, hoses, fittings, or any combination thereof. For brevity, a detailed discussion of conduits is omitted in the subsequent embodiments described herein. However, it should be understood that when a sample, a fraction of a sample, or a portion of a sample is described as moving between two components, a suitable conduit may be provided between the two components. System 100 is capable of separating various types of samples, such as solids, liquids, or gases. Samples may also be combinations of substance types, such as suspensions, slurries, or aerosols. In some cases, solids (e.g., particles, grains, or seeds) may be conveyed (e.g., on a conveyor belt) and separated using the system described herein, wherein a fraction of these solids is carried to the analyzer via a bypass line and another fraction is separated by a separator. In such cases, a conveyor belt system may be used instead of conduits.

[0042] One particular scenario in which a system similar to System 100 can be advantageously used is gas isotope ratio mass spectrometry-elemental analysis. For example, some embodiments of this disclosure involve introducing gaseous samples into an isotope ratio mass spectrometer (IRMS). Typical samples include substances such as CO2, N2, CO, SO2, and H2, in pure form and gaseous mixtures, such as CO2 in He.

[0043] Typically, these gaseous substances are generated from solid or liquid samples through oxidation and / or reduction, pyrolysis, or other chemical processes. Such preparation equipment is commercially available and allows coupling of elemental analyzers (EAs) or gas and liquid chromatographs with IRMS. Examples of equipment providing this capability include the EA IsoLink, LC IsoLink, GC IsoLink II, KielIV carbonate, and GasBench II devices, all manufactured by Thermo Fisher Scientific. TMProvided. For the sake of brevity, this disclosure focuses on EA-IRMS coupling, but it should be noted that various aspects of this disclosure can be used in other environments and are certainly not limited to EA. For example, embodiments of this disclosure can be used with a variety of other peripheral devices. For example, embodiments of this disclosure can be provided in combination with any one or more of the following: a sample preparation apparatus configured to provide a sample to a separator and bypass line; an elemental analyzer-isotope ratio mass spectrometry system (EA-IRMS); an automated carbonate reaction apparatus; an analyte source configured to provide analyte peaks (e.g., in a pulsed manner), preferably wherein the analyte source includes any one or more of the following: a trap; a cryogenic trap; a valve; a gas chromatograph; a liquid chromatograph; a washer; an ion chromatography apparatus; a capillary electrophoresis apparatus or a capillary electrochromatograph; a distillation apparatus; a loop injector; a laser ablation device; a temperature-converting elemental analyzer (TC / EA); and / or headspace vials.

[0044] In many cases, a carrier gas is needed to transport the sample material into the preparation apparatus and into the IRMS, which is called continuous flow IRMS (cf IRMS). In cf IRMS, a continuous stream of inert gas is fed into the IRMS source, carrying the gaseous sample material. The carrier gas flow rate inside the sample preparation apparatus depends on the precise design of the apparatus, but is typically in the range of 1 mL / min to 200 mL / min. For example, EA IsoLink CNS performs combustion of solid or liquid samples in a first reactor containing a catalyst such as WO3. The resulting materials (primarily CO2, N2, NO) are then processed. x NO and SO2 are fed to the second reactor via a He flow of 50 mL / min (range 10 mL / min-180 mL / min), where NO is reacted on copper. x It is reduced to N2. Both reactor materials can also be present in a combined reactor. In general, the system described herein can be a continuous flow device, and the bypass line described herein can be configured to continuously supply the first fraction of the sample to the analyzer for measurement without passing through a separator.

[0045] The isotope ratios of gases N2 and CO2 were measured using IRMS and corresponded to the isotope ratios of the corresponding elements in the sample. Figure 2 The schematic elemental analyzer-isotope ratio mass spectrometry (EA-IRMS) setup is shown. The sample is combusted (oxidized) in the first reactor 280, and the selected species are analyzed in the second reactor (NO). xReduction was performed in 290. The substances were promptly separated by gas chromatography (GC) 230 and provided to IRMS 240 via ConFlo IV apparatus 245. ConFlo IV apparatus 245 is used by Thermo Fisher Scientific. TM The series of advanced IRMS detectors features a continuous flow interface that allows connection of two high-flow-rate peripherals (e.g., EA or temperature converter / EA) plus one low-flow-rate peripheral (e.g., GC-C / TC (GC-combustion) and / or high-temperature converters such as GasBench II or LC IsoLink). ConFlo IV uses techniques such as open-loop splitting to reduce the gas flow from these peripherals to a range that can be handled by the IRMS240 (<1 mL / min). Additionally, ConFlo IV provides the possibility of isotope reference gas and sample gas dilution with helium. Embodiments of this disclosure recognize that, with Figure 2 Compared to other systems, low-flow lines can be used for control, and even with control via low-flow lines, the open shunt design still results in virtually zero loss of sensitivity.

[0046] Sector-field IRMS (SF-IRMS) can measure only one class of matter at a time, thus allowing for the initial separation of individual sample classes. In EA IsoLink, this is achieved by applying gas chromatography to separate N2, CO2, and SO2 in real time. The IRMS is configured to reflect the different masses of isotopes of the three classes, simultaneously obtaining chromatograms. Figure 3 The N2 and CO2 chromatograms of 150 μg of urea are shown. Figure 3 The square pulse in the image represents the IRMS reference gas.

[0047] Because the IRMS source must be maintained under high vacuum, the flow rate of the support into the source should be in the range of <1 mL / min along with helium. In the case of EA IsoLink, the gas flow after GC separation is still significantly higher than this flow rate. Therefore, only a small portion of the support / sample mixture can be fed into the ion source. This can be achieved through several measures, such as: splitting some of the gas upstream of the GC; splitting some of the gas downstream of the GC (e.g., for EA IsoLink, using a 1:10 split between the EA outlet and the ConFlo inlet); or feeding the gas into an open split inside the ConFlo IV and “drawing” the gas in from the open split via the source capillary, instead of connecting the GC outlet directly to the ion source. All these measures result in a decrease in the overall sensitivity of the setup because sample loss is inevitable before IRMS analysis.

[0048] An alternative to splitting a portion of the gas stream is to reduce its flow rate without sacrificing the sample. For EA IsoLink, this can be achieved by reducing the carrier flow rate once the sample gaseous class is loaded into the GC. Another option is to avoid gas chromatography separation altogether, for example, by trapping or cryogenic trapping. In the case of cryogenic trapping, the boiling point of the individual sample classes is used for their separation, rather than their retention time. The carrier is fed through one or more “traps,” which can be glass tubing, stainless steel sections, or fused silica tubing. These traps are cooled to temperatures below the boiling point of the gas, causing them to condense. Depending on the corresponding boiling point, different cooling methods are used, such as Peltier coolers, some mixtures such as dry ice / acetone, but most often liquid nitrogen. Furthermore, depending on the boiling point, some gases may require the traps to be filled with adsorbent. For example, while N2 cannot be effectively condensed using liquid nitrogen (LN2), it can be quantitatively adsorbed onto silica gel at -169°C. By using a combination of traps and / or temperature, gaseous substances such as N2, CO2, and SO2 can be removed from the carrier stream and selectively reintroduced by increasing the temperature of the respective traps again.

