The present application claims priority from Japanese patent application JP 2011-184266 filed on Aug. 26, 2011, the content of which is hereby incorporated by reference into this application.
The present invention concerns a mass spectrometer and an operation method thereof
Apparatus capable of measuring trace substances in mixed samples in situ, conveniently and at a high sensitivity for measurement of contamination in soils and atmospheric air, inspection of residual agricultural chemicals in foods, diagnosis by circulating metabolites, urine drug screening, etc. Mass spectrometry is used as one of methods capable of measuring trace substances at high sensitivity.
A mass spectrometer ionizes substances in a gas phase by an ionization source, introduce ions into a vacuumed part, and subject them to mass analysis. For increasing the sensitivity of the mass spectrometer, improvement in a sample introduction part for efficient transportation of a sample to the ionization source is important in addition to the improvement of an ionization source, a mass analyzer, a detector, etc.
As a method of introducing a sample in a gas state into a gas chromatograph or amass spectrometer, a headspace method is used generally. The headspace method includes a static headspace method and a dynamic headspace method (refer to TrAC Trends in Analytical Chemistry, 21 (2002) 608-617).
The static headspace method is a method of injecting and tightly sealing a sample in a vial or the like while leaving a predetermined space, leaving the sample at a constant temperature till gas-liquid equilibrium is attained, and then sampling a gas present in a gas phase, that is, a headspace gas by a syringe and analyzing the same. This is a method capable of determining the quantity of a volatile substance present in a trace amount in a sample solution with less effect of a solvent in the sample solution. The concentration of the sample gas in the headspace gas can be increased, for example, by a method of overheating the sample solution to a high temperature, or by adding a salt to a sample solution thereby promoting vaporization by a salting-out effect.
The dynamic headspace method is a method of introducing an inert gas such as helium or nitrogen to a vial in which the sample has been injected and driving out the sample gas. The inert gas is introduced into the gas phase in the vial, or introduced into a liquid phase to purge the sample. When the gas is introduced into the liquid phase, since bubbles are generated, the surface area at the gas/liquid boundary is increased to further promote evaporation.
Both in the static headspace method and the dynamic headspace method, a method of concentrating the headspace gas by collection on an absorbent is also proposed.
A method of efficiently extracting a gas from a headspace part in a vial bottle has also been proposed (U.S. Pat. No. 5,869,344). In this method, a headspace gas is sucked by decreasing the pressure at the end of a pipeline on the side of an ionization source for connecting a vial bottle and an ionization source by the Venturi effect and then the gas is ionized by atmospheric pressure chemical ionization.
For promoting the evaporation of a sample, a device of dispersing a sample solution into micro droplets has also been proposed (Japanese Unexamined Patent Publication No. 2011-27557).
Existent headspace methods described not only in “TrAC trends in Analytical Chemistry”, but also the special headspace methods described in U.S. Pat. No. 5,869,344 and JP-A 20011-20557 involve problems that the density of the sample gas in the headspace gas depends on the saturated vapor pressure of the sample. Even when a sample solution is placed in a vial bottle and left for a long time or an inert gas is introduced, the amount of the sample gas in the headspace gas cannot be increased to more than an amount at a saturation vapor pressure. The saturation vapor pressure of water is about 3,000 Pa at 25° C. In the headspace methods described above, the pressure in the headspace part is increased to about the atmospheric pressure or higher. In view of the partial pressure ratio at an atmospheric pressure, for example, of about 100,000 Pa, the existent amount of water molecules in the gas is about 3%. While the saturated vapor pressure of water and sample molecules can be increased when the solution is heated, this results in a problem of requiring electric power for heating, condensation of the heated gas -on cold spots of a pipeline, etc.
While the sample can be concentrated by capturing the sample gas using an adsorbent, this complicates operations such as requirement of a process for desorbing the sample again from the adsorbent, and the throughput is also poor.
According to the invention, the density of a sample in a headspace gas is increased by decreasing the pressure inside of a sample vessel that contains the sample, thereby ionizing the sample efficiently.
