Method for producing gaseous ammonium for ion-molecule-reaction mass spectrometry

Abstract

Method for obtaining gaseous ammonium (NH.sub.4.sup.+) from an ion source, the ion source comprising a first area (1) and a second area (2) in a fluidly conductive connection, comprising the steps of a) introducing N.sub.2 and H.sub.2O into the first area (1) and second area (2) of the ion source; b) applying an ionization method to the mixture of N.sub.2 and H.sub.2O in the first area (1); c) applying at least one electric field or adjusting pressure conditions or a combination of applying at least one electric field and adjusting pressure conditions promoting flow of ions from the first area (1) to the second area (2) and inducing reactions of the ions in the second area (2); d) conducting NH.sub.4.sup.+ out of the ion source. Ion Molecule Reaction-Mass Spectrometry instrument implementing this method for producing NH.sub.4.sup.+ and then conducting NH.sub.4.sup.+ to the reaction region.

Claims

1. A method for ionizing a sample with gaseous ammonium in an Ion-Molecule-Reaction-Mass Spectrometry instrument, comprising: (i) obtaining gaseous ammonium (NH.sub.4.sup.+) from an ion source, the ion source comprising a first area and a second area in a fluidly conductive connection, comprising the steps of: (a1) introducing a controlled flow of N.sub.2 into the first area or second area of the ion source; (a2) introducing a controlled flow of H.sub.2O into the first area or second area of the ion source; (b) applying an ionization method to the mixture of N.sub.2 and H.sub.2O in the first area; (c) applying at least one electric field or adjusting pressure conditions or a combination of applying at least one electric field and adjusting pressure conditions promoting flow of ions from the first area to the second area and inducing reactions of the ions in the second area; (d) conducting NH.sub.4.sup.+ out of the ion source into a reaction chamber connected with the ion source; (e) introducing the sample into the reaction chamber; and (ii) ionizing the sample in the reaction chamber.

2. The method according to claim 1, wherein the first area is a first ionization chamber and the second area is a second ionization chamber being connected to allow fluid exchange.

3. The method according to claim 2, wherein the ionization source for applying the ionization method is in the first ionization chamber and/or the source for the electric field is in the second ionization chamber.

4. The method according to claim 1, further comprising applying a magnetic field.

5. The method according to claim 1, wherein the N.sub.2 source is essentially pure gaseous N.sub.2.

6. The method according to claim 1, wherein N.sub.2 and H.sub.2O are mixed prior to the introduction into the ion source.

7. The method according to claim 1, wherein N.sub.2 and H.sub.2O are introduced into the ion source separately and are mixed directly in the ion source.

8. The method according to claim 1, wherein N.sub.2 and/or H.sub.2O are introduced in the second area and N.sub.2 and/or H.sub.2O flow into the first area from the second ionization chamber.

9. A method of detecting the ion yield of the mass-to-charge ratio of ions produced according to claim 1, by detecting the ions in Mass Spectrometry instrument.

10. An Ion-Molecule-Reaction Mass Spectrometry (IMR-MS) instrument, comprising an ion source with a first area and a second area, an ionization source and at least one source for an electric field; a reaction region connected to said ion source; a mass spectrometer region connected to said reaction region; at least one inlet for source gases; at least one inlet for a sample into the reaction region; an N.sub.2-source; a H.sub.2O source; at least one pump; further comprising: a controlling device controlling flow of N.sub.2 of the N.sub.2-source, flow of H.sub.2O of the H.sub.2O-source, the least one pump, the ionization source, and the source for the electric field, so as to produce gaseous ammonium (NH.sub.4.sup.+) in said second area and then to conduct NH.sub.4.sup.+ to the reaction region via an exit to contact and ionize the sample introduced into the reaction region.

11. The IMR-MS instrument according to claim 10, wherein the controlling device also controls the pressure in the second area.

12. The IMR-MS instrument according to claim 10, wherein the first area and the second area are a first ionization chamber and a second ionization chamber, wherein said second ionization chamber is connected to said first ionization chamber, wherein the first ionization chamber includes the ionization source and the second ionization chamber includes the at least one source for the electric field.