[0049] One advantage of the trapping method is the reduction in carrier gas flow during sample release from the trap. For example, gaseous substances can be present with a carrier flow of 50 mL / min after the reduction reactor. This carrier can be fed through a steel tube immersed in LN2, resulting in CO2 condensation (bp = -78 °C). After a period of time, the carrier flow is reduced to 10 mL / min, and the trap is removed from LN2. CO2 evaporates, and the sensitivity of the measurement can be increased because less gas flow needs to be separated before IRMS. Combinations of elemental analysis and cryogenic trapping, including the reduction of carrier flow, have been previously described in the literature (see, for example, Fry et al., RCMS10 (1996) 953-958).

[0050] Another option is described in WO-2021 / 061904. Here, the substances N2, CO2, and SO2 are separated by gas chromatography in the first step, but CO2 and SO2 are then cryogenically captured using liquid nitrogen. N2 is captured on silica gel at -169°C. The sample substances are delivered out of the trap using a flow rate of 10 mL / min. The setup described in this application is specifically designed for the analysis of small samples (“nano EA”), and therefore requires a gain in sensitivity. Some embodiments of this disclosure are also used in nano EA applications. However, it should be understood that this disclosure can be used without the use of EA, such as in Figure 7 The simplified setup shown is discussed in further detail below.

[0051] While such systems and methods offer increased sensitivity, cryogenic trapping has two significant drawbacks: sensitivity to support background and the need for quantitative trapping of sample gaseous components, particularly for some applications (e.g., isotope ratio analysis). These two issues are interrelated. The isotope ratios of samples exiting the GC vary throughout the peak. Similar behavior can be expected at the exit of the EA or other peripheral equipment. Therefore, for isotope ratio analysis, it is advantageous to consider the full peak area to obtain reliable and accurate results. When performing cryogenic trapping, reliable results are obtained if the trapping begins before the sample peaks reach the trap and ends only when all peaks have been captured. This is in Figure 4 As shown in the diagram. Below a certain value, the capture time cannot be further shortened because this affects the isotope ratio (d). 13 (C value). In Figure 4 In the middle, d 13 The C value varies with the incomplete capture of the CO2 peak derived from EA. When the capture time is greater than 290 s, the peak is completely captured and d 13 C remains approximately constant.

[0052] In practice, the full peak area is traditionally accounted for using very long trapping times, resulting in the trapping time for gaseous compounds being significantly longer than the peak base width. However, if the sample compounds are also present as contaminants in the carrier (i.e., the sample and background are the same), they are trapped along with molecules from the sample. This is of particular concern in the case of N2, which can enter the analyzer's carrier stream from the atmosphere through various small leaks in the system. Without trapping, the N2 background is almost negligible because an increase of a few mV in the IRMS baseline signal can be considered constant and virtually imperceptible. Figure 5 As shown. The sample peak is above this baseline, and can be easily subtracted if necessary. Specifically, Figure 5 The effect of background on EA with chromatographic N2 and CO2 separation is shown. The N2 peak shown is located above the instrument background of approximately 14 mV (m / z = 28), and this peak can be easily subtracted.

[0053] However, when using trapping, the N2 background results in a separate peak (described as a blank) that lies directly below the sample peak. In this case, simple subtraction is not straightforward. Figure 6 The effect of blanks is shown in the diagram. Figure 6 In the above data, data are from a nano-EA setup with trapping, without sample introduction (shown here as m / z = 28). The visible peaks are attributed solely to trace amounts of N2 present in the support. Subtracting the blank peak from the sample peak is not direct and may complicate measurements and / or reduce accuracy.

[0054] The contribution of the blank space is proportional to the background (i.e., the amount of pollutants present in the carrier) and the capture time, and can be calculated as follows:

[0055] Blank space (Vs) = Background (V) × Capture time (s)

[0056] If background cannot be further reduced, it is desirable to use the shortest possible capture time (to reduce blank contribution), but a sufficiently long capture time to avoid incomplete capture of sample classes (which would lead to fractional separation, such as...). Figure 4 (As shown and described above).

[0057] This situation is further complicated by the fact that peak width depends on the sample amount. Therefore, large samples will result in broad peaks, requiring long capture times. However, such long capture times will be detrimental to the blank, which will be even more significant if small samples are measured (because the relative contribution of the blank to the peak becomes more pronounced). Therefore, the embodiments of this disclosure address these problems because they allow capture to begin at the correct time (only before the peak reaches the trap) and to stop capture once the peak is fully captured (but without any longer capture time than necessary).

[0058] exist Figure 7 The image shows a system 700 for separating analytes from a sample according to a second embodiment. System 700 is similar in some respects to... Figure 1 The system 100 is described, and for brevity, discussion of similar features is omitted. System 700 includes a sample preparation device 760 that provides a first-stage sample to a bypass line 703 (which is similar to...). Figure 1 The third conduit 103) and the second fraction of the sample are provided to the separator 730, which in this embodiment is a cryogenic trap (although other types of separators may be used).

[0059] System 700 also includes an analyzer 740 located downstream of separator 730. Analyzer 740 determines when peaks of sample classes are present in the first fraction of the sample received via bypass line 703. The sample is fed to analyzer 740 via interface 745 (e.g., a ConFlo IV device), which may have two ports for providing analyzer 740 with the first fraction of the sample received via bypass line 703 and the second fraction of the sample received via separator 730.

[0060] The cryogenic trap 730 is operated using the readout from analyzer 740 (via the controller, not shown for simplicity) using the following control method:

[0061] (i) When the analyzer 740 detects the analyte in the carrier → capture begins;

[0062] (ii) When the analyzer 740 stops detecting the analyte in the carrier, the capture ends.

[0063] In this way, precise timing control of the activation and deactivation of the cryogenic trap 730 can be achieved. In a general sense, step (i) can be considered as the controller being configured to activate the separator based on a received measurement indicating that the first fraction of the sample includes an analyte amount greater than or equal to the lower threshold. Step (ii) can be considered as the controller being configured to deactivate the separator based on a received measurement indicating that the first fraction of the sample includes an analyte amount less than or equal to the upper threshold. The thresholds used for activation and deactivation can be the same or different. Activation of the separator can be achieved when the analyte signal is at least 2, 3, 4, or 5 standard deviations higher than the blank or background signal. A preferred threshold is 3 standard deviations, which provides an acceptable balance between the statistical certainty of peak initiation and rapid detection of the analyte. The same threshold can be used when deactivating the separator.

[0064] In a variation of this control method, analyzer 740 senses the amount of sample (e.g., using detector signal height) and uses that reading to calculate the expected width or duration of the peak. This method uses a ratio (or another relationship) between signal height and peak width, and can be advantageous if the detector sensitivity is too low to reliably detect the end of the peak. It can also be advantageous if the sample peak has a pronounced tail, where the “peak end” is difficult to detect, particularly when determining the peak height from a relatively small monitoring flow received via bypass line 703.

