Ion mobility spectrometer, and method for analysing substances

Abstract

The invention relates to an ion mobility spectrometer having the following features: a) at least one ion packet provision device which is designed to provide packets of ions successively at time intervals; b) an ion detector; and c) at least one drift chamber through which the ions are guided over a predefined distance in a drift direction to the ion detector in order to be discharged there. The invention also relates to a method for analysing substances using ion mobility spectrometry by means of an an ion mobility spectrometer of the aforementioned type.

Description

[0001] Ion mobility spectrometers and methods for analyzing substances

[0002] The invention relates to an ion mobility spectrometer having the following features: a) at least one ion packet providing device which is designed to provide packets of ions one after the other at time intervals, b) an ion detector, c) at least one drift space through which the ions are guided over a predetermined path in a drift direction to the ion detector to be discharged there.

[0003] The invention also relates to a method for analyzing substances by ion mobility spectrometry using an ion mobility spectrometer of the aforementioned type.

[0004] An ion mobility spectrometer and a corresponding method for gas analysis are already known from DE 10 2013 114 421 B4.

[0005] The invention is based on the object of providing an ion mobility spectrometer and a corresponding method which is further improved with regard to the analysis possibilities.

[0006] This object is achieved in an ion mobility spectrometer of the type mentioned at the outset in that the ion mobility spectrometer has an ion modification region between the ion packet provision device and the at least one drift space, which has an input electrode arrangement on the side facing the ion packet provision device and an output electrode arrangement on the side facing the at least one drift space, wherein a modification chamber for receiving ions is arranged between the input electrode arrangement and the output electrode arrangement, wherein the ion modification region is configured to carry out one or more modifications on the ions located in the modification chamber. Modification is understood to mean, for example, a change in at least one physical and / or chemical property of the ions. The ions can, for example, be trapped in the ion modification region.Traps are not modifications. Traps represent a significant difference compared to the state of the art. The ion modification region is generally not used to discharge ions unless it is used as a filter. Discharge should generally only occur at the ion detector.

[0007] The invention has the advantage that the specified structure of the ion mobility spectrometer with the ion modification region enables further methods for analyzing, modifying and / or influencing ions, with which the ions within the ion mobility spectrometer can be analyzed, modified or influenced in another way 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.

[0008] By modifying specific ions, specific ion species, or ion packets, an additional change to such elements is provided that goes beyond the actual functionality of an ion mobility spectrometer. The actual functionality of an ion mobility spectrometer is understood to be the provision of ion packets, their release in packets at time intervals into a drift space, the movement of the ions through the drift space, and their detection by an ion detector.

[0009] When reference is made to a drift direction of the ions (or drift direction for short), this does not mean the current direction of movement of ions or ion packets, but rather a fixed drift direction with 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 respective part of the ion mobility spectrometer in question. The axial direction can in particular be parallel to the drift direction. The at least one drift space can be arranged between the ion packet provision device and the ion detector, viewed in the drift direction. The ion modification region can be located behind the ion packet provision device and in front of the at least one drift space, viewed in the drift direction of the ions.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 only the short distance from the ion packet delivery device to the ion modification region. Or, to put it another way, the ion source is not located in the ion modification region. In addition to the components mentioned above, the ion mobility spectrometer can have further components, e.g., an ion gate arranged in the drift direction behind an ion source of the ion packet delivery device and in front of the ion modification region, 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 region.

[0010] According to an advantageous embodiment of the invention, the ion packet supply device comprises a pulsed ion source and / or a continuously operated ion source. With a pulsed ion source, the ion packets are provided in packets at timed intervals by the functionality of the ion source itself. In this case, a downstream ion gate is unnecessary. A continuously operated ion source, as the name suggests, releases ions continuously.

[0011] According to an advantageous embodiment of the invention, the ion packet supply device has a pulsed ion gate. The ion gate can be designed, for example, as a shutter, e.g., 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, i.e., between the release of one ion packet and the release of the next, there is a pause 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, i.e., the shutter can be integrated into the input electrode arrangement. This eliminates the need for grid electrodes and thus reduces complexity and ion losses.According to an advantageous embodiment of the invention, a supply connection is provided at the ion modification region, which is designed to introduce at least one further substance, in particular a gaseous substance, into the modification chamber from the outside. This has the advantage that a further substance can be introduced directly into the modification chamber, where it can react with the ions present therein. By means of such an additional substance, for example, chemical reactions can be carried out in the modification chamber which are advantageous for further analysis. Cluster formation of ions can also be promoted by such additional substances. Furthermore, a supply of thermal energy is possible through the introduced gas, e.g. when hot gas is introduced. A heater can therefore also be present on the supply line to heat the gas.

