Technical Field

The invention relates to an ion molecule reactor for generating analyte ions from analytes, in particular for use with a mass spectrometer, as well as a corresponding method for generating analyte ions. Further aspects of the invention are concerned with a mass spectrometer and the use of an ion molecule reactor in mass spectrometry.

Background Art

Mass spectrometry is an analytical technique which is widely used in many different fields of technology for the identification and quantification of individual substances or compounds of interest (so called analytes) in pure samples as well as in complex mixtures.

Mass spectrometry usually involves the measurement of the mass-to-charge ratio of ionized analytes or analyte ions, respectively. Thus, in a first step, analytes, which are typically neutral atoms or molecules, need to be ionized and transferred to a mass analyzer. Thereby, chemical ionization is particularly advantageous because this technique results in minimal fragmentation as well as a high degree of preservation of molecular identity and structure of the analytes.

In chemical ionisation, ionized analytes are produced through collisions of the analytes with reagent or primary ions which typically have been produced in a reagent ion source. In the reagent ion source, reagent ions can e.g. be created from a reagent gas (e.g. methane, ammonia, water, nitrogen oxide, oxygen and the like) by electron ionization, electromagnetic radiation (e.g. x-rays) or radioactive radiation.

However, the efficiency of providing ionized analytes by chemical ionization depends fundamentally on three aspects: ( 1 ) the generation of primary or reactant ions, (2) the reaction of the primary ions and analytes, and (3) the transfer of the analyte ions to a mass analyzer. In this regard, various experimental setups and instruments are known:

US 5, 175,431 (Georgia Tech Research Corporation) discloses a high pressure interface device for connecting a gas chromatograph to a mass spectrometer. In this system, a trace gas is ionized by radioactive radiation in a cryogenically cleaned buffer or carrier gas laminary flowing in a flow tube. As a source of radioactive radiation, radioactive material can e.g. be coated on a ring inside the flow tube or be placed on an injection needle for the analytes. Thereby analytes are introduced in axial direction in to the flow tube in a laminar flow region so that they will get ionized upon interaction with the ionized trace gas and transferred to the exit of the flow tube. US 20 14/0284204 A 1 (Airmodus OY, University of Helsinki) describes a device for ionizing molecules and clusters by chemical ionization in a sample gas before entering a detector, such as a mass spectrometer. Thereby, reagent gas is entered into an ion molecule reactor through an inlet which is arranged on one side of the chamber and ionized with a single x- ray source. Sample gas is introduced into the chamber via another inlet. This inlet is oriented along the longitudinal axis of the ion molecule reactor and perpendicular to the inlet of the reagent gas. Also in this setup, a laminar sheath gas flow is established between the sample gas and the wall structure of the device in order to guide the sample gas and the reagent ions. The trajectory of the reagent ions can be configured to bend from one side of the chamber inward and towards the sample gas flow at the interaction reaction. This can be achieved e.g. by using an electrical field, a deflector, a wing or a throttle, like a venturi tube for example.

However, these systems require high pressures, typically > 100 mbar, of a buffer or sheath gas, respectively, in the flow chamber in order to establish laminar flow which is effective in guiding the reagent ions and analytes. This in turn requires highly pure gas to be used or special cleaning measures in order to avoid for example formation of undesired ionic species with impurities. Moreover, a high pressure in the ion molecule reactor will give rise to memory effects or long recovery times of the chamber, respectively. Also, additional measures are required in order to provide a buffer gas with a desired constant pressure or to establish a well-defined laminar flow.

A further concept is disclosed in US 2008/02 17528 A 1 (Tofwerk AG) which describes inter alia an ion molecule reactor in which reagent ions are produced in a high pressure reagent ion source and then fed in axial direction into an elongated chamber comprising cylindrical rod electrodes as an ion guide. Analyte molecules enter through a lateral sample inlet into the ion molecule reactor and are then ionized by reactions with reagent ions at the crossing point between the reagent ions and the analytes at the first end of the chamber.

However, with such a setup only limited analyte ion yields and limited sensitivity are achievable, in particular due to rather low interaction times between the reagent ions and the analytes. Thus, there is still a need to further improve techniques and instruments for chemical ionisation of analytes which are especially suitable for use in mass spectrometry.

Summary of the invention

It is the object of the present invention to provide improved devices and methods pertaining to the technical field initially mentioned. In particular, improved techniques and instruments for chemical ionisation of analytes shall be provided which are especially suitable for use in mass spectrometry. Thereby, it is desirable to achieve as high analyte ion yields as possible. Also devices and methods should be provided which can improve the sensitivity in mass spectrometry and/or which allow for measuring analytes in ultra- low concentrations, e.g. concentrations in the range of a few ppqv (parts per quadrillion by volume) such as in atmospheric sciences. Moreover, the techniques and instruments should be as fail-safe and as easy to use as possible.

The solution according to this invention is inter alia specified by the features of claim 1. Thus, according to the invention an ion molecule reactor for generating analyte ions from analytes, in particular for use with a mass analyzer and/or in mass spectrometry, comprises: a) a reaction volume in which reagent ions can interact with the analytes in order to form analyte ions, especially by chemical ionisation; b) at least one analyte inlet which allows for introducing the analytes along an inlet path into the reaction volume, whereby a direction of the inlet path runs essentially along a direction of at least a first section of the predefined transit path in the reaction volume; c) at least one reagent ion source and/or at least one reagent ion inlet which allows for providing reagent ions into the reaction volume; d) at least one ion guide comprising an electrode arrangement which is configured for producing an alternating electrical, magnetic and/or electromagnetic field, that allows for guiding the reagent ions and/or the analyte ions at least along a section of the predefined transit path, especially along a first section of the transit path, preferably along the whole transit path, through the reaction volume.

In the present context, the term "ion guide" stands for a device for changing a velocity of ions with an alternating electrical, magnetic and/or electromagnetic field. Preferably, a frequency of the alternating electrical, magnetic and/or electromagnetic field is about 0.01 - 100 MHz, particularly 0. 1 - 10 MHz, especially 0.5 - 5 M Hz.

However, if desired, one or more DC field can be applied in addition to the alternating electrical, magnetic and/or electromagnetic field.

The ion guide is configured to selectively change the velocity of ions, especially without affecting a velocity of neutrals. Thereby the term "velocity" is to be understood as a vector with a direction and magnitude. Thus, when changing the velocity, the direction and/or magnitude of the respective ion are changed. Especially, with the ion guide ions can be accelerated and/or decelerated and/or the direction of movement can be changed. Thereby, the ion guide allows for guiding and/or focussing the analyte ions and/or the reagent ions along the transit path within the reaction volume. In particular, the ion guide provides an ion channel for the analyte ions. Thereby, in particular, the ion channel essentially corresponds to the transit path.

The "reaction volume" is a volume in space within the ion molecule reactor in which ionization of the analytes by collisions with reagent ions takes place. Especially, the reaction volume is the volume in which the ion guide is effective or in which ions are effectively guided, respectively. In particular, the reaction volume is at least partially enclosed in housing and/or a tubular element. In particular, the housing is a tubular element.

The term "predefined transit path" stands for the path on which the analyte ions are guided through the reaction volume and/or for the path along which the analyte ions are intended to move along. The transit path can e.g. be a curved line, a straight line or a line with one or more straight and/or one or more curved sections. Preferably, with respect to the intended direction of movement of the analytes, at least a first section of the predefined transit path runs along a straight line. Especially, a length of the first section, preferably a straight line, is at least 5%, preferably at least 10%, in particular at least 25%, advantageously at least 50%, particularly preferred at least 75%, of the length of the whole transit path through the reaction volume. In particular, the transit path runs along a central and/or longitudinal axis of the reaction volume and/or of the ion molecule reactor. The "analyte inlet" comprises in particular a hollow tubular inlet, especially a cylindrical tube. Thereby, the analytes can be guided through the tubular inlet into the ion molecule reactor and/or the reaction volume. Preferably, the analyte inlet and/or the analyte inlet path runs in parallel or coaxially with a longitudinal axis of the ion guide and/or the ion molecule reactor.

The "inlet path" is the path along which the analytes are introduced into the reaction volume and/or the ion molecule reactor. In particular the inlet path is an essentially straight line. Preferably, the inlet path runs essentially perpendicular to an inlet opening or an inlet orifice of the analyte inlet and/or the inlet path runs along a longitudinal axis of a tubular end of the analyte inlet. Thereby, the tubular end of the analyte inlet ends in the ion molecule reactor.

Surprisingly, it was found that the inventive setup is possible to specifically direct and focus reagent ions within the reaction volume and achieve a high density of reagent ions in an extended section of the reaction volume where the reagent ions can interact with the analytes. Hence, the spatial distribution of the reagent ions can be controlled very efficiently with the inventive setup. Additionally, analyte ions can be guided through the reaction volume along the predefined transit path.

