Operating method, ion mobility spectrometer, and apparatus

Abstract

Aspects of the present disclosure provide a method for operating an ion mobility spectrometer, the ion mobility spectrometer comprising an ionizer, a reaction region adjacent to the ionizer, a gate, and a detector for detecting the arrival of ions, the method comprising: (i) opening the gate for a first ion cloud entry time to allow a first group of sample ions to move from the reaction region through the gate to the detector in order to provide a first signal; (ii) opening the gate for a second ion cloud entry time to allow a second group of sample ions to move from the reaction region through the gate to the detector in order to provide a second signal, wherein during the second ion cloud entry time the gate is closed for a shutter time and then reopened; and (iii) determining the characteristics of the sample ions based on the first and second signals.

Description

【Technical Field】 【0001】 The present invention relates to a method and apparatus for ion mobility spectrometry (IMS), and more particularly to a method and apparatus for improving the ability of an IMS device to distinguish ions. 【Background Art】 【0002】 IMS can identify a material from a sample of interest by ionizing the material (e.g., molecules, atoms, etc.) and measuring the time it takes for the resulting ions to move a known distance under a known electric field. The flight time of each ion can be measured by a detector, and the flight time is related to the mobility of the ion. The mobility of an ion is related to the mass and shape of the ion. Therefore, it is possible to infer identification information about an ion by measuring the flight time of the ion at a detector. The flight time can be displayed as a graph or numerically as a spectrum. Other types of spectrometers, such as mass spectrometers, analyze ions according to the mass-to-charge ratio of the ions. 【0003】 The accuracy of the identification information and the ability of an ion mobility spectrometer to distinguish one species from another are the main problems. Various methods have been proposed to improve the accuracy. Many of these methods require a trade-off between sensitivity and resolution. 【0004】 In a very short IMS cell, the drift time can also be very short. As a result, the low resolution of the system can result in overlapping two peaks, making it difficult to separate the peaks associated with different compounds having similar mobilities. The overlapping peaks can be indistinguishable or ambiguous. One option could be to provide a longer IMS cell with a longer drift time to give more time to separate ions having similar mobilities. However, such a solution is not desirable because of the general motivation to reduce the size of the device, particularly the general motivation to make the device portable or wearable. [Overview of the Initiative] 【0005】 One aspect and example of this disclosure is described in the claims and aims to address the above-mentioned technical problems and other problems. 【0006】 One aspect of the present disclosure provides a method for operating an ion mobility spectrometer, comprising an ionizer, a reaction region adjacent to the ionizer, a gate, and a detector for detecting the arrival of ions. The method includes (i) opening the gate for a first ion cloud entry time to allow a first group of sample ions to move from the reaction region through the gate to the detector in order to provide a first signal, and (ii) opening the gate for a second ion cloud entry time to allow a second group of sample ions to move from the reaction region through the gate to the detector in order to provide a second signal, wherein during the second ion cloud entry time the gate is closed for a shutter time and then reopened, and the method further includes (iii) characterizing the sample ions based on the first signal and the second signal, thereby the first signal providing a baseline spectrum and the second signal providing a notch spectrum. 【0007】 Generally, a gate separates the ionizer from the detector. For example, the gate may be provided between the reaction region and the drift region of an ion mobility spectrometer so that ions must move from the reaction region through the gate to the drift region in order to reach the detector. The ions then move along the drift region to the detector. 【0008】 Both the sample ions from the first group and the sample ions from the second group may be generated from the same sample. 【0009】 The method may include performing multiple cycles of step (i) and step (ii) on the same sample to acquire multiple identical first signals and multiple identical second signals, wherein step (i) and step (ii) are performed alternately. 【0010】 The characteristics may be determined based on a plurality of identical first signals and a plurality of identical second signals. 【0011】 The method may further include obtaining a first sample of gaseous fluid from the flow at the inlet of an ion mobility spectrometer, wherein the sample ions are obtained from the first sample, and obtaining a second sample of gaseous fluid from the flow, wherein the sample ions are obtained from the second sample. 【0012】 Determining the properties of an ion based on a first signal and a second signal may also include determining the properties based on the difference between the first signal and the second signal. 【0013】 The first signal may be used as a baseline for the second signal. 【0014】 The first group of sample ions and the second group of sample ions may be modified to generate daughter ions. The first and second signals are provided by the arrival of the daughter ions in the detector. Modification may include applying an RF electric field to the ions. 