[0012] The ion mobility spectrometer can have a first modification electrode arrangement, by means of 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 arrangement can have one or more electrodes arranged in the modification chamber and / or electrodes that delimit the modification electrode arrangement in the direction of the input electrode arrangement and / or the output electrode arrangement. The first modification electrode arrangement can also be formed entirely or partially by one or more electrodes of the input electrode arrangement and / or the output electrode arrangement.

[0013] According to an advantageous embodiment of the invention, a first modification electrode arrangement is present in the modification chamber, which has at least one electrode spaced apart from the input electrode arrangement and the output electrode arrangement, wherein the modification chamber is divided by the first modification electrode arrangement into at least one first sub-chamber facing the input electrode arrangement and at least one second sub-chamber facing the output electrode arrangement. Even more electrodes of the first modification electrode arrangement and even more sub-chambers are also possible. This has the advantage that different modifications can be carried out on the ions in the first and second sub-chambers. In addition, 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 modification electrode arrangement can be used to specifically 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 such that the ions move back towards the input electrode arrangement.

[0014] According to an advantageous embodiment of the invention, a second modification electrode arrangement is provided at the ion modification region, by means of 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 partial ring electrodes that consist only of opposing surfaces, i.e., that do not extend completely around the circumference of the ion modification region. This has the advantage that the ions can also be exposed 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 region, even combined with each other.

[0015] The object mentioned above is also achieved by a method for analyzing 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 they are moved through the drift space to the ion detector:

[0016] I) Shifting at least one species from the existing ions in a direction different from the drift direction,

[0017] II) reducing or increasing the drift velocity of at least one species of the ions present in the drift direction or shifting at least one species of the ions present in the drift direction,

[0018] III) Reducing or dissolving the clustering of ions and molecules,

[0019] IV) Fragmentation of ions,

[0020] V) Promote chemical reactions and / or cluster formation of ions. It should be noted that the term "displacement" is always used here, even if this effect is compensated by a constant field.

[0021] 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 allows additional information to be obtained. It is also possible to improve the selectivity, linearity, and sensitivity of the analysis.

[0022] It should be noted that all modifications serve to a) change the ion mobility of individual ion species or b) shorten or lengthen the drift distance traveled by individual ion species. Only then can the modification be meaningfully measured in the IMS.

[0023] In modification type I), for example, at least one species from the existing ions of different ion species can be shifted in a direction different from the drift direction. It is also conceivable to implement the process with only one ion species present.

[0024] In modification type II), for example, ion trapping can be performed by moving the ions closer to or further away from the ion detector. This changes the time it takes for them to reach it.

[0025] In modification type III), for example, a cluster of ions can be broken up in such a way, e.g., by supplying additional energy to the ions via electric fields, that the ions and molecules that have joined together to form a cluster are split into individual ions or smaller clusters. The fragmentation of ions, referred to in modification type IV), on the other hand, refers to the breaking up of the ions into individual chemical elements or sub-ions. This can, for example, break the chemical bonds within ions.

[0026] According to an advantageous embodiment of the invention, one, several, or all of the modification types I), II), III), IV), and 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, very efficient targeted displacements, dissolution of clusters, or fragmentation of ions.

[0027] According to an advantageous embodiment of the invention, it is provided that in order to prepare 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 that is sufficient to move ions to be modified from the direction of the input electrode arrangement into the modification chamber, 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 canceled or by adjusting the DC component of the electric field an average movement of all ion species caused by a superimposed alternating electric field in the modification chamber is minimized.

[0028] In this way, the ions can be held in the modification chamber and modified there for a virtually freely adjustable time. The modification can be carried out in the second step according to one, several, or all of the modification types I), II), III), IV), and V). When using an alternating electric field, it is also possible to select the time so that a whole number of full cycles of the alternating field are completed. This is not possible if the ions move through the modification region at their normal drift velocity, since different ion species then have different residence times.

[0029] 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 advisable to perform a third step, in which an electric field with a DC component is generated in the ion modification region, sufficient to move the modified ions out of the modification chamber toward the output electrode array and into the drift space that follows, toward the ion detector.

[0030] 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 located therein. By heating, additional energy can be supplied to the ions located in the modification chamber, which can, for example, reduce or dissolve the cluster formation of ions, fragment ions or promote chemical reactions and / or cluster formation of ions. 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 be designed as an external heating device. The heating device can be supplemented in addition to 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.

[0031] According to an advantageous embodiment of the invention, one, several, or all of the modification types I), II), III), IV), and V) are carried out at least partially by adding a further substance, in particular a gaseous substance, through the feed port into the modification chamber. By adding such a further substance, further modifications to the ions can be carried out, in particular through chemical reactions.

