Ion mobility spectrometers and methods for the analysis of substances

Abstract

Ion mobility spectrometers with the following features: a) at least one ion packet delivery device (100, 101) configured to provide packets of ions successively and at time intervals, b) an ion detector (105), c) at least one drift chamber (11) through which the ions are guided over a predetermined distance in a drift direction (D) to the ion detector (105) in order to be discharged there, d) wherein the ion mobility spectrometer has an ion modification region (103) between the ion packet delivery device (100, 101) and the at least one drift chamber (11), the ion modification region having an input electrode arrangement (7) on the side facing the ion packet delivery device (100, 101) and an output electrode arrangement (8) on the side facing the at least one drift chamber (11), wherein a modification chamber (1) for receiving ions is arranged between the input electrode arrangement (7) and the output electrode arrangement (8), wherein the ion modification region (103) is configured to carry out one or more modifications to the ions located in the modification chamber (1), characterized in that the ion mobility spectrometer is configured to first generate an electric field (12) in the ion modification region (103) to prepare for the modification of ions in the modification chamber (1), e.g.in the drift direction (D), with a DC component sufficient to move ions to be modified from the direction of the input electrode arrangement (7) into the modification chamber (1), and then, when there are sufficient ions in the modification chamber (1), . - to reduce the DC component of the electric field to zero or - to eliminate a movement of at least one ion species to be modified caused by a superimposed alternating electric field in the modification chamber (1) by adjusting the DC component of the electric field or - to minimize the average motion of all ion species caused by a superimposed alternating electric field in the modification chamber (1) by adjusting the DC component of the electric field.

Description

[0001] The invention relates to an ion mobility spectrometer with the following features: a) at least one ion packet delivery device configured to sequentially deliver packets of ions at time intervals, b) an ion detector, c) at least one drift chamber through which the ions are guided over a predetermined distance in a drift direction to the ion detector in order to be discharged there.

[0002] The invention also relates to a method for analyzing substances by ion mobility spectrometry using an ion mobility spectrometer of the type mentioned above.

[0003] An ion mobility spectrometer and a corresponding method for gas analysis are already known from DE 10 2013 114 421 B4. Further embodiments of ion mobility spectrometers are known from US 2010 / 0051800 A1, US 2009 / 0039248 A1, US 2016 / 0054263 A1, and US 2010 / 0127164 A1. US 2015 / 0185190 A1 discloses a gas chromatograph-ion mobility spectrometer system with a double tube. US 2019 / 0056351 A1 discloses a system with a mass spectrometer and an ion mobility spectrometer. US 2010 / 0108878 A1 discloses a mass spectrometer.

[0004] The invention is based on the objective of providing an ion mobility spectrometer with further improved analytical capabilities and a corresponding method.

[0005] This problem is solved by an ion mobility spectrometer according to claim 1. This includes the ion mobility spectrometer having an ion modification region between the ion packet delivery device and the at least one drift chamber. The ion modification region has an input electrode arrangement on the side facing the ion packet delivery device and an output electrode arrangement on the side facing the at least one drift chamber. A modification chamber for receiving ions is arranged between the input electrode arrangement and the output electrode arrangement. The ion modification region is configured to perform one or more modifications on the ions located in the modification chamber. A modification is understood to mean, for example, a change in at least one physical and / or chemical property of the ions. The ions can be trapped in the ion modification region, for example.Ion capture is not a modification. Ion capture represents a significant difference from the prior art. The ion modification area is generally not used to discharge the ions, unless it is intended to function as a filter. Discharge should typically occur at the ion detector.

[0006] The invention has the advantage that the specified setup of the ion mobility spectrometer with the ion modification area enables further methods for the analysis, modification and / or influencing of ions, with which the ions within the ion mobility spectrometer can be analyzed, modified or otherwise influenced again in addition to the actual ion mobility spectrometry, e.g. to obtain additional information, to further improve the selectivity, linearity and / or sensitivity of the analysis.

[0007] Modifying specific ions, ion species, or ion packets provides an additional alteration of these elements that goes beyond the core functionality of an ion mobility spectrometer. The core functionality of an ion mobility spectrometer is understood to be the provision of ion packets, their packet-wise release at time intervals into a drift chamber, the movement of the ions through the drift chamber, and their detection by an ion detector.

[0008] When reference is made to an ion drift direction (or simply drift direction), this does not refer to the current direction of movement of ions or ion bunches, but rather to a fixed, predetermined drift direction in which the ions must move through the drift space to reach the ion detector. When an axial direction is mentioned, this refers to the longitudinal axis of the ion mobility spectrometer or the specific part of the ion mobility spectrometer in question. The axial direction can, in particular, be parallel to the drift direction.

[0009] The at least one drift chamber can be arranged, viewed in the direction of drift, between the ion packet delivery device and the ion detector. The ion modification region can be located, in the direction of ion drift, downstream of the ion packet delivery device and upstream of the at least one drift chamber. In the ion mobility spectrometer according to the invention, it is important that the ions have already traveled a certain drift distance before entering the ion modification region. This can also be just the short distance from the ion packet delivery device to the ion modification region. Or, in other words, the ion source is not located in the ion modification region. The ion mobility spectrometer can have further components in addition to those already mentioned, e.g.an ion gate arranged in the direction of drift behind an ion source of the ion packet delivery device and in front of the ion modification area and / or an additional drift space arranged behind the ion packet delivery device or behind the ion gate and in front of the ion modification area.

[0010] According to an advantageous embodiment of the invention, the ion packet delivery device comprises a pulsed ion source and / or a continuously operated ion source. With a pulsed ion source, the ion packets are provided in batches at time intervals by the very functionality of the ion source. In this case, a downstream ion gate is not required. A continuously operated ion source, as the name suggests, continuously releases ions.

[0011] According to an advantageous embodiment of the invention, the ion packet delivery device has a pulsed ion gate. The ion gate can be designed, for example, as a shutter, such as a field-switching shutter, Bradbury-Nielsen shutter, Tyndall-Powell shutter, or tristate shutter. Such a pulsed ion gate releases the ions provided by the ion source in packets; that is, there is a pause between the release of one ion packet and the release of the next, during which no ions are released. Advantageously, the input electrodes of the ion modification region and the electrodes of the shutter can be the same; that is, the shutter can be integrated into the input electrode arrangement. This saves grid electrodes and thus reduces complexity and ion losses.

