WO2015087645A1

WO2015087645A1 - Mass spectrometry method

Info

Publication number: WO2015087645A1
Application number: PCT/JP2014/079676
Authority: WO
Inventors: 峻熊野; 益之杉山; 益義山田; 和茂西村; 橋本　雄一郎; 秀俊諸熊
Original assignee: 株式会社日立ハイテクノロジーズ
Priority date: 2013-12-12
Filing date: 2014-11-10
Publication date: 2015-06-18
Also published as: JP2015115202A

Abstract

For the purpose of cleaning the inside of a chamber having a mass separator of a mass spectrometer quickly without opening the inside of the chamber to the atmosphere, a large amount of cleaning gas capable of separating a contaminant adhered to the internal walls of the mass spectrometer is introduced into the chamber via a pulse valve so that the maximum chamber pressure value in a cleaning step is higher than the maximum chamber pressure value in a sample measurement step.

Description

Mass spectrometry method

The present invention relates to an apparatus for analyzing chemical substances and a cleaning method thereof.

There is a need for a device that can easily and accurately measure trace substances in mixed samples on the spot, such as soil and air pollution measurements, food pesticide tests, blood metabolite diagnostics, and urine drug tests. . Mass spectrometry is used as one of the methods that enable highly sensitive measurement of trace substances.

質量 Mass spectrometer is a highly sensitive analyzer, but contamination of the apparatus may be a problem. That is, when measuring a sample gas containing a high-concentration target substance or contaminants, there is a problem that these substances adhere to and contaminate the inner wall of the sample introduction part, the inner wall of the ion source, and the inner wall of the vacuum chamber. In addition to the sample itself, contamination by the matrix and solvent also occurs. In addition, when a gas chromatograph is connected, contamination is also caused by leakage of the stationary phase of the gas chromatograph. When contamination occurs, the contaminant is detected over a long period of time. As a result, ionization of the measurement target substance in the next measurement is inhibited, and the detection sensitivity of the measurement target substance is greatly reduced. In addition, when the pollutant is a substance to be quantified, an accurate quantification becomes difficult because a bias is applied to the quantification value of the next measurement.

Because of these problems, the mass spectrometer must be cleaned regularly. As a general technique, there is a method of cleaning by performing a baking process that heats more than in the sample analysis using a heater installed in the sample introduction part or ion source of the mass spectrometer. For example, if the heating temperature of each part is set to 100 ° C during sample analysis, it is heated to 180 ° C during cleaning. Then, the sample adhering to the inner wall of the apparatus is heated and desorbed.

In addition to baking, there is a method to stop the evacuation of the mass spectrometer and disassemble and clean the contaminated part. It can be cleaned by removing the ion source from the device and immersing it in a liquid such as methanol, water, or acetone and performing ultrasonic cleaning. Then put it in the oven and bake. In addition to chemical cleaning, mechanical cleaning such as polishing with a file may be performed.

Patent Document 1 describes a method of introducing a desorbed gas in order to desorb a substance adsorbed on the apparatus. The desorption gas is changed depending on the type of adsorbate. For example, it has been proposed to use a water vapor gas as a desorption gas when the adsorbent is a salt, and a vaporized gas of an organic solvent as a desorption gas when the adsorbate is an organic substance.

Patent Document 2 describes a method for introducing desorbed gas into the apparatus, as in Patent Document 1. In particular, hydrogen gas is said to be effective as a desorption gas. Contamination can be reduced by mixing a small amount of hydrogen gas into the sample gas not only during cleaning but also during sample measurement.

JP 2007-170985 A JP 2013-61324

The cleaning method by baking has a problem that it takes time for the heating process and the natural cooling process after the heating process. For applications that require high throughput, such as on-site analysis, it is important to clean quickly. In addition, in the case of a battery-powered device such as a portable mass spectrometer, it may not have enough power to perform baking. Further, not all devices are made of heat-resistant materials. For example, when a part of the apparatus is a resin, particularly a material having low heat resistance such as a silicon tube, it is impossible to perform sufficient baking.