[0032] According to an advantageous embodiment of the invention, a substance to be analyzed by ion mobility spectrometry is supplied as an additional substance, which forms analyte ions to be analyzed with ions provided by the ion packet provision device and transported into the modification chamber. Accordingly, the actual analytes to be analyzed can only be produced in the ion modification area and do not have to be provided, or at least not completely, by the ion source. This expands the analysis capabilities of an ion mobility spectrometer to include a multitude of other substances that could not be analyzed with previous ion mobility spectrometers.

[0033] In all these methods, it is also advantageous to compare modified and unmodified spectra, i.e., not always modify them. According to an advantageous embodiment of the invention, ion mobility spectra are recorded alternately with and without modification of the ions in the modification chamber. For example, ion mobility spectra can always be recorded alternately with and without modification of the ions. The alternation can also be performed at other intervals, for example, regularly or irregularly.

[0034] The invention is explained in more detail below using exemplary embodiments and drawings.

[0035] It shows

[0036] Figure 1 shows an ion mobility spectrometer in a highly schematic representation, Fig. 2 to 9 embodiments of the ion modification region of the ion mobility spectrometer according to Figure 1,

[0037] Figure 10 Waveforms of electric fields that can be generated with the ion modification region according to Figure 9,

[0038] Figure 11 shows a waveform of an electric field for modification, Figure 12 shows modification possibilities of ions in the ion modification region.

[0039] Figure 1 shows a block diagram of an ion mobility spectrometer (IMS) with an integrated structure for modifying ions in the form of an ion modification region 103. The IMS has an ion source 100, an ion gate 101, the ion modification region 103, a drift space 11, and an ion detector 105. Optionally, an additional drift space 10 can be present behind the ion gate 101 and in front of the ion modification region 103. The arrangement of the individual elements is variable, with the ion source 100, possibly with the ion gate 101, always forming the beginning and the ion detector 105 the end. Any arrangement of drift spaces or the ion modification region 103 in between can be advantageous. The ion source 100 and the ion gate 101 together form the ion packet providing device.In the case of a clocked ion source 100, the ion gate 101 can be omitted, so that the ion packet providing device then only has the clocked ion source 100.

[0040] IMS separate and characterize ions based on their movement through a neutral gas under the influence of an electric field. The ions move from the ion source 100 to the ion detector 105 with a characteristic drift velocity, as shown in Figure 1. The drift velocity, via the ion mobility, depends on the electric field strength within the respective drift regions. For example, the ions move through the drift space 11 with a drift direction D.

[0041] By coupling with highly efficient ionization at atmospheric pressure, even the smallest 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, a setup or method for analyzing, modifying, or influencing ions is presented here, with which the ions within the IMS, particularly in the ion modification region 103, can be further analyzed, modified, or influenced in another way to obtain additional information, selectivity, or sensitivity. In the following, all possible influences on the ions are summarized under the general term "modification" to simplify the language.A modification refers to any kind of change compared to a reference spectrum recorded without modification of the ions. For example, a spectrum with and without modifications can be recorded alternately, so that the effect of the modification can be measured by the differences between the two spectra (as illustrated in Figure 10).

[0042] The ion modification region 103 consists of an input electrode arrangement

[0043] 7 with one or more input electrodes, an output electrode arrangement

[0044] 8 with one or more output electrodes and one or more modification chambers 1, which extend, viewed 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 shown later, significantly more complex designs may also be advantageous. Depending on the arrangement, the ion modification region 103 can also contain several modification chambers or sub-chambers separated from one another by additional electrodes.

[0045] Input electrode arrangement 7, modification chamber(s) 1, and output electrode arrangement 8 are configured to implement the following method for modifying the ions: In a first step, an electric field with a DC component is generated in the ion modification region 103, which is sufficient to move the ions to be modified from the direction of 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 an almost freely adjustable time. This time can be predetermined or, as explained later, determined during execution.In the third step, an electric field with a DC component is generated in the ion modification region 103, which is sufficient to bring the modified ions out of the modification chamber 1 in the direction of the output electrode arrangement 8.

[0046] In the second step, ions can be modified according to one or more of the following options or tested to see whether modifications occur under certain conditions or not:

[0047] 1 . By an asymmetric alternating field, at least one ion species is displaced due to its field-dependent ion mobility or this displacement is compensated by adjusting the direct field.

[0048] 2. Ions are fragmented by an asymmetric or symmetric alternating field.

[0049] 3. Ions are fragmented by heating the analysis area or by hot gas. 4. Reactions or cluster formation occur when additional substances are added.

