Hollow cathode glow discharge reagent ion source for imr / ptr-ms

Abstract

The invention relates to an apparatus and a method to operate the apparatus for Ion Molecule Reaction - Mass Spectrometry (IMR-MS) and / or Proton Transfer Reaction - Mass Spectrometry (PTR-MS) for analyzing a gas for at least one analyte compound by chemical ionization via a specific type of reagent ions comprising a reagent ion source with a Hollow Cathode Glow Discharge (HCD) region (101) and a Source Drift (SD) region (102), a drift tube region (103) adjacent to the reagent ion source comprising at least one inlet (107) for the gas to be analysed and at least one source for an electric field, a mass analyzer region (104) adjacent to the drift tube region (103), and a controlling device, wherein the HCD region (101) comprises at least one port (105) connected to at least one pump, at least two electrodes which are operated as anodes (201, 203) and at least one electrode which is operated as a cathode (202), wherein the SD region (102) comprises at least one port (106) connected to at least one source gas supply, wherein the controlling device is configured to control the discharge current in the HCD region (101), control a source gas flow through the reagent ion source, regulate the pressure in the drift tube region (103) between 1 and 10 hPa, regulate the electric field in the drift tube region (103), wherein the electric field comprises at least a DC field, which is configured to draw ions in the direction of the mass analyzer region (104).

Description

[0001] HOLLOW CATHODE GLOW DISCHARGE REAGENT ION SOURCE FOR IMR / PTR-MS

[0002] The present invention relates to an apparatus for Ion Molecule Reaction - Mass Spectrometry and / or Proton Transfer Reaction - Mass Spectrometry for analyzing a gas for at least one analyte compound by chemical ionization via a specific type of reagent ions comprising a reagent ion source with a Hollow Cathode Glow Discharge region and a Source Drift region, a drift tube region adjacent to the reagent ion source comprising at least one inlet for the gas to be analysed and at least one source for an electric field, a mass analyser region adjacent to the drift tube, and a controlling device. The invention further relates to a method to operate an apparatus for lon-Molecule-Reaction Mass Spectrometry and / or Proton-Transfer-Reaction Mass Spectrometry according to the invention.

[0003] Background of the invention lon-Molecule-Reaction Mass Spectrometry (IMR-MS) or Proton-Transfer-Reaction Mass Spectrometry (PTR-MS) is a direct sample injection method for online detection and quantification of trace gases. Crucially, reagent ions are generated in a spatially separated reagent ion source. Subsequently, the reagent ions and gas containing traces of analytes are injected into an IMR / PTR drift tube, where the analytes undergo chemical ionization by interacting with the reagent ions under the influence of well controlled electric fields. Finally, neutral gas is removed and the ions are introduced into a mass spectrometer / analyzer.

[0004] IMR / PTR-MS instruments known in the art consist of the following elements:

[0005] HCD-SD reagent ion source

[0006] The principal design of the Hollow Cathode glow Discharge (HCD) - Source Drift (SD) reagent ion sources used today has already been introduced in the 1990s (see e.g. A. Hansel, et al., Proton transfer reaction mass spectrometry: on-line trace gas analysis at the ppb level. Int. J. Mass Spectrom. Ion Proc. 149 / 150 (1995) 609-619 and W. Lindinger, et al., On-line monitoring of volatile organic compounds at pptv levels by means of Proton-Transfer-Reaction Mass Spectrometry (PTR-MS) Medical applications, food control and environmental research. Int. J. Mass Spectrom. Ion Proc. 173 (1998) 191-241):

[0007] - an HCD region with an inlet for source gases, followed by

[0008] - an SD region, i.e. a region where the ions generated in the HCD region and neutral source gases react under the influence of an electric field, with an outlet to a vacuum pump. For the production of H ,CF reagent ions pure water vapor (source gas) is introduced into the HCD region usually at about 0.1-10 seem (mL / min at standard conditions), while the discharge current is controlled between 0.5-10 mA. In the HCD region some of the H2O molecules are transformed into O+, OH+, H+, H2+, etc. These ions, together with the neutral H2O vapor, are subsequently drawn into the SD region by an electric field and a pressure difference, where they react predominantly to H3CF via these reactions H2++ H2O H2O++ H2

[0009] H++ H2O H2O++ H

[0010] O++ H2O H2O++ O and finally H2O++ H2O H2O.H++ OH.

[0011] H3CF (H20.H+) reagent ion purity levels achieved with this type of ion source render a mass filter for further purification obsolete, with the main parasite ions being O2+and NO+. Furthermore, H3CF reagent ion currents emitted from this type of reagent ion source are exceptionally high. Finally, the operating pressure in this type of ion source is in the order of magnitude of 10_|- | hPa and thus fits well to the operating pressure of a conventional PTR-MS reaction chamber (1-10 hPa).

[0012] It has been found that with this type of reagent ion source apart from H3CF a series of other reagent ions can be produced with high purity and high intensity, with the most common examples being:

[0013] - O2 when pure O2 is introduced into the HCD region (see A. Jordan, et al., Int. J. Mass Spectrom. 286 (2009) 32-38),

[0014] - NO+when a mixture of N2 and O2 is introduced into the HCD region,

[0015] - Kr+when pure Kr is introduced into the HCD (and a buffer gas is added to the IMR / PTR drift tube) (EP 2606505 Bl and P. Sulzer, et al., Int. J. Mass Spectrom. 321-322 (2012) 66-70),

[0016] - NH4+when a mixture of N2 and H2O vapor (in particular no NH3) is introduced into the HCD region (EP 3503161 Bl).

[0017] Switching between these different reagent ions is performed by changing the source gas(es), adjusting the electric fields and discharge current and adjusting the pumping power in the SD region (affecting the pressure), e.g. via an interconnected valve between the SD region and the vacuum pump.

[0018] Concerning switching times, in literature it is reported that, e.g., switching from H3CF to NH4+takes about 10 s, while switching from NH4+back to H3CF requires several minutes until the reagent ions are fully equilibrated (see M. Muller, et al., Int. J. Mass Spectrom. 447 (2020) 116254).

[0019] It has been demonstrated in literature that, after switching electrical polarities, in an HCD ion source OH" reagent ions can be generated when H2O vapor is used as a source gas (see Y. Pan, et al., J. Am Soc. Mass Spectrom. 28 / 5 (2017) 873-879).

[0020] However, regardless of the produced reagent ions it is important to note that the respective source gas is always introduced into the HCD region and evacuated from the SD region. That is, the source gas flow is always in direction of the flight path of the ions.

[0021] Furthermore, it is remarkable that after decades of development and improvement in IMR / PTR- MS the HCD-SD reagent ion source setup has remained virtually unchanged. This is a clear indication that it works exceptionally well and even the most renowned experts do not see room for conceptual improvements.

[0022] Drift tube

[0023] Directly adjacent to the reagent ion source, i.e. without any mass filter or similar devices interconnected, there is the IMR / PTR reaction chamber. In the very comprehensive PTR-MS literature this reaction chamber is predominantly referred to as the PTR drift tube. Unfortunately, this expression can lead to confusion with the drift tube in Ion Mobility Spectrometry (IMS), which is operated in a pulsed mode and used for separating the ionized analytes according to their mobility in a matrix in a chromatographic manner. Furthermore, in IMS the drift tubes are predominantly operated at or close to atmospheric pressure, i.e. three orders of magnitude higher than in IMR / PTR-MS. Thus, it should be noted that an IMS drift tube is a fundamentally different setup.