[0012] According to an advantageous embodiment of the invention, a feed port is provided at the ion modification area, which is configured to introduce at least one additional substance, in particular a gaseous substance, into the modification chamber from the outside. This has the advantage that an additional substance can be introduced directly into the modification chamber, where it can react with the ions contained therein. For example, chemical reactions can be carried out in the modification chamber using such an additional substance, which are advantageous for further analysis. Cluster formation of ions can also be promoted by such additional substances. Furthermore, thermal energy can be supplied by the introduced gas, for example, if hot gas is introduced. A heater can therefore also be provided at the feed line to heat the gas.

[0013] The ion mobility spectrometer can have a first modification electrode array by which an electric field parallel to the drift direction of the ions, e.g., a field in the axial direction, can be generated in the modification chamber. The first modification electrode array can have one or more electrodes located within the modification chamber and / or electrodes that define the modification electrode array in the direction of the input electrode array and / or the output electrode array. The first modification electrode array can also be formed wholly or partially by one or more electrodes of the input electrode array and / or the output electrode array.

[0014] According to an advantageous embodiment of the invention, a first modification electrode arrangement is provided in the modification chamber, which has at least one electrode spaced apart from the input electrode arrangement and the output electrode arrangement. The modification chamber is divided by the first modification electrode arrangement into at least one first subchamber facing the input electrode arrangement and at least one second subchamber facing the output electrode arrangement. More electrodes of the first modification electrode arrangement and more subchambers are also possible. This has the advantage that different modifications to the ions can be carried out in the first and second subchambers. Furthermore, the first modification electrode arrangement can generate an electric field in the modification chamber that is parallel to the drift direction of the ions.In this way, the modified electrode arrangement can be used to selectively transport the ions in the drift direction, but also to reduce the drift velocity in the drift direction, up to and including reversing the drift direction so that the ions move back towards the input electrode arrangement.

[0015] According to an advantageous embodiment of the invention, a second modification electrode arrangement is provided at the ion modification region, by which an electric field orthogonal to the drift direction of the ions can be generated in the modification chamber. For example, the second modification electrode arrangement can have split ring electrodes or partially ring electrodes consisting only of opposing surfaces, i.e., which do not extend completely around the circumference of the ion modification region. This has the advantage that the ions can also be subjected to electric fields acting orthogonally to the drift direction, in particular alternating fields. This significantly expands the possibilities for modifying the ions.In particular, in combination with the first modification electrode arrangement, it is possible to generate both axial and orthogonal electric fields in the ion modification range, also in combination with each other.

[0016] The aforementioned problem is also solved by a method according to claim 11. The method serves to analyze substances by ion mobility spectrometry using an ion mobility spectrometer of the type described above, wherein the ions in the modification chamber are modified by one, several, or all of the following modification types (I), (II), (III), (IV), (V) before being moved through the drift chamber to the ion detector: I) Displacement of at least one species of ions present in a direction different from the direction of drift, II) Decreasing or increasing the drift velocity of at least one species of ions present in the direction of drift, or shifting at least one species of ions present in the direction of drift, III) Reducing or dissolving the clustering of ions and molecules, IV) Fragmentation of ions, V) Promoting chemical reactions and / or clustering of ions.

[0017] It should be noted that the term "shift" is always used generally here, even though this effect is compensated by a constant field.

[0018] In this way, various modifications can be made to the ions, allowing them to be analyzed again in addition to the actual ion mobility spectrometry. This yields additional information and also makes it possible to improve the selectivity, linearity, and sensitivity of the analysis.

[0019] It should be noted that all modifications serve to a) alter the ion mobility of individual ion species or b) shorten or lengthen the drift distance traveled by individual ion species. Only then is the modification meaningfully measurable in the IMS.

[0020] In modification type I), for example, at least one species from the existing ions of different ion species can be shifted in a direction deviating from the drift direction. It is also conceivable to implement the method with only one ion species present.

[0021] In modification type II), for example, operation with ion capture can be implemented by pushing the ions closer to or further away from the ion detector. This changes the time it takes for them to reach it.

[0022] In modification type III), for example, ion cluster formation can be broken up, e.g., by supplying additional energy to the ions via electric fields, such that ions and molecules joined together in a cluster are separated into individual ions or smaller clusters. In contrast, the fragmentation of ions described in modification type IV) refers to the breaking up of the ions into individual chemical elements or sub-ions. This can involve, for example, breaking the chemical bonds within ions.

[0023] According to an advantageous embodiment of the invention, one, several, or all of the modification types I), II), III), IV), V) are carried out at least partially by generating an alternating electric field, in particular an asymmetric or symmetric alternating field, in the modification chamber. This allows, for example, highly efficient targeted displacements, cluster dissolution, or ion fragmentation.

[0024] According to the invention, to prepare for the modification of ions in the modification chamber, in a first step an electric field, e.g. in the drift direction, with a DC component sufficient to move ions to be modified from the direction of the input electrode arrangement into the modification chamber is generated in the ion modification area, and then, when there are sufficient ions in the modification chamber, in a second step - the DC component of the electric field is reduced to zero or - by adjusting the DC component of the electric field, a movement of at least one ion species to be modified caused by a superimposed alternating electric field in the modification chamber is eliminated or - by adjusting the DC component of the electric field, the average movement of all ion species caused by a superimposed alternating electric field in the modification chamber is minimized.

[0025] In this way, the ions can be held in the modification chamber for a virtually freely adjustable time and modified there. The modification can then be carried out in the second step according to one, several, or all of the modification types I), II), III), IV), and V). Furthermore, when using an alternating electric field, it is possible to select the time such that a whole number of complete cycles of the alternating field are completed. This is not possible if the ions move through the modification region at their normal drift velocity, as different ion species would then have different residence times.

[0026] The time for which the ions are held in the modification chamber can be predetermined or determined during the analysis depending on the results. After the two steps mentioned above, it is useful to perform a third step in which an electric field with a DC component is generated in the ion modification region. This field is sufficient to move the modified ions out of the modification chamber towards the output electrode array and into the drift chamber leading to the ion detector.