Decomposition and cleaning takes more time than baking. Moreover, it requires skilled skills and is not an operation that can be easily performed by general users. Also, due to assembly errors of the apparatus, the sensitivity of the apparatus often changes before and after disassembly and cleaning. Furthermore, even if the cleaning solution itself is contaminated, it cannot be noticed until the evacuation is completed after the device is assembled.

Patent Documents

1 and 2 both introduce cleaning gas into the apparatus. In this case, the higher the probability of collision between the molecules contained in the cleaning gas and the substance attached to the inner wall, the higher the cleaning efficiency. In order to increase the collision probability, it is necessary to increase the flow rate of the cleaning gas. However, the mass separator of the mass spectrometer must be in a high vacuum. For this reason, the introduction flow rate from atmospheric pressure is extremely small. Thus, when only a very small amount of cleaning gas can be introduced, the cleaning efficiency is low.

In order to solve the above-described problems, in the present invention, a valve is disposed between the mass spectrometer and the cleaning gas introduction unit, and the cleaning gas is introduced into the apparatus in a pulsed manner by opening and closing the valve. The conductance between the cleaning gas introduction part and the mass spectrometer is sufficiently large, and when the valve is opened, the pressure inside the apparatus increases greatly. That is, a large amount of cleaning gas is introduced. By introducing a large amount of cleaning gas into the inside of the apparatus, contaminants adhering to the inner wall of the apparatus are removed.

That is, the present invention includes an ion source that ionizes a sample, a chamber having a mass separation unit that separates the ionized sample at a mass-to-charge ratio, a detector that detects ions separated by the mass separation unit, and a cleaning gas. An analysis method using a mass spectrometer having a pipe for introducing a gas into a chamber, an opening / closing mechanism provided in the pipe, and a control unit, introducing a sample into an ion source, ionizing the ionized sample, It has a sample measurement process in which it is introduced into the chamber and separated in the mass separation unit and detected by a detector, and a cleaning process in which a cleaning gas is introduced into the chamber, and the control unit has a maximum chamber pressure in the cleaning process. However, the opening / closing mechanism is controlled so as to be larger than the maximum value of the chamber pressure in the sample measurement process.

In one embodiment, the open / close mechanism is provided between the ion source and the chamber or between the sample inlet to the ion source and the ion source, and in the sample measurement process, the sample ion is placed in the chamber with the open / close mechanism open. When the open / close mechanism is closed, the sample ions are separated by the mass separator and detected by the detector.

In another aspect, a second opening / closing mechanism is further provided between the ion source and the chamber or between the sample inlet to the ion source and the ion source, and the second opening / closing mechanism is open in the sample measurement step. Then, sample ions are introduced into the chamber, and the sample is separated by the mass separation unit with the open / close mechanism closed and detected by the detector.

According to the present invention, contaminants inside the apparatus can be quickly removed by introducing a large amount of cleaning gas into the apparatus in pulses using a valve.

Issues, configurations, and effects other than those described above will be clarified by the following description of the embodiments.