Moreover, the inventive introduction of the analytes into the reaction volume along a direction of at least a first section of the predefined transit path through the reaction volume furthermore results in a high density of analytes in the reaction volume. At the same time, the density of unnecessary and lost analytes outside the reaction volume can be kept low. Thus, with the inventive setup relatively high densities of reagent ions as well as analytes are obtainable in the reaction volume. This in turn allows for a very efficient chemical ionisation of the analytes, because the probability of collisions with reagent ions is increased. This is e.g. in strong contrast to a setup where analytes are introduced into an ion molecule reactor in a direction essentially perpendicular to the predefined transit path, such as e.g. according to US 2008/02 17528 A1 , where essentially all of the analytes which are not ionized immediately at the crossing point with the reagent ions are lost. Hence, in such a setup only a very limited volume of interaction between the reagent ions and the analytes is available.

Moreover, because of the inventive setup, reagent ions can be kept for a longer time within the reaction volume what further enhances the probability of collisions with analytes or the ionization efficiency of analytes, respectively. Also, analyte ions produced by collisions with reagent ions can be guided by the ion guide through the reaction volume on the predefined path. Hence, loss of reagent ions or analyte ions by collision with other atoms or molecules present in the ion molecule reactor or with elements of the ion molecule reactor, such as walls and the like, can greatly be reduced.

As it turned out, the functional and synergistic interplay between the special way of introducing the analytes into the reaction volume and the specific ion guide greatly increases the efficiency of chemical ionisation and allows for providing ionized analytes with a surprisingly high yield.

Thereby, the ion molecule reactor can be operated at pressures well below 10 mbar. Thus the problem of undesired impurities and loss of analyte ions by a high rate of collisions with non-analyte gas associated with systems using high pressure buffer or sheath gas can be greatly reduced.

Moreover, with the inventive setup, analyte ions as well as primary ions can effectively be guided along spatially well-defined paths within the reaction chamber. This allows for keeping the ions away from the walls of the ion molecule reactor which results in a low rate of adsorption of the ions on the walls of the ion molecule reactor. Consequently, the number of ions or molecules later on desorbing from the ion molecule reactor walls will be on a low level as well. Overall this results in a reduced memory effect.

A reduced memory effect in turn leads to reduced recovery times of the ion molecule reactor so that the reactor can be reused more quickly after a measurement. Also, if the ion molecule reactor is for example used for time resolved measurements of varying analyte concentrations, the time resolution of the measurements can be greatly improved. Accordingly, if varying concentrations of analytes are to be measured, a low number of unwanted and previously adsorbed analyte ions or molecules desorbing from the ion molecule reactor walls back into the reaction volume or the transit path will ensure a minimal effect on the actual analyte concentration. Therefore, fluctuations in analyte concentrations can be measured with higher precision or with higher time resolution, respectively.

If the walls of the ion molecule reactor furthermore comprise at least one porous and/or gas permeable section, ions as well as neutrals reaching the walls of the ion molecule reactor additionally can at least partly be removed from the walls, e.g. by pumping. This will furthermore reduce the number of unwanted ions or molecules desorbing from the ion molecule reactor walls back into the reaction volume and thus reduce the memory effect. More details with regard to embodiments comprising porous and/or gas permeable sections in the walls of the ion molecule reactor are given below.

In particular, the sensitivity in mass spectrometry can be increased by at least one order of magnitude with the inventive ion molecule reactor, especially in proton transfer reaction based chemical ionization systems.

Preferably, the reagent ion source and/or the reagent ion inlet is located radially outwards with respect to the first section of the predefined transit path and/or the inlet path. This allows for a highly compact setup as well as an efficient introduction of reagent ions into the reaction volume. However, other arrangements may be suitable as well.

Especially, the at least one reagent ion source and/or the at least one reagent ion inlet is configured such that the reagent ions can be introduced into the reaction volume along at least two distinct directions and/or from at least two distinct positions. The at least two distinct directions are in particular non-parallel directions, preferably both intersecting the inlet path and/or the first section of the transit path. The at least two distinct positions are two positions separated in space. Preferably, the at least two distinct positions are located in at least two different radial directions with respect to the inlet path and/or the analyte inlet. Thereby, the at least two different radial directions run essentially perpendicular to the direction of the inlet path and/or the analyte inlet. Especially, the at least two distinct positions are comprised within an area of an annulus sector or an annular area surrounding the inlet path and/or the analyte inlet. Especially, an angle between the two radial directions, where the two most distant of the at least two distinct positions are located, is at least 2°, for example at least 5°, especially at least 10°, in particular at least 22.5°, for example at least 30°, advantageously at least 45°, particularly at least 45°, especially preferred at least 60°, for example at least 90°, at least 120°, or at least 180°. In between the two most distant positions, any number of additional positions may be present. If there are several reagent ion sources and/or analyte inlets, preferably all of the reagent ion sources and inlets are configured such that the reagent ions can be introduced into the reaction volume along at least two distinct directions and/or from at least two distinct positions.

Surprisingly, it was found that such a setup allows for even more efficiently providing and introducing reagent ions into the reaction volume. When the reagent ions are introduced into the reaction volume along at least two distinct directions and/or from at least two distinct positions, it is possible to specifically direct and focus the reagent ions towards the reaction volume and further increase the density of reagent ions in an extended section of the reaction volume. Hence, the spatial distribution of the reagent ions can be very precisely controlled with such a setup. Specifically, this setup will further reduce the tendency of reagent ions to diverge and collide with the wall when entering the reaction volume.

Nevertheless, for example for special applications, other arrangements may be beneficial as well. The ion molecule reactor can comprise at least one reagent ion source which can be installed within the ion molecule reactor and/or outside the ion molecule reactor. Also, it is possible to have different reagent ion sources inside and/or outside the ion molecule reactor at the same time. Instead or additionally to the at least one reagent ion source, the ion molecule reactor may comprise at least one reagent ion inlet. In this case, reagent ions can e.g. be produced with an external reagent ion source and then be guided through the reagent ion inlet into the ion molecule reactor. The reagent ion inlet may for example be a tubular inlet, optionally with elements for guiding the reagent ions. Preferably, the ions source is configured to produce an overall beam of reagent ions which is directed and/or focussed towards the reaction volume.

Especially, the at least one reagent ion source and/or the at least one reagent ion inlet is configured to produce one or more beams of reagent ions with an inlet direction which runs at an angle of 0 - 100°, in particular 5 - 100°, especially, 45 - 95°, for example 60 - 90° or essentially orthogonal, to the direction of the inlet path and/or the first section of the transit path. However, especially in connection with beams of reagent ions which are ring-sector shaped, ring-shaped, disc-shaped, in particular as described below, the one or more beams of reagent ions preferably run at an angle of 0 - 10°, more preferably 0 - 5°, most preferably 0° to the direction of the inlet path and/or the first section of the transit path. With such a setup, the reagent ions can be directed and/or focussed directly into the reaction volume or the first section of the transit path. This will give rise to a high concentration of reagent ions in the reaction volume.

Nevertheless, reagent ion sources and/or ion inlets with other characteristics may be used as well. Preferably, the at least one reagent ion source and/or the at least one reagent ion inlet is configured to produce an overall beam of reagent ions with rotational symmetry or circular symmetry. Put differently, the overall beam of reagent ions is axis-symmetric in this case. Thereby the symmetry is preferably given with regard to an axis defined by the direction of first section of the transit path, the analyte inlet and/or the inlet path. The rotational symmetry can e.g. be an n-fold symmetry with n > 2. Circular symmetry is given if n→∞. The "overall beam" is meant to be the sum or superposition of all partial beams originating from the at least one reagent ion source and/or the at least one reagent ion inlets or from all of the reagent ion sources and all of the reagent gas inlets together. Thereby, the reagent ions are introduced into the reaction volume along at least two distinct directions and/or from at least two distinct positions.

Such kind of symmetric reagent ion beams have been shown to be highly beneficial for achieving a high density of reagent ions with essentially homogeneous distribution in the reaction volume.

However, for example for special applications, reagent ion sources with an overall beam without rotational or circular symmetry can be used as well.

In particular, the reagent ion source is configured to produce an overall ring-sector shaped, ring-shaped, disc-shaped and/or cone-shaped beam of reagent ions, especially a ring- shaped beam of reagent ions. Thereby, preferably, the beam is axis symmetric with regard to an axis defined by the direction of first section of the transit path, the analyte inlet and/or the inlet path. In particular, a cone-shaped beam can have a form of a conical surface or of a conical volume.

In a ring-shaped or disc-shaped beam, the reagent ions move in particular from an outer circumference towards a central longitudinal axis of the ring-shape or the disc-shape, respectively.

With a cone-shaped beam, the reagent ions move in particular from a base towards the apex of the cone. Also, if present, a cone-shaped beam is preferably oriented such that an apex of the cone-shaped beam is directed towards the reaction volume, in particular onto the first section of the transit path.

In any case, with such ion beams the reagent ions can in principle be introduced into the reaction volume along an infinite number of distinct directions and/or from an infinite number of distinct positions. This allows for further increasing the density and homogeneity of the reagent ions in the reaction volume. This in turn will increase the efficiency of ionisation reactions in the reaction volume and improve the yield of analyte ions. Especially preferred, the at least one reagent ion source and/or the at least one reagent ion inlet is of annular shape and/or has a shape of one or more ring sectors. Preferably the at least one reagent ion source and/or the at least one reagent ion inlet is/are arranged coaxially around the first section of the transit path, the inlet path and/or the analyte inlet. Especially preferred, the ion molecule reactor comprises exactly one annular reagent ion source or exactly one annular reagent ion inlet.