The mass spectrometer, as one aspect of the present invention, comprises a sample vessel in which a sample is sealed, an ionization housing connected to the sample vessel and having an ionization source for taking in the sample gas present in the sample vessel and ionizing the same, in which the pressure is lower than the pressure inside of the sample vessel, a vacuum chamber (or vacuumed chamber) connected to the ionization housing and having amass analyzer for analyzing the ionized sample, and means for decreasing the pressure inside of the sample vessel.
The mass analyzing method, as another aspect of the present invention, uses a sample vessel in which a sample is sealed, an ionization source connected to the sample vessel for taking in the sample and ionizing the same, and a vacuum chamber connected to the ionization housing and having amass analyzer for analyzing the ionized sample, and includes the steps of decreasing the pressure inside of the vacuum chamber, decreasing the pressure inside of the sample vessel, taking in a sample gas present in the sample vessel into the ionization housing and ionizing the gas, and analyzing the ionized sample in the mass analyzer.
The present invention can provide amass spectrometer and a mass analyzing method capable of efficiently ionizing a sample with less carry-over.
The sample 7 may be liquid or solid. The pressure inside of the vial bottle 1 is decreased by the pump 2. The pressure inside the vacuum chamber is kept at 0.1 Pa or lower, and the pressure in the ionization housing 3 is determined by the exhaust velocity of the pump 4, conductance of an orifice 11, conductance of a tube 13 connecting the vial bottle 1 and the ionization housing 3. However, the pressure in the ionization housing 3 is lower than the pressure in the vial bottle 1, and the headspace gas flows from the vial bottle 1 into the ionization housing 3. As the pressure in the ionization housing 3 approaches the pressure in the vacuum chamber 5, loss of the ions upon introduction from the ionization housing 3 into the vacuum chamber 5 is decreased further. Accordingly, the sensitivity of the device is improved more when a sample is ionized under a reduced pressure than when the sample is ionized under an atmospheric pressure. In this embodiment, a plasma 10 is generated by barrier discharge in the ionization housing 3. Sample molecules are ionized by way of reaction between charged molecules generated by the plasma 10 and water molecules. A pressure range where the plasma 10 is generated stably is present and a typical value is 100 to 5,000 Pa. Further, a pressure range capable of efficiently ionizing the sample is from 500 to 3,000 Pa. If the pressure is lower than the lower limit, ion fragmentation is increased. Further, at a pressure of 1 Pa or lower, the plasma 10 is not generated. Also at a pressure of 3,000 Pa or higher, the plasma 10 is less generated and the ionization efficiency is lowered.
Since the saturated vapor pressure of a sample does not depend on the ambient pressure, a partial pressure ratio of the sample increases more as the pressure inside of the vial bottle 1 decreases. For example, the vapor pressure of the sample is assumed as constant at 10 Pa. When the inner pressure of the vial bottle 1 is at an atmospheric pressure of 100,000 Pa, the ratio of the sample occupying the headspace gas is 0.01%. When the inner pressure of the vial bottle 1 is decreased to 50,000 Pa, the ratio of the sample is 0.02% and when it is decreased to a 5,000 Pa, the ratio is 0.2%. As described above, when the inner pressure in the vial bottle 1 is decreased to 1/20, the ratio of the sample gas in the headspace gas is increased theoretically to 20 times. Assuming the pressure in the ionization housing 3 and the pressure in the vacuum chamber 5 are constant, the flow rate of the headspace gas introduced into the vacuum chamber 5 does not change irrespective of the inner pressure in the vial bottle 1. Accordingly, increase of the ratio of the sample gas in the headspace gas along with decrease of the inner pressure in the vial bottle as described above means increase in the amount of the sample gas introduced into the vacuum chamber 5 and the sensitivity of the device is increased.