【0015】 The RF electric field may be applied during the movement of ions from the reaction region to the detector. 【0016】 One embodiment provides a method for operating an ion mobility spectrometer to identify the presence of a target substance, the method comprising: performing a first operation including time-of-flight ion mobility spectroscopy to provide an ion mobility signal from a sample; and, if the ion mobility signal is ambiguous, performing a second operation including any of the aforementioned methods to identify the presence of the target substance based on a baseline spectrum and a notch spectrum. 【0017】 One embodiment provides a method for operating an ion mobility spectrometer, the method comprising: providing a first operation of an ionizer to ionize a sample, opening the gate for a gate width after a gate delay to allow ions from the sample to pass through the gate, and then closing the gate to prevent other ions from passing through the gate, thereby determining the time of flight of ions from the gate to the detector in order to provide an ion mobility signal; providing a second operation of an ionizer to ionize a sample, opening the gate for an ion cloud entry time after the second operation of the ionizer to allow a second group of ions from the sample to pass through the gate to reach the detector, during which the gate is closed for a shutter time in order to provide an inverse ion mobility signal; and determining the characteristics of the sample based on the ion mobility signal and the inverse ion mobility signal. 【0018】 These methods may include a second operation to obtain an inverse ion mobility signal if the ion mobility signal satisfies a trigger criterion. 【0019】 The trigger criteria may include at least one of the following: (a) the ion mobility signal has a peak in a predetermined detection window; (b) the ion mobility signal has a peak exceeding a threshold peak width; or (c) the ion mobility signal provides ambiguous identification of a candidate substance. 【0020】 The gate may be left open during further ion cloud entry time to allow additional groups of sample ions to move from the reaction region through the gate to the detector, in order to provide a baseline signal for the reverse ion mobility signal, and the characterization of the sample is further based on the baseline signal. 【0021】 One aspect of the present disclosure provides an ion mobility spectrometer comprising: an ionizer; a gate; a detector; and a controller positioned to control the ionizer and the gate and configured to control the ion mobility spectrometer to perform one or more of the methods described or claimed herein. 【0022】 Generally, a gate separates the ionizer from the detector. For example, the gate may be provided between the reaction region and the drift region of an ion mobility spectrometer so that ions need to move from the reaction region through the gate to the drift region in order to reach the detector. The ions then move along the drift region to the detector. 【0023】 One aspect of the present disclosure provides a computer program product configured to program a controller for an ion mobility spectrometer to perform any of the methods described or claimed herein. The controller may be configured to control the ionizer and gate of the ion mobility spectrometer. The controller may also be configured to control an ion reformer and / or a pressure pulser to take in a sample from the inlet. 【0024】 Embodiments of the present disclosure may aim to reduce the broadening of peaks in IMS signals. In particular, this is applicable to drift tube type IMS systems. As an ion packet moves through a drift tube, the ion packet may become broader (spread in the drift direction) as the ions repel each other. This may be referred to as the Coulomb broadening effect (since the Coulomb broadening effect is due to the mutual repulsion of ions within an ion peak). The diffusion effect also tends to broaden peaks in conventional IMS. When this peak broadening effect is particularly exacerbated, peaks that are close to each other may appear as a single broad peak, or the peak may be overlapping and ambiguous regardless of whether one or two or more other peaks are present. The effective drift time resolution is also reduced. 【0025】 Embodiments of the present disclosure may provide a system and a method for performing ion mobility spectrometry in which the diffusion effect and the Coulomb effect are used to improve rather than degrade the ability of a spectrometer to accurately elucidate the drift time of ions. 【Brief Description of the Drawings】 【0026】 Here, embodiments of the present disclosure are described in detail with reference to the accompanying drawings. [Figure 1] FIG. 1 shows an ion mobility spectrometer. [Figure 2] FIG. 2 comprises a series of plots of an exemplary timing diagram regarding the operation of an ion mobility spectrometer, such as that shown in FIG. 1. [Figure 3] FIG. 3 shows a detection signal obtained by operating an ion mobility spectrometer according to the method of the present disclosure. [Figure 3A] FIG. 3A shows a “baseline” detection signal obtained by opening and holding the gate throughout the ion cloud entry time. [Figure 3B] FIG. 3B shows a “notch” detection signal obtained by opening and holding the gate during the ion cloud entry time except for the shutter interval. [Figure 3C] FIG. 3C shows the difference between the baseline and the notch signal. [Figure 4] FIG. 4 includes a flowchart showing a method of operating an ion mobility spectrometer. 【0027】 In the drawings, like reference numerals are used to indicate like elements. DETAILED DESCRIPTION OF THE INVENTION 【0028】 FIG. 1 is a partial cross-sectional view of an ion mobility spectrometer (IMS) 100. The spectrometer shown in FIG. 1 includes an ionizer 102 separated from a drift chamber 104 by a gate 106. The gate 106 can control the passage of ions from the ionizer 102 into the drift chamber 104. 