13. The IMR-MS instrument according to claim 10, further comprising an additional source for a magnetic field.

14. The method according to claim 2, wherein the mixing ratio of N.sub.2 to H.sub.2O in the first ionization chamber is between 3:7 and 7:3.

15. The method according to claim 2, wherein the mixing ratio of N.sub.2 to H.sub.2O in the first ionization chamber is approximately 1:1.

16. The IMR-MS instrument according to claim 10, wherein the controlling device is configured to cause a mixing ratio of N.sub.2 to H.sub.2O in the first area is between 1:9 and 9:1.

17. A method for ionizing a sample with gaseous ammonium, comprising: (i) obtaining gaseous ammonium (NH.sub.4.sup.+) from an ion source, the ion source comprising a first area and a second area in a fluidly conductive connection, comprising the steps of: (a1) introducing a controlled flow of N.sub.2 into the first area or second area of the ion source; (a2) introducing a controlled flow of H.sub.2O into the first area or second area of the ion source; (b) applying an ionization method to the mixture of N.sub.2 and H.sub.2O in the first area; (c) applying at least one electric field or adjusting pressure conditions or a combination of applying at least one electric field and adjusting pressure conditions promoting flow of ions from the first area to the second area and inducing reactions of the ions in the second area; and (d) conducting NH.sub.4.sup.+ out of the ion source; and (ii) ionizing the sample in a reaction chamber being connected with the ion source, wherein the mixing ratio of N.sub.2 to H.sub.2O in the first area is between 1:9 and 9:1.

18. The method according to claim 17, wherein the first area is a first ionization chamber and the second area is a second ionization chamber being connected to allow fluid exchange.

19. An Ion-Molecule-Reaction-Mass Spectrometry (IMR-MS) instrument, comprising an ion source with a first area and a second area, an ionization source and at least one source for an electric field, wherein the first area is a first ionization chamber and the second area is a second ionization chamber being connected to allow fluid exchange; a reaction region connected to said ion source; a mass spectrometer region connected to said reaction region; at least one inlet for source gases; at least one inlet for a sample into the reaction region; an N.sub.2-source; a H.sub.2O source; at least one pump; further comprising: a controlling device controlling flow of N.sub.2 of the N.sub.2-source, flow of H.sub.2O of the H.sub.2O-source, the least one pump, ionization source, and the source for the electric field, so as to produce gaseous ammonium (NH.sub.4.sup.+) in said second area and then conducting NH.sub.4.sup.+ to the reaction region via an exit, wherein the controlling device is configured to cause a mixing ratio of N.sub.2 to H.sub.2O in the first ionization chamber is between 1:9 and 9:1.

Description

DETAILED DESCRIPTION OF THE INVENTION

(1) FIG. 1 is a schematic view of a typical IMR-MS instrument, comprising a first ionization chamber 1, a second ionization chamber 2, a reaction region 3 (e.g. drift, flow or flow-drift tube in PTR-, SIFT- and SIFDT-MS, respectively), a mass spectrometer region 4 (e.g. TOF, multipole, ion trap, MS.sup.n, etc.), one or more inlet(s) 5 for source gases, one or more inlet(s) 6 for sample and, if needed, carrier or buffer gas, region 7 between 2 and 3.

(2) FIG. 2 shows a schematic view of the parts needed for the present invention: first ionization chamber 1, second ionization chamber 2, one or more inlet(s) 5 for source gases.

(3) FIG. 3 shows a part of a mass spectrum obtained with the instrument running in H.sub.3O.sup.+ mode.

(4) FIG. 4 shows a part of a mass spectrum obtained with the instrument running in NH.sub.4.sup.+ mode, i.e. in the mode according to the invention.

(5) The present invention solves all of the above-mentioned problems associated with the use of NH.sub.3 source gas and enables the generation of NH.sub.4.sup.+ reagent ions at high purity levels without the introduction of NH.sub.3, so that the NH.sub.4.sup.+ can directly be used in IMR-MS instruments, which are not equipped with a filter for reagent ions, e.g. PTR-MS instruments. The invention can also be used in IMR-MS instruments, which are equipped with a filter for reagent ions, e.g. multipole mass filters in SIFT-MS or SIFDT-MS instruments. The invention does neither require any form of NH.sub.3 nor any other toxic, harmful, environmentally hazardous or corrosive chemicals. The minimum required parts of an IMR-MS instrument necessary for the realization of the invention are schematically shown in FIG. 2.