With such a setup, it is in particular possible to produce axis symmetrical beams of reagent ions with highly homogeneous distribution. Also, with a reagent ion source and/or a reagent ion inlet of annular shape and/or which has a shape of one or more ring sectors, the reagent ions can be introduced into the reaction volume along at least two distinct directions and/or from at least two distinct positions in an easy and reliable manner.

According to another advantageous embodiment, the ion molecule reactor comprises at least two, especially at least three, four, five, six, seven or even more, individual reagent ion sources and/or reagent ion inlets, which are preferably arranged on a circular line around the first section of the transit path, the inlet path and/or the analyte inlet, whereby, preferably, the circular line is concentric with regard to the first section of the transit path, the inlet path and/or the analyte inlet.

Especially, if present, the at least two individual reagent ion sources and/or the at least two individual reagent ion inlets are arranged symmetrically around the first section of the transit path, the inlet path and/or the analyte inlet.

With at least two individual reagent ion sources and/or reagent ion inlets, the partial beams of reagent ions from the two sources and/or inlets can be controlled flexibly and thus be introduced into the reaction volume independently along the at least two distinct directions and/or from the at least two distinct positions. However, it is still possible to obtain a high density and homogeneous distribution of reagent ions in the reaction volume. This is in particular true with a symmetrical arrangement.

In particular, the at least one reagent ion source and/or the at least one reagent ion inlet comprises a ring-shaped nozzle and/or a ring sector-shaped nozzle. In particular, these nozzles have at least one ring-shaped and/or slit-shaped opening. Also it is possible that several openings, e.g. round and/or elongated openings, are arranged in a ring-like manner.

Such kind of nozzles allow as well for producing axis-symmetrical beams of reagent ions with highly homogeneous in a reliable manner. Nevertheless, it is for example possible to use other nozzles instead of or additionally to ring-shaped and/or ring sector-shaped nozzles. For example, the at least one reagent ion source and/or the at least one reagent ion inlet can have two individual tubular nozzles.

According to a further preferred embodiment, the at least one reagent ion source and/or the at least one reagent ion inlet comprises at least one guiding element for guiding reagent ions before entering the reaction volume. Thus, the guiding element is different from the ion guide for guiding the reagent ions and/or the analyte ions at least along a section of the predefined transit path through the reaction volume. Specifically, in a direction of movement of the reagent ions, the guiding element is located in front of the reaction volume. Preferably, the guiding element is configured to produce an electrical, magnetic and/or electromagnetic field that allows for guiding the reagent ions before entering the reaction volume, in particular by focusing, accelerating and/or decelerating the reagent ions. By doing so, the reagent ions can be directed flexibly and with high precision into the reaction volume with a predefined energy and/or velocity. This further increases the ionization rate of analytes in the reaction volume what in turn will increase to overall yield of analyte ions produced in the ion molecule reactor. Also, if a change from one reagent gas to another reagent gas is made, the guiding element of the at least one reagent ion source and/or the at least one reagent ion inlet allows for compensating different characteristics of the reagent gases in a quite easy and efficient manner without need for changes in the mechanical setup.

Especially, if present, the guiding element of the at least one reagent ion source and/or the at least one reagent ion inlet comprises an electrode arrangement, preferably comprising at least two electrodes. For example the guiding element comprises a multipole electrode arrangement, an ion funnel and/or an ion carpet. The electrode arrangement, multipole electrode arrangement, the ion funnel and/or the ion carpet of the guiding element can be similar to the multipole electrode arrangement, the ion funnel and/or the ion carpet as described in connection with the ion guide below.

However, guiding elements of the at least one reagent ion source and/or the at least one reagent ion inlet are only optional and can be omitted.

If present, the at least one reagent ion source is preferably selected from electrical discharge based reagent ion sources, plasma based reagent ion sources, photoionization based reagent ion sources, x-ray reagent ion sources and/or radioactive reagent ion sources. For example, the reagent ion source is a glow discharge based reagent ion source, a radio frequency based reagent ion source, a microwave based reagent ion source, a corona discharge based reagent ion source and/or a dielectric barrier glow discharge based reagent ion source.

Such kinds of reagent ion sources are in principle known to the person skilled in the art and allow for a well controllable ionisation of a reagent gas to form specific reagent ions. Nevertheless, for specific applications, it might be beneficial to use other reagent ion sources.

Preferably, the reagent ions used in the present invention are positively charged ions, such as e.g. H ₃ 0 ⁺ , 0 ₂ ⁺ , CH ⁺ , NH ⁺ ,isobutane ions, and/or NO ⁺ . Thus, the ions source is in particular capable of producing these types of ions. However, other reagent ions, including negatively charges ions, might be suitable as well.

Especially preferred, H ₃ 0 ⁺ is as the reagent ions in the present invention. This allows for generating analyte ions by Proton-Transfer-Reaction (PTR), a process which is highly beneficial in connection with analysing volatile organic compounds (VOC).

The ion guide comprises in particular an electrode arrangement with at least two, in particular at least three, especially at least four, preferably at least five, particularly at least six or at least eight electrodes, for generating an alternating electrical, magnetic and/or electromagnetic field for guiding, focusing, accelerating and/or decelerating ions, in particular analyte ions and reagent ions, within the reaction volume and/or along the predefined transit path. Especially, the ion guide can comprise an electrode arrangement with exactly two, three, four, five, six or eight electrodes. The electrodes are in particular selected from conductive rods, ring electrodes, coatings and/or stripes.

Especially, the electrode arrangement is configured for generating a guiding field for guiding and/or focussing ions, in particular analyte ions and/or reagent ions, along the transit path. This guiding field preferably is an electromagnetic field, especially a radiofrequency (RF) field, generating an effective potential confining the ions to a region along the transit path. Such a guiding field greatly helps to focus the ions in the reaction volume and preventing them from hitting the walls of the ion molecule reactor. This in turn will greatly increase the overall yield of analyte ions.

Preferably, the electrode arrangement is configured for generating a transport field for accelerating and/or decelerating ions in a direction along the transit path. With such a transport field, for example, the reaction time between reagent ions and analytes can be controlled very precisely. Especially, this transport field is an electrical field, especially a DC field, which runs essentially along the transit path. However, the first field may as well be a superposition of electromagnetic fields.

In particular, the electrode arrangement is configured for generating a rotating field. Preferably, the rotating field results in an ion motion orbiting around the mean flight path of the ions. This allows in particular for setting a constant energy of the ions. A possible implementation of such an electrode arrangement in a multipole arrangement is described below. However, other implementations might be suitable as well.

Most preferred, the ion guide comprises an electrode arrangement which is configured for generating a transport field independently of the guiding field. Even more preferred, the ion guide comprises an electrode arrangement which is additionally configured for generating a rotating field. With such a setup, the velocity of the ions along the predefined path can be controlled independently of the focussing and/or guiding of the ions in a highly efficient manner.

However, other means for guiding neutrals and/or ions may be used alternatively or additionally as well. In particular, the ion molecule reactor comprises at least one voltage generator which can be electrically connected to the ion guide or the electrode arrangement of the ion guide or the at least two electrodes, respectively. Especially, the at least one voltage generator is capable of providing alternating voltage and optionally direct voltage in addition. Preferably, there are at least two voltage generators or at least one voltage generator with at least two individually controllable outputs, whereby a first voltage generator or a first output, respectively, can be connected to a first electrode and a second voltage generator or a second output, respectively, can be connected to a second electrode. Thereby, each of the electrodes can be used for separately generating electrical and/or electromagnetic fields.

In particular, if a guiding element of the at least reagent ion source and/or the at least one ion inlet is present, the ion molecule reactor comprises at least one further voltage generator which can be electrically connected to the guiding element.

Preferably, the ion guide comprises a multipole electrode arrangement, an ion funnel and/or an ion carpet.

An ion funnel can for example comprise a stack of at least two electrodes, especially ring electrodes whose inner diameter gradually decreases. Preferably, an ion funnel comprises at least three, four, five or even more electrodes. In particular, the ring electrodes are arranged coaxial with regard to the analyte inlet and/or at least a first section of the predefined transit path in the reaction volume or that a longitudinal axis of the ion funnel is arranged coaxially with respect to the analyte inlet and/or at least a first section of the predefined transit path in the reaction volume.

The ion funnel is preferably configured such that in operation reagent ions and/or analyte ions are radially confined as they pass through the ion funnel. Especially, in operation, out- of-phase alternating potentials, e.g. radio frequency potentials, can be applied to adjacent electrodes. Put differently, the phase of the voltage, alternates from electrode to electrode. Additionally, a direct voltage gradient (DC gradient) can be applied in the direction of the longitudinal axis of the ion funnel in order to accelerate and/or decelerate the ions. An ion carpet preferably comprises an essentially planar arrangement of at least two electrodes, preferably a plurality of electrodes, e.g. dots, strips and/or rings, that can each have different voltages applied to them. The electrodes themselves can be arranged in a radial pattern and/or in linear arrays. According to a highly advantageous embodiment, the electrodes comprise at least two or more individual concentric rings.