[0024] In the IMR / PTR drift tube chemical ionization of the analytes via interactions with the reagent ions takes place. While a certain flow of gas containing the analytes is continuously injected, an electric field draws ions along the drift tube. Commonly, air containing traces of impurities (e.g. traces of volatile organic compounds) is analyzed by IMR / PTR-MS, but many other matrices containing compounds of interest (e.g. remaining impurities in purified gases, gas standards, etc.) have been successfully investigated with various reagent ions. In some embodiments the matrix containing the analytes (e.g. air with traces of volatile organic compounds) is diluted with a buffer gas prior to injection into the IMR / PTR drift tube (e.g. for simple dilution purposes or for the use of particular reagent ions).

[0025] Some of the common reactions between the reagent ion and the analyte taking place in the IMR / PTR drift tube are: Proton transfer reactions, either non-dissociative or dissociative, with A.H+being the reagent ion (in most cases H20.H+) and BC being the analyte

[0026] A.H++ BC -> A + BC.H+

[0027] A.H++ BC - A + B + C.H+

[0028] Charge transfer reactions, either non-dissociative or dissociative, with A+being the reagent ion (e.g. C>2+, NO+, Kr+, etc.) and BC being the analyte:

[0029] A++ BC -> A + BC+

[0030] A++ BC - A + B + C+

[0031] Clustering reactions, with A+being the reagent ion (e.g. H O+, NO+, NH4+etc.) and BC being the analyte:

[0032] In addition, other types of reactions can occur (e.g. ligand switching).

[0033] H+extraction can be observed in case of the negatively charged reagent ion OH"

[0034] Most common IMR / PTR drift tubes consist of a series of ring electrodes electrically connected via resistors with equal resistance (other reported embodiments are e.g. tubes with resistive coating), so that a DC voltage U can be applied across an IMR / PTR drift tube of the length d, resulting in the electric field strength E = U / d (in V / cm) (1). Another important IMR / PTR drift tube parameter is the gas number density A, which is defined by equation (1):

[0035] Here, NA is the Avogadro constant (6.022 x 1023mol’1), VM (22.414 x 103cm3mol’1) is the molar volume at 1013.25 hPa and at 273.15 K, Ta is the temperature in K and Pd is the pressure in hPa in the IMR / PTR drift tube.

[0036] Dividing A by N leads to the reduced electric field strength, which is related to the collision energies of ion-molecule reactions in the IMR / PTR drift tube and most commonly simply denoted as E / N with the unit Townsend (1 Td = IO’17V cm2).

[0037] Recently, novel drift tubes, which provide improved sensitivity and / or selectivity, have been introduced. Most of these include one or more RF (Radio Frequency) devices, such as ion funnels or ion guides for focusing the ions and thus, avoiding losses on the walls and on the orifices to the mass analyzer.

[0038] However, the crucial prerequisite for any IMR / PTR drift tube is, that the chemical ionization conditions can be well controlled, either via direct adjustment of the parameters in equation (1) or via the method introduced in EP 3309817 Bl. This is one of the main differences between IMR / PTR-MS as being used herein and IMR-MS in general, which comprises chemical ionization technologies utilizing generic reaction chambers that offer less to no control of the ion chemistry during the ionization process.

[0039] IMR / PTR drift tubes operate between 1 and 10 hPa (most commonly 2 - 4 hPa). At pressures <1 hPa ionization of the analytes becomes inefficient and thus the overall sensitivity of the device is insufficient for real-time trace gas analysis. For pressures >10 hPa the ion chemistry is not well-controlled anymore (e.g. strong formation of H3O+.(H2O)nreagent ion clusters, extremely high voltages needed), which considerably complicates quantification.

[0040] Mass analyzer and detector

[0041] Various types of mass spectrometers have been employed in IMR / PTR-MS instruments. The most prominent example for a low resolution mass spectrometer is the quadrupole mass filter, whereas for high mass resolution measurements Time-Of-Flight (TOF) analyzers are commonly used. However, the use of other types of mass spectrometers, such as e.g. ion trap analyzers, has also been reported and even MSncould be realized. The mass spectrometer separates the ions injected from the IMR / PTR drift tube according to their m / z and quantifies the ion yields of the separated m / z with a suitable detector (e.g. secondary electron multiplier, microchannel plate, etc.). It has to be noted that each mass spectrometer has a mass dependent ion transmission, which is further influenced by the transfer system between the IMR / PTR drift tube and the analyzer and other devices. Therefore, in order to get comparable measurement results and, even more importantly, comparable branching ratios, the obtained ion yields should be corrected for the mass dependent transmission. This can be done rather easily by analyzing a gas standard containing well-defined amounts of compounds distributed over a (preferably) broad mass range and approximating the correction factors with an appropriate fitting function. With this fitting function the correction factors for all relevant m / z can be calculated with high accuracy.

[0042] Differentiation from corona discharge ion sources

[0043] Corona discharge ion sources are predominantly being utilized in IMS setups as an alternative to radioactive ion sources (see M. Tabrizchi, et al., Rev. Sci. Instrum. 71 (2000) 2321). In IMS the operating pressures are in the region of atmospheric pressure and the requirements on ion purity are rather low. Thus, corona discharge ion sources are an ideal choice, because they operate very well in the high-pressure regime. It has been demonstrated that when at atmospheric pressure the flow of dry air past the corona needle is reversed, unwanted ozone and NOx can be reduced (see S. K. Ross, et al., Int. J. Mass Spectrom. 218 (2002) L1-L6). In 2017, Breitenlechner et al. (Anal. Chem. 89 / 11 (2017) 5824-5831) introduced the "PTR3", an instrument based on PTR-MS principles, but with considerable modifications. The pressure in the reaction region (tripole with rotating electric fields, no DC fields) is between 50 and 80 hPa, while for a conventional IMR / PTR drift tube it is between 1 and 10 hPa (most commonly 2 - 4 hPa). The pressure in the PTR3 reagent ion source is around 80 hPa. At this high pressure it is necessary to employ a corona discharge reagent ion source instead of a HCD ion source. In order to improve the corona discharge ion source's performance, they introduced a mixture of N2 and H2O (instead of pure H2O vapor) and additional N2 at a total flow of 100 seem into the ion source and pumped about 50 seem upstream the corona discharge, while about 50 seem of the mixture were introduced into the PTR3 reaction region. It is stated that the dominant reagent ions are the clusters H3CF.H2O, with an intensity 3.8 times higher than H3CF.

[0044] Differentiation from Selected Ion Flow Tube - Mass Spectrometry (SIFT-MS)

[0045] In SIFT-MS microwave discharge reagent ion sources with moist air as the source gas are used. These ion sources emit a plethora of ions, which mandates the use of a mass filter between the reagent ion source and the IMR reaction region. Thus, the reagent ion purity after the mass filter is very high, but the reagent ion yield is limited due to inevitable transmission losses in the mass filter.

[0046] One advantage of the SIFT-MS setup is that due to the mass filter 02' can be used as reagent ions in the reaction region. This is not possible with known IMR / PTR-MS setups (i.e. without mass filter) because of poor reagent ion purity when 02' is attempted to be produced in a HCD- SD reagent ion source.