[0027] According to an advantageous embodiment of the invention, one, several, or all of the modification types I), II), III), IV), V) are carried out, at least in part, by heating the interior of the modification chamber and / or the ions contained therein. Heating can supply additional energy to the ions in the modification chamber, which can, for example, reduce or break up ion cluster formation, fragment ions, or promote chemical reactions and / or ion cluster formation. The heating can be carried out, for example, by means of a heating device. The heating device can be part of the ion mobility spectrometer or designed as an external heating device. The heating device can supplement the energy supplied by the electric fields.The advantage of the invention is that electric fields can be adjusted much faster than conventional heating methods.

[0028] According to an advantageous embodiment of the invention, one, several, or all of the modification types I), II), III), IV), V) are carried out, at least in part, by adding a further substance, in particular a gaseous substance, through the feed port into the modification chamber. The addition of such a further substance allows for further modifications to the ions, in particular by chemical reactions.

[0029] According to an advantageous embodiment of the invention, a further substance to be analyzed by ion mobility spectrometry is supplied, which forms analyte ions to be analyzed with ions provided by the ion packet supply device and transported into the modification chamber. Accordingly, the actual analyte ions to be analyzed can only be produced in the ion modification chamber and do not need to be provided, or at least not completely, by the ion source. This extends the analytical capabilities of an ion mobility spectrometer to a multitude of additional substances that could not be analyzed with previous ion mobility spectrometers.

[0030] In all these methods, it is also advantageous to compare modified and unmodified spectra, i.e., not to always modify them. According to an advantageous embodiment of the invention, it is therefore provided that ion mobility spectra with and without modification of the ions are recorded alternately in the modification chamber. For example, ion mobility spectra with and without modification of the ions can always be recorded alternately. The alternation can also be carried out at other intervals, for example, regularly or irregularly.

[0031] The invention is explained in more detail below with reference to exemplary embodiments and drawings.

[0032] They show Fig. 1. An ion mobility spectrometer in a highly schematic representation, Fig. 2 to 9 embodiments of the ion modification range of the ion mobility spectrometer according to Fig. 1, Fig. 10 waveforms of electric fields associated with the ion modification range according to Fig. 9 can be generated, Fig. 11 a waveform of an electric field for modification, Fig. 12 modification possibilities of ions in the ion modification range.

[0033] The Fig. Figure 1 shows a block diagram of an ion mobility spectrometer (IMS) with an integrated ion modification system in the form of an ion modification chamber 103. The IMS comprises an ion source 100, an ion gate 101, the ion modification chamber 103, a drift chamber 11, and an ion detector 105. Optionally, an additional drift chamber 10 can be located downstream of the ion gate 101 and upstream of the ion modification chamber 103. The arrangement of the individual elements is variable, with the ion source 100, optionally including the ion gate 101, always forming the beginning and the ion detector 105 the end. Any arrangement of drift chambers or the ion modification chamber 103 can be advantageous in between. The ion source 100 and the ion gate 101 together form the ion packet delivery device. In the case of a pulsed ion source 100, the ion gate 101 can be omitted, so that the ion packet delivery device then only has the pulsed ion source 100.

[0034] IMS separates and characterizes ions based on their movement through a neutral gas under the influence of an electric field. The ions move with a characteristic drift velocity, as shown in... Fig. Figure 1 shows the drift from the ion source 100 to the ion detector 105, where the drift velocity depends on the electric field strength within the respective drift regions via the ion mobility. The ions move, for example, through the drift space 11 with a drift direction D.

[0035] By coupling this with highly efficient ionization at atmospheric pressure, even minute concentrations of substances can be detected based on the signals at the ion detector 105. However, separation solely via ion mobility or single-stage ionization is often insufficient to achieve the desired separation efficiency, selectivity, linearity, or sensitivity. Therefore, this document describes a setup and method for analyzing, modifying, or influencing ions. This allows for further analysis, modification, or other influence of the ions within the IMS, particularly in the ion modification area 103, to obtain additional information, selectivity, or sensitivity. For the sake of simplicity, all possible ion modifications will be grouped under the general term "modification" in the following discussion.A modification refers to any kind of change compared to a reference spectrum recorded without any modification of the ions. For example, a spectrum with and without modifications can always be recorded alternately, so that the effect of the modification is shown by differences between the two spectra (as in...). Fig. (illustrates) can be measured.

[0036] The ion modification region 103 consists of an input electrode arrangement 7 with one or more input electrodes, an output electrode arrangement 8 with one or more output electrodes, and one or more modification chambers 1, which extend in the drift direction D from the last electrode of the input electrode arrangement 7 to the first electrode of the output electrode arrangement 8. In the simplest case, both the input electrode arrangement 7 and the output electrode arrangement 8 are each formed by a single grid, although, as will be shown later, significantly more complex designs can also be advantageous. Depending on the arrangement, the ion modification region 103 can also include several modification chambers or sub-chambers separated from each other by additional electrodes.

[0037] Input electrode arrangement 7, modification chamber(s) 1, and output electrode arrangement 8 are configured to implement the following ion modification procedure: In a first step, an electric field with a DC component is generated in the ion modification region 103. This component is sufficient to move the ions to be modified from the direction of the input electrode arrangement 7 into the modification chamber 1. In a second step, the DC component is set to zero, or to a value that compensates for the movement of at least one ion species to be modified caused by an alternating electric field, or to a value that minimizes the average movement of all ion species caused by an alternating electric field. This allows the ions to be modified for a virtually freely adjustable time. This time can be predetermined or, as explained later, determined during the process.In the third step, an electric field with a DC component is generated in the ion modification area 103, which is sufficient to bring the modified ions out of the modification chamber 1 in the direction of the output electrode arrangement 8.

[0038] In the second step, ions can be modified according to one or more of the following possibilities, or it can be tested whether modifications occur under certain conditions or not: 1. An asymmetric alternating field displaces at least one ion species due to its field-dependent ion mobility, or this displacement is compensated by adjusting the constant field. 2. Ions are fragmented by an asymmetric or symmetric alternating field. 3. Ions are fragmented by heating in the analysis area or by hot gas. 4. The addition of further substances leads to reactions or cluster formation.