[0050] With regard to point 1, it should be noted that the term "displacement" is always used here, even if this effect is compensated by a DC field. In this case, the DC field used for compensation is a measure of the field-dependent ion mobility. In addition to the previous points, the second step can also include waiting times without further modification, for example, to allow excited reactions to complete.

[0051] Advantageously, the method is only carried out on a part of the recorded spectra so that a comparison can be made between spectra without modification (reference spectrum) and spectra with modification (modified spectrum).

[0052] Mechanical structure

[0053] Typically, the inventive design is used as part of an ion mobility spectrometer, i.e., 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 take 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.

[0054] Figure 2 shows an embodiment of the ion modification region 103 in which a first drift region 10 is provided in the ion modification region 103 by the input electrode arrangement 7. A second drift region 11 is provided in the ion modification region 103 by the output electrode arrangement 8. Between the first and the second drift region there is a first axial modification chamber 1 which is formed between the last electrode in the drift direction D of the input electrode arrangement 7 and the first electrode of the output electrode arrangement 8. These electrodes form a first modification electrode arrangement by means of which an electric field 12 acting in the axial direction can be generated in the modification chamber 1. For example, axial alternating fields in the ion modification region 103 can generate a displacement, declustering and / or fragmentation of ions.

[0055] Figure 3 shows an embodiment of a second modification electrode arrangement with electrodes 9, by means of which an electric field 14 orthogonal to the drift direction of the ions can be generated in the modification chamber 1. Declustering and / or fragmentation of ions can be generated by orthogonal alternating fields in the ion modification region.

[0056] For example, the electrodes of the input electrode arrangement 7 and / or the output electrode arrangement 8 are formed by grids, as these influence the electric field across the entire diameter of the ion modification region, regardless of the selected 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 consisting only of opposing surfaces. It should be noted that, as shown in Figure 3, only axial alternating fields allow both displacement and declustering and fragmentation, while orthogonal alternating fields only allow declustering and fragmentation.

[0057] According to an advantageous embodiment, the field in the ion modification region, particularly when using grids as electrodes, is generated only by the respective inner electrodes of the input electrode arrangement 7 and the output electrode arrangement 8, as shown in Figure 2. Likewise, as shown in Figure 3, it is also possible to generate the alternating field in the ion modification region only or primarily via divided or partially ring electrodes 9 as modification electrodes.

[0058] 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 even 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, 8 each consist of a grid. This design makes it possible to simultaneously generate electric fields of different signs in the first sub-chamber T1 and the second sub-chamber T2 using only one alternating voltage source 17.

[0059] Figure 4 also shows that the electrodes arranged one behind the other can be connected to each other via a resistive voltage divider 16. A voltage source 17, e.g., an alternating voltage source, can be connected to the voltage divider 16 or to certain electrodes.

[0060] As shown in Figure 4, additional ring electrodes 9 are also possible in the modification chamber 1 or in the first subchamber T1 and / or the second subchamber T2, whose potentials are adjusted, 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. Through a voltage divider, these ring electrodes 9 then follow the desired electrical potential profile created by the combination of DC and AC fields in the ion modification region 103. Likewise, the ion modification region 103 can also contain additional grids.

[0061] Advantageously, a further modification electrode 90 is provided between the first subchamber T1 and the second subchamber T2, to which the voltage from the voltage source 17 is applied to generate the alternating field, so that an electric field 12 exists in the first subchamber T1 and an electric field 13 with opposite sign exists in the second subchamber T2. As a result, the resulting displacements of ions have different signs, allowing displacement in both directions with only one alternating voltage source. If ring electrodes are used in this case, their voltage dividers can be connected to the modification electrode 90 as well as the respective inner electrodes 28, 29 of the input electrode arrangement 7 and the output electrode arrangement 8. The alternating voltage source can, as shown later, be implemented, for example, by direct voltage sources and switches.

[0062] As mentioned above, the electrodes of the input electrode arrangement

[0063] 7 and output electrode arrangement 8 are often formed by grids, as 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 partial ring electrodes can also be used for all electrodes of the input electrode arrangement, the ion modification regions, and the output electrode arrangement.

[0064] For this purpose, it is particularly advantageous, as shown in Figure 5, to create a structure consisting of several parallel channel-like structures for modifying ions, each of which contains 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, so that the efficiency of the ring electrodes is greater. In this case, a larger DC electric field can advantageously be used in the first step in the input electrode arrangement 7 than in the area in front of it in order to focus the ions into the modification chambers 3, 4, 5, 6 and avoid losses.

[0065] Figure 5 illustrates an embodiment with four parallel ion modification structures (hatched). Due to the small diameter of each ion modification structure, the electrodes of the 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.