Especially, the electrodes are surrounding an orifice in the ion carpet. Thereby, in operation, voltage is applied to the electrodes of the ion carpet, such that an alternating electric field is generated which funnels reagent ions and/or analyte ions through the orifice. Sometimes, ion carpets are also called planar ion funnels. A highly beneficial embodiment of a planar ion funnel and its operation is described in US 20 13/0 120897 A1 (Amerom et al.).

Especially preferred, the ion guide comprises a multipole electrode arrangement, for example a quadrupole and/or an octapole electrode arrangement. The multipole electrode arrangement preferably comprises elongated electrodes being arranged along and/or around the transit path. In this case, preferably, the transit path runs along a longitudinal multipole axis, e.g. along a quadrupole axis.

Such an arrangement is especially preferred for generating a guiding field for guiding and/or focussing ions along the transit path. It is known that an oscillatory inhomogeneous electrical field forms a so-called effective potential which is proportional to E ² , where E is the amplitude of the electrical field strength oscillations (see e. g. Landau L. D., Lifshitz E. M.: Mechanics, Pergamon Press, Oxford 1976; Gerlich, D. "Inhomogeneous Electrical Radio Frequency Fields: A Versatile Tool for the Study of Processes with Slow Ions" in: State-Selected and State-to-State Ion-Molecule Reaction Dynamics, edited by C. Y. Ng and M. Baer. Advances in Chemical Physics Series, LXXXIL 1 , 1992). In case of a quadrupolar RF electrical field the effective potential results in a net force on the ion towards the quadrupole axis. This force is inverse proportional to the ion mass-to-charge ratio (m/Q) and directly proportional to the ion distance from the quadrupole axis. This fundamental property of the effective potential results in that an ion with a given m/Q will perform slow oscillations around the quadrupole axis with a characteristic frequency which is inversely proportional to its m/Q, i. e. the quadrupole field and similarly higher multipole fields are confining fields suitable for guiding and focussing analyte ions and/or reagent ions according to the present invention.

Linear RF multipole fields that are particularly well adapted for the inventive ion guide are usually produced using co-axial rods of parabolic or circular shape. Other shapes may be used e. g. in order to approximate quadrupole fields. Preferably, a primary RF-only field is applied between opposing set of electrodes or rods.

In a particularly preferred embodiment a rotating multipole field is generated at the at least one electrode, in particular a rotating quadrupole field. In principle, the utilization of such fields is known, e. g. from fundamental kinetic studies (see V. V. Raznikov, I. V. Soulimenkov, V. I. Kozlovski, A. R. Pikhtelev, M. 0. Raznikova, Th. Horvath, A. A. Kholomeev, Z. Zhou, H. Wollnik, A. F. Dodonov; "Ion rotating motion in a gas-filled radio- frequency quadrupole ion guide as a new technique for structural and kinetic investigations of ions"; Rapid Communications in Mass Spectrometry; Volume 15, Issue 20, Pages 1912-192 1). When properly tuned, such a rotating field can result in an ion motion orbiting around the mean flight path of the ions. This makes it possible to set the ion or energy, respectively, independently of the focussing and/or transport field. Also, the length of the flight path can be increased thanks to the rotating field which in turn increases the probability of ionization of analyte molecules.

Further details of suitable arrangements of electrodes and operations thereof are given in US patent application US 2008/02 17528 A 1 (Tofwerk AG).

According to a special embodiment, the ion guide comprises at least two different multipole electrode sections. For example the ion guide comprises a quadrupole section which is followed by an octupole section. Thereby, a first section, for example the octupole section, can e.g. be adapted or used for compressing reagent ions in order to increase ionisation reactions with analytes, whereas the second section, e.g. the quadrupole section, is used for focusing and/or guiding analyte ions along the transit path. Such an arrangement will further enhance the overall efficiency of the process

However, multipole arrangements are optional and can be omitted if not required. Also more complex multipole arrangements can be foreseen for special applications. Instead or in addition of a multipole, for example an ion funnel and/or an ion carpet as described above can be used. Also, any other ion guide comprising an electrode arrangement which is configured for producing an alternating electrical, magnetic and/or electromagnetic field, that allows for guiding the reagent ions and/or the analyte ions at least along a section of the predefined transit path, preferably along the whole transit path may be suitable.

According to a special embodiment, the ion guide comprises a multipole arrangement, especially as described above, in combination with an ion funnel and/or an ion carpet, preferably as described above. It was found that such a setup even better allows for specifically directing and focussing reagent ions within the reaction volume and achieving a high density of reagent ions in an extended section of the reaction volume. Hence, the overall yield of analyte ions can further be improved.

Especially, the ion funnel and/or the ion carpet is arranged in a direction of the transit path behind the ion guide. This allows for specifically extracting analyte ions in a defined direction and with a high yield out of the reaction volume.

However, such combinations of different ion guiding elements are optional and can be omitted if not desired or required, respectively.

Preferably, the ion molecule reactor further comprises a tubular element at least partially, preferably fully, surrounding the reaction volume and/or the transit path. The tubular element is preferably of cylindrical shape, especially with a circular cross section. However, rectangular or square cross-sections are possible as well. Moreover it is possible to use tubular elements with at least two different cross-sections. Also, the tubular element can be straight or bent.

Especially a length of the tubular element in a longitudinal direction is > 10 mm, especially > 100 mm, in particular > 500 mm, particularly > 1 Ό00 mm, > 2Ό00 m, > 5Ό00 mm or > 10Ό00 mm. An inner diameter to length-ratio of the tubular element may for example be between 1 : 1.5 - 1 :5'000, particularly 1. 1 - 500, especially 1 :2 - 1 :50, in particular 1 :5 - 1 :20. A ratio of the wall thickness if the tubular element to the inner diameter may for example be between 1 : 1 - 1 :50, especially 1 :5 - 1 :20. The tubular element can at least partially or fully be flexible or bendable, e.g. when made from plastics material. However, it is also possible to use a rigid tubular element, for example made out of glass and/or ceramics. An embodiment with a bendable tube makes it for example possible to use the ion molecule reactor as a probe or a probe head, respectively, e.g. for taking analyte samples at random positions. Thereby, ions might be transferred over quite long distances, e.g. over several meters. This might work similar to a vacuum cleaner.

If the ion molecule reactor comprises at least one electrode as described above, the at least one electrode can be arranged inside the tubular element, within the walls of the tubular element and/or outside the tubular element. Also, it is possible to apply a coating onto the tubular element which can serve as an electrode. In a preferred embodiment, at least one electrode is made from a material with lower electrical resistivity than the material of the tubular element.

Especially preferred, at least one electrode is arranged within the walls of the tubular element and/or outside the tubular element. This helps in particular to reduce contamination of the electrodes.

If the at least one electrode is of elongated structure, at least one electrode can be positioned in a longitudinal direction with respect to the tubular element and/or wound around the tubular element. However, other arrangements are possible as well. In a particular embodiment, the tubular material is made of an electrically isolating material and/or of a material of high ohmic resistance, for example of perfluoralkoxy polymers (PFA), e.g. Teflon, and/or of polytetrafluorethylen (PTFE). In this case, the tubular element can be used as the at least one electrode or as a further electrode, in particular as an electrode for generating a transport field, especially an electrical field, e.g. a DC field. However it is also possible to use ring electrodes instead or in addition to the electrode in the form of the tubular element.

Further details about tubular elements and possible arrangements of electrodes are given in US patent application US 2008/02 17528 A 1 (Tofwerk AG). Especially, the tubular element comprises at least one porous and/or gas permeable section in particular for introducing a fluid into the reaction volume and/or for removing neutrals and ions having left the predefined transit path out of the reaction volume and/or the ion molecule reactor. In a special embodiment, the tubular element is porous and/or gas permeable along its whole length. Especially, the porous and/or gas permeable section covers at least 5%, in particular at least 25%, especially at least 50% or at least 75% of the surface of the tubular element.

The at least one porous and/or gas permeable section can e.g. comprise a filter, a mesh and/or a frit. Especially, the at least one porous or gas permeable section surrounds the reaction volume at least along a partial section of the transit path or along the full transit path in the reaction volume. Preferably, the at least one porous or gas permeable section is a ring-shaped or annular section of the tubular element.

The fluid can e.g. be a sheet and/or buffer gas which can be introduced in the ion molecule reactor, especially in a radial direction, e.g. in order to reduce wall or memory effects. The fluid can be introduced into the ion molecule reactor for example driven by a pressure difference between inside and outside pressure of the tubular element.

However, it is also possible to introduce a reagent gas and/or reagent ions through the at least one porous and/or gas permeable section of the tubular element, especially in a radial direction, into the reaction volume. In this case, the at least one porous section of the tubular element has the function of a reagent ion inlet. The reagent ions can for example be produced outside the tubular element with a reagent ion source as described above.

When removing neutrals and ions having left the predefined transit path out of the reaction volume and/or the ion molecule reactor through the porous and/or gas permeable section, the efficiency of the ion molecule reactor can further be improved since wall and memory effects can be reduced and the overall pressure in the reaction volume can be reduced. Thus at the same exit pressure, higher analyte ion yields are achievable.