【0029】 A controller 107 is connected to operate the ionizer and the gate 106. In the example shown in FIG. 1, since the drift chamber 104 is between the ionizer 102 and the detector 118, ions can reach the detector 118 by traversing the drift chamber 104. 【0030】 The controller 107 is configured to operate the IMS 100 to generate a reverse gate IMS signal by opening and holding the gate after the sample is ionized, then temporarily closing the gate 106 for a period herein referred to as the "shutter time", and reopening the gate 106 while the ion cloud generated from the sample is moving through the gate 106. This short closure and reopening of the gate during the passage of the ion cloud through the gate results in a gap in the ion cloud. Then, the ion cloud having the gap moves through the drift chamber towards the detector 118. The arrival of the ions at the detector 118 generates a signal indicating the arrival time of the ions. The gap is reflected in the signal as a "notch" or dip in the ion count. 【0031】 Furthermore, controller 107 operates IMS to generate a “baseline” IMS signal. Controller 107 does this by operating ionizer 102 to ionize the sample and keeping the gate open without closing it while the ion cloud moves through the gate. In other words, controller 107 ionizes the sample and moves all the ions toward the detector only while the gate is kept open. The same sample may be used for both the inverse-gate IMS signal and the baseline. 【0032】 This provides two different detection signals. One is the so-called inverse gate IMS signal, where the "notch" is given in the ion cloud by the closing and reopening of gate 106 during the passage of the ion cloud. The other is a baseline signal that characterizes the ion cloud itself. 【0033】 The difference between the notch signal and the baseline signal can be used to provide an inverse-gated IMS spectrum, and the effect of using a discontinuous ion source is accounted for by the baseline signal. 【0034】 As shown, the IMS 100 includes an inlet 108 that allows material to be introduced from the sample of interest into the ionizer 102. This may be a pinhole inlet or a membrane inlet positioned to take in the sample from an airflow. A pressure pulsar (not shown) may be provided to allow the sample to be taken in. Other methods of introducing the sample through the inlet 108 may also be used. The inlet 108 is positioned to introduce the sample into the reaction region 105 of the ionization chamber 103. The ionizer 102 comprises an ionizer positioned in the ionization chamber and generally configured to operate selectively to generate ions at controlled intervals, e.g., intermittently, as opposed to continuous operation. Examples of the ionizer 102 include a corona point source and a dielectric barrier discharge (DBD) ion source. The ionizer 102 may operate to generate ions, which may be called reaction ions, that can be mixed with the sample in the reaction region 105 to ionize the sample. This process may be called indirect ionization. 【0035】 The controller 107 may be configured to control the operation of the pressure pulser, the ionizer 102, and the gate 106. For example, the controller 107 may be connected to a voltage supply unit 200, such as a digitally controlled voltage source, such as a DAC, which is arranged to provide control voltages to these components. Similarly, the controller 107 may be arranged to control the ion reformers 126, 127 (described later). For example, as shown in Figure 1, the voltage supply unit 200 may be connected to be controlled by the controller 107. The voltage supply unit 200 may also be connected to provide a voltage to the ionizer 102 to allow material from the sample to be ionized. In this embodiment, the voltage supply unit 200 is connected to the gate electrode 106 to control the passage of ions from the ionization chamber into the drift chamber 104. 【0036】 Furthermore, the voltage supply unit 200 may be connected to drift electrodes 120a, 120b to provide a voltage profile for moving ions from the ionizer 102 toward the detector 118. In the context of this disclosure, it will be understood that the drift chamber 104 may comprise a series of drift electrodes 120a, 120b that apply a voltage profile along the drift chamber 104 for moving ions from the ionizer 102 toward the detector 118 along the drift chamber 104. 【0037】 The IMS100 may be configured to provide a drift gas flow in a direction generally opposite to the ion migration path toward the detector 118. For example, the drift gas may flow from near the detector 118 toward the gate 106. As shown, the drift gas inlet 122 and the drift gas outlet 124 may be used to allow the drift gas to pass through the drift chamber. Examples of drift gases include, but are not limited to, nitrogen, helium, air, and recirculated air (e.g., purified and / or dry air). 【0038】 The detector 118 may be connected to provide a signal to the controller 107. The current from the detector 118 may be used by the controller 107 to infer that ions have reached the detector 118. Examples of detectors include a Faraday cup and other types of ion detectors configured to provide a signal indicating that ions have reached the detector 118. For example, the detector may include conductive electrodes that can be charged to capture ions. 【0039】 The electrodes 120a and 120b may be positioned to guide ions toward the detector 118, for example, the drift electrodes 120a and 120b may include a ring that can be positioned around the drift chamber 104 to concentrate ions toward the detector 118. The example in Figure 1 includes only two drift electrodes 120a and 120b, but in some examples, multiple electrodes or a single electrode may be used in combination with the detector 118 to apply an electric field to guide ions toward the detector 118. 