FIG. 1 is a schematic diagram showing the apparatus configuration of a mass spectrometer of Example 1. FIG. 2 is a schematic diagram showing a specific example of the device configuration of the first embodiment. The figure which shows an example of a measurement sequence. The schematic diagram which shows the typical time-dependent change of the pressure of a vacuum chamber. The figure which shows an example of a washing | cleaning sequence. The schematic diagram which shows the pressure change of the mass separation part at the time of sample measurement and at the time of washing | cleaning. The schematic diagram which shows the pressure fluctuation at the time of repeating opening and closing of a valve | bulb. The figure which shows the spectrum of the fragment | piece of methamphetamine before and behind washing | cleaning. The comparison figure of the cleaning effect when changing valve opening time. The figure which shows an example of the operation | movement sequence of a mass spectrometer which has a sample measurement mode and an apparatus washing mode. The figure which shows an example of a data display screen. The figure which shows the example of the cleaning gas supply method. FIG. 3 is a schematic diagram showing the apparatus configuration of a mass spectrometer of Example 2. FIG. 3 is a schematic configuration diagram showing another form of the mass spectrometer of Example 2. FIG. 4 is a schematic diagram showing the apparatus configuration of a mass spectrometer of Example 3. FIG. 6 is a schematic configuration diagram showing another form of the mass spectrometer of Example 3. FIG. 6 is a schematic configuration diagram showing another form of the mass spectrometer of Example 3. FIG. 6 is a schematic configuration diagram showing another form of the mass spectrometer of Example 3.

Hereinafter, embodiments of the present invention will be described with reference to the drawings.

[Example 1]
FIG. 1 is a schematic configuration diagram showing an example of a mass spectrometer according to the present invention. This device mainly has a gas inlet 1 for introducing sample gas and cleaning gas into the device, a valve 3 that can introduce sample gas and cleaning gas in a pulsed manner, an ion source 2 that ionizes sample molecules, and a mass charge of ions A vacuum chamber 4 having a mass separation unit for analyzing according to the ratio, a vacuum pump 5 for depressurizing the inside of the apparatus, a detector 6 for detecting ions, a control circuit 7 for controlling the apparatus, a control computer 8 for controlling the entire apparatus, It comprises a data display 9 that displays data. The gas inlet 1 may be a pipe or a fine hole.

Specimen gas and cleaning gas are sucked from the gas inlet 1. The measurement target substance of this device may be any of gas, liquid, and solid. In the case of a gas sample, it can be introduced as it is. In this case, the gas vaporized from the solid sample is introduced as in the liquid sample. When the valve 3 is closed, the sample gas and the cleaning gas are not introduced into the ion source 2. When the valve 3 is opened, the sample gas and the cleaning gas are introduced into the ion source 2. Depending on the device configuration and vacuum pump capacity, the valve opening time is preferably 1 second or less. Typical valve opening time is 10 to 100 ms. The valve 3 is opened to introduce gas into the apparatus, and the valve 3 is closed to prevent further gas introduction. The valve 3 only needs to be able to introduce a pulse of gas, and a pinch valve, a ball valve, a shutter valve, or the like can be used. A pulse valve composed of a silicon tube and a pinch valve is inexpensive and stable and easy to use. During measurement, the valve should be opened and closed repeatedly to introduce the sample gas into the device intermittently.

In the ion source 2, neutral molecules in the gas are ionized. As the ion source 2, a low vacuum barrier discharge ion source, a low vacuum glow discharge ion source, or the like is used, but is not limited thereto. The pressure of the ion source 2 varies depending on the conductance between the outside of the apparatus and the ion source, the conductance between the ion source and the pump, the valve opening time, and the pump displacement. When using a low-vacuum barrier discharge ion source, it is necessary to adjust the conductance and the like so that the pressure at which ionization efficiency is maximized.

The ions generated by the ion source 2 are introduced into a vacuum chamber 4 having a mass separation unit. A pressure gauge 32 is connected to the vacuum chamber to monitor the pressure. A typical mass separator is a linear ion trap. Any mechanism other than the linear ion trap can be used as long as it can separate ions by mass-to-charge ratio. The linear ion trap is composed of, for example, four rod electrodes and plate electrodes arranged before and after the rod electrodes. Ions are trapped by the pseudopotential generated by the RF voltage applied to the rod electrode and the potential difference between the incap voltage and the offset voltage of the rod electrode. The trapped ions are discharged to the detector for each mass to charge ratio. The inside of the vacuum chamber 4 may be divided into several rooms, and the pressure in each room may be different. The vacuum chamber 4 may include not only a mechanism for separating ions based on mass-to-charge ratio, but also a mechanism for separating ions based on ion mobility, a mechanism for converging the flow of ions by the force of an electromagnetic field, and the like.