[0047] Definition IMR / PTR-MS

[0048] Herein, the abbreviation IMR / PTR-MS is used as the more accurate term for what in literature is commonly depicted as Proton-Transfer-Reaction - Mass Spectrometry (PTR-MS). When PTR-MS was invented in the 1990s, H3CF was the only relevant reagent ion available. Chemical ionization with H3CF reagent ions proceeds mainly via proton transfer to the analyte, hence the name PTR. However, throughout the following decades methods were developed to produce alternative reagent ions (NO+, O2"1", Kr+, etc.) with only minor modifications to the PTR-MS setup. Some of these devices were labeled SRI-MS (Switchable Reagent Ions or Selective Reagent Ionization) instruments but many publications still use PTR-MS despite of the minor incorrectness. "IMR / PTR-MS" in this document should be understood as the technology utilizing all major components of a PTR-MS instrument, but without the limitation to chemical ionization via proton transfer. "IMR / PTR-MS" in this document should not be understood in its broadest sense, i.e. including all types of instrumentation where ion molecule reactions can occur (e.g. methods and devices for increasing the internal energy of ions with electric fields in Electro Spray Ionization (ESI), so-called "Iodide CIMS" or "Acetate CIMS", etc.).

[0049] Short description of the invention

[0050] The object of the present invention is to improve the IMR / PTR-MS device with an HCD-SD reagent ion source and well-controlled ion chemistry known from PTR-MS.

[0051] A solution to the above-mentioned problem is provided by an apparatus for Ion Molecule Reaction - Mass Spectrometry (IMR-MS) and / or Proton Transfer Reaction - Mass Spectrometry (PTR-MS) for analyzing a gas for at least one analyte compound by chemical ionization via a specific type of reagent ions comprising

[0052] • a reagent ion source with a Hollow Cathode Glow Discharge (HCD) region and a Source Drift (SD) region,

[0053] • a drift tube region adj acent to the reagent ion source comprising at least one inlet for the gas to be analysed and at least one source for an electric field,

[0054] • a mass analyzer region (104) adjacent to the drift tube region,

[0055] • and a controlling device, wherein the HCD region comprises at least one port connected to at least one pump, at least two electrodes which are operated as anodes and at least one electrode which is operated as a cathode, wherein the SD region comprises at least one port connected to at least one source gas supply, wherein the controlling device is configured to

[0056] • control the discharge current in the HCD region,

[0057] • control a source gas flow through the reagent ion source,

[0058] • regulate the pressure in the drift tube region between 1 and 10 hPa,

[0059] • regulate the electric field in the drift tube region, wherein the electric field comprises at least a DC field, which is configured to draw ions in the direction of the mass analyzer region. Thus, for the inventive apparatus it is possible to interchange the devices connected to the HCD region port and the SD region port compared to IMR / PTR-MS devices known from the state of the art and thus, to reverse the source gas flow. That is, the source gas enters the SD region and flows into the HCD region, where it is pumped out. The source gas flow is "backwards", upstream the ion flight direction.

[0060] This backward source gas flow so far has not been used in HCD-SD reagent ion sources for IMR / PTR-MS instruments. Indeed, experiments of producing the reagent ions NHC or NO+show discouraging results. When introducing N2 and H2O vapor or N2 and O2 into the SD region and pumping the source gas from the HCD region, even after adjusting the source gas flows, the gas flow to the vacuum pump and optimizing the voltages and the discharge current via the controlling device neither sufficient intensity nor purity of NH4+or NO+can be obtained.

[0061] However, when introducing H2O vapor or O2 into the SD region and pumping the source gas from the HCD region, after adjusting the source gas flow, the gas flow to the vacuum pump and optimizing the voltages and the discharge current via the controlling device excellent H ,CP or O2 intensity and purity are obtained.

[0062] Absolute values for purities and intensities are difficult to be determined, as tuning the reagent ion source for maximum reagent ion purity comes at the cost of lower reagent ion yield and vice versa. For example, the 99.5% H3CF reagent ion purity for common HCD-SD ion sources stated in literature is a maximum value that is only achievable by sacrificing reagent ion intensity, which results in lower overall sensitivity of the PTR-MS device. Therefore, most PTR-MS instruments are tuned for about 95-97% H ,CF purity and, at the same time, high H3CF intensity.

[0063] Further, the controlling device may be configured to switch electrical polarities and adjust reagent ion source extraction voltages, drift tube region and mass analyzer for negatively or positively charged ions. That is, either positively or negatively charged reagent ions can be extracted out of the reagent ion source and the controlling device allows to switch the polarities.

[0064] So far, one skilled in the art would refrain from reversing the common ("forward") source gas flow direction in an HCD-SD reagent ion source, because it comes with the considerable drawback of not being able to produce NO+nor NH4+reagent ions anymore.

[0065] However, most surprisingly, when operating the IMR / PTR-MS instrument in negative ion mode via the controlling device, introducing essentially pure O2 as a source gas into the SD region and pumping the source gas from the HCD region (i.e. backward source gas flow), for the first time pure and abundant 02' reagent ions could be produced for subsequent chemical ionization of analytes in the IMR / PTR drift tube. As mentioned in the background section, so far this could only be done when employing a mass filter adjacent to the reagent ion source for filtering 02' from the vast amounts of parasitic ions (which limits the 02' reagent ion yield; compare SIFT-MS paragraph).

[0066] Thus, in a preferred embodiment the apparatus comprises an O2 -source, wherein the controlling device is configured to control the injection of O2 through the at least one port into the SD region and the pumping of O2 out of the HCD region so as to produce 02' in the reagent ion source, and to adjust the reagent ion source extraction voltages such that the produced reagent ions are conducted to the drift tube region. Preferably, the reagent ion purity of 02' is higher than 90 %. As explained above, this is possible with the inventive apparatus due to the backward source gas flow.

[0067] In another embodiment the apparatus further comprises a CO2 -source, wherein the controlling device is configured to separately control the injection of O2 and CO2 through the at least one port into the SD region and the pumping of O2 and CO2 out of the HCD region so as to produce COT in the reagent ion source, and to adjust the reagent ion source extraction voltages such that the produced reagent ions are conducted to the drift tube region. Preferably, the reagent ion purity of COs' is higher than 80 %. As explained above, this is possible with the inventive apparatus due to the backward source gas flow.

[0068] When operating the IMR / PTR-MS instrument in negative ion mode via the controlling device, introducing essentially pure O2 and CO2 (either as a mixture or via two separate source gas inlets) as source gases into the SD region and pumping the source gases from the HCD region (i.e. backward source gas flow), pure and abundant CCh' reagent ions can be produced for subsequent chemical ionization of analytes in the IMR / PTR drift tube.

[0069] Thus, in a preferred embodiment the apparatus comprises an O2 and a CO2 source, wherein the controlling device is configured to separately control the injection of O2 and CO2 through the at least one port into the SD region and the pumping of the O2 and CO2 mixture out of the HCD region so as to produce CCh' in the reagent ion source, and to adjust the reagent ion source extraction voltages such that the produced reagent ions are conducted to the drift tube region. In summary, reversing the source gas flow through the HCD-SD reagent ion source results in at least the following capabilities:

[0070] - 02' reagent ions can be produced with excellent purity and intensity when O2 is used as a source gas. (negative ion mode)

[0071] - H3O+reagent ions can be produced with excellent purity and intensity when gaseous H2O is used as a source gas. (positive ion mode)

[0072] - CO3‘ reagent ions can be produced with excellent purity and intensity when O2 and CO2 are used as source gases, (negative ion mode)

[0073] - O2 reagent ions can be produced with excellent purity and intensity when O2 is used as a source gas. (positive ion mode)

[0074] While the following disadvantages are observed, compared to the common ("forward") gas flow direction:

[0075] - NH4+reagent ions cannot be produced with high purity and intensity by introducing N2 and gaseous H2O into the SD region, (positive ion mode)

[0076] - NO+reagent ions cannot be produced with high purity and intensity by introducing N2 and O2 into the SD region, (positive ion mode)

[0077] In a further embodiment the at least one port of the HCD region is connected to at least one source gas supply. In this preferred embodiment the IMR / PTR-MS apparatus is capable of switching the source gas flow between forward and backward direction.