[0039] Regarding point 1, it should be noted that the term "shift" is always used generally here, even though this effect is compensated by a constant field. In this case, the constant field used for compensation is a measure of the field-dependent ion mobility. In addition to the preceding points, the second step can also include waiting periods without further modification, so that, for example, stimulated reactions can complete.

[0040] Advantageously, the procedure is only carried out on a portion of the recorded spectra, so that a comparison can be made between spectra without modification (reference spectrum) and spectra with modification (modified spectrum). Mechanical design

[0041] The apparatus according to the invention is typically used as part of an ion mobility spectrometer. This means that an ion source 100 and at least one first drift chamber 10 are located upstream of the input electrode arrangement 7, and at least one second drift chamber 11 and an ion detector 105 are located downstream of the output electrode arrangement 8. However, the first drift chamber 10 can also be omitted, so that all ions injected from the ion source 100 are analyzed or modified. The ion source 100 can assume any form known from ion mobility spectrometry, for example, a reaction chamber with a Bradbury-Nielsen, Tyndall-Powell, three-grid, or tristate ion gate, or a field-switching ion gate with an integrated field-free reaction chamber.

[0042] The Fig. Figure 2 shows an embodiment of the ion modification region 103, in which a first drift region 10 is provided within the ion modification region 103 by the input electrode arrangement 7. A second drift region 11 is provided within the ion modification region 103 by the output electrode arrangement 8. A first axial modification chamber 1 is located between the first and second drift regions, formed between the last electrode of the input electrode arrangement 7 in the drift direction D and the first electrode of the output electrode arrangement 8. These electrodes form a first modification electrode arrangement, by which an axially acting electric field 12 can be generated in the modification chamber 1. Thus, for example, axial alternating fields in the ion modification region 103 can generate displacement, declustering, and / or fragmentation of ions.

[0043] The Fig. Figure 3 shows an embodiment of a second modification electrode arrangement with electrodes 9, by which an electric field 14 orthogonal to the drift direction of the ions can be generated in the modification chamber 1. Orthogonal alternating fields in the ion modification region can induce declustering and / or fragmentation of ions.

[0044] For example, the electrodes of the input electrode arrangement 7 and / or the output electrode arrangement 8 are formed by grids, since these influence the electric field over the entire diameter of the ion modification region, regardless of the chosen diameter of the ion modification region. However, other electrode shapes can also be used, for example, ring electrodes 15, split ring electrodes, or partial ring electrodes 9, which consist only of opposing surfaces. It should be noted that, as in Fig. Figure 3 shows that only axial alternating fields allow both displacement and declustering and fragmentation, while orthogonal alternating fields only allow declustering and fragmentation.

[0045] According to an advantageous embodiment, the field in the ion modification range, particularly when using grids as electrodes, is as described in Fig. 2 shown is generated only by the respective inner electrodes of input electrode arrangement 7 and output electrode arrangement 8. It is the same as in Fig. Figure 3 also shows that it is possible to generate the alternating field in the ion modification range only or mainly via split or partially ring electrodes 9 as modification electrodes.

[0046] The Fig. Figure 4 shows an embodiment of a first modification electrode arrangement in which at least one electrode 90 is arranged at a distance from both the input electrode arrangement 7 and the output electrode arrangement 8, e.g., in the center of the modification chamber 1 or off-center. The electrode 90 divides the modification chamber 1 into a first sub-chamber T1 and a second sub-chamber T2. The input and output electrode arrangements 7 and 8 each consist of a grid. This design makes it possible to simultaneously generate electric fields of opposite polarity in the first sub-chamber T1 and the second sub-chamber T2 using only one alternating voltage source 17.

[0047] The Fig. Figure 4 also shows that the electrodes arranged in series can be connected to each other via a resistive voltage divider 16. A voltage source 17, e.g. an AC voltage source, can be connected to the voltage divider 16 or to specific electrodes.

[0048] It's like in Fig. Figure 4 also shows that additional ring electrodes 9 are possible in the modification chamber 1 or in the first subchamber T1 and / or the second subchamber T2, the potentials of which are set, for example, via the voltage divider 16 between the respective inner electrodes 28, 29 of the input electrode arrangement 7 and the output electrode arrangement 8. These ring electrodes 9 then follow the desired course of the electric potential, determined by the combination of static and alternating fields in the ion modification region 103, via a voltage divider. The ion modification region 103 can also contain further grids.

[0049] Advantageously, a further modification electrode 90 is provided between the first sub-chamber T1 and the second sub-chamber T2, to which the voltage of the voltage source 17 is applied to generate the alternating field, so that an electric field 12 exists in the first sub-chamber T1 and an electric field 13 with the opposite sign exists in the second sub-chamber T2. This results in the displacements of ions having opposite signs, which allows displacement in both directions with only one AC voltage source. If ring electrodes are used in this case, their voltage dividers can be connected to the modification electrode 90 as well as to the respective inner electrodes 28, 29 of the input electrode arrangement 7 and output electrode arrangement 8. The AC voltage source can be implemented, for example, by DC voltage sources and switches, as will be shown later.

[0050] As mentioned above, the electrodes of the input electrode arrangement 7 and output electrode arrangement 8 are often formed by grids, since these influence the electric field across the entire diameter, regardless of the selected drift region diameter. For small diameters at the location of the ion modification region 103, for example, a maximum of five times, preferably a maximum of twice, or equal to or smaller than the dimension of the ion modification region in the drift direction D, ring electrodes are almost as efficient as grids. In this case, ring electrodes, split ring electrodes, or partially ring electrodes can also be used for all electrodes of the input electrode arrangement, the ion modification regions, and the output electrode arrangement.

[0051] It is particularly advantageous to proceed as described in Fig. Figure 5 shows a structure consisting of several parallel channel-like configurations for modifying ions, each containing a rear electrode 7 of the input electrode arrangement 7, one or more modification chambers 3, 4, 5, 6, and a front electrode 8 of the output electrode arrangement 8. The individual modification chambers 3, 4, 5, 6 have smaller diameters than the original modification chamber 1, thus increasing the efficiency of the ring electrodes. In this case, it is advantageous to use a larger static electric field in the input electrode arrangement 7 than in the region upstream of it in the first step to focus the ions into the modification chambers 3, 4, 5, 6 and avoid losses.