The detector 6 may be anything as long as it can detect ions. For example, a channeltron or a microchannel plate is used. Conversion dynodes are often used to convert ions to electrons. A detector using a scintillator and a photomultiplier tube may be used.

The device is controlled by the control circuit 7, and the control circuit is controlled by the control computer 8. The control computer 8 may be mounted on the apparatus or connected externally. The obtained result is displayed on the data display 9. A liquid crystal display is often used as the data display device 9. The data display device 9 may also serve as a user interface. In addition to the liquid crystal display mounted on the apparatus main body, an externally connected liquid crystal display may exist. A liquid crystal display mounted on the apparatus main body may be a touch panel so that measurement parameters and the like can be input from the touch panel.

FIG. 2 is a schematic diagram of an example in which the device configuration of FIG. 1 is further embodied. The figure shows a sample vial 23 containing a sample solution 24, a gas inlet 1 for introducing a sample gas, a valve 3 composed of a silicon tube 14 and a pinch valve 15, a glass tube 18, an externally wound discharge electrode 17, a discharge Low-vacuum barrier discharge ion source 2 composed of internal electrode 19, high-voltage AC power source 25, linear ion trap composed of rod electrode 21 and incap 20 which is a plate electrode, end cap 22, pump 5 and detector 6 Is described. The control circuit, control computer, and data display are not shown.

The sample molecules 16 in the sample vial 23 are introduced into the low vacuum barrier discharge ion source through the pinch valve 15. Neutral molecules in the gas are ionized and the ions are introduced into the vacuum chamber 4. The ions are trapped by the linear ion trap of the mass separation unit, separated based on the mass-to-charge ratio, and discharged to the detector 6.

FIG. 3 is a diagram showing an example of the positive ion measurement sequence of the apparatus. In the case of negative ion measurement, the relationship between the incap voltage and the offset potential of the rod electrode may be reversed. The trap RF amplitude is the amplitude of the RF voltage applied to the rod electrode 21 of the linear ion trap, and ions can be trapped only while the voltage is applied. While the barrier discharge voltage is applied, plasma is formed in the ion source, and neutral molecules are ionized. The AC amplitude for ion ejection is the amplitude of the AC voltage applied to the rod electrode when ions trapped in the linear ion trap are ejected. When the ion discharge AC voltage is applied, ions are discharged for each mass-to-charge ratio. When the incap voltage is a negative voltage, ions pass through the incap 20 and are introduced into the ion trap. On the other hand, when the incap voltage becomes positive and the electric field is reversed, ions cannot pass through the incap and are not introduced into the ion trap.

Hours 1 in the measurement sequence of Fig. 3 is the barrier discharge stabilization time. Time 2 is the ion storage time, and ions generated by the ion source are introduced into the ion trap. During

time

1 and 2, the valve is open. Time 3 is the cooling time for cooling trapped ions. Time 4 is the ion analysis time. The trapped ions are separated for each mass-to-charge ratio and discharged to the detector. Time 5 is an ion exclusion time, and is a time for excluding all ions that have not been ejected during the ion analysis time to the outside of the trap. Repeat the sequence shown in Fig. 3 when measuring the sample.

In the case of the configuration of FIG. 2, when the valve 3 is open, ions are introduced into the mass separation unit and trapped in the mass separation unit. After the valve 3 is closed, the ions are separated for each mass-to-charge ratio and discharged to the detector. That is, one mass spectrum is obtained every time the sequence of FIG. 3 is completed, and a plurality of mass spectra are acquired by repeating the sequence. The longer the valve opening time, the worse the measurement throughput, so the valve opening time is typically less than 1 second, depending on the capacity of the device and pump.