When the pressure inside of the vial bottle is decreased as: 50,000, 30,000 and 10,000 Pa, the amount of the sample gas to be introduced into the vacuum chamber 5 increase as about twice, 3.5 times, and 10 times, and the peak intensity of the mass spectrum measured for the sample at an identical concentration is increased. However, as the degree of depressurization increases, sealing performance demanded for the vial bottle 1 becomes severer. This increases the cost of the vial bottle 1. In addition, it is necessary to connect a pump of a large displacement for depressurization at high degree, which results increase in the cost and increase in the weight. The device has to be designed while considering the balance between the problems described above and the improvement in the sensitivity.
Further, an evaporation velocity is in proportion to a diffusion velocity of a gas and the diffusion velocity of the gas is in inverse proportion to a pressure. Accordingly, as the pressure decreases, the evaporation velocity increases and the time till a sample reaches a saturated vapor pressure is shortened. However, when the sample is liquid, since it causes explosive boiling, the pressure of the headspace part cannot be decreased to lower than the saturated vapor pressure of the liquid.
When a first discharge electrode 8 and a second discharge electrode 9 are disposed in the ionization housing and a voltage is applied therebetween, dielectric barrier discharge is generated to form a plasma 10. The plasma 10 generates charged particles, water cluster ions are generated based thereon, and the sample 7 is ionized by the ion molecule interaction between the water cluster ions and the sample gas. The method of the invention provides soft ionization utilizing discharge plasma with less fragmentation of the sample ions, when compared with electron impact ionization that causes much fragmentation. When it is intended to positively cause fragmentation, an electric power applied to the discharge electrodes may be increased as to be describer later. The sample ions generated by the discharge plasma 10 are introduced through an orifice 11 into the vacuum chamber 5. A mass analyzer 12 and a detector 6 are disposed in the vacuum chamber 5. The introduced ions are separated on every m/z ratio in the mass analyzer 12 such as a quadrupole mass filter, an ion trap, a time-of-flight mass spectrometer, etc. and detected by the detector 6 such as an electron multiplier.
A typical distance between the first discharge electrode 8 and the second discharge electrode 9 is about 5 mm and as the distance between the discharge electrodes is longer, higher electric power is necessary for discharge. For example, an AC voltage is applied to one of the discharge electrodes, and a DC voltage is applied to the other of the discharge electrodes from the power source 51. The AC voltage to the applied may be in a rectangular waveform or a sinusoidal waveform. In a typical example, the applied voltage is about 0.5 to 10 kV and the applied frequency is about 1 to 100 kHz. For an identical voltage amplitude, the density of the plasma 10 increases more by using the rectangular wave. On the other hand, in a case of using the sinusoidal wave, since the voltage can be stepped-up by coils when the frequency is high, this provides a merit of decreasing the cost of the power source 51 than that in a case of using the rectangular waveform. Since the charged power increases more as the voltage and the frequency are higher, the density of the plasma 10 tends to be higher. However, when the charged power is excessively high, the plasma temperature is increased tending to cause fragmentation. The frequency and the amplitude of the AC voltage may be changed on every samples or ions as the target for measurement. For example, the charged power is increased in a case of measuring molecules that undergo less fragmentation such as inorganic ions and in a case of intentionally causing fragmentation to target ions. On the other hand, the charged power is decreased in a case of measuring molecules liable to undergo fragmentation. Further, when the power source is switched so as to apply the voltage to discharge electrodes only when it is necessary, the consumption power of the power source 51 can be decreased.
The arrangement of the discharge electrodes can be changed variously so long as discharge is caused byway of the dielectric substance.
Sample carry-over is a problem always present in the mass spectroscopy by using the headspace method. If a pipeline (that is sample transfer line) is cleaned or exchanged on every exchange of the sample, the throughput is worsened. By decreasing the pressure inside of the vial bottle 1, the conductance of the sample transfer line necessary for maintaining the pressure at an optimal value in the ionization housing 3 or the vacuum chamber 5 can be increased and the inner diameter of the sample transfer line can be enlarged. This can decrease desorption of the sample to suppress carry-over. As described above, the evaporation speed is increased by depressurization. This means that molecules adsorbed to the sample transfer line are removed rapidly to decrease the carry-over.