[0078] Forward source gas flow direction means that the source gas is introduced into the HCD region and removed from the SD region and / or the drift tube region (common gas flow direction).

[0079] Backward source gas flow direction means that the source gas is introduced into the SD region and removed from the HCD region.

[0080] Further, the apparatus may comprise an N2 - source and an H2O - source, wherein the controlling device is configured to control the injection of a mixture of N2 and H2O source gases into the HCD region through the at least one port and the pumping out of the SD region through the at least one port and / or the drift tube region so as to produce NH4+in the reagent ion source, control the injection of H2O source gas into the SD region through the at least one port and the pumping out of the HCD region so as to produce H3O+in the reagent ion source, and to electronically switch between the production of NH4+and H3O+ions in the reagent ion source. Preferably, the controlling device is further configured to control the injection of a mixture of N2 and O2 source gases into the HCD region through the at least one port and the pumping out of the SD region and / or the drift tube region so as to produce NO+in the reagent ion source, control the injection of O2 source gas into the SD-region through the at least one port and the pumping out of the HCD region so as to produce O2"1" in the reagent ion source, wherein the controlling device is further configured to switch between the different reagent ions electronically.

[0081] Summarizing, by switching between forward and backward source gas flow direction at least H,CF (backward / forward also possible), NO+(forward), C>2+(backward / forward also possible), NH4+(forward), 02' (backward), and CO (backward) reagent ions can all be produced in excellent purity and intensity.

[0082] When constructing and testing a prototype of such a switchable source gas flow direction IMR / PTR-MS apparatus a completely unexpected effect was observed. Switching time of reagent ions HsO+(backward) to NH4+(forward) and back could be reduced from between 10 s and several minutes, respectively, (compare background section) to <2 s. Furthermore, these 2 s were determined by the response time of the utilized mass flow controllers for the source gases and could be further improved by alternative, more rapidly responding gas feed setups.

[0083] The invention also relates to a method to operate an apparatus for lon-Molecule-Reaction Mass Spectrometry and / or Proton-Transfer-Reaction Mass Spectrometry with a reagent ion source with a Hollow Cathode glow Discharge (HCD) region and a Source Drift (SD) region, wherein the SD region comprises at least one port connected to at least one source gas supply and the HCD region comprises at least one port connected to at least one pump, characterized by the following steps:

[0084] • introducing a controlled flow of source gas into the SD region via the at least one port and pumping the source gas out of the HCD region,

[0085] • applying an ionization method to the source gas thereby producing reagent ions in the reagent ion source,

[0086] • introducing the reagent ions and a gas to be analyzed into a drift tube region, wherein the analytes get ionized via interactions with the reagent ions in the drift tube region, wherein subsequent to the drift tube region the ions are analyzed in a mass analyzer region. Thus, via this method a backward source gas flow can be achieved in the reagent ion source and 02' reagent ions can be produced with excellent intensity and purity. Additionally, CCh' reagent ions can be produced with excellent intensity and purity.

[0087] Preferably, switching between positively or negatively charged reagent ions, which are produced in the reagent ion source, is accomplished by switching electrical polarities and adjusting reagent ion source extraction voltages, drift tube and mass analyzer for negatively or positively charged ions. The switching can be achieved preferably electronically via the controlling device.

[0088] Further, the at least one port of the HCD region may be connected to at least one source gas supply, wherein depending on the reagent ions to be produced either source gas is introduced in the SD region and pumped out of the HCD region to produce a backward source gas flow, or source gas is introduced in the HCD region and pumped out of the SD region and / or the drift tube region to produce a forward source gas flow, wherein different reagent ions are produced by electronically switching between forward and backward source gas flow and / or using different source gases. Thus, it is possible to produce a large variety of reagent ions with the same apparatus with excellent intensity and purity by simply switching the direction of the source gas flow and the source gas.

[0089] Preferably, the time to switch between different reagent ions of the same polarity is less than 2 s.

[0090] In an especially preferred embodiment O2 source gas is introduced into the SD region and pumped out of the HCD thereby producing a backward source gas flow and 02' or C>2+as reagent ions, or a mixture of N2 and H2O source gases is introduced into the HCD region and pumped out of the SD region and / or the drift tube region thereby producing a forward source gas flow and NH4+as reagent ions or a mixture of N2 and O2 source gases is introduced into the HCD region and pumped out of the SD region and / or the drift tube region thereby producing a forward source gas flow and NO+as reagent ions, or

[0091] H2O source gas is introduced into the SD region and pumped out of the HCD region thereby producing a backward source gas flow and H3CF as reagent ions, wherein a controlling device allows to electronically switch the production of the different reagent ions.

[0092] In another embodiment O2 source gas is introduced into the SD region and pumped out of the HCD region thereby producing a backward source gas flow and 02' or C>2+as reagent ions, or a mixture of O2 and CO2 source gases are introduced into the SD region and pumped out of the HCD region thereby producing a backward source gas flow and CCh' as reagent ions, or a mixture of N2 and H2O source gases are introduced into the HCD region and pumped out of the SD region and / or the drift tube region thereby producing a forward source gas flow and NH4+as reagent ions, or a mixture of N2 and O2 source gases are introduced into the HCD region and pumped out of the SD region and / or the drift tube region thereby producing a forward source gas flow and NO+as reagent ions, or

[0093] H2O source gas is introduced into the SD region and pumped out of the HCD region thereby producing a backward source gas flow and H3CF as reagent ions, wherein switching the production of the different reagent ions is done electronically via a controlling device.

[0094] Detailed description and preferred embodiments

[0095] The foregoing and other objects, features and advantages of the invention will become more apparent from the following detailed description, which proceeds with reference to the accompanying figures.

[0096] Fig. 1 shows schematics of the components of an IMR / PTR-MS instrument incl. several ports. Fig. 2 shows schematics of an HCD-SD reagent ion source.

[0097] Fig. 3 shows an exploded-view of a specific embodiment of an HCD-SD reagent ion source. Fig. 4 shows schematic electric wiring of an HCD-SD reagent ion source.

[0098] Fig. 5 shows measured switching times between H3CF and NH4+reagent ions.

[0099] A schematic overview of the main sections of an IMR / PTR-MS instrument according to the invention is given in Fig. 1 : An HCD-SD reagent ion source region comprising an HCD region 101 and an SD region 102; a drift tube region 103; and a mass spectrometer / analyzer (including a differential pumping region) 104. Each region may be equipped with at least one port 105- 108 for introducing and / or removing gases.

[0100] The at least one port of the HCD region 105 can be connected to at least one vacuum pump and optionally to at least one source gas supply.

[0101] The at least one port of the SD region 106 can be connected to at least one source gas supply and optionally to least one vacuum pump.

[0102] The at least one port of the drift tube region 107 can be connected to at least one inlet for the gas to be analyzed and optionally to at least one vacuum pump.

[0103] The at least one port of the mass analyzer region 108 can be connected to at least one vacuum pump.

[0104] Preferably, the gas flows from the gas supplies and to the vacuum pumps are well-defined and / or can be controlled with devices known in the art, e.g. flow-restricting capillaries, mass flow controllers, proportional valves (valves to control the gas flow rate by varying the size of the flow passage via a restrictor), shut-off valves, etc.