[0065] Generally, in this variant, the controller can be configured to: determine a time period based on the received measurement results; and deactivate the separator after the determined time period. This time period can be based on: the intensity of the received measurement results (e.g., peak height); and / or a calibration peak with a known relationship between the measured intensity and peak width. Therefore, the deactivation time of the trap can be advantageously controlled even when it is difficult to detect where the peak ends. Such a known relationship between the measured intensity and peak width can be determined using calibration samples, and the results of such calibration can be stored by the controller. Generally, the controller can be configured to: identify peaks with peak heights (e.g., local maxima in the measured signal intensity) based on the received measurement results. The controller can then be configured to determine the value of a time period corresponding to the predicted peak width of the peak based on the peak height. For example, the time period can be set to be equal to or approximately equal to the possible duration of a peak with the identified peak height (e.g., differing from the possible duration of a peak with the identified peak height by no more than a certain amount). In this way, the relationship between typical peak shapes (i.e., the typical relationship between signal intensity and time) can be used to determine when to deactivate the separator.

[0066] The high sensitivity of the analyzer 740 is advantageous, for example, having a detection limit of less than 1 ppb. For instance, in some cases, it might be desirable to be able to achieve a detection limit of 3 × 10⁻⁶. 8 A 10mV N2 signal was observed on the ohm amplifier, which is equivalent to 3 × 10⁻⁶ per second. -11 A current or 2×10 8 2 / 3 of the N2 molecules were observed not entering the MS source from the monitoring stream, therefore approximately 6 × 10⁻⁶ N₂ molecules were required. 8 One molecule or 2.7 × 10 -17 kg. At a flow rate of 200 mL / min, this amount is present in 3.3 mL of He (or 6 × 10⁻⁶ kg / min). -7 In kg), therefore <1×10 -10 The sensitivity may be advantageous, although it should be understood that lower (or higher) sensitivity may be required when considering other analytes and flow rates. High sensitivity is advantageous because trapping is useful for small samples in which very little analyte is expected to be present (e.g., for EA containing a few hundred ng of material per sample). One example of an analyzer 740 that can be used in embodiments of this disclosure is an electron capture detector (ECD) with high sensitivity at least for N2. However, ECDs are expensive and (typically) work with radioactive sources, limiting their applicability. In some embodiments, using a non-destructive detector as analyzer 740 may be useful, allowing the sample to be used after it has already been analyzed. However, the monitoring flow provided by the bypass line 703 can be delivered to a highly sensitive but destructive detector, such as a mass spectrometer.

[0067] The monitoring flow rate in the system described herein is typically much smaller than the carrier flow rate entering the separator or trap (e.g., 1 mL / min to the detector, 50 mL / min to the trap). Therefore, in the system described herein, the first fraction of the sample (for the monitoring flow via the bypass line) may include a first percentage of the sample (typically a volume percentage, but this percentage can be by weight) that is: less than or equal to 1%; less than or equal to 2%; less than or equal to 5%; or less than or equal to 10%. Therefore, the second fraction of the sample may include a second percentage of the sample (again typically a volume percentage, but this percentage can be by weight) that is: greater than or equal to 90%; greater than or equal to 95%; greater than or equal to 98%; or greater than or equal to 99%. Thus, a large portion of the sample can be provided to the analyzer without passing through the bypass line. Therefore, accurate measurements can be made without wasting a large amount of sample on the generation of control signals.

[0068] exist Figure 7 In system 700, separator 730 is a trap, which in this case comprises tubing immersed in liquid nitrogen (LN2). If analyzer 740 detects the presence of an analyte in the monitoring stream, the tubing is lowered into LN2 to immediately activate separator 730, thereby ensuring that only a small fraction of the analyte passes through the separator when it is not activated. Sample particles are trapped by activation of cryogenic trap 730. Activation of cryogenic trap 730 causes it to separate the second fraction of the sample (i.e., the fraction received without passing through bypass line 703) into a trapped first fraction and an untrapped second fraction. This process continues as long as analyzer 740 detects the presence of an analyte. Once analyzer 740 detects the presence of no more than a certain amount of analyte from the monitoring stream received via bypass line 703, the tubing can be raised from LN2, releasing the trapped first fraction of the analyte into analyzer 740 for measurement. Therefore, the bypass line 703 is used to provide improved timing control of the activation of the separator 730, wherein the monitoring flow received via the bypass line 703 is used to determine when the separator 730 should be activated and deactivated. In this way, very little analyte loss (due to the precise timing of activation) is achieved, while reducing the risk of sample contamination (e.g., by allowing the separator to operate for longer than necessary).

[0069] It should be understood that... Figure 7System 700 can be modified in many ways. The sample preparation apparatus can be an elemental analyzer (with or without a subsequent GC), but it can also be another device such as GasBench II. Furthermore, if it is necessary to detect sample peaks in the monitoring stream, analyzer 740 can be equipped with a set of amplifiers. Additionally, although separator 730 is shown as a cryogenic trap, other separators can also be used. Furthermore, analyzer 740 is described as an IRMS, but various other types of analyzers can be used. If analyzer 740 itself includes appropriate ports for receiving samples from various components of system 700, such as separator 730 and bypass line 703, the interface 745 for analyzer 740 can be completely omitted.

[0070] exist Figure 8 The image shows a system 800 for separating analytes from a sample according to a third embodiment. System 800 includes a sample preparation apparatus 860, a bypass line 803, a separator 830 (a trap in this embodiment), an analyzer 840, and an interface 845 for the analyzer 840. These operate similarly to the aforementioned components of the first and second embodiments. As previously described, the bypass line 803 is used to monitor the amount of analyte within the sample. This bypass line provides improved control over the timing of the activation of the separator 830, wherein the monitoring flow received via the bypass line 803 is used to determine when the separator 830 should be activated and deactivated. In this way, very little analyte loss (due to precise timing of activation) is achieved, while reducing the risk of sample contamination (e.g., by allowing the separator to operate for longer than necessary).

[0071] Figure 8 The motivation for system 800 is that, in some cases, the detector may not provide sufficient selectivity for the species to be captured. For example, CO2 and N2 can be generated in an EA designed for capturing N2. The abundance sensitivity of the sector-field MS may not allow for complete differentiation of N2 from CO2, and a common peak of the two species may be detected. In such cases, further separation of the respective species can be achieved. This can be achieved by placing a GC 831, a cryogenic trap 832, and / or a selective trap 833 (which constitutes an additional separator) upstream of detector 840 to remove interfering species (or at least reduce their influence). Therefore, Figure 8The system 800 includes more than one separator. In general, the system described herein may include one or more additional separators. At least one additional separator may be located upstream of a bypass line. Preferably, at least two additional separators (e.g., GC and a cryogenic trap, although various other combinations may be used depending on the specific analyte) are located upstream of the bypass line. Furthermore, in some cases, the bypass line may include at least one additional separator, which may be a trap or a selective trap (e.g., a chemical trap). When using multiple separators, the controller described herein may be configured to control the activation of one, several, or all of the separators based on measurements received from the analyzer.