Advantageously, in a longitudinal direction, the tubular element has at least one first section which is non-porous or gas-tight and a second section which is porous or gas permeable. Preferably, the gas tight section is oriented towards the analyte inlet whereas the gas permeable section is oriented downstream with regard to the direction of movement of the analyte ions. With such a setup, the ionisation reaction of the analytes with the reagent ions can take place in the gas-tight sections which is beneficial in terms of ionisation yield of analyte ions. Further downstream, the efficiency of analyte ion transfer can be increased due to the porous or gas permeable section which allows for reducing the density of non-ionized analytes and other substances.

According to a further preferred embodiment, the tubular element is comprised within an outer tubular element. In particular, the outer tubular element is gas-tight or non-porous. For example it is made of stainless steel.

Especially, the inner diameter of the outer tubular element is larger than the out diameter of the tubular element. Thus, in this case, there is a free volume between the tubular element and the outer tubular element. This volume can e.g. be used to provide a fluid, e.g. a gas, which is to be introduced trough a porous section or gas permeable section of the tubular element in to the reaction volume. Also it is possible to reduce the pressure within the free volume to a value below a pressure in the reaction volume in order to remove neutral analytes and other substances from the reaction volume driven by a pressure difference.

Preferably, the outer tubular element comprises an opening for introducing fluids and/or for evacuating the free volume between the two tubular elements.

Preferably, the ion molecule reactor comprises a housing, in particular an elongated housing, especially a cuboidal and/or cylindrical tubular member, with a longitudinal axis. Preferably the housing has an exit orifice for the analyte ions. If there is a tubular element and/or an outer tubular element, it can be part of the housing. Especially, the analyte inlet and/or the analyte inlet direction runs in parallel or coaxially with a longitudinal axis of the housing and/or the analyte inlet direction is directed towards the exit orifice.

If the analyte inlet direction is directed towards the exit orifice, the analytes and analyte ions can for example move along an essentially straight line through the reaction volume. Thus it is possible to define a straight transit path which can be beneficial in terms of efficiency and analyte ion yield.

Especially, the ion molecule reactor comprises a housing with an exit orifice for the analyte ions whereby, preferably, an aperture area of the exit orifice is from 0.002 - 79 mm ² , especially 0.03 - 20 mm ² , in particular 0.07 - 7 mm ² , preferably 0.2 - 3. 1 mm ² , 0.4 - 1.8 mm ² . Especially, the exit orifice is circular with an aperture diameter of the exit orifice from 0.05 - 10 mm, especially 0.2 - 5 mm, in particular 0.3 - 3 mm, preferably 0.5 - 2 mm or 0.7 - 1.5 mm.

Thus, compared with ion molecule reactors known so far, the aperture area or aperture diameter, respectively, of the exit orifice can be reduced without significant losses of analyte ions. This is due to the inventive setup which allows for effectively focussing and guiding reagent ions and/or analyte ions within a well-defined and radially narrow area. Therefore, even exit orifices with rather small aperture areas or aperture diameters can be used. Since the conductance (volume flow rate; e.g. in liter per second) of the exit orifice is proportional to the aperture area, the smaller the aperture area of the exit orifice, the lower the conductance of the exit orifice. Thus, with a small aperture area exit orifice, less unwanted gas exits the ion molecule reactor into subsequent chambers though the exit orifice. This in turn allows to keep a predefined pressure in subsequent chambers with smaller pumps or with pumps with lower pumping capacities, respectively. With smaller pumps it is possible to realize more compact instruments comprising ion molecule reactors.

For example, in the case of a circular exit orifice, the aperture area is proportional to the square of the aperture diameter. A reduction of the aperture diameter by a factor of 10 therefore will reduce the aperture area by a factor of 100. Thus, the aperture diameter is a highly effective parameter for controlling the conductance of the exit orifice and the overall size of the instrument comprising the ion molecule reactor.

Preferably, the ion molecule chamber is operated under such conditions that a cross sectional area of the beam of analyte ions reaching the exit orifice is equal or smaller than an aperture area of the exit orifice. Under such conditions, the yield of analyte ions is maximum.

The ion molecule reactor can be used for mass spectrometry. Thus, the present invention is furthermore concerned with a mass spectrometer comprising an ion molecule reactor according as described above.

The mass spectrometer can for example comprise a time-of-flight mass analyzer, a quadrupole mass analyzer, an ion trap analyzer, a sector field mass analyzer, a Fourier transform ion cyclotron resonance analyzer, especially in an analyzer housing. However, it is possible to make use of other mass analyzers as well.

Thereby, the ion molecule reactor is in particular connected to the mass analyzer such that analyte ions produced in the ion molecule reactor can be introduced into the mass analyzer. If required, a transfer device, e.g. an ion transfer tube, can be arranged between the ion molecule reactor and the mass analyzer. This allows for example for providing one or more intermediate pressure regions between the ion molecule reactor and the mass analyzer. Since mass analyzers are typically operated under high vacuum conditions, the pressure can be reduced stepwise with such measures.

Also, it is possible to foresee additional mass and/or energy filters between the ion molecule reactor and the mass analyzer.

Advantageously, the ion molecule reactor comprises a housing as described above. With such a setup, the ion molecule reactor can easily be attached to various mass analyzers which are comprised in an analyzer housing. However, in principle, it is also possible to include the ion molecule reactor and the mass analyzer in a common housing.

A further aspect of the present invention is concerned with a method for generating analyte ions with an ion molecule reactor, in particular with an ion molecule reactor as described above, comprising the steps of: a) Introducing analytes into a reaction volume of the chamber through an analyte inlet; b) Providing reagent ions and introducing the reagent ions into the reaction volume; c) Letting the reagent ions interact with the analytes in order to form analyte ions; d) Guiding the reagent ions and/or the analyte ions with an ion guide along a predefined path through the reaction volume with an alternating electrical, magnetic and/or electromagnetic field; whereby the analytes are introduced into the reaction volume along an inlet path into the reaction volume whereby the inlet path runs essentially along at least a first section of the predefined transit path in the reaction volume.

Thereby, steps c) and d) can take place at least partially simultaneously. Put differently, while guiding the reagent ions at least along a section of the transit path, the reagent ions can interact with analytes in order to form analyte ions.

In particular, the analyte ions are generated from the analytes and the reagent ions by chemical ionisation, especially by proton transfer reaction (PTR). Thereby, hydronium ions are used as the reagent ions.

This has been shown to be highly beneficial in connection with the inventive method, especially in connection with analytes in the form of volatile organic compounds. However, other reagent ions can be used as well, for example reagent ions as described above in connection with the inventive ion molecule reactor.

Especially preferred, in the inventive method a pressure in the ion molecule reactor is below 100 mbar, preferably below 10 mbar, especially below 1 mbar. In such pressure ranges, the efficiency of the ionisation reaction as well as the yield of analyte ions is surprisingly high. This allows inter alia for measuring analytes in ultra-low concentrations, e.g. concentrations in the range of a few ppq.

Although less preferred, for special purposes it is possible to carry out the inventive method with a pressure of 100 mbar or more. In particular, the reagent ions and/or the analyte ions are guided, focussed, accelerated and/or decelerated with an alternating electrical, magnetic and and/or an electromagnetic field within the reaction volume and/or along the predefined transit path, in particular as described above in connection with the ion molecule reactor.

Especially, a guiding field for guiding and/or focussing ions, in particular analyte ions and/or reagent ions, along the transit path is generated. This guiding field preferably is an electromagnetic field, especially a radiofrequency (RF) field, generating an effective potential confining the ions to a region along the transit path.

Preferably, a transport field is generated for accelerating and/or decelerating ions in a direction along the transit path. Preferably, the transport field is an electrical field, especially a DC field, which runs essentially along the transit path. Especially, a rotating field is generated, in particular for setting an essentially constant energy of the ions. Preferably, the rotating field results in an ion motion orbiting around the mean flight path of the ions.

More preferable, a transport field and a guiding field is generated simultaneously. Most preferred, a rotating field is generated additionally to the transport and the guiding field. This allows for controlling the velocity of the ions along the transit path independently of the focussing and/or guiding of the ions in a highly efficient manner.

For generating these fields, electrodes, voltage generating devices and other means as described above in connection with the ion molecule reactor can be used. Also, it is preferred to perform the inventive method with an ion guide, e.g. a multipole arrangement, an ion funnel, an ion carpet or combinations thereof, as described above.

In particular, the ion molecule reactor and/or the transit path is at least partially surrounded by a tubular element, especially as described above.

In a further preferred method, a fluid is introduced into the reaction volume through at least one porous and/or gas permeable section of the tubular element. In particular, a sheath or buffer gas is introduced into the reaction volume, e.g. in order to reduce wall or memory effects, for example due to pressure difference between inside and outside pressure of the tubular element, or for dilution of analytes. However, it is also possible to introduce a reagent gas and/or reagent ions through the at least one porous section of the tubular element into the reaction volume. In this case, the at least one porous section of the tubular element has the function of a reagent ion inlet.

According to a highly advantageous method, neutrals and/or ions having left the predefined transit path are removed out of the reaction volume and/or the ion molecule reactor through the at least one porous and/or gas permeable section of the tubular element.