A pressure gauge 32 is connected to the vacuum chamber 4 to monitor the change in pressure over time. FIG. 4 is a schematic diagram showing a typical change over time in the pressure of the vacuum chamber. While the valve 3 was closed, the pressure was maintained at 0.01 Pa or less, the pressure continued to rise during t1 when the valve was open, and reached the maximum pressure at the moment when the valve was closed. When valve 3 was closed, the pressure decreased and became 0.01 Pa or less again. Typically, the pressure increases more than 100 times. A 100-fold increase in pressure means that a large amount of gas has been introduced.

When measuring a sample, the sample gas flows into the pump 5 through the gas inlet 1, the silicon tube 14, the ion source 2, and the mass separation unit. In this process, molecules contained in the gas are adsorbed on the inner wall of each part. In particular, highly polar molecules such as amines adsorb well on metal surfaces. If the amount contained in the gas is low, the amount of adsorption is small and this is not a problem. However, when a high concentration gas is measured, it is adsorbed on the inner wall of the device in large quantities. At this time, even if the sample gas is not introduced, the adsorbate gradually desorbs and continues to be measured over a long period of time. Such contamination becomes a problem when it is desired to quantify the amount of the sample. In order to solve this problem, the inventors have used a valve 3 to introduce a large amount of cleaning gas in a pulsed manner into the apparatus and desorb the adsorbate.

¡In order to separate ions with high accuracy, the pressure of the mass separation section must be kept below 0.1 Pa. For this reason, the vacuum pump 5 depressurizing the mass separation unit has an exhaust characteristic that is assumed to be used at 0.1 Pa or less. Therefore, if the pressure is maintained at a pressure much higher than 0.1 Pa for a long time, the exhaust of the pump 5 stops or the pump 5 is destroyed. However, if the pressure in the mass separation section is increased to 0.1 Pa or more if it is temporary rather than a long time, there will be no problem with the pump 5. Temporary is typically no more than a second. Therefore, the inventors have found that if a large amount of cleaning gas is introduced into the apparatus in a pulsed manner by the valve 3, the inside of the apparatus can be cleaned quickly without damaging the pump 5. The pulse shape here means a change in pressure within one second. If the valve 3 is opened for more than 1 second and the high pressure is maintained in the vacuum chamber, the pump 5 will be damaged.

FIG. 5 is a diagram showing an example of a cleaning sequence during cleaning. Unlike sample measurement, the trap RF amplitude, ion discharge AC amplitude, and incap voltage are set to zero. In the example of FIG. 5, the valve opening time and the barrier discharge voltage ON time are the same, but they are not necessarily the same. Typical time is 60 to 200 ms for valve opening time and 60 to 200 ms for barrier discharge voltage ON time. The opening time of the valve 3 is longer than that at the time of measurement. This is to introduce a larger amount of gas. Repeat the washing sequence as well as the measurement sequence. The washing sequence is usually cycled once every 0.5 to 2 seconds.

One feature of the present invention is that it has at least two modes: a sample measurement mode driven by the sequence of FIG. 3 and an apparatus cleaning mode driven by the sequence of FIG. However, FIG. 3 and FIG. 5 are examples of sequences, and are not limited to these.

FIG. 6 is a schematic diagram showing changes in pressure of the mass separation unit during sample measurement and during cleaning. When the valve opening time is changed, the ultimate pressure of the mass separation unit also changes. That is, a larger amount of gas is introduced by opening the valve 3 longer. However, if the ultimate pressure is very high, discharge may occur in the mass separator. For this reason, it is recommended to lower each voltage in the vacuum chamber 4 during cleaning rather than during sample measurement. It is not always necessary to lower it to 0V, and it is not necessary to lower all voltages. Moreover, it is not necessary to lower the voltage if it is not discharged. FIG. 7 is a schematic diagram showing pressure fluctuation when the opening and closing of the valve is repeated. The sample gas is intermittently introduced into the device by repeatedly opening and closing the valve when cleaning the sample gas and when cleaning.