(6) NH.sub.4.sup.+ reagent ions are generated by introducing N.sub.2 and H.sub.2O via a source gas inlet 5 into the first ionization chamber (FIC) 1 of an ion source, where N.sub.2 and H.sub.2O are ionized e.g. in a hollow cathode discharge, corona discharge, point discharge, plane electrode discharge, microwave discharge, radioactive ionization, electron ionization involving a filament, or via any other ionization method. The ionization products as well as (remaining) neutral N.sub.2 and H.sub.2O are introduced into a second ionization chamber (SIC) 2, which can either be spatially separated and connected via an aperture or form a part of the FIC 1. The pressure (and possibly also the electric fields) in the SIC 2 are adjusted so that via ion-molecule reactions the partly ionized species react to NH.sub.4.sup.+ and only minor parasitic ions are left (e.g. below 10% and preferably below 5%). The pressure in the SIC 2 can e.g. be adjusted via a pump ring, which can be installed in or adjacent to the SIC 2 and connected to a pump via a valve or a pressure limiting aperture or via any other pressure adjusting mechanism applied to the SIC 2. The electric fields can be adjusted by adjusting the voltages and currents applied to different parts of the ion source.

(7) In order to achieve NH.sub.4.sup.+ in purity levels of higher than 90% and preferably higher than 95% (in relation to parasitic ions) primarily the ratio between the source gas flows into the FIC 1, i.e. N.sub.2 and H.sub.2O, and the pressure in the SIC 2 have to be optimized. The actual values depend strongly on the ion source used. The N.sub.2:H.sub.2O flow ratio typically is between 1:9 and 9:1, preferably between 3:7 and 7:3 and in some embodiments at about 1:1. The source of N.sub.2 can be any N.sub.2 source, preferably from an N.sub.2 gas cylinder or an N.sub.2 gas lab supply line. Using air as an N.sub.2 source is also possible, as air largely consists of N.sub.2. The purity of the generated NH.sub.4.sup.+ is, however, negatively affected by the use of air, i.e. more parasitic ions are generated. This can be acceptable in case no pure N.sub.2 is available or a reagent ion filtering device is used (e.g. in SIFT-MS, SIFDT-MS). The source of H.sub.2O can be water vapor, preferably from the headspace of a water reservoir, which is evacuated by the suction created by the vacuum in the ion source. The flow rates of N.sub.2 and H.sub.2O can be controlled e.g. by mass flow controllers, valves, pressure limiting apertures, lines with suitable inner diameters, etc.

(8) In one embodiment N.sub.2 and H.sub.2O are mixed prior to the source gas inlet 5 and introduced as a mixture. In another embodiment an additional source gas inlet is installed and N.sub.2 and H.sub.2O are introduced separately into the FIC 1. In another embodiment H.sub.2O is introduced into the FIC 1 and N.sub.2 is introduced via an additionally installed source gas inlet into the SIC 2, so that it expands into the FIC 1 and N.sub.2 and H.sub.2O are present in the FIC 1 and SIC 2. In another embodiment N.sub.2 is introduced into the FIC 1 and H.sub.2O is introduced via an additionally installed source gas inlet into the SIC 2, so that it expands into the FIC 1 and N.sub.2 and H.sub.2O are present in the FIC 1 and SIC 2. In another embodiment N.sub.2 and H.sub.2O are introduced via additionally installed source gas inlets into the SIC 2, so that the gases expand into the FIC 1 and N.sub.2 and H.sub.2O are present in the FIC 1 and SIC 2. Any other means of introducing N.sub.2 and H.sub.2O into the FIC 1 and SIC 2 are also possible. This includes, but is not limited to, backflow of N.sub.2 and/or H.sub.2O from any part of the instrument into FIC 1 and SIC 2, e.g. from the drift tube in case of a PTR-MS instrument.