[0072] The multi-port valve within system 800 can be used to redirect the gas flow to the correct trap and pass the carrier feed through various traps. By providing GC 831 and / or cryogenic trap 832 upstream of the monitoring flow split point, CO2 can be prevented from entering the monitoring flow, while monitoring is performed only for N2. Therefore, the control signal provided based on the monitoring flow can be significantly improved.

[0073] System 800 can be configured such that the sample reaches the trap 830 after it has been sensed in the monitoring stream. If the sample reaches the trap 830 before it has been sensed in the monitoring stream, the trap 830 may decelerate too late. Therefore, as a mitigation, a delay line 870, such as a long capillary (e.g., several meters in length), can be installed between the shunt point (the point where the bypass line 803 begins) and the separator 830. The capillary serves as a delay and can be used in a manner similar to that described in US-8,402,814B2 regarding intelligent EAs. The entire contents of US-8,402,814B2, and in particular the long capillary described herein, are incorporated herein by reference.

[0074] Returning to the broader terminology used previously, the systems described herein may include a delay line configured to delay a second fraction of the sample relative to a first fraction of the sample. Such a delay line may include a capillary (e.g., a silica fitting) sized (i.e., long enough to provide a perceptible delay) to delay the second fraction of the sample relative to the first fraction of the sample. The precise dimensions of the delay line will depend on the total flow rate within the system and the relative amount of sample flowing through the bypass line and reaching the separator. It should be understood that the precise configuration of the delay line can be modified to provide a desired level of delay. The delay line may provide a fixed delay or an adjustable delay. Alternatively, the systems described herein may be configured such that the first fraction of the sample reaches the analyzer before the second fraction of the sample reaches the separator without the use of a delay line.

[0075] The system 800 uses an IRMS 840 to detect the presence of the analyte before trapping occurs. This has at least two main advantages. First, the IRMS 840 has been provided for the purpose of performing isotope ratio measurements. Furthermore, the IRMS 840 is not only highly sensitive to N2. That is, the mass spectrometer is a destructive detector, thus resulting in some sample loss, but this is acceptable in many contexts. Due to the extremely high sensitivity of the analyzer 840, a control signal for the separator 830 can be reliably generated using only a very small fraction of the carrier gas flow (i.e., the first fraction received via bypass line 803), which is split for MS analysis and results in only a small sample loss. Such a bypass line 803 can be used from a total flow of 50 mL / min at approximately 1 mL / min (monitoring flow rate) via interface 845 (which is... Figure 8 The ConFlo IV device (in which the feed is fed) is fed into the IRMS 840. Interface 845 has two inputs for a flow rate of approximately 10 mL / min (high flow rate) and a single input for a low flow rate (1 mL / min). Switching between the inputs can be performed within seconds. The output of the trap 830 is connected to one of the high flow rate inputs of interface 845, while the monitored flow rate is fed into the low flow rate input.

[0076] like Figure 9 As shown, since the abundance sensitivity of a single focused SF-IRMS may not allow for reliable differentiation between various species (such as N2 and CO2), the GC column 831 and / or cryogenic trap 832 can be placed downstream of the preparation apparatus 860. Specifically, in Figure 9 The reduced selectivity of SF-IRMS can be seen by considering EA analysis of a 188 μg caffeine sample with GC separation. Although operating at m / z = 28 (i.e., targeting N2), the CO2 peak is visible, even though CO2 has m / z = 44. This is due to the dissociation of CO2, leading to the formation of CO, O2, and C through various interactions, and CO happens to have m / z = 28, the same as N2. Therefore, this disclosure is particularly advantageous in scenarios where CO2 and N2 may interfere. However, it should be understood that a large number of interfering substances exist, and therefore the invention is not limited to the use of N2 or CO2.

[0077] Additionally or alternatively, trap 833 (which, in addition to trap 830, which also acts as a separator, can be considered an additional separator) may also be placed in the monitoring stream of bypass line 803. In this case, CO2 can be removed by a selective chemical trap (which may be irreversible, such as Ascarite (RTM), which is silica coated with sodium hydroxide that can be used as a carbon dioxide adsorbent). Therefore, the accuracy of the control signal provided based on the monitoring stream is increased due to the elimination or reduction of contaminants in the monitoring stream. In the general terminology previously used, a separator may include a selective trap or a chemical trap. The bypass line may include such a separator. Specifically, the bypass line of this disclosure may include an additional separator, which may be a trap, such as a cryogenic trap, a selective trap, or a chemical trap.

[0078] In use, Figure 8 The system 800 operates as follows. At the start of the measurement, the IRMS 840 is set according to the mass of the corresponding analyte (e.g., N2: m / z = 28, 29, 30, to indicate isotopic variants), and the low-flow (LF) port of interface 845 is opened. Once the IRMS 840 detects a significant increase in signal, it activates the trap 830 by reducing it to LN2, and thus collects the analyte. Simultaneously, any gas entering the high-flow (HF) port of interface 845 is vented to discard a portion of the sample that passed through the trap 830 when it is activated. Therefore, in general, the system described herein may also include an outlet (e.g., a vent), and the controller is configured such that the outlet discards (e.g., drains) or delivers (e.g., to another separator or another analyzer) a second fraction of the sample that passed through the separator when it is activated.

[0079] When the analyte is no longer detected by IRMS 840, the port of interface 845 is changed to the HF port, the trap 830 is raised to deactivate the trap, and thus the evaporated analyte is released from the trap 830 and transported to interface 845 with a (reduced, approximately 10 mL / min) inert gas stream.

[0080] Therefore, returning to the previously used general terminology, in a system where the separator includes a trap, the controller can be configured to deactivate the trap to release the second fraction of the sample to the analyzer based on a received measurement indicating that the first fraction of the sample contains an analyte amount less than or equal to an upper threshold. Thus, the majority of the sample can only be released for measurement if it has been sufficiently trapped and separated. When using an interface including a first port and a second port, the first port can be configured to receive the first fraction of the sample and provide it to the analyzer; and the second port is configured to receive the second fraction of the sample and provide it to the analyzer. The controller can be configured to deactivate the first port and activate the second port when (e.g., only when) the received measurement indicates that the first fraction of the sample contains an analyte amount less than or equal to an upper threshold. The first port can be a low-flow port, and the second port can be a high-flow port. For example, a low-flow port may not be able to or suitable for receiving the same flow rate as a high-flow port. In other words, the first port may be able to handle relatively low flow rates, while the second port may be able to handle relatively high flow rates.

[0081] It should be understood that... Figure 8 The implementation scheme can be modified in many ways. For example, optionally, if it is necessary to detect sample peaks in the monitoring stream, the analyzer 840 may be equipped with a set of amplifiers. Thus, in general, the system described herein may include one or more amplifiers configured to amplify measurements obtained by the analyzer with respect to: the first fraction of the sample; and / or the second fraction of the sample. Furthermore, although the separator 830 is shown as a cryogenic trap, other separators may also be used. The separator may be a valve (such as a 3-way valve, 4-way valve, 5-way valve, or 6-way valve). In some cases, the separator 830 may include a loop with the valve. For example, analyte peaks arriving at such a valve may be loaded into the loop and flushed out into the analyzer 840 at a lower flow rate. Additionally or alternatively, the separator 830 may include a GC. Once the analyte is in the GC column, the carrier flow rate decreases, thus increasing the concentration of the analyte in the carrier. Simultaneously increasing the GC temperature can be used to counteract peak broadening. GB2537915B describes a system for concentrating analyte gas in a gas stream of an analytical system, and it should be understood that the system described therein may be used in this disclosure.