When the vapor pressure of the sample is excessively low at a room temperature, the vial bottle 1 is heated by attaching a heater 14 as shown in
Different from the first embodiment, a pulse valve 30 is interposed between an ionization housing 3 and a vial bottle 1, and a gas is introduced discontinuously into the ionization housing 3. Upon introduction of the gas, the pressure in the ionization housing 3 increases temporality, and the pressure in the ionization housing 3 is lowered when the pulse valve 30 is closed. Accordingly, compared with the continuous gas introduction system of the first embodiment, even when the inner diameter of the orifice 11 is increased to increase the flow rate of the gas introduced into the vacuum chamber 5, the pressure in the vacuum chamber 5 can be maintained to 0.1 Pa or lower after closing the pulse valve 30. Since the headspace gas does not flow to the ionization housing 3 during closure of the pulse valve 30, time of the gas staying in the ionization housing 3 is shortened to decrease adsorption of the gas. Assuming that the gas introduction amount to and the vacuum chamber 5 is identical with that in the continuous introduction system, a small-sized pump of lower evacuation speed can be used. The pressure in the ionization source and the pressure in the vacuum chamber can be controlled by the conductance of the sample transfer line and the opening time of the valve. Further, by opening the pulse 30 again in a state of trapping the ions in the mass analyzer 12, the inner pressure of the vacuum chamber 5 can be increased to a pressure where collision induced dissociation is generated efficiently. That is, since the pulse valve 30 is present, pressure in the vacuum chamber 5 can be controlled simply and conveniently. However, compared with the first embodiment, since the pressure in the vacuum chamber 5 is increased by the on-off of the valve even when it is done temporary, load is applied on the pump, and the frequency of exchanging pump 4 is increased. Further, a circuit and a power source for controlling the pulse valve 30 are necessary and the configurational complicated compared with the first embodiment.
The flow of measurement is substantially identical with that of the first embodiment. After setting the depressurized vial bottle 1 to the device, the device for the barrier discharge is powered on and the pulse valve 30 is opened and closed thereby introducing a headspace gas into the ionization housing.
As shown in
The heater 14 for heating the vial bottle 1 shown in the first embodiment is applicable also in this embodiment.
The heater 14 for heating the vial bottle 1 shown in the first embodiment is applicable also in this embodiment.
Compared with the first and second embodiments, since the pump for decreasing the pressure inside of the vial bottle 1 and the sample transfer line are not necessary, the size of the device is decreased. Further, since the step of setting the vial bottle 1 after depressurizing the device is saved, the flow of measurement carried out by a measuring operator per se can be simplified. However, since the pulse valve 30 is opened and closed in a state of setting the vial bottle 1 at an atmospheric pressure to the device, a headspace gas is be introduced at a great flow rate into the vacuum chamber 5 and may possibly damage the pump. Further, the great amount of gas may possibly contaminate the ionization housing 3.
A pump 70 for supplying a solution for generating charged droplets to the probe 60 is necessary for electrospray ionization, which makes the structure complicate. Further, for stably generating charged droplets, an inert gas such as nitrogen is preferably introduced as an auxiliary gas in a manner concentrical with the jetting port of the probe 60 for electrospray ionization. While the probe 60 for electrospray ionization is situated vertically to the tube 13 in
The heater 14 for heating the vial bottle 1 shown in the first embodiment and the pulse valve 30 shown in the second embodiment are applicable also in this embodiment.
The heater 14 for heating the vial bottle 1 shown in the first embodiment and the pulse valve shown in the second embodiment are applicable also in this embodiment.
The heater 14 for heating the vial bottle 1 shown in the first embodiment and the pulse valve 30 shown in the second embodiment are applicable also in this embodiment.
Number | Date | Country | Kind |
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2011-184266 | Aug 2011 | JP | national |