[0105] Forward source gas flow

[0106] The source gas is introduced into the HCD region 101 via port 105. Due to the fluid connection between HCD region 101 and SD region 102 the source gas spreads into SD region 102, where it is pumped away either by means of a vacuum pump connected to port 106 and / or by the vacuum of the IMR / PTR-MS drift tube 103. Because of continuous source gas supply to the HCD region 101 and continuous pumping of SD region 102, there is a source gas flow in downstream direction of the HCD-SD reagent ion source.

[0107] Backward source gas flow

[0108] The source gas is introduced into the SD region 102 via port 106. Due to the fluid connection between SD region 102 and HCD region 101 the source gas spreads into HCD region 101, where it is pumped away by means of a vacuum pump connected to port 105. Because of continuous source gas supply to SD region 102 and continuous pumping of HCD region 101, there is a source gas flow in upstream direction of the HCD-SD reagent ion source.

[0109] Switching of the source gas flow

[0110] In a preferred embodiment the source gas flow direction can be electronically switched from forward gas flow to backward gas flow and from backward gas flow to forward gas flow. For this embodiment the port of the HCD region 105 needs to be at least connected to a source gas supply and a vacuum pump. The port of the SD region 106 needs to be at least connected to a source gas supply. Optionally, this port 106 can be additionally connected to a vacuum pump. The switching is controlled via the controlling device. Devices used to control the supply and pumping gas flows are commonly known electronically controllable devices such as, e.g. valves and mass flow controllers, and are interconnected between the respective ports and the gas supplies / vacuum pumps with gas lines.

[0111] Detailed discussion of the HCD-SD reagent ion source

[0112] Fig. 2 shows a schematic view of the HCD-SD reagent ion source components. Fig. 3 shows an exploded-3D-view with approximate dimension ratios of a particular embodiment of an HCD- SD reagent ion source.

[0113] Elements 201, 202, 203, 204 and 205 are electrodes made from electrically conducting material. Preferably the material is metal. Most preferably the material is stainless steel of the type EN 1.4301, 1.4405 or 1.4407.

[0114] In a preferred embodiment electrodes 201, 202 and 204 are cylindrical hollow electrodes, while electrodes 203 and 205 are annular plate electrodes with much smaller center orifices. In one embodiment electrode 205 is also the first electrode of the IMR / PTR drift tube, i.e. with a small center orifice facing electrode 204 and thus defining the downstream border of SD region 102 and a port 107 on the side facing the IMR / PTR drift tube region 103 for introducing sample gas into the IMR / PTR drift tube.

[0115] Elements 206 are electrically insulating gaskets that provide gastight seals between the electrodes 201-204 so that a vacuum can be created in the inner volume of the HCD-SD reagent ion source. The material of the gaskets 206 can be any non-conductive material. Preferably the material is polytetrafluoroethylene (PTFE) or poly ether ether ketone (PEEK). Typical pressures in the HCD-SD reagent ion source are between 0.1 - 10 hPa, preferably between 0.2 and 4 hPa. Different shapes and dimensions of the elements 201 - 206 are possible and known in the art. Element 207 is a gas line connected to the at least one port 105 of the HCD region 101. Element 208 is a gas line connected to the at least one port 106 of the SD region 102.

[0116] Fig. 4 shows a schematic view of the electrical connections of the electrodes of the HCD-SD reagent ion source. Regardless of the polarity of the extracted reagent ions, electrode 201 is always operated as an anode, electrode 202 as the cathode and electrode 203 as an anode. Preferably, anodes 201 and 203 are electrically connected. Initially, a voltage sufficiently high to ignite the glow discharge is applied to these electrodes. The discharge current Ihc flowing between anodes and cathode is controlled to an adjustable value. Typical values for Ihc are between 0.5 and 10 mA, preferably between 1 and 6 mA. The extraction voltages Usand Uso affect the transport of the ions between the HCD region 101, the SD region 102 and the drift tube region 103. That is, by adjusting these voltages the ion extraction and thus the IMR interaction time in the SD region 102 can be adjusted. In other words, by optimizing Usand Usothe intensity and purity of the reagent ions entering the drift tube region 103 can be optimized. Furthermore, when switching between positively and negatively charged reagent ions, only the polarities of Usand Uso(and obviously the respective polarities of 103 and 104) are changed so that positively or negatively charged ions are extracted and transported, while the direction of Ihc remains unchanged. That is, anodes 201, 203 remain anodes and cathode 202 remains a cathode regardless of the reagent ion polarity.

[0117] Typical absolute voltage ranges for Usand Usoare between 0 - 500 V, respectively.

[0118] In a preferred embodiment the power supplies of the HCD-SD region are electrically floating on the DC voltages of the drift tube region 103.

[0119] The necessary power supplies and control units for providing and controlling the electric power for the IMR / PTR-MS instrument are well known in the art and not discussed in detail herein.

[0120] Devices used for measuring the pressures in different regions of the setup are well known in the art and can be any type of vacuum gauges (e.g. capacitance gauges, Pirani gauges, etc.) connected to the respective regions. Pressures in different regions of the setup can also be theoretically calculated based on gas flows and setup dimensions. Typically, in commercial HCD-SD reagent ion sources no vacuum gauges are needed, as the dependences between gas flows and resulting pressures are well known from the prototyping stadium.

[0121] Exemplary embodiment 1

[0122] The port 105 of the HCD region 101 is at electrode 201 and connected to a gas line 207. Gas line 207 is connected to a turbomolecular pump (e.g. second stage of a "HiPace SplitFlow" from Pfeiffer Vacuum) via a proportional valve. The turbomolecular pump is backed by a multi-stage diaphragm pump.

[0123] The port 106 of the SD region 102 is at electrode 204 and connected to a gas line 208. Gas line 208 is connected to an O2 supply (e.g. oxygen gas cylinder with purity 5.0) via a mass flow controller.

[0124] All valves and mass flow controllers are electrically controllable.

[0125] By setting the mass flow controller to a value between 0.5 - 10 seem and opening the proportional valve the HCD-SD reagent ion source is operated in backward gas flow direction. The pressure in the HCD-SD reagent ion source is kept between 0.1 - 10 hPa, preferably between 0.2 - 4 hPa.

[0126] Electrode 201 is operated as an anode, electrode 202 as a cathode and electrode 203 as an anode (electrically connected to 201). The discharge current Ihc, which flows between anodes and cathode, is set to a value between 0.5 - 10 mA.

[0127] Usis set to extract negatively charged ions from HCD region 101 to SD region 102. Usois set to extract negatively charged ions from SD region 102 to drift tube region 103. The drift tube region 103 is of the "conventional type", i.e. a series of ring electrodes connected via a resistor chain to which a voltage between 0 - 1000 V (absolute value) can be applied in order to accelerate the ions downstream at a well-controlled E / N. Preferably the E / N can be set to a value between 50 and 250 Td. Between the ring electrodes are electrically insulating gaskets so that the inner volume of the drift tube is gastight. The power supplies of the HCD / SD reagent ion source are electrically floating on the IMR / PTR drift tube power supplies.

[0128] Port 107 of the drift tube region 103 is connected to an inlet system consisting of capillaries, mass flow controllers and pressure controllers so that sample gas is continuously delivered to the drift tube region 103. The drift tube region 103 is evacuated via the fluid connection to the differential pumping region within 104. The pressure in the IMR / PTR drift tube region 103 can be adjusted between 1 - 10 hPa. Preferably, the pressure it set to 2 - 4 hPa.

[0129] Mass spectrometer / analyzer region 104 comprises a differential pumping region and a subsequent TOF analyzer including an ion detector. Ports 108 of mass spectrometer / analyzer region 104 are connected to three turbomolecular pumps in order to pump the gas entering from the drift tube region 103 eventually down to a vacuum sufficient for the TOF analyzer to work (e.g. between 10'5- 10'10hPa).