Details of the tubular element as well as the at least one porous and/or gas permeable section have been described above in connection with the ion molecule reactor. Preferably, the tubular element is comprised within an outer tubular element as mentioned above.

Another aspect of the present invention is the use of an ion molecule reactor as described above in mass spectrometry and/or with a mass spectrometer. Thereby, the mass spectrometer or a mass analyzer used for mass spectrometry is defined as described above.

Also it should be noted that a tubular element comprising at least one porous and/or gas permeable section as described above can be of use independently of the other components of the ion molecule reactor described herein. For example, a tubular element comprising at least one porous and/or gas permeable section can be used instead of an ion guide according to the present invention. However, it can also be used for other applications.

Thus, another aspect of the present invention is concerned with a tubular element comprising at least one porous and/or gas permeable section, in particular for use as an ion transfer tube and/or an ion molecule reactor. Especially, the at least one porous or gas permeable section is a ring-shaped or annular section of the tubular element. In a special embodiment, the tubular element is porous and/or gas permeable along its whole length.

According to a further preferred embodiment, this tubular element comprising at least one porous and/or gas permeable section is comprised within an outer tubular element as described above. Thus, in particular, the outer tubular element is gas-tight or non-porous. For example it is made of stainless steel.

Especially, the inner diameter of the outer tubular element is larger than the out diameter of the tubular element. Thus, in this case, there is a free volume between the tubular element and the outer tubular element. This volume can e.g. be used to provide a fluid, e.g. a gas, which is to be introduced trough a porous section of the tubular element in to the reaction volume. Also it is possible to reduce the pressure within the free volume to a value below a pressure in the reaction volume in order to remove neutral analytes and/or other substances from the reaction volume, e.g. due to the pressure difference. Preferably, the outer tubular element comprises an opening for introducing fluids and/or for evacuating the free volume between the two tubular elements.

Especially, the tubular element comprising at least one porous and/or gas permeable section comprises at least one electrode as described above. Further preferable features of the tubular element have been described above. In particular, the tubular element comprising at least one porous and/or gas permeable section is part of an ion molecule reactor and/or a mass spectrometer.

If the tubular element comprising at least one porous and/or gas permeable is used as an ion molecule reactor, it preferably comprises a reagent ion source as described above.

In particular, the tubular element comprising at least one porous and/or gas permeable section can be used instead of an ion guide in an ion molecule reactor as described above.

Therefore, another aspect of the present invention is an ion molecule reactor for generating analyte ions from analytes, in particular for use with a mass spectrometer and/or in mass spectrometry, comprising: a) a reaction volume in which reagent ions can interact with the analytes in order to form analyte ions, especially by chemical ionisation; b) at least one tubular element comprising at least one porous and/or gas permeable section surrounding the reaction volume at least partially for guiding the reagent ions and/or the analyte ions along a predefined transit path through the reaction volume; c) at least one analyte inlet which allows for introducing the analytes along an inlet path into the reaction volume, whereby a direction of the inlet path runs essentially along a direction of at least a first section of the predefined transit path in the reaction volume; d) at least one reagent ion source and/or at least one reagent ion inlet which allows for providing reagent ions into the reaction volume.

Thereby, preferably, the at least one reagent ion source and/or the at least one reagent ion inlet is located radially outwards with respect to the first section of the predefined path, the inlet of the analytes and/or the direction of the inlet path, and is configured such that the reagent ions can be introduced into the reaction volume along at least two distinct directions and/or from at least two distinct positions.

With such a setup, a fluid can be introduced through the porous and/or gas permeable section from an outside to the inside of the tubular element. The fluid can e.g. be a reagent gas, reagent ions, a sheath gas and/or a buffer gas. In particular, if the fluid is introduced in a radial direction, the incoming fluid effectively prevents atoms and/or molecules, e.g. analytes and/or analyte ions, from reaching the inner walls of the tubular element.

However, in contrast to prior art systems, no high pressure laminar flow of sheath gas is required.

Other advantageous embodiments and combinations of features come out from the detailed description below and the totality of the claims.

Brief description of the drawings

The drawings used to explain the embodiments show: Fig. 1 A cross-section of a first ion molecule reactor with an annular reagent ion inlet around the analyte inlet and an ion guide composed of a multipole electrode arrangement;

Fig. 2 A cross-section of a second ion molecule reactor with two separate reagent ion inlets mounted diametrically opposite in the cylindrical peripheral surface of a housing of the chamber and an ion guide composed of a multipole electrode arrangement;

Fig. 3 A cross-section of a third ion molecule reactor with a housing comprising a gas permeable section and an out tubular element enclosing the housing in order to remove and/or introduce fluids from or into the reaction volume, respectively. Additionally, the third ion molecule reactor a multipole electrode arrangement within the ring-shaped free volume between the tubular element and the housing which in operation can generate a rotating multipole field. As well an ion funnel is arranged outside the housing where the analyte ions leave the housing of the ion molecule reactor;

Fig. 4 A cross-section of a fourth ion molecule reactor with an ion guide composed of a multipole electrode arrangement and furthermore comprising an integrated ion-source which allows for introducing reagent ions through a gas permeable section of the housing; Fig. 5 A mass spectrometer setup comprising the second ion molecule reactor of

Fig. 2 as well as a differential pumping stage and a mass analyzer;

Fig. 6 A cross-section of a fifth ion molecule reactor comprising a gas permeable section along the whole length of the reaction volume;

Fig. 7 A cross-section of a sixth ion molecule reactor comprising an ion guide consisting of a multipole electrode arrangement in combination with an ion funnel; Fig. 8 A cross-section of a seventh ion molecule reactor comprising an ion guide consisting of an ion carpet;

Fig. 9 A cross-section of an eighth ion molecule reactor comprising reagent ion inlets with additional guiding elements and an ion funnel as an ion guide which are connected to separate voltage generators;

Fig. 10 A top view along the longitudinal axis of the ion funnel of the ion molecule reactor shown in Fig. 3;

Fig. 1 1 A top view along the longitudinal axis of the ion carpet used in the ion molecule reactor shown in Fig. 8. In the figures, the same components are given the same reference symbols. Preferred embodiments

Fig. 1 shows a cross section of a first ion molecule reactor 100. The ion molecule reactor 100 comprises a hollow cylindrical housing 1 10 having a longitudinal axis 1 1 1 and a reaction volume 140 inside the housing 1 10. Thereby, the housing 1 10 forms a tubular element surrounding the reaction volume. The housing is e.g. made from a doped lead silicate glass with a resistive layer on the inside. A length of the housing in longitudinal direction is for example 100 mm, an inner diameter is 10 mm and an outer diameter is 13 mm. The electrical resistance between the right axial end 1 13 and the left axial end 1 14 of the housing 1 10 is e.g. 1 GQ. At the right side in Fig. 1 the housing 1 10 has a circular opening 1 12 at the right axial end 1 13 being concentric with the longitudinal axis 1 1 1. The circular opening is an exit orifice, e.g. with an aperture diameter of 1 mm. In Fig. 1 at the left axial end 1 14, a hollow cylindrical analyte inlet 120 runs along the longitudinal axis 1 1 1 of the ion molecule reactor 100. Through the analyte inlet 120, analytes 12 1 , e.g. volatile organic compounds, can be introduced into the reaction volume 140 along an inlet path 122. The inlet path 122 of the analytes runs along a predefined transit path 141 in the reaction volume 140 whereby the transit path 141 runs along the longitudinal axis 1 1 1 of the housing 1 10. Also at the left side in Fig 1 , an annular or ring-shaped reagent ion inlet 130 is arranged concentrically around the analyte inlet 120. Thus, the reagent ion inlet 130 is located radially outwards with respect to the predefined transit path 141 and the inlet path 122. Due to the ring-shaped or annular form, reagent ions 131 can be introduced into the reaction volume 1 0 from essentially all of the positions on the ring-shaped opening. The reagent ions are produced in a reagent ion source, e.g. a conventional plasma discharge reagent ion source, which is not shown in Fig. 1.

In operation, analytes 12 1 will undergo chemical ionisation upon collisions with reagent ions 131. Thereby, charged analyte ions 123 are formed. In order to guide the analyte ions and the reagent ions through the reaction volume 140 along the transit path 141 , the first ion molecule reactor 100 comprises an ion guide which is composed of several electrodes. Specifically, the housing 1 10 is surrounded by a set of four cylindrical rod electrodes 150, 15 1 (only two electrodes are visible in Fig. 1). All of the rod electrodes 150, 15 1 are regularly arranged around the housing 1 10 in equal angular distances and run in a direction parallel to the longitudinal axis 1 1 1 of the housing 1 10. In operation, the four rod electrodes 150, 151 are connected to an RF generating device (not shown), where two opposite rod electrodes 150, 151 each are connected in parallel. Between neighbouring electrodes an RF-only voltage is applied, for example with a frequency of 1 - 10 MHz. Thereby, a multipole guiding field is generated which allows for guiding and focussing analyte ions 123 and reagent ions 131 along the transit path 141.

Additionally, between the right axial end 1 13 and the left axial end 1 14 of the housing, a voltage generating device (not shown) can be connected which allows for applying a voltage and generating a transport field (DC field) which runs in parallel to the longitudinal axis 1 1 1 of the housing 1 10. Thus, the housing as such acts as a further electrode. The transport field allows for accelerating and/or decelerating the ions towards the opening 1 12 at the right axial end.