【0040】 Ion reformers 126,127 may be positioned between the ionizer 102 and the detector 118 in the path of ions moving from the ionizer 102 toward the detector 118. The ion reformers may comprise two electrodes 126,127 that span the drift chamber 104 across the ion path. Ions moving through the region between the two electrodes may be subjected to an alternating electric field, such as an RF field, by applying an RF voltage to the electrodes. 【0041】 The ion reformer electrodes 126 and 127 may be separated from the gate electrode 106. As shown, the ion reformer electrodes 126 and 127 may be positioned between the gate electrode and the detector in the drift chamber. In embodiments, the ion reformer electrodes may be positioned between the ionization chamber, for example, the inlet 108 and the gate 106. Each of the ion reformer electrodes 126 and 127 may comprise an array of conductors arranged across the drift chamber. The ion reformer electrodes 126 and 127 may be separated from each other along the drift direction, for example, the longitudinal direction of the drift chamber. As shown, the conductors of each of the ion reformer electrodes 126 and 127 may have a gap between them so that ions can pass through each electrode by moving through the gap. In one example, ions enter the region 129 between electrodes 126 and 127 by passing through the gap between the conductors of electrode 126 and exiting the region through the gap between the conductors of electrode 127. While an ion is in the region between electrodes 126 and 127, it may be subjected to an alternating RF electric field. This RF electric field may be configured to fragment or modify the ion in region 129 between electrodes 126 and 127. 【0042】 During operation, the controller operates a pressure pulser to acquire a sample of material into the ionization chamber 103. The controller 107 and the voltage supply unit 200 then supply electrical energy to the ionizer 102 to generate an ion cloud by ionizing the sample. After the sample is ionized, the controller 107 opens and holds the ion gate 106 for an ion cloud entry time to allow the sample ion cloud to enter the drift region 104. The detector 118 provides the controller 107 with a baseline signal representing the ion count associated with the arrival of this ion cloud in the detector. 【0043】 To generate a “notch” spectrum, another ion cloud is generated, similar to the baseline signal. Gate 106 is kept open and held for the same ion cloud entry time after the ionizer operation. However, during the ion cloud entry time, the gate is closed and then reopened, and the interval during which the shutter is closed may be referred to as the shutter time. This results in a gap in the ion cloud, which in other cases may extend from the reaction region to the detector. The spatial width of this gap generally changes according to the ion velocity, corresponding to the shutter time. The gap in the ion cloud moves toward the collector and is detected as an “inverse peak” or notch in the IMS spectrum. If a single ion species is present, the gap reaching the detector may substantially correspond to the gap introduced by the gate. On the other hand, if ion species with different mobilities are present, the shape of the gap changes according to the different mobilities as the cloud moves through the drift chamber. For example, multiple inverse peaks ("notches") may be formed in the signal due to the influence of different mobilities in the gap introduced by gate 106. 【0044】 The advantage of this method is that the Coulomb effect and diffusion effect work to keep the inverse peak narrow, rather than broadening it as they do in a normal IMS. However, the use of a pulsed ion source means that it may not always be possible to extract an accurate inverse-gate IMS spectrum from the "notch" detector signal. Embodiments of this disclosure address this problem by acquiring a baseline signal obtained from the ion cloud without a "shutter time" gap and subtracting the baseline signal from the notch signal. 【0045】 The controller may be configured to operate an ion reformer to fragment or reform ions. Generally, when an ion reformer is used, the same operation of the reformer may be used for both the "notch" and "baseline" operations of the device. Also, generally, the same sample is used for both operations, but in some embodiments, separate samples may be used for each of the two operations. Generally, two separate identical samples are taken from the same airflow. 【0046】 The method for operating the above device will be described in more detail with reference to Figure 2. 【0047】 Figure 2 shows a series of timing diagrams, where the horizontal axis represents time and the vertical axis represents the operation or state of the components of the IMS device 100. 【0048】 The first timing diagram 201 shows, for example, the operation of the inlet 108, which acquires a sample of gaseous fluid through the operation of a pressure pulser and provides the sample to the ionizer 102. 【0049】 The second timing diagram, 203, shows the timing of the operation of the ionizer 102 that ionizes the sample. 【0050】 The third timing diagram 205 shows the optional operation of ion reformers 126 and 127, which reform or fragment ions. 【0051】 The fourth timing diagram, 207, shows the operation of the gate 106, which opens and closes to allow ions into the drift chamber 104. 【0052】 As shown, first, the pressure pulser 209 operates to draw the gaseous fluid sample toward the ionizer 102. Then, a pulse of electrical energy 211 is supplied to the ionizer 102 to provide reactive ions. The reactive ions are mixed with the sample in the reaction region 105 to generate a sample ion cloud. 