(9) The pressure in the SIC 2 should be at least at 0.01 hPa, should be below 100 hPa and has to be adjusted so that NH.sub.4.sup.+ is efficiently generated. Further improvement of effective NH.sub.4.sup.+ generation and suppression of parasitic ions can be achieved by applying electric fields, which accelerate ions in the FIC 1 and the SIC 2, respectively, from the FIC 1 into the SIC 2 and/or extract ions from the ion source.

(10) Switching between NH.sub.4.sup.+ generation and any other reagent ion can be done by switching the source gases, adjusting the source gas flows, adjusting the pressure in the SIC 2 and adjusting the electric fields. In particular, switching from NH.sub.4.sup.+ to H.sub.3O.sup.+ can be done by shutting off the N.sub.2 flow, adjusting the H.sub.2O flow, adjusting the pressure in the SIC 2 and adjusting the electric fields. Switching from H.sub.3O.sup.+ (which is generated from H.sub.2O) to NH.sub.4.sup.+ can be done by adding N.sub.2 to the ion source, adjusting the H.sub.2O and N.sub.2 flows, adjusting the pressure in the SIC 2 and adjusting the electric fields.

(11) In the following example we applied the invention to a commercially available IMR-MS instrument, namely a PTR-TOF 1000 from IONICON Analytik GmbH., Austria. The example should by no means limit the applicability of the invention to a specific instrument or specific settings. For this particular instrument the FIC 1 is a hollow cathode ion source, the SIC 2 is a source drift region, the reaction region 3 is a drift tube consisting of a series of electrically isolated stainless steel rings with an applied voltage gradient and the mass spectrometer region 4 is a TOF mass spectrometer.

(12) The source gas inlet 5 is connected to two source gas lines, with a mass flow controller installed in each line. The headspace above purified water and N.sub.2 from a gas cylinder (99.999% purity) is connected to the lines, respectively. Sample inlet 6 is fed with purified air. At the intermediate position 7 between the SIC 2 and the reaction region 3 a pump ring is installed, which is connected to a split-flow turbo-molecular pump via an electronically controllable proportional valve. Thus the pressure in the SIC 2 can be adjusted by adjusting this so-called source valve, where 0% means the valve is fully closed, i.e. no pumping power is applied, and 100% means the valve is fully opened, i.e. maximum pumping power is applied. As this is a PTR-MS instrument, no filtering device is installed between the ion source and the reaction region and therefore, if purified air is introduced to the sample inlet, i.e. negligible impurities are introduced into the reaction region, the purity of the reagent ions can be directly measured with the mass spectrometer 4. For the measurements a drift tube pressure of 2.3 hPa and a drift tube temperature of 60° C. were selected. The hollow cathode ion source 1 was operated at a discharge current of 3.5 mA.

(13) FIG. 3 shows a part of the mass spectrum with a mass-to-charge ratio m/z between 15 and 50, i.e. the region where impurities from the ion source are expected. The ion source is operated with the established H.sub.3O.sup.+ reagent ions. The H.sub.2O source gas is set to 6.5 sccm (cm.sup.3 per min at standard conditions), no N.sub.2 source gas is added. The source valve is set to 54%. The voltage, which is applied to extract ions from the FIC 1 to the source drift region 2 is set to 130 V. It has to be noted that the detector gets overloaded by the high ion yield at m/z 19, which corresponds to H.sub.3O.sup.+. Therefore, the ion yield at m/z 21, which corresponds to a naturally occurring isotope of H.sub.3O.sup.+ has to be multiplied by a factor of 500 in order to get the number of reagent ions. With these ion source settings and a drift tube voltage of 600 V applied, a H.sub.3O.sup.+ reagent ion yield of about 22×10.sup.6 cps (ion counts per second) is achieved. The relative amount of parasitic ions are about 4.6% plus about 2.4% water cluster 2(H.sub.2O).H.sup.+ at m/z 37, which is dependent on the drift tube voltage.