[0130] With the controlling device, the voltages, currents, electrically controllable valves, mass flow controllers, etc. are optimized. The controlling device may be for example a control computer. Optimization of reagent ion production is done by introducing zero air as a sample gas into the IMR / PTR drift tube and monitoring the m / z separated ion intensities detected with the TOF analyzer. Optimization is aimed for highest purity and intensity of 02' reagent ions. 02' reagent ion purities of >90% can be easily achieved at extremely high reagent ions yields. Reagent ion purities >98% are possible.

[0131] With such a setup, analytes can be detected and quantified at extremely high sensitivity. Among these analytes are many compounds which cannot be ionized with traditional PTR-MS, such as inorganic acids. Furthermore, fragmentation of analytes is widely suppressed, which makes interpretation of mass spectra and compound quantification particularly easy. Product ions upon chemical ionization of analytes MH with 02' are mostly, but not exclusively, M". Some examples for product ions of the multitude of tested compounds are: Br" for HBr, Cl" for HC1, HCO2' for H2CO2, etc.

[0132] Exemplary embodiment la

[0133] By applying the following changes to exemplary embodiment 1 chemical ionization with CCh' is enabled with an IMR / PTR-MS instrument:

[0134] Gas line 208 (connected to port 106 of the SD region 102) is split into two gas lines. One of these two gas lines is connected to an O2 cylinder via a mass flow controller, while the other gas line is connected to a CO2 cylinder via a mass flow controller.

[0135] In order to introduce a mixture of O2 and CO2 into SD region 102 both mass flow controllers are opened. Preferred flows are between 0.1 and 15 seem for each source gas. Preferably, the ratio between the flows O2:CO2is between 1 : 1 and 10: 1. Preferably, the O2 flow is higher than the CO2 flow so that the concentration of O2 is higher than the concentration of CO2 in the reagent ion source. One example of source gas flows is 5 seem O2 and 1 seem CO2.

[0136] Preferably, the drift tube region 103 comprises RF ion focusing measures in addition to the DC voltage along the drift tube length. The DC voltage can be varied between 0 - 1000 V. Particularly when low E / N is used for chemical ionization of analytes via COs' reagent ions, RF ion focusing prevents excessive ion losses in the drift tube region 103 and thus considerable depletion of the IMR / PTR-MS instrument's sensitivity. The pressure in the drift tube region 103 can be adjusted between 1 - 10 hPa. Preferably, a somewhat higher pressure than for H3CC reagent ions is used, i.e. between 4 - 6 hPa.

[0137] One example of an analyte that can be particularly well analyzed with COs' reagent ions is SO2. In the prototype IMR / PTR-MS instrument SO2 ionization with COs' yielded SOs' ions at nominal m / z 112.

[0138] Exemplary embodiment 2

[0139] The port 105 of the HCD region 101 is connected to a gas line 207, which itself is split into three gas lines. One of these gas lines is connected to a reservoir filled with purified water via a mass flow controller. Another gas line is connected to a N2 cylinder (purity 6.0) via a mass flow controller. The third gas line is connected to a turbomolecular pump (e.g. second stage of a "HiPace SplitFlow" from Pfeiffer Vacuum) via a proportional valve.

[0140] The port 106 of the SD region 102 is at electrode 204 and connected to a gas line 208. Gas line 208 is connected via a mass flow controller to a reservoir filled with purified water. For economic reasons this may be the same reservoir as connected via a (different) mass flow controller to the port of the HCD region 101. Optionally, gas line 208 may additionally be connected to a turbomolecular pump via a proportional valve. This turbomolecular pump may be the same second stage of a "HiPace SplitFlow" as for the port 105 of the HCD region 101. However, it has been found that for this exemplary embodiment 2, when operated in forward source gas flow direction, the evacuation of the SD region 102 through the small orifice of electrode 205 into the drift tube region 103 can be sufficient. That is, the rather costly additional proportional valve at gas line 208 can be omitted for economic reasons.

[0141] All valves and mass flow controllers are electrically controllable. Preferably, each source gas mass flow controller can be set to a value between 0 - 10 seem.

[0142] The pressure in the HCD-SD reagent ion source is kept between 0.1 - 10 hPa, preferably between 0.2 - 4 hPa.

[0143] Usis set to extract positively charged ions from HCD region 101 to SD region 102. Usois set to extract positively charged ions from SD region 102 to drift tube region 103. The IMR / PTR drift tube is of an "advanced type", i.e. a series of ring electrodes with constant orifice dimensions and gas tight gaskets in between followed by a series of ring electrodes in an ion funnel configuration without gastight gaskets in between. The whole IMR / PTR drift tube is surrounded by a pumped vacuum chamber defining an outer space around the ring electrodes and thus part of the introduced sample gas is already removed in the drift tube region 103 for this design.

[0144] RF voltages can be added to the DC voltages applied to the electrodes for ion focusing. The power supplies of the HCD-SD reagent ion source are electrically floating on the IMR / PTR drift tube DC power supplies.

[0145] The port 107 of the drift tube region 103 is connected to an inlet system consisting of capillaries, mass flow controllers and pressure controllers so that sample gas is continuously delivered directly into space enclosed by the electrodes of the drift tube region 103. An additional port 107 is connected to a vacuum pump so that the outer space surrounding the ring electrodes can be evacuated. This also evacuates the space enclosed by the electrodes of the drift tube region 103 through the gaps between the ion funnel electrodes. The pressure in the drift tube region 103 can be adjusted between 1 - 10 hPa. Preferably, the pressure is set to 2 - 4 hPa.

[0146] Mass spectrometer / analyzer region 104 comprises a differential pumping region with a hexapole ion guide for ion focusing and a subsequent TOF analyzer including an ion detector. Ports 108 of region 104 are connected to three turbomolecular pumps in order to pump the gas entering from the drift tube region 103 down to a vacuum sufficient for the TOF analyzer to work (e.g. between 10'5- 10'10hPa). With the controlling device connected to the IMR / PTR-MS device the voltages, currents, valves, mass flow controllers, etc. are optimized. Optimization is done by introducing zero air as a sample gas into drift tube region 103 and monitoring the m / z separated ion intensities detected with the TOF analyzer.

[0147] The proportional valve at gas line 207 is opened and the two mass flow controllers at gas line 207 are closed, so that the HCD region 101 is evacuated by the turbomolecular pump. By adjusting the mass flow controller at gas line 208 gaseous H2O (the purified water in the reservoir evaporates due to the low pressure) is introduced into the SD region 102. If present, the proportional valve connected to gas line 208 is closed. The source gas flow in this configuration therefore is in backward direction. Voltages, currents, valves, mass flow controllers, etc. are optimized for high purity and intensity of H3CF reagent ions. Once found, the optimized parameters can be stored as "H3O+set" on a storage device, e.g. the control computer. They can be also stored on the controlling device, which may include a storage device.

[0148] Subsequently, the proportional valve at gas line 207 is closed and the two mass flow controllers (for N2 and H2O, respectively) connected to gas line 207 are opened and adjusted. If present, the proportional valve connected to gas line 208 is opened. The source gas flow in this configuration is in forward direction. Voltages, currents, valves, mass flow controllers, etc. are optimized for high purity and intensity of NH4+reagent ions. Once found, the optimized parameters can be stored as "NH4+set" on a storage device, e.g. the control computer and / or the controlling device.