The four cylindrical rod electrodes 150, 151 and the housing 1 10 together constitute an effective ion guide which allows for selectively guiding ions in the reaction volume 140 without affecting neutrals. Fig. 2 shows a cross section of a second ion molecule reactor 200. Apart from the reagent ion inlet, ion molecule reactor 200 is essentially identical with the first ion molecule reactor 100. Thus, all of the elements and parts 2 10, 2 1 1 , 2 12, 2 13, 2 14, 220, 22 1 , 222, 223, 231 , 240, 241 , 250 and 25 1 of the second reactor 200 correspond to elements and parts 1 10, 1 1 1 , 1 12, 1 13, 1 14, 120, 12 1 , 122, 123, 131 , 140, 141 , 150 and 15 1 of the first reactor 100. For example, analyte inlet 220 of the second ion molecule reactor 200 is essentially identical to analyte inlet 120 of the first ion molecule reactor 100, et cetera.

However, the second ion molecule reactor 200 does not comprise a ring-shaped reagent ion inlet which is arranged concentrically around the analyte inlet as with the first ion molecule reactor 100. Instead, the second ion molecule reactor 200 comprises two separate analyte inlets 230a, 230b which are mounted diametrically opposite in the cylindrical peripheral surface of the housing 2 10 at positions near the left axial end 2 14. Both of the two analyte inlets 230a, 230b are hollow cylindrical tubes which run in a direction orthogonal to the longitudinal axis 2 1 1 of the ion molecule reactor 200. Thus, reagent ions 231 can be introduced into the reaction volume 240 from essentially two different positions and in opposing directions, each of them essentially perpendicular to the longitudinal axis 2 1 1. Also in this case, the reagent ions 231 are produced in a reagent ion source, e.g. a conventional plasma discharge reagent ion source, which is not shown in Fig. 2. Without being bound by theory it is believed that due to the introduction of the reagent ions from two opposing directions, the reagent ions are decelerated in front of the analyte inlet 220 by electrostatic repulsion and captured by the ion guide elements, i.e. the four cylindrical rod electrodes 250, 25 1 (only two of the four electrodes are shown in Fig. 2) and the housing 2 10. Fig. 3 shows a cross section of a third ion molecule reactor 300 which is partly similar to the second ion molecule reactor 200. Specifically, all of the elements and parts 310, 31 1 , 312, 313, 314, 320, 32 1 , 322, 323, 330a, 330b, 331 , 340, 341 , 350 and 35 1 of the third reactor 300 correspond to elements and parts 2 10, 2 1 1 , 2 12, 2 13, 2 14, 220, 22 1 , 222, 223, 230a, 230b, 231 , 240, 241 , 250 and 25 1 of the second reactor 200. For example, analyte inlet 320 of the third ion molecule reactor 300 is essentially identical to analyte inlet 220 of the second ion molecule reactor 200, et cetera.

However, in addition to the second ion molecule reactor 200, the third ion molecule reactor 300 furthermore comprises an outer tubular element 370 of hollow cylindrical shape, which is e.g. made from stainless steel and which encloses the housing 310 concentrically over most of its length. The inner diameter of the outer tubular element 370 is larger than the outer diameter of the housing 310, such that the four rod electrodes 350, 35 1 are located within the ring-shaped free volume 372 between the housing 310 and the outer tubular element 370. At the outer surface of the outer tubular element 370, an opening 371 for introducing fluids and/or for evacuating the free volume 372 between the two tubular elements is mounted.

Also, the housing 310, in a section that is enclosed by the outer tubular element 370, comprises a ring-shaped and gas permeable section 360, e.g. made of a frit material. Apart from the opening 371 and the gas permeable section 360, the outer tubular element is mounted in a gas tight manner on the housing 310. Thus, the tubular housing 310 comprises a first section which is non-porous or gas tight and a second section which is porous or gas-permeable.

In operation, when evacuating the free volume 372 between the two tubular elements 310, 370, neutrals (e.g. non-ionized analytes 32 1 ) or ions having left the transit path 341 , path can be removed from the reaction volume 340 and the ion molecule reactor 300 via the opening 37 1. Therefore, conventional vacuum pumps can be used (not shown in Fig. 3).

Additionally, the ion molecule reactor 300 comprises an ion funnel 380 which is arranged behind the opening 312 at the right axial end 313 outside the housing 310. The ion funnel 380 consists of a stack of four metallic ring electrodes 38 1 whose inner diameter gradually decreases. This allows for specifically extract analyte ions in a defined direction and with a high yield out of the reaction volume 340. Fig. 10 shows a top view of the ion funnel 380.

Moreover, if in operation an appropriate rotating multipole field is generated with the four cylindrical rod electrodes 350, 351 , analyte ions 323 can orbit around the mean flight path in a spiral like trajectory (dashed spiral line in Fig. 3) while being transported towards the opening 312.

Fig. 4 shows a cross section of a fourth ion molecule reactor 400 which is partly similar to the third ion molecule reactor 300. Specifically, all of the elements and parts 410, 41 1 , 412, 413, 414, 420, 42 1 , 422, 423, 431 , 440, 441 , 450, 451 , 470, 47 1 and 472 of the fourth reactor 400 correspond to elements and parts 310, 31 1 , 312, 313, 314, 320, 32 1 , 322, 323, 331 , 340, 341 , 350, 35 1 , 370, 371 and 372 of the third reactor 300. For example, analyte inlet 420 of the fourth ion molecule reactor 400 is essentially identical to analyte inlet 320 of the third ion molecule reactor 300, et cetera.

However, with the fourth reactor 400, there are no separate analyte inlets which are mounted diametrically opposite in the cylindrical peripheral surface of the housing. Instead, the housing 410, in a section that is enclosed by the outer tubular element 470, comprises a ring-shaped and gas permeable section 460, which is arranged close to the left axial end 414. Radially outwards, a ring-shaped x-ray source 490 is mounted on the outside surface of the outer tubular element 470.

In operation, neutral reagents 431 a can be introduced into the ring-shaped free volume 472 between the housing 410 and the outer tubular element 470. Thereby, the pressure in the ring-shaped free volume 472 is chosen higher than in the reaction volume 440, such that the reagents are forced to enter the reaction volume 440 through the gas permeable section 460. In the region of the x-ray source, neutral reagents are ionized by the x-rays such that the gas permeable section 460 functions as an annular reagent ion inlet providing reagent ions from all radial directions perpendicular with respect to the longitudinal axis 41 1.

Fig. 5 shows a schematic view of a mass spectrometer 500 comprising the second ion molecule reactor 200 as described with Fig. 2. Thereby, analyte ions emerging from the circular opening 2 12 of the ion molecule reactor are fed into an optional differential pumping interface 50 1 in order to further reduce the pressure and then into a mass analyzer 502, e.g. a time-of-flight mass analyzer. Fig. 6 shows a cross section of a fifth ion molecule reactor 600. The ion molecule reactor 600 comprises a hollow cylindrical housing 610 having a longitudinal axis 61 1 and a reaction volume 640 inside the housing 610. Thereby, the housing 610 forms a tubular element surrounding the reaction volume 640. At the circular left and right end sides 613, 614, the housing is e.g. made from stainless steel while the whole curved surface area of the housing 6 10 is made of a ring-shaped and gas permeable section 660, e.g. a frit.

In addition, an outer tubular element 670 of hollow cylindrical shape, which is e.g. made from stainless steel, encloses the housing 6 10 concentrically over the complete length of the housing 6 10. The inner diameter of the outer tubular element 670 is larger than the out diameter of the housing 610 such that a ring-shaped free volume 672 between the housing 610 and the outer tubular element 670 is formed. At the outer surface of the outer tubular element 670, an opening 671 for introducing fluids, e.g. neutral reagent gas 631 a, is mounted. Radially outwards, a ring-shaped x-ray source 690 is mounted on the outside surface of the outer tubular element 670.

At the right side in Fig. 6, the housing 610 has a circular opening 612 at the right axial end 613 being concentric with the longitudinal axis 61 1. In Fig. 6 at the left axial end 614, a hollow cylindrical analyte inlet 620 runs along the longitudinal axis 6 1 1 of the ion molecule reactor 600. Through the analyte inlet 620, analytes 62 1 , e.g. volatile organic compounds, can be introduced into the reaction volume 640 along an inlet path 622. The inlet path 622 of the analytes runs along a predefined transit path 641 in the reaction volume 640 whereby the transit path 641 runs along the longitudinal axis 6 1 1 of the housing 1 10.