【0053】 Following the operation of the ionizer 211, the ion gate 106 is then opened and remains open for the duration of the ion cloud entry time (213). This ion cloud entry time may be long enough to allow substantially all of the ion cloud to pass from the reaction region 105 through the gate 106 toward the detector 118. 【0054】 In response to the arrival of the ion cloud at detector 118, detector 118 provides a signal 300 to controller 107. As shown in Figure 3B, the signal 300 may represent the ion count reaching detector 118 as a function of time. The signal obtained by opening and holding the gate and allowing substantially all of the ion cloud to pass through the gate produces an IMS spectrum that is substantially very coarse or low resolution, as can be obtained, for example, by using a very long gate width. This signal characterizes the ion cloud as a whole in that different ion species in the cloud with different mobilities arrive at the detector at different times after the operation of the ionizer and the opening of the gate, but the timing resolution is very low because there are no constraints on where the ions begin to move in the reaction region. Different identical ion species do not have to be immediately adjacent to the gate, as in a standard time-of-flight IMS. 【0055】 The pressure pulser may then operate again to acquire further samples through the inlet (215), but this is optional, as only the remainder of the previous sample may be reused. The ionizer 102 then operates to generate a new ion cloud (217), and the gate 106 is then opened for the duration of the ion cloud entry time (219). The ion cloud entry time used is the same as that with respect to the baseline, but during this time, while the ion cloud is still moving through the ion gate, the ion gate is closed and then reopened again to create a gap in the ion cloud (221). Generally, the time the ion gate is closed during the ion cloud entry time (shutter time) corresponds to the gate width in a conventional IMS system. In some embodiments, longer shutter times may be used to increase the signal-to-noise ratio (SNR). Coulomb repulsion and diffusion effects may result in narrowing of the "notch" in the ion cloud, which may allow for the use of longer shutter times than the gate width in a conventional IMS system. The period between the operation of the ionizer and the closing of the gate, which may also be called the shutter delay, is generally selected to correspond to the gate delay in conventional IMS systems. For example, this period may be selected based on the passage time of the target ion species from the ionizer to the ion gate (for example, thus the shutter time occurs while the target ion is passing through the gate). 【0056】 After passing through the gate, the ion cloud then moves along the drift chamber toward the detector. Different ion species in the cloud with different mobilities require different amounts of time to reach the detector. The gap in the ion cloud created by closing the gate during the shutter time also moves through the drift region at a rate determined by the ion's mobility. If ions with different mobilities are present in the IMS cell, the gap is separated into multiple gaps. After each gap reaches the collector, the ion current in the detector returns to the level corresponding to the "baseline" cloud. As shown in Figure 3B, the result is signal 310, which corresponds to the "baseline" but with a notch (reduction in ion count). 【0057】 Next, the controller 107 determines the difference between the detection signal acquired from the "baseline" cloud (with the ion gate open throughout) and the signal acquired from the closure of the ion gate during the ion cloud entry time. As shown in Figure 3C, this provides an inverse ion spectrum 320 that does not significantly extend the peaks due to the Coulomb repulsion effect and diffusive expansion. Another advantage of such a method is that, unlike standard inverse-gate IMS systems, it does not require the use of a continuous ion source. This may provide an increased lifetime of components and reduce detector degradation (e.g., degradation due to material adhesion on the collector electrode). 【0058】 Both the sample ion cloud used to generate the baseline and the sample ion cloud used to generate the notch may be generated from the same gaseous fluid sample, or they may be generated by different (usually consecutive) operations of the ionizer. Alternatively, the sample ion cloud used to generate the baseline and the sample ion cloud used to generate the notch may each be generated from different samples taken in from the airflow through the inlet. 【0059】 Optionally, RF electrical energy may be applied to the ion cloud to fragment or reform the ions (223, 225). For example, this may be done using electrodes 126, 127, or using electrodes of ion gates which may be separated from each other in the drift direction. When such ion reforming is used, the same reforming may be applied to both the baseline ion cloud and the notch ion cloud. 【0060】 The same ion cloud entry time may be used for both baseline 213 and notch 219. The ion cloud entry time may be selected so that substantially all ions generated from the sample by the operation of the ionizer move through the gate into the drift region. 【0061】 The ion reformer is optional. Ion reforming is not required at all, and in some embodiments, ion reforming can be performed without a separate ion reformer structure. For example, the two electrodes of an ion gate may operate to provide ion reforming. To do this, an RF voltage may be applied between the electrodes of an ion shutter during the ion group passage time while the gate is open and held. This may allow the gate to provide the function of an ion reformer without the need to provide electrodes 126, 127. Other methods of reforming or fragmenting ions may also be used, such as other methods of increasing the effective temperature of ions, such as by applying thermal energy or by other means such as exposing ions to an RF electric field. 