[0052] The Fig. Figure 5 illustrates an embodiment with four parallel structures for ion modification (hatched). Due to the small diameter of each ion modification structure, the electrodes of input electrode arrangement 7, modification chambers 3, 4, 5, 6, and output electrode arrangement 8 can be designed as ring electrodes or partially as ring electrodes. Instead of an axial alternating electric field, an orthogonal alternating electric field between the parallel modification electrodes 9 of the modification chambers 3, 4, 5, 6 can advantageously be used for the modification in this arrangement.

[0053] The Fig. Figure 6 shows an embodiment of an ion modification chamber 103 in which additional substances or hot gas can be introduced into the modification chamber 1 or the subchambers T1, T2 through gas inlets 20, 21 for further modification in the ion modification chamber 103. Outlets 22, 23 can also be provided directly in the ion modification chamber 103 for the direct removal of the substances or gases supplied through the gas inlets 20, 21. The additional inlets or outlets 18, 19 can be used, for example, for the supply or removal of drift gas. They can also be arranged within the input electrode arrangement 7 and / or the output electrode arrangement 8.

[0054] The Fig. Figure 6 shows a section of an IMS with a setup for modifying ions (hatched), where the input electrode arrangement 7 is designed as a three-grid ion gate. The two subchambers T1, T2 of the modification chamber 1 are separated from each other by a modification electrode 90. The output electrode arrangement 8 shields the ion detector from the alternating electric fields in subchambers T1, T2. Additional substances or hot gas for further modification of the ions in subchambers T1, T2 can be introduced through the gas inlets 20, 21. The inlets and outlets 18, 19 serve to supply and remove the drift gas, respectively, and can also be located within the input or output electrode arrangement.

[0055] According to an advantageous embodiment, parts of the input electrode arrangement or the entire input electrode arrangement 7 form as shown in Fig. Figure 6 shows an ionator, particularly when a first drift region is present. It is even more advantageous to utilize the variable potential of the modification electrode 90 to construct an ionator. In this way, only a portion of the ions can be permitted for modification. All known ionators can be used, such as the Bradbury-Nielsen, Tyndall-Powell, three-electrode, or tristate ionator.

[0056] The use of a three-electrode or tristate ion gate is particularly advantageous, where the central electrode is formed from mutually insulated structures, for example, a grid of rods or a split or partial ring electrode. Alternatively, when using grids, at least two of the grids can be offset orthogonally to each other relative to the drift direction. This allows, in addition to the normal closing electric field in the longitudinal direction, an orthogonal static or alternating electric field to be used in the closed state to selectively eliminate non-transmitted ions.

[0057] According to an advantageous embodiment, parts of the output electrode arrangement or the entire output electrode arrangement 8 also form an ion gate. This allows ions that unintentionally escape from the modification chamber 1 during the modification process to be discharged and removed from the modified spectrum. The same design variants used for the input electrode arrangement 7 can be employed here.

[0058] According to an advantageous embodiment, at least the last electrode of the output electrode arrangement 8 in the drift direction D is at a fixed potential in order to shield the ion detector 105 from alternating voltages and / or voltage pulses in the ion modification region 103.

[0059] The Fig. Figure 6 shows additional, optional gas inlets 20, 21 in the first and second subchambers T1, T2 and gas outlets 22, 23 in the first and second subchambers T1, T2 to supply hot gas for heating the ion modification areas or to supply substances for further reactions in the ion modification area 103.

[0060] The Fig. Figure 7 shows a variant of the ion modification area 103, in which the modification chamber 1 has only one gas inlet 20 and one gas outlet 22.

[0061] According to an advantageous embodiment, the subchambers T1 and T2 have both dedicated gas inlets 20 and 21, as well as dedicated gas outlets 22 and 23, so that the gas flows selectively only through the respective subchamber T1 and T2. Such gas inlets 20 and 21 and gas outlets 22 and 23 can also be present in an undivided modification chamber. For this purpose, a gas flow similar to that described in DE 10 2019 125 482 for field-switching ion doors is particularly suitable. By ensuring a laminar gas flow only through the respective subchamber T1 and T2, the modification steps can be carried out without affecting the rest of the IMS.

[0062] According to an advantageous embodiment, during the second step, the one or two electrodes of the input electrode arrangement 7 and / or the output electrode arrangement 8 closest to the modification chamber 1 are at the same potential in order to reduce external field penetration. According to an advantageous embodiment, all electrodes of the input electrode arrangement and / or the output electrode arrangement are at the same potential. According to an advantageous embodiment, drift rings outside the analysis area are also placed at the same potential as the respective end of the analysis area during the second step, advantageously over at least one and a half, two, or three times the diameter of the drift tube.

[0063] Advantageous widths of the ion modification region 103 or the modification chamber 1 are 1 mm, 2 mm, 3 mm, 4 mm, and 5 mm, i.e., their dimension in the drift direction D. If the modification chamber 1 has several subchambers T1 and T2, the aforementioned dimensions apply to the respective subchambers. According to an advantageous embodiment, the distances between the electrodes of the input electrode arrangement 7 and between the electrodes of the output electrode arrangement 8 are smaller than the width of the ion modification region 103 or the modification chamber 1. It may be advantageous to select the distance between the two electrodes of the input electrode arrangement closest to the modification chamber 1 and / or the distance between the two electrodes of the output electrode arrangement closest to the modification chamber 1 as equal to or at least within 20% of the width of the modification chamber in order to avoid electrical breakdowns.According to an advantageous embodiment, the width of the modification chamber is m times the spatial extent of the ion packet of the ion species to be analyzed. m should, but need not, be greater than 1, preferably greater than 2. The spatial extent of the ion packet can be reduced or increased by adjusting the ratio of the electric field strength at a field transition, for example, between the region upstream of the input electrode arrangement and the region within the input electrode arrangement, in order to set m.