[0066] Figure 6 shows an embodiment of an ion modification region 103 in which additional substances or hot gas for further modification can be introduced into the modification chamber 1 or the subchambers T1, T2 through gas inlets 20, 21. Furthermore, outlets 22, 23 for the direct removal of the substances or gases supplied through the gas inlets 20, 21 can also be present directly in the ion modification region 103. The additional inlets or outlets 18, 19 can be used, for example, for the supply or removal of the drift gas. They can also be arranged within the input electrode arrangement 7 and / or the output electrode arrangement 8.

[0067] 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 sub-chambers 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 the sub-chambers T1, T2. Additional substances or hot gas for further modification of the ions in the sub-chambers 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.

[0068] According to an advantageous embodiment, parts of the input electrode arrangement or the entire input electrode arrangement 7, as shown in Figure 6, form an ion gate, particularly if a first drift region is present. It is even more advantageous to utilize the variable potential of the modification electrode 90 to construct an ion gate. This allows only a portion of the ions to be permitted for modification. All known ion gates can be used, such as Bradbury-Nielsen, Tyndall-Powell, three-electrode, or tristate ion gates.

[0069] Particularly advantageous is the use of a three-electrode or tristate ion gate, the central electrode of which is formed from mutually insulated structures, for example, in the case of a grid of rods or, in the case of ring electrodes, from a split or partial ring electrode. Alternatively, when using grids, at least two of the grids can be offset from each other orthogonally to the drift direction. This allows, in the closed state, in addition to the normal, closing electric field in the longitudinal direction, an orthogonal direct or alternating electric field to be used to specifically eliminate non-transmitted ions. According to an advantageous embodiment, parts of the output electrode arrangement or the entire output electrode arrangement 8 also form an ion gate. In this way, ions that unintentionally escape from the modification chamber 1 during modification can be discharged and removed from the modified spectrum.The same design variants as for the input electrode arrangement 7 can be used here.

[0070] 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.

[0071] Figure 6 shows additional, optional gas inlets 20, 21 in the first and second sub-chambers T1, T2 as well as gas outlets 22, 23 in the first and second sub-chambers T1, T2 in order to supply hot gas for heating the ion modification regions or to supply substances for further reactions in the ion modification region 103.

[0072] Figure 7 shows a variant of the ion modification region 103, in which only one gas inlet 20 and one gas outlet 22 are present in the modification chamber 1.

[0073] According to an advantageous embodiment, the subchambers T1, T2 have both dedicated gas inlets 20, 21 and dedicated gas outlets 22, 23, so that the gas flows only through the respective subchamber T1, T2. Such gas inlets 20, 21 and gas outlets 22, 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 gates is particularly suitable. By ensuring a laminar gas flow only through the respective subchamber T1, T2, the modification steps can be carried out without affecting the rest of the IMS.

[0074] 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 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 region are also placed at the same potential as the respective end of the analysis region during the second step, advantageously over at least one and a half times, twice, or three times the diameter of the drift tube.

[0075] Advantageous widths of the ion modification region 103 or of the modification chamber 1 are 1 mm, 2 mm, 3 mm, 4 mm, 5 mm, i.e. their dimensions in the drift direction D. If the modification chamber 1 has several sub-chambers T1, T2, the stated dimensions apply to the respective sub-chambers. According to an advantageous embodiment, the distances under the electrodes of the input electrode arrangement 7 and under the electrodes of the output electrode arrangement 8 are smaller than the width of the ion modification region 103 or of the modification chamber 1. In this case, it can 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 to be 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 does not have to, be greater than 1, preferably greater than 2. The spatial extent of the ion packet can be reduced or increased by adjusting m by the ratio of the electric field strength at a field transition, for example, between the region in front of the input electrode arrangement and the region within the input electrode arrangement.

[0076] 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.

[0077] Modification modes: 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 for the displacement or fragmentation of ions. This can be varied to achieve different displacements or fragmentations.

[0078] From the shift at different reduced field strengths, an analysis can be performed either via the constant field required to compensate for the movement or via the shift 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 shift at a specific field strength can also provide 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 shift. It is particularly advantageous if this shift of the standard is negligibly small.Likewise, the displacement can be used to eliminate one or more unwanted ion species from the ion modification region by cleverly selecting the DC field, while the movement of one or more other ion species is compensated to such an extent that they do not reach the electrodes.