[0082] Additionally, analyzer 840 is described as an IRMS, but various other types of analyzers can be used. If analyzer 840 is capable of receiving samples from various components of system 800, interface 845 for analyzer 840 may be omitted in some cases.

[0083] Next turn Figure 10A splitter 1000 is shown in systems 100, 700, 800, and 1100 applicable to the first, second, third, and fourth embodiments. In each case, a bypass line delivers a primary fraction of the sample to the analyzer without passing through a detector. To achieve this, a splitter 1000 in the carrier stream can be used. This splitter 1000 can also be used to remove waste from the separator of previous embodiments.

[0084] The shunt may be formed as part of the catheter system described with respect to the first embodiment. The shunt may be integrally formed with the aforementioned catheter, or it may be configured for attachment to the aforementioned catheter. Figure 10 In this design, the splitter includes a first conduit 1001 that receives a sample (e.g., from a sample preparation device) and supplies a first fraction of the sample to a second conduit 1002 and a second fraction of the sample to a third conduit 1003. Thus, the splitter 1000 acts as a fork in the sample flow, dividing the sample into fractions. It should be understood that the splitter 1000 may include valves and may be controllable and adjustable to allow adjustment of the relative flow rates in the second and third conduits 1002 and 1003. Furthermore, the splitter 1000 is shown as having three conduits of substantially equal diameter, but the conduits may have different diameters to provide different flow rates through each respective conduit.

[0085] Next turn Figure 11 A system 1100 for separating one or more analytes from a sample, according to a fourth embodiment, is shown. The system 1100 can be described as a cascaded arrangement including separators. The system 1100 includes a plurality of conduits 1101, 1102, 1103a, 1103b, 1104a, 1104b, 1105a, and 1105b. The sample passes through these conduits when it is separated by the system 1100.

[0086] The sample is fed into the system via a first conduit 1101, and is split and conveyed to a second conduit 1102 and a primary third conduit 1103a. The second conduit 1102 conveys the first fraction of the sample to a primary separator 1130a, while the primary third conduit 1103a (which acts as a bypass line) conveys the first fraction of the sample directly to the analyzer 1140 without passing through the primary separator 1130a. The primary separator 1130a separates the analytes from the sample in the same manner as the separator 130 of the first embodiment. Similarly, the analyzer 1140 measures the sample in the same manner as the analyzer 140 of the first embodiment. The system also includes a controller 1150 capable of controlling the primary separator 1130a and receiving measurement results from the analyzer 1140. This is similar to the configuration of the controller 150 in the first embodiment. In this way, analyzer 1140 can control the activation of primary separator 1130a based on measurements of the fractionation of the sample received via primary bypass line 1103a. This ensures precise timing control of the activation / deactivation (and changes in activation level) of primary separator 1130a.

[0087] In the same manner as in the first embodiment, a portion of the sample produced from the primary separator 1130a is delivered to the analyzer 1140 via the primary fourth conduit 1104a. However, in this embodiment, a primary fifth conduit 1105a is provided to utilize another portion of the sample produced from the primary separator 1130a. This other portion of the sample may be a portion of the sample not targeted by the primary separator 1130a. The first fraction of the sample passing through the primary fifth conduit 1105a is delivered directly to the analyzer 1140 via the secondary third conduit (or secondary bypass line) 1103b without passing through the second-stage separator 1130b. The other fraction of the sample passing through the primary fifth conduit 1105a is delivered directly to the secondary separator 1130b for separation, wherein the output of the secondary separator 1130b is connected to the analyzer 1140 via the secondary fourth conduit 1104b. The secondary fifth conduit 1105b can be used to deliver another portion of the sample produced from the secondary separator 1130b elsewhere. For example, the secondary fifth conduit 1105b can be used to discard certain types of items that are not of interest. Alternatively, the secondary fifth conduit 1105b can be connected to another separator configured in the same manner as the secondary separator 1130b.

[0088] In the fourth embodiment, the measurement results obtained by the analyzer 1140, based on the fractionation of the sample provided by the secondary bypass line 1103b, can be used by the controller 1150 to control the activation of the secondary separator 1130b. Therefore, the secondary separator 1130b is used in a similar manner to the primary separator 1130a. Thus, the fourth embodiment is similar to the first embodiment, with the main difference being that the fifth conduit 105 of the first embodiment is connected to the secondary separator 1130b and the secondary bypass line 1103b. The secondary separator 1130b and the secondary bypass line 1103b can be used to separate additional analytes (or multiple additional analytes) from the sample. For example, the primary separator 1130a can be configured to separate a first analyte from the sample, and the secondary separator 1130b can be configured to separate a second analyte (which may be different from the first analyte) from the sample. Therefore, the system 1100 may be able to separate multiple different classes of substances with a high degree of control.

[0089] Figure 11 System 1100 can be modified in various ways. For example, analyzer 1140 may include a single analyzer with multiple ports that allow simultaneous reception of multiple fractions and portions of a sample. Alternatively, analyzer 1140 may include multiple analyzers (e.g., one analyzer per separator, with switching ports / valve to allow analysis of multiple samples). One or more analyzer interfaces may also be provided (e.g., similar to...). Figure 7 and Figure 8 Interfaces 745 and 845 are used to control the manner in which samples are supplied to analyzer 1140. Additionally, a separate separator (e.g., similar to) may be provided in one or both of bypass lines 1103a and 1103b. Figure 8 (Another separator 833). Similarly, one or more additional separators may be provided upstream of separators 1130a and 1130b (e.g., in the first conduit 1101), similar to... Figure 8 How are separators 831 and 832 located upstream of separator 830?

[0090] Therefore, returning to the previously used general terminology, the separator described herein can be a primary separator (e.g., 1130a). The system described herein may include additional separators (e.g., separator 1130b), which may alternatively be described as secondary separators downstream of the primary separator. For example, the additional separator downstream of the primary separator may be configured to receive a portion of the sample output from the primary separator. Preferably, the system may include an additional bypass line (e.g., 1103b) configured to provide additional fractions of the sample to an analyzer (e.g., 1140) for measurement without passing through the additional separator downstream of the primary separator. In this way, multiple analytes can be efficiently separated from the sample.

[0091] The separators and other separators described herein may include any one or more of the following: gas chromatographs; and liquid chromatographs; cryogenic traps; chemical traps; selective traps; scrubbers; traps; cryogenic traps; valves; gas chromatographs; liquid chromatographs; ion chromatography equipment; capillary electrophoresis equipment or capillary electrochromatographs; and / or distillation equipment. Furthermore, the analyzers described herein may include any one or more of the following: concentration-correlated detectors; mass spectrometers; isotope ratio mass spectrometers (IRMS); electron capture detectors; thermal conductivity detectors; flame ionization detectors; and / or ultraviolet-visible spectroscopy equipment.