An experiment was conducted to investigate the cleaning effect using methamphetamine (MA), a kind of stimulant. High concentration MA gas was introduced to contaminate the equipment. The apparatus has the configuration shown in FIG. The measurement sequence is as shown in FIG. MA is detected at a position of m / z 150 on the mass spectrum. In addition, when fragmentation is performed by collision induced dissociation (CID), they are detected at the positions of m / z 91 and m / z 119. If high concentration MA is used as a sample, the inside of the device is contaminated with MA. For this reason, even if a sample not containing MA is measured, a peak derived from MA is detected on the mass spectrum. In the experiment, the equipment contaminated with MA was cleaned using cleaning gas. A 20% aqueous methanol solution was used as a cleaning gas generation source. Methanol gas evaporated from the aqueous solution was used as the cleaning gas. The cleaning sequence is as shown in FIG. Fig. 8 shows the spectrum after CIDing MA showing the measurement results before and after cleaning. It can be seen that the MA-derived signal that appeared strongly decreased to near the lower detection limit by washing.

The following equilibrium relationship is established in the cleaning process.

Here, the contaminant is A, the adsorption site on the inner wall of the device is M, and the molecules contained in the cleaning gas are B. The more the equilibrium is shifted to the right, the more pollutants are desorbed, that is, they are washed. Equilibrium tends to shift to the right when the affinity for B adsorption sites is higher. One way to shift the equilibrium to the right is to introduce a large amount of B. The present invention utilizes this point. Repeating the sequence of introducing a large amount of cleaning gas in a pulsed manner using the valve 3 means that the concentration of B in the above equation (1) is repeatedly increased and decreased. The pressure fluctuation curves in FIGS. 6 and 7 may be read as B concentration fluctuation curves. The moment when the valve 3 is closed becomes the highest concentration, and even after the valve 3 is closed, the time during which the constant concentration B exists at a high concentration continues. As described above, in the case of continuous introduction due to the problem of the exhaust characteristics of the pump 5, the pressure inside the apparatus must be maintained at a low pressure, and B is constantly present in a low concentration state. The use of valve 3 makes it possible to make the inside of the device at a higher pressure than the continuous introduction system, so the use of valve 3 tends to shift the equilibrium to the right and has a higher cleaning effect.

¡When the opening time of valve 3 is changed, the amount of gas introduced into the device changes. FIG. 9 is a diagram showing a result when the opening time of the valve 3 in the apparatus cleaning mode is doubled (t2 = 2 × t1). Methanol gas was used as the cleaning gas. As shown in the results, the contamination was almost eliminated by extending the valve opening time. As the amount of gas introduced increases, the cleaning effect increases at an accelerated rate. However, keeping the vacuum chamber at a high pressure for a long time will damage the pump, so it is preferable to set the valve open time within 1 second.

In order to significantly increase the cleaning efficiency, it is desirable that the pressure in at least one place in the mass spectrometer changes 10 times or more when the valve 3 is opened and closed and the cleaning gas is introduced. For example, if the pressure of the mass separation part when the valve 3 for introducing the cleaning gas is closed is 0.1 Pa, the ultimate pressure when the valve is opened must be 1 Pa or more. Furthermore, it is more effective when the pressure in at least one place in the mass spectrometer changes more than 100 times. However, since the vacuum pump 5 used to depressurize the mass separator to 0.1 Pa or less is designed for use under low pressure, it can withstand excessive high pressure even temporarily. Absent. For this reason, the pressure in the mass separation section must be at most 200 Pa. In general, the mass separator is depressurized by two or more vacuum pumps 5. For example, high vacuum pumps and roughing pumps. If cleaning is performed with the high vacuum vacuum pump stopped and only the roughing pump running, there is no problem even if the pressure in the mass separation section exceeds 200 Pa.