【0062】 It will be understood that the aforementioned embodiments of the present disclosure provide a method for generating an inverse-gate IMS signal using a pulsed ionization source. An example of such a method may include: (i) providing a first operation of an ionizer to generate sample ions; (ii) opening the gate at a predetermined time interval after the first operation of the ionizer to allow a first group of sample ions to pass through the gate; (iii) detecting the first group in a detector to provide a first signal; (iv) providing a second operation of the ionizer to generate further sample ions; (v) opening the gate at a predetermined time interval after the second operation of the ionizer to allow a second group of further sample ions to pass through the gate to reach a detector; (vi) closing the gate for a shutter time at a predetermined time interval after the second operation of the ionizer, wherein the gate is reopened for the remainder of the predetermined time interval after the shutter time; (vii) detecting a second group in a detector to provide a second signal; and (viii) determining the characteristics of the ions based on the first and second signals. 【0063】 Determining the characteristics may include determining the difference between the first signal and the second signal. This difference may provide an inverse-gate IMS signal. The inverse-gate IMS signal may have a peak indicating the mobility of ion species in the ion cloud. 【0064】 A predetermined time interval, or a time referred herein as the same predetermined time interval and also called the ion cloud entry time, may be defined by a gate delay and a gate width, where the gate delay is the time delay between the operation of the ionizer and the opening of the gate, and the gate width is the length of time the gate is open and held after the gate delay. The shutter time, during which the gate is closed and then reopened, occurs during the ion cloud entry time. 【0065】 In the context of this disclosure, it will be understood that the notch signal and the baseline signal may be acquired in any order. For example, the baseline signal may be acquired first, followed by the notch spectrum, or vice versa. 【0066】 These methods and other methods described herein may be employed in a variety of ways. One example is shown using the flowchart in Figure 4. 【0067】 Figure 4 is a flowchart illustrating a method for operating an ion mobility spectrometer, such as the spectrometer described with reference to Figures 1 through 4. In this method, the inverse-gate IMS signal of the present disclosure is used to resolve ambiguity in the IMS signal acquired using a conventional time-of-flight drift tube IMS. 【0068】 First, the sample is drawn into the ionization chamber (400), and the ionizer 102 operates to generate reaction ions that will be mixed with the sample in the reaction region (402). 【0069】 Next, the controller 107 waits for a gate delay time after the operation of the ionizer, and then opens the gate 106 for a gate width time to allow packets of ions to enter the drift chamber. The packets of ions move through the drift chamber 104 and are separated according to the mobility of the ion species in the packets of ions. The arrival time of the ions at the detector 118 generates an ion count signal, which may also be called a spectrum (404). The presence of a peak in this signal at a specific detection interval, which may also be called a window, may be used to identify the presence of the target substance (406). This time-of-flight IMS method, or any other suitable time-of-flight IMS method, may be used to generate this initial identification signal. 【0070】 Next, the controller 107 determines whether the signal clearly identifies the target substance, for example, whether a peak (or multiple peaks) exceeding a threshold is detected within a window (or multiple windows) associated with the target substance (408). If the signal clearly identifies the substance, a signal indicating the presence of the identified substance may be provided to the user (410). Alternatively, if the signal is ambiguous, the controller 107 may cause the IMS cell to perform a pulsed ionization reverse gate IMS method, for example, the pulsed ionization reverse gate IMS method described above, referring to Figures 1 to 4. As described above, the method may proceed as follows. 【0071】 The ionizer 102 operates to generate an ion cloud by further ionizing the sample (410). The controller 107 opens and holds the ion gate 106 for the duration of the ion cloud entry time to allow the sample ion cloud to enter the drift region 104 (412). The detector 118 provides the controller 107 with a baseline signal representing the ion count associated with the arrival of this ion cloud at the detector (414). 【0072】 Next, the ionizer 102 operates again to generate a further ion cloud from the sample (416). The gate 106 is opened and held after the operation of the ionizer for the same ion cloud entry time, then closed for a shutter time to provide a gap in the ion cloud during the ion cloud entry time, and then reopened, so that a "notch" signal is generated from the arrival of the ion cloud at the detector 118 (418). 