[0079] Fragmentation at different reduced field strengths can also be analyzed. In particular, after separation in the second drift space, 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. So-called thermometer ions, which have a bond that breaks at a known energy, can be used as a standard. According to an advantageous embodiment, a substance that forms clusters with one or more ion species can be added to the reaction space, the first drift space, or even the ion modification region itself, so that the dissociation of these clusters at different reduced field strengths can be analyzed. This is particularly helpful for the analysis of ions that cannot be fragmented due to their high stability.Likewise, unwanted clusters can be dissociated extremely efficiently through the ion modification region. 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 region, leaving only the desired ion species, which can be transferred to the drift space behind the ion modification region for separation.

[0080] In particular, a combination of displacement and fragmentation is also possible, for example, to analyze several ion species with the same ion mobility at low reduced field strengths. For example, during the second step, all but one ion species can be eliminated by displacement using an alternating field suitable for displacement. The remaining ion species can then be fragmented using an alternating field suitable for fragmentation. The resulting fragments can then be separated in the second drift space. This process can be repeated for all ion species at different reduced field strengths for fragmentation to obtain a comprehensive picture.

[0081] According to the Wannier equation, the energy transferred to the ions by high reduced electric field strengths depends quadratically on the ion mobility. Therefore, fragmentation via high reduced electric field strengths alone is only effective for high-mobility ions. To assist fragmentation or even directly fragment them, hot gas can be passed through the ion-modified region, or the ion-modified region can be heated in some other way, locally limited to the ion-modified region. It is particularly advantageous to select the temperature so that the resulting energy is just below the fragmentation energy of the most easily fragmented ion species to be analyzed. Thus, analysis of the unmodified ion species is still possible without an alternating electric field, and the energy range adjustable by the alternating electric field is maximized.Heating the entire IMS is also possible in principle, but reduces the achievable resolution, potentially leads to fragmentation in the drift spaces, and, depending on the temperature, limits the choice of materials in the design. Figure 8 shows a section of an IMS with a field-switching ion gate with an integrated reaction space 24, a structure for modifying ions (hatched, ion modification region 103), and a drift space 11. The gas inlets 20, 25 and outlets 22, 24 are designed such that different gas compositions prevail in region 27 and in the modification chamber 1 during the formation of the reactant ions. The drift gas in the drift space 11 can advantageously be supplied to or removed through the gas inlet or outlet 19 in the output electrode arrangement 8. The output electrode arrangement 8 serves here, similar to DE 10 2018 107 909 A1, as a field-free area for shielding during the modification.

[0082] The substances added to the ion modification region 103 through the gas inlet 20 can also contain the actual sample, as illustrated in Figure 8. As a result, only reactant ions are present in the ion source and, if applicable, the first drift space 10 (not shown in the figure). This has several advantages:

[0083] First, the reactant ions can react over an extended period of time in the ion source, for example, until they reach their equilibrium state, and then only be brought into contact with the analyte molecules in the ion modification region. This prevents intermediates in the formation of reactant ions from participating in the formation of analyte ions, which is particularly advantageous when using so-called dopants, i.e., substances intended to influence the formation of reactant ions. Furthermore, the reaction time for the formation of reactant ions and the reaction time for the formation of analyte ions can be adjusted independently of each other. This allows, in particular, extremely short reaction times to increase the linear range and minimize competing reactions.

[0084] Secondly, the first drift space, especially in combination with an ion gate in the input electrode arrangement, allows for the targeted selection of only one reactant ion for the formation of the analyte ions, even when multiple reactant ion species are formed. Furthermore, only reactant ions of one polarity participate in the reactions, thus eliminating recombination as a loss mechanism for the analyte ions. Thirdly, the alternating field can influence the reactant ions during the formation of the analyte ions. For example, water clusters can be broken up to increase the reactivity of the reactant ions.

[0085] Waveform and electrical circuitry

[0086] According to an advantageous embodiment, an alternating field consisting of a short pulse, e.g. in rectangular shape, with a high field strength in one of the two directions in combination with a longer period of lower field strength in the opposite direction is used to displace the ions. Particularly advantageously, the short pulse makes up 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 height and length in both directions (high and low level) is used to fragment the ions. Particularly advantageous is an alternating field in which each direction makes up 50% of the period. Generally, longer pulses lead to greater fragmentation, since the ion only absorbs sufficient energy over a longer period of time and also distributes it across its internal states.Therefore, a targeted reduction of the pulse duration by a shorter period or a smaller portion of the pulse can be helpful to achieve displacement without fragmentation.

[0087] 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.

[0088] According to an advantageous embodiment, parameters such as reduced field strength, period duration, proportion of the pulse to the period duration or time until the second step are adjusted such that during the modification none of the ion species to be analyzed and their product ions are discharged on the input electrode arrangement or the output electrode arrangement or the electrodes in between.