[0064] According to an advantageous embodiment, the surfaces of the electrodes exposed to the high electric field strengths, for example the input electrode arrangement, the output electrode arrangement and the electrodes in between, have a high work function in order to prevent electrical discharge between the electrodes. Modification modes

[0065] According to an advantageous embodiment, a reduced field strength of the alternating electric field greater than 10 Td, 30 Td, 60 Td, 90 Td or 120 Td is used to displace or fragment ions. This can be varied to achieve different displacements or fragmentations.

[0066] The displacement observed at different reduced field strengths can be analyzed either via the constant field required to compensate for the motion or via the displacement relative to another known ion species. From this, the so-called alpha function, the change in ion mobility with the reduced field strength, can also be determined. The absence of a displacement at a specific field strength can also provide valuable information. According to an advantageous embodiment, a standard with a known change in ion mobility with the reduced field strength is used to determine the displacement. It is particularly advantageous if this displacement of the standard is negligibly small.Likewise, the displacement can be used to eliminate one or more unwanted ion species from the ion modification area by cleverly choosing the constant field, while compensating for the movement of one or more other ion species so that they do not reach the electrodes.

[0067] Fragmentation at different reduced field strengths can also be analyzed. In particular, after separation in the second drift chamber, the ratios of one or more fragments to the original ion quantity can be analyzed. The absence of fragmentation at a specific reduced field strength can also provide information. As a standard, so-called thermometer ions can be used, which exhibit a bond that breaks at a known energy. According to an advantageous embodiment, a substance can be added to the reaction chamber, the first drift chamber, or even the ion modification chamber itself. This substance forms clusters with one or more ion species, allowing the dissociation of these clusters to be analyzed at different reduced field strengths. This is particularly helpful in the analysis of ions that cannot be fragmented due to their high stability.

[0068] Similarly, unwanted clusters can be dissociated extremely efficiently in the ion modification zone. This is the case, for example, when the ionization source is electrospray ionization (ESI). The resulting clusters of target substances and solvent can be dissociated in the ion modification zone, leaving only the desired ion species, which can then be transferred to the drift chamber downstream of the ion modification zone for separation.

[0069] In particular, a combination of, for example, displacement and fragmentation is also possible, allowing the analysis of several ion species with the same ion mobility at low reduced field strengths. For instance, during the second step, all but one ion species can first be eliminated using a displacement-based alternating field. Then, the remaining ion species can be fragmented using a fragmentation-based alternating field, and finally, the resulting fragments can be separated in the second drift chamber. This process can be repeated for all ion species at different reduced field strengths to obtain a comprehensive picture.

[0070] The energy transferred to the ions by high reduced electric field strengths depends quadratically on the ion mobility, according to the Wannier equation. Therefore, fragmentation using high reduced electric field strengths alone is only efficient for ions with high mobility. To support or even directly fragment the ions, hot gas can be passed through the ion modification zone, or the zone can be heated locally by other means. It is particularly advantageous to choose a temperature such that the resulting energy is just below the fragmentation energy of the most easily fragmented ion species being analyzed. This allows for the analysis of unmodified ion species even without an alternating electric field, and maximizes the energy range achievable through the alternating electric field.Heating the entire IMS is also possible in principle, but reduces the achievable resolution, may lead to fragmentation in the drift spaces, and, depending on the temperature, restricts the choice of materials for the design.

[0071] The Fig. Figure 8 shows a section of an IMS with a field-switching ion gate with an integrated reaction chamber 24, a setup for modifying ions (hatched, ion modification area 103), and a drift chamber 11. The gas inlets 20, 25 and outlets 22, 24 are arranged such that different gas compositions predominate during the formation of the reactant ions in area 27 and in the modification chamber 1. The drift gas in the drift chamber 11 can advantageously be supplied to or removed from the output electrode arrangement 8 via the gas inlet or outlet 19. Similar to DE 10 2018 107 909 A1, the output electrode arrangement 8 serves here as a field-free area for shielding during the modification.

[0072] The substances added through gas inlet 20 in ion modification zone 103 can also contain the actual sample, as shown in Fig. Figure 8 illustrates this. As a result, only reactant ions are present in the ion source and, if applicable, the first drift chamber 10 (not shown in the figure). This has a number of advantages: First, the reactant ions can react in the ion source over a longer period, for example, until they reach equilibrium, and only then be brought into contact with the analyte molecules in the ion modification region. This prevents intermediate products from participating in the formation of the analyte ions, which is particularly advantageous when using so-called dopandes, i.e., substances intended to influence the formation of the reactant ions. Furthermore, the reaction time for the formation of the reactant ions and the reaction time for the formation of the analyte ions can be set independently of each other. This allows for extremely short reaction times, in particular, to increase the linear region and to minimize competing reactions.

[0073] Secondly, the first drift chamber, particularly in combination with an ion gate in the input electrode arrangement, allows for the selective choice of only one reactant species for analyte formation, even when multiple reactant ion species are formed. Furthermore, only reactants of a single polarity participate in the reactions, thus eliminating recombination as a loss mechanism for analyte ions.

[0074] Thirdly, the alternating field can influence the reactants during the formation of the analytes. For example, water clusters can be broken up to increase the reactivity of the reactants. Waveform and electrical circuitry

[0075] According to an advantageous embodiment, an alternating field consisting of a short pulse, e.g., in rectangular form, with a high field strength in one of the two directions, combined with a longer period of lower field strength in the opposite direction, is used to displace the ions. It is particularly advantageous if the short pulse comprises less than 30%, less than 20%, or less than 10% of the period. According to an advantageous embodiment, an alternating field consisting of pulses of similar amplitude and length in both directions (high and low levels) is used to fragment the ions. An alternating field in which each direction comprises 50% of the period is particularly advantageous. Generally, longer pulses lead to greater fragmentation because the ion only absorbs sufficient energy and distributes it across its internal states over a longer period.Therefore, a targeted reduction of the pulse duration by a shorter period or a smaller fraction of the pulse can be helpful in achieving displacement without fragmentation.

[0076] All voltages described as pulses can be approximated by similar functions, for example trapezoidal voltages, exponential curves such as in a back-overshoot generator, or the superposition of one or more sinusoidal oscillations.

[0077] According to an advantageous embodiment, parameters such as reduced field strength, period, pulse fraction of the period or time until the second step are adjusted so that during the modification none of the ion species to be analyzed and their productions are discharged on the input electrode arrangement or the output electrode arrangement or the intermediate electrodes.