[0092] It will be understood that many changes can be made to the aforementioned devices, systems, and methods while retaining the advantages mentioned above. For example, where a particular component has been described, an alternative component providing the same or similar functionality can be provided.

[0093] The ConFlo IV device has been extensively described and illustrated, but any interface used for the analyzer can be employed. For example, an analyzer with an integrated interface can be provided.

[0094] Furthermore, the above embodiments primarily describe the separation of gaseous samples; however, other forms of substances can be separated using the system described herein. N2 and CO2 are primarily described, but various other analytes can be considered.

[0095] A method for manufacturing and / or operating any system disclosed herein is also provided. This method may include steps of providing each of the disclosed features and / or configuring or using a corresponding feature for its stated functionality. For example, a method for separating an analyte from a sample is provided, the method comprising: providing a first fraction of the sample to an analyzer for measurement without passing it through a separator, the analyzer being downstream of the separator; receiving a measurement result obtained by the analyzer regarding the first fraction of the sample, the measurement result indicating that the first fraction of the sample includes a threshold amount of the analyte; and controlling the activation of the separator based on the received measurement result. This method may include performing any additional steps described herein.

[0096] Unless otherwise stated, each feature disclosed in this specification may be replaced by an alternative feature for the same, equivalent, or similar purpose. Therefore, unless otherwise stated, each disclosed feature is merely one example of a series of equivalent or similar attribute features.

[0097] As used herein (including in the claims), unless the context otherwise indicates, the singular form of a term herein should be understood to include the plural form, and vice versa, where the context permits. For example, unless the context otherwise indicates, the singular form included herein in the claims, such as “a” (e.g., a separator or an analyzer), means “one or more” (e.g., one or more separators, or one or more analyzers). In the description and claims of this disclosure, the words “comprising,” “including,” “having,” and “containing” indicate that the described feature includes the following additional feature and are not intended to exclude the presence of other components.

[0098] The use of any and all examples or exemplary language (“e.g.,” “such as,” and similar languages) provided herein is intended only to better illustrate this disclosure and, unless otherwise required, does not indicate any limitation on the scope of this disclosure. No language in this specification should be construed as indicating any unrequired element necessary for the practice of this disclosure.

[0099] Unless otherwise stated or required by context, any steps described in this specification may be performed in any order or simultaneously. Furthermore, the description of a step as performed after another step does not preclude intermediate steps being performed.

[0100] All aspects and / or features disclosed in this specification can be combined in any combination, except for at least some mutually exclusive combinations of such features and / or steps. Specifically, preferred features of this disclosure apply to all aspects and embodiments of this disclosure and can be used in any combination. Similarly, features described in non-essential combinations can be used individually (not in combination).

[0101] Terms:

[0102] 1. A system for separating an analyte from a sample, comprising:

[0103] A separator configured to separate the analyte from the sample;

[0104] An analyzer configured to obtain a measurement indicating the amount of the analyte in the sample, wherein the analyzer is downstream of the separator;

[0105] A bypass line, configured to provide a first fraction of the sample to the analyzer for measurement without passing through the separator; and

[0106] The controller is configured to:

[0107] Receive a measurement result obtained by the analyzer regarding the first fraction of the sample received via the bypass line, the measurement result indicating that the first fraction of the sample received via the bypass line includes a threshold amount of the analyte; and

[0108] The activation of the separator is controlled based on the received measurement results.

[0109] 2. The system according to Clause 1, wherein the controller is configured to activate the separator based on a received measurement indicating that the first fraction of the sample includes an amount of the analyte greater than or equal to a lower threshold.

[0110] 3. The system according to Clause 2, wherein the controller is configured to:

[0111] The time period is determined based on the received measurement results; and

[0112] The separator is activated after the determined time period.

[0113] 4. The system according to Clause 3, wherein the controller is configured to determine the time period based on: the intensity of the received measurement result; and / or a calibration peak having a known relationship between the measurement intensity and the peak width.

[0114] 5. The system according to any of the preceding clauses, wherein the controller is configured to deactivate the separator based on a received measurement indicating that the first fraction of the sample includes an amount of the analyte less than or equal to an upper threshold.

[0115] 6. The system according to any of the preceding clauses, wherein the controller is configured to:

[0116] Receive multiple measurement results of the first fraction of the sample obtained by the analyzer at different times; and

[0117] The activation of the separator is controlled based on each of the received measurement results;

[0118] Preferably, wherein:

[0119] The controller is configured to activate the separator based on a first received measurement result, the first received measurement result indicating that the first fraction of the sample includes at least a lower limit threshold amount of the analyte; and

[0120] The controller is configured to deactivate the separator based on a second received measurement result received after the first received measurement result, the second received measurement result indicating that the first fraction of the sample includes an amount of the analyte less than or equal to an upper threshold.

[0121] 7. The system according to any of the preceding clauses, wherein the bypass line is configured to continuously supply the first fraction of the sample to the analyzer for measurement without passing through the separator.

[0122] 8. The system according to any of the preceding clauses, wherein the first fraction of the sample comprises a first percentage of the sample, wherein the first percentage is: less than or equal to 1%; less than or equal to 2%; less than or equal to 5%; or less than or equal to 10%.

[0123] 9. A system according to any of the preceding clauses, configured to provide a second fraction of the sample to the analyzer without passing through the bypass line, preferably wherein the system is configured such that the second fraction of the sample passes through the separator.

[0124] 10. The system according to Clause 9 is configured such that the first fraction of the sample reaches the analyzer before the second fraction of the sample reaches the separator.

[0125] 11. The system according to Clause 9 or Clause 10 further includes a splitter upstream of the separator, the analyzer and the bypass line, wherein the splitter is configured to split the sample into a first fraction and a second fraction of the sample.

[0126] 12. The system according to any one of clauses 9 to 11 further includes an outlet, wherein the controller is configured to cause the outlet to discard or remove a portion of the second fraction of the sample passing through the separator when the separator is activated.

[0127] 13. The system according to any one of clauses 9 to 12 further includes a delay line configured to delay the second fraction of the sample relative to the first fraction of the sample.

[0128] 14. The system according to Clause 13, wherein the delay line includes a capillary whose dimensions are designed to delay the second fraction of the sample relative to the first fraction of the sample.

[0129] 15. The system according to any one of clauses 9 to 14, wherein:

[0130] The separator includes a trap; and

[0131] The controller is configured to deactivate the trap based on a received measurement result to release at least a portion of the second fraction of the sample to the analyzer, the received measurement result indicating that the first fraction of the sample includes an amount of the analyte less than or equal to an upper threshold.

[0132] 16. The system according to any one of clauses 9 to 15, wherein the second fraction of the sample comprises a second percentage of the sample, wherein the second percentage is: greater than or equal to 90%; greater than or equal to 95%; greater than or equal to 98%; or greater than or equal to 99%.

[0133] 17. The system according to any of the preceding clauses, wherein the system is configured such that a majority of the sample is provided to the analyzer without passing through the bypass line.