[0089] Three points are particularly relevant here: First, the time until the second

[0090] The first step should be selected so that the ion packet of the ion species to be analyzed is placed as symmetrically as possible between the respective inner electrodes 28, 29 of the input electrode arrangement 7 and the output electrode arrangement 8 in order to maximize the possible amplitude of the movement in the alternating field. Second, the period length should be selected so that these electrodes are not yet reached by the ion packet during the movement in the alternating field, or are 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 taken, should be selected so that the diffusion of the ion packet does not yet lead to the electrodes being reached. The last two points in particular should be considered in combination.

[0091] According to an advantageous embodiment, the optimal time until the second step is calculated based on the drift time in the reference spectrum, determined by measurement with a standard, or determined experimentally by varying the time until the second step and selecting the value with the lowest losses. For experimental determination, the other parameters must be selected 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 no longer appears in the spectrum.

[0092] According to an advantageous embodiment, the maximum possible period duration is calculated based on the ion mobility determined via the drift time in the reference spectrum or is determined experimentally by varying the period duration and selecting the largest value at which no disturbing losses occur.

[0093] According to an advantageous embodiment, the maximum total duration of the modification, i.e., the maximum duration for which the second step is used, is calculated based on the ion mobility determined from the drift time in the reference spectrum and the resulting diffusion coefficients, or it is determined experimentally by varying the duration of the second step and selecting the largest value at which no disruptive losses occur. However, the total duration of the modification can also be set shorter based on other parameters, for example, so that a certain percentage of the ions have already been fragmented.

[0094] The values ​​of the individual parameters at which losses occur, or the resulting losses, can be determined both by varying the parameter and measuring the amount of charge at the detector, as well as by using current amplifiers at the inner electrodes 28, 29 of input electrode arrangement 7 and output electrode arrangement 8. The first can be implemented without additional technical effort; the second is particularly helpful for the period duration and the total duration of the modification, since different parameter values ​​do not have to be tried out; instead, the critical point can be detected directly during the measurement.

[0095] Figure 9 shows an ion modification region 103 similar to Figure 7, additionally illustrating the electrical wiring of 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 cleverly arranging switches 34 and voltage sources 30, 31, 32, an efficient generation of electric fields can be generated in the modification chamber 1, through which an efficient displacement of ions in both directions as well as fragmentation can be carried out with only one modification chamber 1 and one high-voltage source 32, i.e., all of the waveforms shown in Figure 12 can be generated.The input electrode arrangement 7 and the output electrode arrangement 8 can each additionally form an ion gate.

[0096] According to an advantageous embodiment, as shown in Figure 9, switches 34 are provided on the input electrode arrangement 7 and the output electrode arrangement 11 in order to switch at least the potential of the respective 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 circuit shown in Figure 9, other variants are also conceivable, in which, for example, the voltage sources 30, 31 are obtained from the voltage divider of the drift spaces. The integration of further switches and voltage sources is also conceivable in order to carry out additional modification steps, for example completely without electric fields in the ion modification region 103. Furthermore, it is advantageous to replace the switches 34 and voltage sources 30, 31, 32 with rapidly adjustable voltage sources in order to simplify the circuit.

[0097] Since the exact position of the formation of ions and fragments in the ion modification region 103 is unknown, additional methods for determining mobility are advantageous. In an advantageous embodiment, the voltage across the second drift space 11 is varied, and the respective mobility of the substances is determined from the resulting change in drift time. For simplification, this can be done once in a single measurement, and then 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 required for many calculations without modification.

[0098] Figure 10 illustrates various basic functional principles of the ion modification region of the IMS using three diagrams. The upper diagram shows how ion fragmentation can be generated compared to a reference spectrum by controlling the electrodes of the ion modification region. The middle diagram illustrates how a shift of ions relative to a reference spectrum can be generated in the ion modification region. The lower diagram illustrates how ions can also be filtered by the ion modification region. The diagrams in Figure 10 each show the ion quantity versus the drift time in the drift space 11.

[0099] Figure 11 illustrates an advantageous waveform of an alternating electric field that can be used to perform ion modification in the ion modification range. It can be seen that in the period before tstart, no electric field is present (field strength = 0). Starting at time tstart, an alternating electric field is generated that lies between the limit values ​​Ehigh and Ei. ow The value of Ei ow < 0, meaning that in this case a field strength is generated in the opposite direction to the normal drift direction. The value of Ehigh is always greater than zero. At time t s to P The ion modification by means of the alternating electric field ends. As an alternating electric field, this waveform has a zero DC component, but, as already mentioned, it can be superimposed with a DC component.