In operation, neutral reagent gas 631 a is ionized by the x-ray source 690 in order to form reagent ions 631 which are introduced radially through the gas permeable section 660 into the reaction volume 640. Thereby, analytes 62 1 in the reaction volume 640 will undergo chemical ionisation upon collision with reagent ions 631. Thereby, charged analyte ions 123 are formed. Due to the radial flow of reagent ions 631 the flow of analytes 62 1 and analyte ions 641 towards the wall or the gas permeable section 660, respectively, is reduced or inhibited. Fig. 7 shows a cross section of a sixth ion molecule reactor 700 which is similar to the first ion molecule reactor 100 shown in Fig. 1. Specifically, all of the elements and parts 710, 71 1 , 712, 7 13, 714, 720, 72 1 , 722, 723, 730, 731 , 740, 741 , 750 and 751 of the sixth chamber 700 correspond to elements and parts 1 10, 1 1 1 , 1 12, 1 13, 1 14, 120, 12 1 , 122, 123, 130, 131 , 140, 141 , 150 and 151 of the first reactor 100. For example, analyte inlet 720 of the sixth ion molecule reactor 700 is identical to analyte inlet 120 of the first ion molecule reactor 100, et cetera.

Additionally, the sixth reactor comprises an ion funnel 780 which is located inside the housing 710 in front of the right axial end 713. The ion funnel 780 comprises a stack of four metallic ring electrodes 78 1 and is essentially identical with the ion funnel 380 shown in Fig. 3 and 10. The electrodes 78 1 of the ion funnel 780 are coaxial with respect to the transit path 741 or the longitudinal axis 71 1 , respectively. In operation, the four ring electrodes 78 1 are connected to an RF generating device (not shown), whereby out-of- phase alternating RF potentials, typically with a frequency of 0. 1 - 10 MHz, are applied to adjacent electrodes, such that charged analyte ions 723 are radially confined as they pass through the ion funnel 780.

Fig. 8 shows a cross section of a seventh ion molecule reactor 800 which is partly similar to the second ion molecule reactor 200 shown in Fig. 2. Specifically, all of the elements and parts 810, 81 1 , 8 12, 8 13, 814, 820, 82 1 , 822, 823, 830a, 830b, 831 , 840 and 841 of the seventh reactor 800 correspond to elements and parts 2 10, 2 1 1 , 2 12, 2 13, 2 14, 220, 22 1 , 222, 223, 230a, 230b, 231 , 240 and 241 of the second reactor 200. For example, analyte inlet 820 of the seventh ion molecule reactor 800 is identical to analyte inlet 220 of the second ion molecule reactor 200, et cetera.

However, the ion molecule reactor 800 does not comprise any rod electrodes. Instead, the seventh reactor 800 comprises an ion carpet 880 which is located in the reaction volume 840 close to the analyte inlet 820 and the reagent ion inlets 830a, 830b. The ion carpet 880 consists of an essentially planar arrangement of five metallic ring electrodes 881 which are mounted concentrically on an isolating support with a central orifice. The electrodes 88 1 as well as the central orifice of the ion carpet 880 are coaxial with respect to the transit path 8 1 or the longitudinal axis 8 1 1 , respectively. Fig. 1 1 shows a top view of the ion carpet 800 along the longitudinal axis 8 1 1.

In operation, the five ring electrodes 88 1 are connected to an RF generating device (not shown) and a voltage is applied to the electrodes 881 , such that an alternating electric field, typically with a frequency of 0. 1 - 10 MHz, is generated which funnels reagent ions and/or analyte ions through the central orifice. Thereby, a guiding field is generated which allows for guiding and focussing analyte ions 823 and reagent ions 831 along the transit path 841. A similar device and its operation is described for example in US 2013/0 120897 A 1 (Amerom et al.). Fig. 9 shows a cross section of an eighth ion molecule reactor 900 which is partly similar to the second ion molecule reactor 200 shown in Fig. 2. Specifically, all of the elements and parts 9 10, 91 1 , 912, 913, 914, 920, 92 1 , 922, 923, 930a, 930b, 931 , 940 and 941 of the eighth reactor 900 correspond to elements and parts 2 10, 2 1 1 , 2 12, 2 13, 2 14, 220, 22 1 , 222, 223, 230a, 230b, 231 , 240 and 241 of the second reactor 200. For example, analyte inlet 920 of the eighth ion molecule reactor 800 is identical to analyte inlet 220 of the second ion molecule reactor 200, et cetera.

However, the ion molecule reactor 900 does not comprise any rod electrodes inside the housing 910. Instead, the eighth reactor 900 comprises an ion funnel 980 which is located in the reaction volume 940 close to the analyte inlet 920 and the reagent ion inlets 930a, 930b and which is arranged coaxially with respect to the longitudinal axis 91 1. The ion funnel 940 consists of four ring electrodes and is essentially identical to ion funnels 380, 780 shown in Fig. 3, 7 and 10 and is also operated in a similar manner.

Moreover, with the eighth ion molecule reactor 900, each of the regent ion inlets 930a, 930b comprises a guiding element 990a, 990b for guiding the reagent ions 931 before entering the reaction volume 940. The guiding elements 990a, 990b consist for example of four rod electrodes which are regularly arranged around the reagent ion inlets 930a, 930b. Thereby, opposing electrodes are connected in parallel whereas between neighbouring electrodes an RF-only voltage, typically with a frequency of 0.1 - 10 MHz, is applied. Thereby, a multipole guiding field is generated which allows for guiding and focussing reagent ions 931 before entering the inner volume of the housing 910 or the reaction volume 940, respectively.

For applying appropriate voltages to the ion funnel 980, a first voltage generating device 90 1 with an RF voltage and a DC voltage output is connected to the electrodes of the ion funnel 980. A further voltage generating device 902 is connected to the guiding elements 990a, 990b which allows for supplying appropriate voltages to the guiding elements 990a, 990b.

While the ion molecule reactors, mass spectrometers and methods described herein constitute preferred embodiments of this invention, it is to be understood that the invention is not limited to these embodiments, and that changes may be made therein without departing from the scope of the invention.

For example, in all of the ion molecule reactors 100, 200, 300, 400, 700, 800, 900 different and/or additional ion guides and/or electrode arrangements can be used to guide and/or focus the ions along the predefined transit paths. For example, instead of a quadrupole setup as used in reactors 100, 200, 300 400, an octapole setup or a setup with any another number of rod electrodes can be used. Also a combined quadrupol/octapol setup can be suitable. Also, in all ion molecule reactors, e.g. additional ring electrodes can be attached inside and/or outside the housing.

In all ion molecule reactors 100, 200, 300, 400, 700 the cylindrical rod electrodes can for example be arranged within the housings. Also it is possible to use housings with electrodes integrated in the walls of the housing instead of external cylindrical rod electrodes. With ion molecule reactors 800, 900 additional ion guides in the form of multipole electrodes can e.g. be added in order to further guide the ions inside or outside the reaction volumes. Also, the size, shapes and numbers of the electrodes described in the exemplary embodiments can be different. For example, the rod electrodes described with Fig. 1 , 2, 3, 4 and 7 can have a non-circular cross section. Moreover, the number and shape of the electrodes of the ion funnels or ion carpets described in Fig. 3, 7, 8, 10 and 1 1 can be adapted if desired.

Although in the present ion molecule reactors, the predefined transit path is defined along a straight line along the longitudinal axis, transit paths which run along a non-longitudinal axis and/or transit paths with curved sections are possible.

Moreover, it is possible to foresee reagent ion inlets and/or reagent ion sources with other geometries. For example, in the embodiment of Fig. 2, a reagent ion inlet with ring-shaped nozzle could be used instead of the two separate inlets 230a, 230b. Also more than two separate inlets could be foreseen, e.g. 3, 4, 5, 7 or even more inlets which are preferably arranged symmetrically around the reaction volume.

Concerning the shape of the housings, non-cylindrical shapes, e.g. cuboidal shaped housing or even more complex shapes are possible as well. Specific sizes and proportions of the housings of the ion molecule reactors are not limited at all and can be adapted to specific needs if desired. Also, the housing can be made of at least partially or fully flexible or bendable material, e.g. from plastics material. In a special embodiment, the ion molecule reactors or their housings, respectively, can be made of a bendable tube. Such a setup allows for example to effectively transfer ions over quite long distances, e.g. several meters. An embodiment with a bendable tube makes it for example possible to use the ion molecule reactor as a probe or a probe head, respectively, for taking analyte samples at random positions, e.g. similar to a vacuum cleaner.

If desired, means for heating and/or cooling can be included in the ion molecule reactors, which e.g. allow for heating and/or cooling the housings.

Also the gas permeable sections in the embodiments shown in Fig. 3 and 4 can be used to introduce a sheath gas in order to further reduce wall effects.

Especially, in the embodiment of Fig. 3, the gas permeable section 360 can be used to introduce a sheath gas instead of removing neutrals from the reaction volume. This is an alternative approach for reducing wall effects in the ion molecule reactor. Thereby, the gas permeable section 360 can cover the whole cylindrical surface area of the housing 310 within the outer tubular element 370. In contrast to prior art systems which use a laminar flow of sheath gas with rather high pressures, the present setup results in a much lower pressure in the reaction volume.

Also, in the embodiment of Fig. 6, reagent inlets such as e.g. shown in Fig. 1 or 3 can be foreseen. In this case, instead of introducing regent ions through the gas permeable section 660, a sheath gas can be introduced into the housing 610 for reducing wall effects in the ion molecule reactor. In summary, it is to be noted that highly beneficial setups for ion molecule reactors are provided which allow for greatly increasing the efficiency of chemical ionisation and providing ionized analytes with a surprisingly high yield.