[0134] 18. The system described in any of the preceding clauses may include one or more additional separators.

[0135] 19. The system according to Clause 18, wherein at least one additional separator is upstream of the bypass line, preferably wherein at least two additional separators are upstream of the bypass line.

[0136] 20. The system according to Clause 18 or Clause 19, wherein the bypass line includes at least one additional separator, preferably wherein the bypass line includes a trap or selective trap.

[0137] 21. The system according to any one of clauses 18 to 20, wherein at least one additional separator is downstream of the separator, preferably wherein the system includes an additional bypass line configured to provide additional fractions of the sample to the analyzer for measurement without passing through the additional separator.

[0138] 22. The system according to any one of Clauses 18 to 21, wherein the one or more additional separators comprise any one or more of the following: gas chromatograph; liquid chromatograph; cryogenic trap; chemical trap; selective trap; scrubber; trap; cryogenic trap; valve; gas chromatograph; liquid chromatograph; ion chromatography apparatus; capillary electrophoresis apparatus or capillary electrochromatograph; and / or distillation apparatus.

[0139] 23. The system according to any of the preceding clauses, wherein the system includes a plurality of separators, and the controller is configured to control the activation of one, a plurality of or all of the separators based on measurement results received from the analyzer.

[0140] 24. The system according to any of the preceding clauses further includes an interface for the analyzer, the interface including a first port and a second port, wherein:

[0141] The first port is configured to receive the first fraction of the sample and provide the first fraction of the sample to the analyzer; and

[0142] The second port is configured to receive the second fraction of the sample and provide the second fraction of the sample to the analyzer; preferably, wherein:

[0143] The first port is a relatively low-traffic port, and the second port is a relatively high-traffic port.

[0144] 25. The system according to Clause 24, wherein the controller is configured to deactivate the first port and activate the second port when a received measurement indicates that the first fraction of the sample includes an amount of the analyte less than or equal to an upper threshold amount.

[0145] 26. The system according to any of the preceding clauses, wherein the separator comprises any one or more of the following: gas chromatograph; liquid chromatograph; cryogenic trap; chemical trap; selective trap; scrubber; trap; cryogenic trap; valve; gas chromatograph; liquid chromatograph; ion chromatography apparatus; capillary electrophoresis apparatus or capillary electrochromatograph; and / or distillation apparatus.

[0146] 27. The system according to any of the preceding clauses, wherein the analyzer comprises one or more of the following: a concentration-related detector; a mass spectrometer; an isotope ratio mass spectrometer (IRMS); an electron capture detector; a thermal conductivity detector; a flame ionization detector; and / or a UV-Vis spectroscopy device.

[0147] 28. The system according to any of the preceding clauses further includes one or more amplifiers configured to amplify measurements obtained by the analyzer with respect to: the first fraction of the sample; and / or the second fraction of the sample.

[0148] 29. The system according to any of the preceding clauses, wherein the system is configured to separate one or more of the following analytes from the sample: N2; CO2; CO; SO2; H2; a gaseous mixture of CO2 and He; SF6; CH4; NO x (x = 1, 2 or 0.5); Ar; and / or O2.

[0149] 30. The system according to any of the preceding clauses, wherein the system includes one or more of the following:

[0150] A sample preparation apparatus configured to provide the sample to the separator and the bypass line;

[0151] Elemental analyzer - isotope ratio mass spectrometry system (EA-IRMS);

[0152] Automatic carbonate reaction equipment;

[0153] An analyte source configured to provide analyte peaks, preferably wherein the analyte source comprises any one or more of the following: a trap; a cryogenic trap; a valve; a gas chromatograph; a liquid chromatograph; a washer; an ion chromatography apparatus; a capillary electrophoresis apparatus or a capillary electrochromatograph; a distillation apparatus; a loop injector; a laser ablation apparatus; a temperature-converting elemental analyzer (TC / EA); and / or a headspace vial.

[0154] 31. A method for separating an analyte from a sample, comprising:

[0155] The first fraction of the sample is provided to an analyzer for measurement without passing through a separator, the analyzer being downstream of the separator;

[0156] Receive a measurement result obtained by the analyzer regarding the first fraction of the sample, the measurement result indicating that the first fraction of the sample includes a threshold amount of the analyte; and

[0157] The activation of the separator is controlled based on the received measurement results.

[0158] 32. The method according to Clause 31, wherein controlling the activation of the separator comprises any one or more of the following:

[0159] The separator is activated based on the received measurement results, which indicate that the first fraction of the sample includes an amount of the analyte greater than or equal to a lower threshold.

[0160] The time period is determined based on the received measurement results, and the separator is activated after the determined time period; and / or

[0161] The separator is deactivated based on the received measurement results, which indicate that the first fraction of the sample includes an amount of the analyte less than or equal to an upper threshold.

[0162] 33. The method according to Clause 31 or Clause 32, wherein controlling the activation of the separator includes determining a time period based on received measurement results and deactivating the separator after the determined time period, the method further comprising determining the time period by the following steps:

[0163] Identify peaks with heights based on the received measurement results; and

[0164] The value of the time period corresponding to the predicted peak width of the peak is determined based on the peak height.

Claims

1. A system for separating an analyte from a sample, comprising: A separator configured to separate the analyte from the sample; An analyzer configured to obtain a measurement indicating the amount of the analyte in the sample, wherein the analyzer is downstream of the separator; A bypass line, the bypass line being configured to provide a first fraction of the sample to the analyzer for measurement without passing through the separator; and The controller is configured to: Receive a measurement result obtained by the analyzer regarding the first fraction of the sample received via the bypass line, the measurement result indicating that the first fraction of the sample received via the bypass line includes a threshold amount of the analyte; as well as The activation of the separator is controlled based on the received measurement results; The system is configured to provide a second fraction of the sample to the analyzer without passing through the bypass line, and is configured such that the first fraction of the sample reaches the analyzer before the second fraction of the sample reaches the separator.

2. The system of claim 1, wherein the controller is configured to activate the separator based on a received measurement result indicating that the first fraction of the sample includes an amount of the analyte greater than or equal to a lower threshold.

3. The system according to claim 2, wherein the controller is configured to: The time period is determined based on the received measurement results; and The separator is activated after the determined time period.

4. The system of claim 3, wherein the controller is configured to determine the time period based on: the intensity of the received measurement result; and / or a calibration peak having a known relationship between the measurement intensity and the peak width.

5. The system according to any one of claims 1 to 4, wherein the controller is configured to deactivate the separator based on a received measurement result indicating that the first fraction of the sample includes an amount of the analyte less than or equal to an upper threshold.

6. The system according to any one of claims 1 to 4, wherein the controller is configured to: Receive multiple measurement results of the first fraction of the sample obtained by the analyzer at different times; and The activation of the separator is controlled based on each of the received measurement results.

7. The system according to claim 6, wherein: The controller is configured to activate the separator based on a first received measurement result, the first received measurement result indicating that the first fraction of the sample includes at least a lower limit threshold amount of the analyte; and The controller is configured to deactivate the separator based on a second received measurement result received after the first received measurement result, the second received measurement result indicating that the first fraction of the sample includes an amount of the analyte less than or equal to an upper threshold.