[0100] Figure 12 uses three diagrams to show the electric fields to be generated in the ion modification region 103 or in the modification chamber 1, for example with the circuitry shown in Figure 9. The upper diagram shows an advantageous application of an alternating electric field, which can be used to fragment and filter ions. This generates an alternating field symmetrical around a field strength value of zero. The middle diagram shows an alternating electric field, similar to that in Figure 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. The average electric field strength is significantly lower than in the middle diagram, in particular on average below the field strength value of zero.All of these waveforms have a DC component of zero, but as already mentioned, they can be superimposed with a DC component.

Claims

Patent claims: 1 . Ion mobility spectrometer with the following features: a) at least one ion packet providing device (100, 101) which is designed to provide packets of ions one after the other at time intervals, b) an ion detector (105), c) at least one drift space (11) through which the ions are guided over a predetermined travel distance in a drift direction (D) to the ion detector (105) in order to be discharged there, characterized in that d) the ion mobility spectrometer has an ion modification region (103) between the ion packet providing device (100, 101) and the at least one drift space (11), which has an input electrode arrangement (7) on the side facing the ion packet providing device (100, 101) and an input electrode arrangement (7) on the side facing the at least one drift space (11) facing side has an output electrode arrangement (8),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 adapted to carry out one or more modifications on the ions located in the modification chamber (1).

2. Ion mobility spectrometer according to claim 1, characterized in that the ion packet providing device (100, 101) has a clocked ion source (100) and / or a continuously operated ion source (100).

3. Ion mobility spectrometer according to one of the preceding claims, characterized in that the ion packet providing device (100, 101) has a clocked ion gate (101).

4. Ion mobility spectrometer according to one of the preceding claims, characterized in that a feed connection (20, 21) is present at the ion modification region (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 in that an outlet connection (22, 23) is provided on the ion modification region (103) opposite the feed connection (20, 21), which outlet connection is designed to discharge the at least one further substance supplied via the feed connection (20, 21) from the modification chamber (1).

6. Ion mobility spectrometer according to one of the preceding claims, characterized in that the ion mobility spectrometer has a first modification electrode arrangement by means of 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 in 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 (10) and the output electrode arrangement (8) closest to the modification chamber (1).

8. Ion mobility spectrometer according to one of claims 6 to 7, characterized in that in the modification chamber (1) there is a first modification electrode arrangement which has at least one electrode (90) spaced apart from the input electrode arrangement (10) and the output electrode arrangement (8), wherein the modification chamber (1) is The first modification electrode arrangement is divided into at least one first sub-chamber (T1) facing the input electrode arrangement (10) and at least one second sub-chamber (T2) facing the output electrode arrangement (8). Ion mobility spectrometer according to one of the preceding claims, characterized in that a second modification electrode arrangement is present at the ion modification region (103), by means of which an electric field (14) orthogonal to the drift direction (D) of the ions can be generated in the modification chamber (1). Ion mobility spectrometer according to one of the preceding claims, characterized in that the extension of the modification chamber (1) or of the sub-chambers (T1, T2) in the direction of the drift movement of the ions corresponds to at least one time, in particular two times, in particular five times, in particular ten times, in particular twenty times the value of the half-width of the ion packet of the ions to be analyzed.Method for analyzing substances by ion mobility spectrometry using an ion mobility spectrometer according to one of the preceding claims, characterized in that 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 they are moved through the drift space (104) to the ion detector (105):. I) shifting at least one species from the ions present in a direction different from the drift direction (D), II) reducing or increasing the drift velocity of at least one species of the ions present in the drift direction (D) or shifting at least one species of the ions present in the drift direction (D), III) Reducing or dissolving the clustering of ions and molecules, IV) Fragmentation of ions, V) Promote chemical reactions and / or cluster formation of ions. Method according to claim 11, characterized in 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). Method according to claim 11 or 12, characterized in that, in preparation for the modification of ions in the modification chamber (1), first an electric field (12), e.g. in the drift direction (D), is generated in the ion modification region (103) with a DC component sufficient to move ions to be modified from the direction of the input electrode arrangement (10) into the modification chamber (1), 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 cancelled out, or - by adjusting the DC component of the electric field, an average movement of all ion species caused by a superimposed alternating electric field in the modification chamber (1) is minimized. Method according to one of claims 11 to 13, characterized in 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 located therein. Method according to one of claims 11 to 14, characterized in that 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 connection into the modification chamber (1). Method according to claim 15, characterized in that a substance to be analyzed by ion mobility spectrometry is supplied as a further substance, which forms analyte ions to be analyzed with ions provided by the ion packet provision device and transported into the modification chamber (1). Method according to one of claims 11 to 16, characterized in that ion mobility spectra are recorded alternately with and without modification of the ions in the modification chamber (1).

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