[0078] Three points are particularly relevant here. First, the time until the second step should be selected such that the ion packet of the ion species to be analyzed is positioned as symmetrically as possible between the inner electrodes 28, 29 of input electrode arrangement 7 and output electrode arrangement 8, in order to maximize the possible amplitude of the motion in the alternating field. Second, the period should be selected such that these electrodes are not yet reached by the ion packet during the motion in the alternating field, or at least not yet reached by a significant percentage of the ions. Third, the total duration of the modification, i.e., the duration for which the second step is performed, should be selected such that the diffusion of the ion packet does not yet lead to the electrodes being reached. The last two points, in particular, must be considered in combination.

[0079] According to an advantageous embodiment, the optimal time to the second step is calculated based on the drift time in the reference spectrum, determined by measurement with a standard, or experimentally determined by varying the time to the second step and selecting the value with the lowest losses. For experimental determination, the other parameters must be chosen such that losses already occur. Alternatively, the optimal time can also be determined by switching the ion gate formed by the input electrode arrangement and the ion gate formed by the output electrode arrangement, whereby the ion species to be analyzed just appears or just disappears from the spectrum.

[0080] According to an advantageous embodiment, the maximum possible period is calculated based on the ion mobility determined via the drift time in the reference spectrum or is determined experimentally by varying the period and choosing the largest value at which no disturbing losses occur.

[0081] According to an advantageous embodiment, the maximum total duration of the modification, i.e., the maximum duration for which the second step is taken, is calculated based on the ion mobility determined via the drift time in the reference spectrum and the diffusion coefficient calculable from it, or is determined experimentally by varying the duration of the second step and choosing the largest value at which no disturbing losses occur.

[0082] In particular, the total duration of the modification can also be shortened based on other parameters, for example by ensuring that a certain percentage of the ions have already been fragmented.

[0083] The values ​​of the individual parameters at which losses occur, or the resulting losses, can be determined either by varying the parameter and measuring the charge quantity at the detector, or by using current amplifiers at the inner electrodes 28, 29 of input electrode arrangement 7 and output electrode arrangement 8. The first method can be implemented without additional technical effort; the second is particularly helpful for determining the period and the total duration of the modification, since it is not necessary to try out different parameter values, but rather the critical point can be detected directly during the measurement.

[0084] The Fig. Figure 9 shows an ion modification range 103 similar to the Fig. Figure 7, which additionally shows an electrical circuit for the input electrode arrangement 7 and the output electrode arrangement 11. The input electrode arrangement 7 and the output electrode arrangement 8 each consist of two grid electrodes. The grid electrodes 28, 29 adjacent to the modification chamber 1 simultaneously form the first modification electrode arrangement. By a clever arrangement of switches 34 and voltage sources 30, 31, 32, an efficient generation of electric fields can be achieved in the modification chamber 1, enabling efficient displacement of ions in both directions as well as fragmentation with only one modification chamber 1 and one high-voltage source 32, i.e., all in Fig. The 12 waveforms shown can be generated using this method. The input electrode arrangement 7 and the output electrode arrangement 8 can each additionally form an ion gate.

[0085] According to an advantageous embodiment, there exist as in Fig. 9 shown at input electrode arrangement 7 and output electrode arrangement 11, switch 34 to switch at least the potential of the innermost electrodes 28, 29. Thus, with a single high-voltage source 32, both displacements in both directions and fragmentation can be efficiently realized in only one ion modification region. In addition to the Fig. Other variations of the circuit shown in Figure 9 are also conceivable, for example, where the voltage sources 30 and 31 are derived from the voltage divider of the drift chambers. The integration of further switches and voltage sources is also conceivable in order to perform additional modification steps, for example, entirely without electric fields in the ion modification region 103. Furthermore, it is advantageous to replace the switches 34 and voltage sources 30, 31, and 32 with rapidly adjustable voltage sources to simplify the circuit.

[0086] Since the exact position of ion and fragment formation in the ion modification region 103 is unknown, additional methods for determining mobility are advantageous. In a preferred embodiment, the voltage across the second drift chamber 11 is varied, and the respective mobility of the substances is determined from the resulting change in drift time. For simplification, this can be performed once in a single measurement, and subsequently, the time axis can be converted into a mobility axis based on the points thus known. Likewise, both the drift time and such a method can be used to determine the ion mobility necessary for many calculations without modification.

[0087] The Fig. Figure 10 uses three diagrams to illustrate various fundamental operating principles of the ion modification range of the IMS. The upper diagram shows that by controlling the electrodes of the ion modification range, fragmentation of the ions can be generated compared to a reference spectrum. The middle diagram shows how a shift of ions relative to a reference spectrum can be generated in the ion modification range. The lower diagram clarifies that ion filtering can also occur via the ion modification range. The diagrams in the Fig. Figures 10 show the amount of ions over the drift time in the drift space 11.

[0088] The Fig. Figure 11 illustrates an advantageous waveform of an alternating electric field that can be used to carry out ion modification in the ion modification region. It can be seen that in the period before t startThere is no electric field present (field strength = 0). From time t start An alternating electric field is generated, which lies between the limit values ​​E high and E low It switches back and forth. The value of E is... low < 0, meaning that in this case a field strength is generated in the opposite direction to the normal drift direction. The value of E high is always greater than zero. At time t stop The ion modification process ends with the application of an alternating electric field. This waveform, as an alternating electric field, has a DC component of zero, but as already mentioned, it can be superimposed with a DC component.

[0089] The Fig. Figure 12 shows, using three diagrams, the following, for example, in the wiring according to... Fig. 9 electric fields to be generated in the ion modification area 103 or in the modification chamber 1. The upper diagram shows an advantageous application of an alternating electric field, which allows fragmentation and filtering of ions. Here, an alternating field symmetrical around the field strength value of zero is generated. The middle diagram shows an alternating electric field, e.g., similar to that in Fig.11, which can be used to shift the ions and perform further filtering. The lower diagram shows an alternating electric field, which can be used to perform an inverted shift and further filtering. Here, the average electric field strength is significantly lower than in the middle diagram, in particular, on average below zero. All these waveforms have a DC component of zero, but as already mentioned, they can be superimposed with a DC component.