8. The system according to any one of claims 1 to 4, wherein the bypass line is configured to continuously supply the first fraction of the sample to the analyzer for measurement without passing through the separator.

9. The system according to any one of claims 1 to 4, wherein the first fraction of the sample comprises a first percentage of the sample, wherein the first percentage is: less than or equal to 1%; less than or equal to 2%; less than or equal to 5%; or less than or equal to 10%.

10. The system according to any one of claims 1 to 4, wherein the system is configured such that the second fraction of the sample passes through the separator.

11. The system according to any one of claims 1 to 4, further comprising a splitter upstream of the separator, the analyzer and the bypass line, wherein the splitter is configured to split the sample into a first fraction and a second fraction of the sample.

12. The system according to any one of claims 1 to 4, further comprising an outlet, wherein the controller is configured to cause the outlet to discard or remove a portion of the second fraction of the sample passing through the separator when the separator is activated.

13. The system according to any one of claims 1 to 4, further comprising a delay line configured to delay the second fraction of the sample relative to the first fraction of the sample.

14. The system of claim 13, wherein the delay line comprises a capillary, the capillary being sized to delay the second fraction of the sample relative to the first fraction of the sample.

15. The system according to any one of claims 1 to 4, wherein: The separator includes a trap; and The controller is configured to deactivate the trap based on a received measurement result to release at least a portion of the second fraction of the sample to the analyzer, the received measurement result indicating that the first fraction of the sample includes an amount of the analyte less than or equal to an upper threshold.

16. The system according to any one of claims 1 to 4, wherein the second fraction of the sample comprises a second percentage of the sample, wherein the second percentage is: greater than or equal to 90%; greater than or equal to 95%; greater than or equal to 98%; or greater than or equal to 99%.

17. The system according to any one of claims 1 to 4, wherein the system is configured such that a majority of the sample is provided to the analyzer without passing through the bypass line.

18. The system according to any one of claims 1 to 4, comprising one or more additional separators.

19. The system of claim 18, wherein at least one additional separator is upstream of the bypass line.

20. The system of claim 19, wherein at least two additional separators are upstream of the bypass line.

21. The system of claim 18, wherein the bypass line includes at least one additional separator.

22. The system of claim 21, wherein the bypass line comprises a trap or a selective trap.

23. The system of claim 18, wherein at least one additional separator is downstream of the separator.

24. The system of claim 23, wherein the system includes an additional bypass line configured to provide an additional fraction of the sample to the analyzer for measurement without passing through the additional separator.

25. The system of claim 18, wherein the one or more additional separators comprise any one or more of the following: a gas chromatograph; a liquid chromatograph; a cryogenic trap; a chemical trap; a selective trap; a scrubber; a trap; a cryogenic trap; a valve; a gas chromatograph; a liquid chromatograph; an ion chromatography apparatus; a capillary electrophoresis apparatus or a capillary electrochromatograph; and / or a distillation apparatus.

26. The system according to any one of claims 1 to 4, wherein the system comprises a plurality of separators, and the controller is configured to control the activation of one, a plurality of or all of the separators based on measurement results received from the analyzer.

27. The system according to any one of claims 1 to 4, further comprising an interface for the analyzer, the interface including a first port and a second port, wherein: The first port is configured to receive the first fraction of the sample and provide the first fraction of the sample to the analyzer; and The second port is configured to receive the second fraction of the sample and provide the second fraction of the sample to the analyzer.

28. The system of claim 27, wherein the first port is a relatively low-traffic port and the second port is a relatively high-traffic port.

29. The system of claim 27, wherein the controller is configured to deactivate the first port and activate the second port when a received measurement result indicates that the first fraction of the sample includes an amount of the analyte less than or equal to an upper threshold amount.

30. The system according to any one of claims 1 to 4, wherein the separator comprises any one or more of the following: a gas chromatograph; a liquid chromatograph; a cryogenic trap; a chemical trap; a selective trap; a scrubber; a trap; a cryogenic trap; a valve; a gas chromatograph; a liquid chromatograph; an ion chromatography apparatus; a capillary electrophoresis apparatus or a capillary electrochromatograph; and / or a distillation apparatus.

31. The system according to any one of claims 1 to 4, wherein the analyzer comprises any one or more of the following: a concentration-related detector; a mass spectrometer; an isotope ratio mass spectrometer (IRMS); an electron capture detector; a thermal conductivity detector; a flame ionization detector; and / or a UV-Vis spectroscopy device.

32. The system according to any one of claims 1 to 4, further comprising one or more amplifiers configured to amplify measurements obtained by the analyzer with respect to: the first fraction of the sample; and / or the second fraction of the sample.

33. The system according to any one of claims 1 to 4, wherein the system is configured to separate one or more of the following analytes from the sample: N2; CO2; CO; SO2; H2; a gaseous mixture of CO2 and He; SF6; CH4; NO x (x=1, 2 or 0.5); Ar; and / or O2.

34. The system according to any one of claims 1 to 4, wherein the system comprises one or more of the following: A sample preparation apparatus configured to provide the sample to the separator and the bypass line; Elemental Analyzer - Isotope Ratio Mass Spectrometry System (EA-IRMS); Automatic carbonate reaction equipment; An analyte source is configured to provide analyte peaks.

35. The system of claim 34, wherein the analyte source comprises any one or more of the following: a trap; a cryogenic trap; a valve; a gas chromatograph; a liquid chromatograph; a washer; an ion chromatography apparatus; a capillary electrophoresis apparatus or a capillary electrochromatograph; a distillation apparatus; a loop injector; a laser ablation apparatus; a temperature conversion elemental analyzer (TC / EA); and / or a headspace vial.

36. A method for separating an analyte from a sample, comprising: The first fraction of the sample is provided to the analyzer for measurement via a bypass line without passing through a separator, the analyzer being downstream of the separator; The second fraction of the sample is provided to the analyzer without passing through the bypass line, wherein the first fraction of the sample arrives at the analyzer before the second fraction of the sample arrives at the separator; Receive a measurement result of the first fraction of the sample obtained by the analyzer, the measurement result indicating that the first fraction of the sample includes a threshold amount of the analyte; as well as The activation of the separator is controlled based on the received measurement results.

37. The method of claim 36, wherein controlling the activation of the separator comprises any one or more of the following: The separator is activated based on the received measurement results, which indicate that the first fraction of the sample includes an amount of the analyte greater than or equal to a lower threshold. The time period is determined based on the received measurement results, and the separator is activated after the determined time period; and / or The separator is deactivated based on the received measurement results, which indicate that the first fraction of the sample includes an amount of the analyte less than or equal to an upper threshold.

38. The method of claim 36 or claim 37, wherein controlling the activation of the separator includes determining a time period based on received measurement results and deactivating the separator after the determined time period, the method further comprising determining the time period by the following steps: Identify peaks with heights based on the received measurement results; and The value of the time period corresponding to the predicted peak width of the peak is determined based on the peak height.

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