【0073】 Next, the controller 107 uses the baseline signal and the notch signal to resolve any ambiguity in the original spectrum (e.g., that generated in step 406). For example, the controller may determine the difference between the baseline and the notch to generate an inverse-gated IMS signal, as shown in Figure 3C (420). Based on this inverse signal, the controller 107 may determine whether the substance of interest is present in the sample, for example, by comparing the peak in the inverse signal with the corresponding detection window (422). Alternatively, the controller 107 may use the original IMS signal (obtained in 406) to determine the presence of the substance. 【0074】 In the context of this disclosure, it will be understood that the method described above may be performed by successive ionization of the same sample, as described. Alternatively, one or more of the original IMS signal, the notch signal, and the baseline signal may be obtained using different samples. The order of operations may also be changed; for example, the inverse gate IMS step (410 to 420) may be performed first, followed by the use of a conventional time-of-flight ion mobility method to resolve ambiguity in the inverse signal. 【0075】 Furthermore, as mentioned above, ion reforming may also be used in this method. 【0076】 The ion cloud entry time may be chosen to be long enough to allow virtually all of the slowest ion species in the cloud to pass through the gate, and is therefore generally longer than the gate delay used in conventional IMS systems. 【0077】 The gate may be opened to initiate ion cloud entry time before the ionizer operates to ionize the sample, simultaneously with the ionizer's operation (e.g., during operation), or after the ionizer's operation has finished. In some embodiments, the voltage of at least one gate of the electrode may be circulated after the ionizer's operation is complete to prevent the gate from latching due to the effects of the ionizer. 【0078】 The shutter time during which the gate is closed while the ion cloud enters is generally equivalent to (e.g., equal to) the gate width in a conventional IMS system. The shutter delay, i.e., the period between the operation of the ionizer and the closing of the shutter during the shutter period, is generally selected based on the time required for the target ion species to reach the gate from the ionizer. 【0079】 The apparatus and method of this disclosure may be used with any type of sampling inlet, and although membranes and pinholes are mentioned, they may be used with any type of inlet suitable for taking in a gaseous fluid sample and providing the sample to an ionizer, depending on the situation. Other examples include capillary inlets, electro-spray inlets, and other types of inlets. 【0080】 The apparatus described herein is shown to include an ion reformer, but this is optional. In some embodiments, no ion reformer is present at all. In other embodiments, ion reforming may be used but without providing a separate ion reformer structure. For example, the electrodes of an ion gate may act as an ion reformer (e.g., to reform or fragment ions as they move through the gate). 【0081】 Any feature relating to any one of the examples disclosed herein may be combined with any selected feature relating to any of the other examples described herein. For example, a feature of a method may be implemented in appropriately configured hardware, and a particular hardware configuration described herein may be employed in a manner that is implemented using other hardware. 【0082】 From the above description, it will be understood that the embodiments shown in the figures are merely illustrative and include features that may be generalized, omitted, or replaced as described herein and in the claims. Referring to the drawings, it will be understood that schematic functional block diagrams are used to illustrate the functions of the systems and devices described herein. However, it will be understood that functions do not need to be divided in this way and should not be interpreted as suggesting any specific hardware structure other than those described and claimed below. One or more functions of the elements shown in the drawings may be further subdivided and / or distributed throughout the entire device of this disclosure. In some embodiments, the functions of one or more elements shown in the drawings may be integrated into a single functional unit. 【0083】 In some examples, the functionality of controller 107 may be provided by a general-purpose processor that can be configured to perform any one of the methods described herein. In some examples, controller 107 may comprise digital logic such as a field-programmable gate array (FPGA), an application-specific integrated circuit (ASIC), a digital signal processor (DSP), or any other suitable hardware. In some examples, one or more memory elements may store data and / or program instructions used to implement the operations described herein. Embodiments of this disclosure provide a tangible non-temporary storage medium containing program instructions that can operate to program a processor to perform any one or more of the methods described herein and / or claimed, and to provide a data processing device described herein and / or claimed. Controller 107 may comprise an analog control circuit that provides at least a portion of this control functionality. Embodiments provide an analog control circuit configured to perform any one or more of the methods described herein. 【0084】 The embodiments described above should be understood as illustrative. Further embodiments are conceivable. Any feature described in relation to any one embodiment may be used alone or in combination with other features described, or in combination with one or more features of any other embodiment or any combination of any other embodiments. Furthermore, equivalents and modifications not described herein may be adopted without departing from the scope of the invention as defined in the appended claims.