[0149] It is found that by switching between "NH4+set" and "H3O+set", i.e. essentially switching the source gas flow direction and the source gases, full equilibrium of the respective reagent ions is reached within <2 s (compared to minutes reported in literature for forward source gas flow direction only). Furthermore, it is found that the time to equilibrium is mainly limited by the response of the mass flow controllers. By installing additional valves and gas lines, so that the well-defined gas flows through the mass flow controllers can be kept constant and source gas supplies to HCD region 101 and SD region 102 can be switched on or off via fast acting valves, the time to equilibrium and thus the reagent ion switching time can be further improved.

[0150] Reagent ion purities of >95% for both, NH4+and H3CF can be easily achieved, while purities of >98% are possible. The rapid reagent ion switching capability considerably increases the selectivity of the IMR / PTR-MS instrument, as data for both reagent ions can be obtained virtually simultaneously, i.e. only 1 s of data is "lost" during the switching process. Fig. 5 shows measurement results from a device according to exemplary embodiment 2. Traces of D5-Siloxane (M) were added to the sample air entering the IMR / PTR drift tube. With "H3CF set" applied M.H+is detected as the product ion. Switching to "NH4+set" is fully completed within about 1 s and the product ion detected in this mode is predominantly the cluster M.NH4+. Product ion intensities are comparable for both reagent ions indicating that the reagent ions are of comparable (high) intensity. Furthermore, except for the expected statistical noise the product ion intensities are constant immediately after switching indicating that indeed equilibrium has been reached.

[0151] Exemplary embodiment 3

[0152] This embodiment is capable of producing at least H3CF, NO+, O2"1", NF+and 02' reagent ions. Additional reagent ions are possible by adding the respective feeds for source gases.

[0153] The at least one port 105 of the HCD region 101 is at least connected to:

[0154] - a vacuum pump via a flow regulating device

[0155] - an H2O source via a flow regulating device

[0156] - an N2 source via a flow regulating device

[0157] - an O2 source via a flow regulating device.

[0158] The at least one port 106 of the SD region 102 is at least connected to:

[0159] - an H2O source via a flow regulating device

[0160] - an O2 source via a flow regulating device

[0161] - optionally a vacuum pump via a flow regulating device.

[0162] All flow regulating devices are electrically controllable via the controlling device. Preferably, each source gas flow regulating device can be set to a value between 0 - 10 seem.

[0163] The pressure in the HCD-SD reagent ion source is kept between 0.1 - 10 hPa, preferably between 0.2 - 4 hPa.

[0164] Production of the at least above-mentioned reagent ions:

[0165] - H3CF: Introduction of a controlled flow of gaseous H2O source gas into SD region 102. Pumping of source gas from HCD region 101 with the vacuum pump at port 105. 1.e. backward source gas flow direction. Optimization of HCD-SD reagent ion source for the production of H3O+at high purity and intensity. Configuration of HCD-SD reagent ion source extraction voltages, IMR / PTR drift tube and mass spectrometer / detector for positive ions.

[0166] - NO+: Introduction of a controlled flow of N2 and O2 source gases into HCD region 101. Pumping of source gas from SD region 102 via the orifice of electrode 205 to the drift tube region 103 and / or optional vacuum pump at the port 106 of the SD region 102. I.e. forward source gas flow direction. Optimization of HCD-SD reagent ion source for the production of NO+at high purity and intensity. Configuration of HCD-SD reagent ion source extraction voltages, IMR / PTR drift tube and mass spectrometer / detector for positive ions.

[0167] - O2+: Introduction of a controlled flow of O2 source gas into SD region 102. Pumping of source gas from HCD region 101 with vacuum pump at port 105. I.e. backward source gas flow direction. Optimization of HCD-SD reagent ion source for the production of O2+at high purity and intensity. Configuration of HCD-SD reagent ion source extraction voltages, IMR / PTR drift tube and mass spectrometer / detector for positive ions.

[0168] - NH4+: Introduction of a controlled flow of N2 and gaseous H2O source gases into HCD region 101. Pumping of source gas from SD region 102 via the orifice of electrode 205 to the drift tube region 103 and / or optional vacuum pump at the port 106 of the SD region 102. I.e. forward source gas flow direction. Optimization of HCD-SD reagent ion source for the production of NH4+at high purity and intensity. Configuration of HCD-SD reagent ion source extraction voltages, IMR / PTR drift tube and mass spectrometer / detector for positive ions.

[0169] - 02': Introduction of a controlled flow of O2 source gas into SD region 102. Pumping of source gas from HCD region 101 with vacuum pump at port 105. I.e. backward source gas flow direction. Optimization of HCD-SD reagent ion source for the production of 02' at high purity and intensity. Configuration of HCD-SD reagent ion source extraction voltages, IMR / PTR drift tube and mass spectrometer / detector for negative ions.

[0170] Additional reagent ions can be produced by introducing the respective source gases to either HCD region 101 or SD region 102 and optimizing the HCD-SD reagent ion source for the production of the respective reagent ions.

[0171] Optimized settings for each type of reagent ions can be stored on the controlling device and / or a storage device, e.g. the control computer of the IMR / PTR-MS apparatus, so that the respective reagent ions can be conveniently activated by selecting a set of settings. It should be noted that because of the high voltages of the IMR / PTR drift tube and particularly of the mass spectrometer, switching electrical polarities (i.e. configuration for positive to configuration for negative ions, and back) typically takes somewhat longer than switching between reagent ions of the same polarity. Observed times needed for electrical polarity switching at the prototype were between 5 and 30 s.

[0172] The IMR / PTR-MS drift tube may be of the "conventional type" or the "advanced type". The IMR / PTR-MS drift tube may also be of a mixed type between conventional and advanced. That is, surrounding the IMR / PTR-MS drift tube consisting of ring electrodes and an ion funnel with gas-tight gaskets between each element, there can be a vacuum chamber evacuated to a somewhat lower pressure than inside the IMR / PTR-MS drift tube. This option has the advantage that the IMR / PTR-MS drift tube can be of the conventional type, but small vacuum leaks do not cause contaminations to enter the reaction region. The electric field(s) in the IMR / PTR-MS drift tube may be DC-only or additional RF fields. Preferably, the IMR / PTR- MS drift tube is operated at a pressure between 1 and 10 hPa.

[0173] Preferably, the E / N in the IMR / PTR-MS drift tube can be adjusted to a certain value or a value range between 50 - 250 Td.

[0174] Exemplary embodiment 3a

[0175] By additionally connecting a CO2 source via a flow regulating device to the at least one port 106 of the SD region 102 exemplary embodiment 3 is capable of producing CCh' reagent ions: Introduction of a controlled flow of O2 and a controlled flow of CO3 into SD region 102. Pumping of source gas from HCD region 101 with vacuum pump at port 105. I.e. backward flow direction. Optimization of HCD-SD reagent ion source for the production of COs' at high purity and intensity. Configuration of HCD-SD reagent ion source extraction voltages, IMR / PTR drift tube and mass spectrometer / detector for negative ions.

Claims

Claims:

1. Apparatus for Ion Molecule Reaction - Mass Spectrometry (IMR-MS) and / or Proton Transfer Reaction - Mass Spectrometry (PTR-MS) for analyzing a gas for at least one analyte compound by chemical ionization via a specific type of reagent ions comprising• a reagent ion source with a Hollow Cathode glow Discharge (HCD) region (101) and a Source Drift (SD) region (102),• a drift tube region (103) adjacent to the reagent ion source comprising at least one port (107) for introducing the gas to be analysed and at least one source for an electric field,• a mass analyzer region (104) adjacent to the drift tube region (103),• and a controlling device, wherein the HCD region (101) comprises at least one port (105) connected to at least one pump, at least two electrodes which are operated as anodes (201, 203) and at least one electrode which is operated as a cathode (202), wherein the SD region (102) comprises at least one port (106) connected to at least one source gas supply, wherein the controlling device is configured to• control the discharge current in the HCD region (101),• control a source gas flow through the reagent ion source,• regulate the pressure in the drift tube region (103) between 1 and 10 hPa,• regulate the electric field in the drift tube region (103), wherein the electric field comprises at least a DC field, which is configured to draw ions in the direction of the mass analyzer region (104).