(14) FIG. 4 shows a part of the mass spectrum with a mass-to-charge ratio m/z between 15 and 50 after the invention has been applied. The switching time takes about 3-5 s and is mainly limited by the response time of the mass flow controllers controlling the source gas flows. The H.sub.2O flow is set to 3 sccm and the N.sub.2 flow is set to 3 sccm, i.e. the ratio between H.sub.2O and N.sub.2 is 1:1. The source valve is set to 45%, i.e. lower than for H.sub.3O.sup.+ generation, which means that the pressure in the source drift region 2 is increased. The voltage, which is applied to extract ions from the FIC 1 to the source drift region 2 is set to 250 V, i.e. higher than for H.sub.3O.sup.+ generation. It has to be noted that the detector gets overloaded by the high ion yield at m/z 18, which corresponds to NH.sub.4.sup.+. Therefore the ion yield at m/z 19, which corresponds to a naturally occurring isotope of NH.sub.4.sup.+ and can be separated from the parasitic H.sub.3O.sup.+ sharing the same nominal m/z, because of the high mass resolution of the utilized TOF mass spectrometer 4, has to be multiplied by a factor of 250 in order to get the number of NH.sub.4.sup.+ reagent ions.

(15) With these ion source settings and a drift tube 3 voltage of 650 V applied, a NH.sub.4.sup.+ reagent ion yield of about 19×10.sup.6 cps, i.e. a comparable intensity to the H.sub.3O.sup.+ mode, is achieved. The relative amounts of parasitic ions are about 2.4%, i.e. the reagent ions are even more pure than in H.sub.3O.sup.+ mode, plus about 0.1% 2(NH.sub.3).H.sup.+ at m/z 35, which is dependent on the drift tube voltage.

(16) With this particular instrumental setup we could achieve NH.sub.4.sup.+ ion yields with high purity and high abundance at pressures in the source drift region 2 between about 2-4 hPa and electric field strengths in the source drift region 2 of 350-800 V/cm.sup.2. These pressure and field strength regions will vary considerably depending on the geometry and the type of the ion source.

(17) Switching back to H.sub.3O.sup.+ by applying the above-mentioned settings for H.sub.3O.sup.+ mode again just takes seconds and the relative amount of remaining parasitic NH.sub.4.sup.+ drops below 10% nearly instantaneously and below 4% after some tens of seconds.

(18) In cases where extremely high purity of NH.sub.4.sup.+ is needed and even minor amounts of parasitic H.sub.3O.sup.+ and 2(H.sub.2O).H.sup.+ ions need to be avoided, a compound with a PA, which is higher than the PA of 2(H.sub.2O) (808 kJ/mol; thus also higher than the PA of H.sub.2O), but lower than the PA of NH.sub.3 (i.e. PA between 808 and 854 kJ/mol) can be added in sufficient concentration to the reaction region 3, e.g. via the sample inlet 6. This will cause the parasitic H.sub.3O.sup.+ and 2(H.sub.2O).H.sup.+ to react with this compound, leading to depletion of the parasitic water and water cluster ions.

(19) In summary the invention enables the powerful capability of operating an IMR-MS instrument with NH.sub.4.sup.+ reagent ions. No NH.sub.3 or any other harmful, toxic, environmentally hazardous, corrosive, etc. compounds are necessary for NH.sub.4.sup.+ production. The only compounds needed are N.sub.2 and H.sub.2O. These compounds are injected into the ionization region of a FIC 1 and subsequently left in a SIC 2 until the partially ionized products predominantly react to NH.sub.4.sup.+. In our example we used a PTR-MS ion source, originally designed for being operated with H.sub.3O.sup.+ reagent ions, introduced N.sub.2 and H.sub.2O with a ratio of 1:1 into the ionization region 1 and increased the pressure in the source drift region 2 (compared to the pressure used for H.sub.3O.sup.+ generation) in order to get NH.sub.4.sup.+ reagent ions with a purity of more than 97%. Additionally, we increased the voltage extracting ions from the FIC 1 into the SIC 2 compared to the voltage used for H.sub.3O.sup.+ generation. Switching between reagent ions could be achieved within seconds. The invention is by no means limited to this example, but works with any IMR-MS ion source.