Claims

[1] ion mobility spectrometer with the following features: a) at least one ion packet delivery device (100, 101) configured to provide packets of ions successively and at time intervals, b) an ion detector (105), c) at least one drift chamber (11) through which the ions are guided over a predetermined distance in a drift direction (D) to the ion detector (105) in order to be discharged there, d) wherein the ion mobility spectrometer has an ion modification region (103) between the ion packet delivery device (100, 101) and the at least one drift chamber (11), the ion modification region having an input electrode arrangement (7) on the side facing the ion packet delivery device (100, 101) and an output electrode arrangement (8) on the side facing the at least one drift chamber (11), wherein a modification chamber (1) for receiving ions is arranged between the input electrode arrangement (7) and the output electrode arrangement (8), wherein the ion modification region (103) is configured to carry out one or more modifications to the ions located in the modification chamber (1), characterized by, that the ion mobility spectrometer is set up to first generate an electric field (12), e.g. in the drift direction (D), with a DC component sufficient to move ions to be modified from the direction of the input electrode arrangement (7) into the modification chamber (1), in preparation for the modification of ions in the modification chamber (1), and then, when there are sufficient ions in the modification chamber (1), - to reduce the DC component of the electric field to zero or - to eliminate a movement of at least one ion species to be modified caused by a superimposed alternating electric field in the modification chamber (1) by adjusting the DC component of the electric field or - to minimize the average motion of all ion species caused by a superimposed alternating electric field in the modification chamber (1) by adjusting the DC component of the electric field. [2] ion mobility spectrometer according to claim 1, characterized by , that the ion packet delivery device (100, 101) has a pulsed ion source (100) and / or a continuously operated ion source (100). [3] ion mobility spectrometer according to any of the preceding claims, characterized by , that the ion packet delivery device (100, 101) has a clocked ion gate (101). [4] ion mobility spectrometer according to any of the preceding claims, characterized by , that a feed port (20, 21) is provided at the ion modification area (103) which is designed to introduce at least one further substance, in particular a gaseous substance, into the modification chamber (1) from the outside. [5] ion mobility spectrometer according to claim 4, characterized by , that on the ion modification area (103) opposite the feed port (20, 21) there is an outlet port (22, 23) which is designed to discharge the at least one further substance supplied via the feed port (20, 21) from the modification chamber (1). [6] ion mobility spectrometer according to any one of the preceding claims, characterized by , that the ion mobility spectrometer has a first modification electrode arrangement by which an electric field parallel to the drift direction of the ions can be generated in the modification chamber. [7] ion mobility spectrometer according to claim 6, characterized by, that the first modification electrode arrangement is formed wholly or partly by one or more electrodes of the input electrode arrangement and / or the output electrode arrangement, in particular by the electrodes of the input electrode arrangement (7) and the output electrode arrangement (8) that are closest to the modification chamber (1). [8] ion mobility spectrometer according to one of claims 6 to 7, characterized by , that the first modification electrode arrangement is present in the modification chamber (1), which has at least one electrode (90) spaced apart from the input electrode arrangement (7) and the output electrode arrangement (8), wherein the modification chamber (1) is divided by the first modification electrode arrangement into at least one first subchamber (T1) facing the input electrode arrangement (7) and at least one second subchamber (T2) facing the output electrode arrangement (8). [9] ion mobility spectrometer according to any of the preceding claims, characterized by , that a second modification electrode arrangement is present at the ion modification area (103), by which an electric field (14) orthogonal to the drift direction (D) of the ions can be generated in the modification chamber (1). [10] ion mobility spectrometer according to any one of the preceding claims, characterized by , that the extent of the modification chamber (1) or the sub-chambers (T1, T2) in the direction of the drift motion of the ions corresponds at least to the single, in particular to 2 times, in particular to 5 times, in particular to 10 times, in particular to 20 times the value of the half-width of the ion packet of the ions to be analyzed. [11] Method for analyzing substances by ion mobility spectrometry using an ion mobility spectrometer according to one of the preceding claims, wherein the ions in the modification chamber (1) are modified by one, several or all of the following modification types I), II), III), IV), V) before being moved through the drift chamber (104) to the ion detector (105): I) Displacement of at least one species from the existing ions in a direction different from the drift direction (D), II) Decreasing or increasing the drift velocity of at least one species of the existing ions in the drift direction (D) or shifting at least one species of the existing ions in the drift direction (D), III) Reducing or dissolving the clustering of ions and molecules, IV) Fragmentation of ions, V) Promoting chemical reactions and / or cluster formation of ions, characterized by, that to prepare for the modification of ions in the modification chamber (1) an electric field (12), e.g. in the drift direction (D), with a DC component sufficient to move ions to be modified from the direction of the input electrode arrangement (7) into the modification chamber (1), is first generated in the ion modification area (103), and then, when there are sufficient ions in the modification chamber (1), - the DC component of the electric field is reduced to zero or - by adjusting the DC component of the electric field, a movement of at least one ion species to be modified caused by a superimposed alternating electric field in the modification chamber (1) is eliminated or - by adjusting the DC component of the electric field, the average motion of all ion species caused by a superimposed alternating electric field in the modification chamber (1) is minimized. [12] Method according to claim 11, characterized by , that one, several or all of the modification types I), II), III), IV), V) are carried out at least in part by generating an alternating electric field, in particular an asymmetric or symmetric alternating field, in the modification chamber (1). [13] Method according to any one of claims 11 to 12, characterized by , that one, several or all of the modification types I), II), III), IV), V) are carried out at least in part by heating the interior of the modification chamber (1) and / or the ions contained therein. [14] Method according to any one of claims 11 to 13, characterized by , that one, several or all of the modification types I), II), III), IV), V) are carried out at least in part by adding another substance, in particular a gaseous substance, through the feed port into the modification chamber (1). [15] Method according to claim 14, characterized by, that a further substance to be analyzed by ion mobility spectrometry is supplied, which forms analyte ions to be analyzed with ions provided by the ion packet supply device and transported into the modification chamber (1). [16] Method according to any one of claims 11 to 15, characterized by , that ion mobility spectra with and without modification of the ions are recorded alternately in the modification chamber (1).

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