2. Apparatus according to claim 1, wherein the controlling device is configured to switch electrical polarities and adjust reagent ion source extraction voltages, drift tube region (103) and mass analyzer (104) for negatively or positively charged ions.

3. Apparatus according to claim 1 or claim 2, wherein the apparatus comprises an O2 - source, wherein the controlling device is configured to control the injection of O2 through the at least one port (106) into the SD region (102) and the pumping of O2 out of the HCD region (101) so as to produce 02' in the reagent ion source, and to adjustreagent ion source extraction voltages such that the produced reagent ions are conducted to the drift tube region (103).

4. Apparatus according to claim 3, wherein the reagent ion purity of Cb'is larger than 90 %.

5. Apparatus according to claim 1 or claim 2, wherein the apparatus comprises an Ch- source and a CCh -source, wherein the controlling device is configured to control the injection of a mixture of Ch and CCh through the at least one port (106) into the SD region (102) and the pumping of Ch and CCh out of the HCD region (101) so as to produce CC ' in the reagent ion source, and to adjust reagent ion source extraction voltages such that the produced reagent ions are conducted to the drift tube region (103).

6. Apparatus according to claim 5, wherein the reagent ion purity of CCh' is larger than 80 %.

7. Apparatus according to any of the preceding claims, wherein the at least one port (105) of the HCD region (101) is connected to at least one source gas supply.

8. Apparatus according to claim 7, wherein the apparatus comprises an N2 - source and a H2O - source, wherein the controlling device is configured to• control the injection of a mixture of N2 and H2O source gases into the HCD region (101) through the at least one port (105) and the pumping out of the SD region (102) and / or the drift tube region (103) so as to produce NH4+in the reagent ion source,• control the injection of H2O source gas into the SD region (102) through the at least one port (106) and the pumping out of the HCD region (101) so as to produce HsO+in the reagent ion source,• and to electronically switch between the production of NH4+and H3CC ions in the reagent ion source.

9. Apparatus according to claim 7 and any of the preceding claims, wherein the controlling device is further configured to• control the injection of a mixture of N2 and O2 source gases into the HCD region (101) through the at least one port (105) and the pumping out of the SD region(102) and / or the drift tube region (103) so as to produce NO+in the reagent ion source,• control the injection of O2 source gas into the SD-region (102) through the at least one port (106) and the pumping out of the HCD region (101) so as to produce O2"1" in the reagent ion source, wherein the controlling device is further configured to switch between the different reagent ions electronically.

10. Apparatus according to any of the preceding claims, wherein the controlling device is configured to regulate the pressure in the reagent ion source between 0.1 - 10 hPa, preferably between 0.2 - 4 hPa.

11. Method to operate an apparatus for lon-Molecule-Reaction Mass Spectrometry and / or Proton-Transfer-Reaction Mass Spectrometry with a reagent ion source with a Hollow Cathode glow Discharge (HCD) region (101) and a Source Drift (SD) region (102), wherein the SD region (102) comprises at least one port (106) connected to at least one source gas supply and the HCD region (101) comprises at least one port (105) connected to at least one pump, characterized by the following steps:• introducing a controlled flow of source gas into the SD region (102) via the at least one port (106) and pumping the source gas out of the HCD region (101),• applying an ionization method to the source gas thereby producing reagent ions in the reagent ion source,• introducing the reagent ions and a gas to be analyzed into a drift tube region (103), wherein the analytes get ionized via interactions with the reagent ions in the drift tube region (103),• wherein subsequent to the drift tube region (103) the ions are analyzed in a mass analyzer region (104).

12. Method according to claim 11, wherein O2 source gas is introduced into the SD region (102) and pumped out of the HCD region (101) thereby producing a backward source gas flow and 02' as reagent ions.

13. Method according to claim 11 , wherein a mixture of O2 and CO2 source gas is introduced into the SD region (102) and pumped out of the HCD region (101) thereby producing a backward source gas flow and CCh' as reagent ions.

14. Method according to any one of claims 11 to 13, wherein positively and negatively charged reagent ions are produced in the reagent ion source, wherein switching between positively and negatively charged reagent ions is accomplished by switching electrical polarities and adjusting reagent ion source extraction voltages, drift tube and mass analyzer for negatively or positively charged ions.

15. Method according to any of the claims 11 to 14, wherein the at least one port (105) of the HCD region (101) is connected to at least one source gas supply, wherein depending on the reagent ions to be produced either source gas is introduced in the SD region (102) and pumped out of the HCD region (101) to produce a backward source gas flow, or source gas is introduced in the HCD region (101) and pumped out of the SD region (102) and / or the drift tube region (103) to produce a forward source gas flow, wherein different reagent ions are produced by electronically switching between forward and backward source gas flow and / or using different source gases.

16. Method according to claim 15, wherein the time to switch between different reagent ions of the same polarity is less than 2 s.

17. Method according to claim 15 or 16, wherein a mixture of N2 and H2O source gases is introduced into the HCD region (101) and pumped out of the SD region (102) and / or the drift tube region (103) thereby producing a forward source gas flow and NH4+as reagent ions, orH2O source gas is introduced into the SD region (102) and pumped out of the HCD region (101) thereby producing a backward source gas flow and H3CC as reagent ions, wherein switching the production of H3CC and NH4+reagent ions is done electronically via a controlling device.

18. Method according to claim 15 or 16, wherein O2 source gas is introduced into the SD region (102) and pumped out of the HCD region (101) thereby producing a backward source gas flow and 02' or O2"1" as reagent ions, ora mixture of N2 and H2O source gases is introduced into the HCD region (101) and pumped out of the SD region (102) and / or the drift tube region (103) thereby producing a forward source gas flow and NH4+as reagent ions, or a mixture of N2 and O2 source gases is introduced into the HCD region (101) and pumped out of the SD region (102) and / or the drift tube region (103) thereby producing a forward source gas flow and NO+as reagent ions, orH2O source gas is introduced into the SD region (102) and pumped out of the HCD region (101) thereby producing a backward source gas flow and H3CC as reagent ions, wherein switching the production of the different reagent ions is done electronically via a controlling device.

19. Method according to claim 15 or 16, wherein O2 source gas is introduced into the SD region (102) and pumped out of the HCD region (101) thereby producing a backward source gas flow and 02' or O2"1" as reagent ions, or wherein a mixture of O2 and CO2 source gases are introduced into the SD region (102) and pumped out of the HCD region (101) thereby producing a backward source gas flow and CCh' as reagent ions, or a mixture of N2 and H2O source gases are introduced into the HCD region (101) and pumped out of the SD region (102) and / or the drift tube region (103) thereby producing a forward source gas flow and NH4+as reagent ions, or a mixture of N2 and O2 source gases are introduced into the HCD region (101) and pumped out of the SD region (102) and / or the drift tube region (103) thereby producing a forward source gas flow and NO+as reagent ions, orH2O source gas is introduced into the SD region (102) and pumped out of the HCD region (101) thereby producing a backward source gas flow and H3CC as reagent ions, wherein switching the production of the different reagent ions is done electronically via a controlling device.

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