Claims

[Claim 1] A method for operating an ion mobility spectrometer, The ion mobility spectrometer described above is Ionizer and, The reaction region adjacent to the ionizer, The gate, A detector that detects the arrival of ions, Equipped with, The aforementioned method, (i) Opening the gate for a first ion cloud entry time so as to move a first group of sample ions from the reaction region through the gate to the detector in order to provide a first signal, (ii) Opening the gate for a second ion cloud entry time to allow a second group of sample ions to move from the reaction region through the gate to the detector in order to provide a second signal, wherein during the second ion cloud entry time the gate is closed for a shutter time and then reopened, (iii) Determining the characteristics of the sample ion based on the first signal and the second signal, including, A method characterized by the following: [Claim 2] Both the sample ions of the first group and the sample ions of the second group are generated from the same sample. The method according to claim 1. [Claim 3] To acquire a plurality of the first signals and a plurality of the second signals, multiple cycles of steps (i) and (ii) are performed on the same sample. Includes, Steps (i) and (ii) are performed alternately. The method according to claim 2. [Claim 4] The characteristics are determined based on the plurality of first signals and the plurality of second signals. The method according to claim 3. [Claim 5] This involves obtaining a first sample of a gaseous fluid from the flow at the inlet of an ion mobility spectrometer, wherein the first group of sample ions is obtained from the first sample. This involves obtaining a second sample of the gaseous fluid from the aforementioned flow, and the sample ions of the second group are obtained from the second sample. including, The method according to claim 1. [Claim 6] Determining the characteristics of the ion based on the first signal and the second signal is: For example, by using the first signal as a baseline for the second signal, the characteristics are determined based on the difference between the first signal and the second signal. including, The method according to any one of claims 1 to 5. [Claim 7] In order to generate daughter ions, the sample ions of the first group and the sample ions of the second group are modified. Includes, The first signal and the second signal are provided by the arrival of the daughter ions in the detector. The method according to any one of claims 1 to 6. [Claim 8] The aforementioned modification involves applying an RF electric field to the ions. including, The method according to claim 7. [Claim 9] The RF electric field is applied during the movement of the ions from the reaction region to the detector. The method according to claim 8. [Claim 10] A method for operating an ion mobility spectrometer to identify the presence of a target substance, A first operation is performed, including time-of-flight ion mobility spectroscopy, to provide an ion mobility signal from the sample. When the ion mobility signal is ambiguous, a second operation including the method according to any one of claims 1 to 9 is performed so that the first signal provides a baseline spectrum and the second signal provides a notch spectrum. Based on the baseline spectrum and the notch spectrum, the presence of the target substance is identified. including, A method characterized by the following: [Claim 11] A method for operating an ion mobility spectrometer, To provide an ionizer first operation to ionize a sample, to open the gate for a gate width after a gate delay to allow ions from the sample to pass through the gate, and then to close the gate to prevent other ions from passing through the gate, and to determine the time of flight of the ions from the gate to the detector in order to provide an ion mobility signal, To provide a second operation of the ionizer to ionize the sample, the gate is opened for an ion cloud entry time after the second operation of the ionizer to allow a second group of ions from the sample to pass through the gate to reach the detector, during which the gate is closed for a shutter time to provide a reverse ion mobility signal. Based on the ion mobility signal and the inverse ion mobility signal, the characteristics of the sample are determined. including, A method characterized by the following: [Claim 12] If the ion mobility signal satisfies the trigger criterion, the second operation is performed to obtain the inverse ion mobility signal. including, The method according to claim 10 or 11. [Claim 13] The trigger criteria are: (a) The ion mobility signal has a peak in a predetermined detection window, (b) The ion mobility signal has a peak that exceeds the threshold peak width, (c) The ion mobility signal provides ambiguous identification of candidate substances, At least one of the following, including, The method according to claim 12. [Claim 14] The method involves opening the gate for a further ion cloud entry time to allow a further group of sample ions to move from the reaction region through the gate to the detector in order to provide a baseline signal relating to the inverse ion mobility signal. Includes, Determining the characteristics of the sample further involves, based on the baseline signal, The method according to any one of claims 11 to 13, which is dependent on claim 11. [Claim 15] An ion mobility spectrometer, Ionizer and, The gate, A controller, positioned to control the ionizer and the gate, and configured to control the ion mobility spectrometer to perform the method according to any one of claims 1 to 14, Having, An ion mobility spectrometer characterized by the following features. [Claim 16] A computer program product configured to program a controller for an ion mobility spectrometer to perform the method described in any one of claims 1 to 15, For example, the controller is arranged to control the ionizer and gate of the ion mobility spectrometer. A computer program product characterized by the following features.

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