イオン Ionization may be adversely affected by the accumulation of contaminants. For example, in the mass spectrometer having the configuration shown in FIG. 2, barrier discharge is generated in the ion source 2 and plasma is generated only when the valve 3 is opened and the pressure of the ion source 2 is increased. When the pulse valve is closed again, the pressure of the ion source 2 decreases and the plasma disappears. This is because an optimum pressure exists during plasma generation. When not only the pressure problem but also the plasma light adversely affects the detector, it is necessary to extinguish the plasma when detecting ions. Some apparatuses repeat generation and disappearance of plasma in this way. If contaminants accumulate in the ion source 2, plasma generation may fail. Introducing a pulse of cleaning gas is also effective against such problems. Plasma can be stably generated by desorbing contaminants accumulated in the ion source 2 by the cleaning gas.

In the case of the ion source 2 using plasma, the cleaning effect of the plasma itself can be used. The plasma cleaning effect can be increased by increasing the discharge voltage and lengthening the discharge time during cleaning rather than during measurement. When the introduction of the cleaning gas pulse and the plasma cleaning are combined, the cleaning effect is remarkably increased. Charged particles generated by the discharge collide with the inner wall of the apparatus and sputtering occurs. At that time, pollutants are ejected from the inner wall together with the adsorption sites. After that, it collides with the cleaning gas molecules and the pollutants are desorbed from the adsorption site. Sputtering can break the bond between the contaminant and the adsorption site, and only the contaminant can jump out. Since the cleaning gas is pulsed, the inside of the system is filled with a large amount of cleaning gas, and contaminants rarely recombine with the adsorption sites. When the cleaning gas pulse introduction and the discharge cleaning are performed at the same time, the effect of the cleaning gas and the effect of the cleaning by the plasma are more than simply added.

It is not always necessary to use the plasma used for the ion source 2 for cleaning. Even if the ion source 2 is not the plasma ion source 2, plasma cleaning may be performed by installing a plasma generation mechanism at a location that is easily contaminated.

¡Contaminants can be removed more effectively by introducing a cleaning gas into the apparatus and baking at the same time. By heating, the bond between the contaminant and the adsorption site is easily released, and the contaminant is desorbed by introducing a cleaning gas there.

As described above, in order to realize a mass spectrometer capable of rapid cleaning, it is desirable to have at least two modes: a sample measurement mode and an apparatus cleaning mode. A system that allows the device to automatically select the sample measurement mode and the cleaning mode according to the state of the device, or allows the user to arbitrarily select two modes. FIG. 10 is a diagram illustrating an example of an operation sequence of a mass spectrometer having at least a sample measurement mode and an apparatus cleaning mode.

Measure and analyze the sample in the sample measurement mode (S11). The amount of contamination is estimated from the obtained mass spectrum (S12). For example, it is determined that the device is in a contaminated state when the TIC intensity is above a certain level, or when the ionic strength of a molecule that is known to be easily contaminated is high. Although not shown in the figure, an operation method in which a blank sample for contamination confirmation is measured after sample measurement may be used. A blank sample is a sample used for judging the contamination state of the apparatus. The type and amount of molecules contained in the blank sample as a contamination confirmation substance are known. Contamination is suspected if a signal other than a known molecule is detected when a blank sample is measured. Further, the degree of contamination can be determined by comparing the intensity of ions derived from the blank sample and the intensity of contaminants. If it is determined that there is no suspicion of contamination or the degree of contamination is mild, measure the next sample. On the other hand, if it is determined that there is a suspicion of contamination or the degree of contamination is severe, cleaning is performed (S13). In the cleaning, as described above, the cleaning gas is introduced into the apparatus in a pulsed manner using the valve 3. The apparatus shifts from the sample measurement mode to the apparatus cleaning mode. If the pollutant has been identified, the optimum cleaning gas can be selected for each pollutant. For example, it is effective to introduce a basic gas when the pollutant is a basic substance and to introduce an acidic gas when the pollutant is an acidic substance. The cleaning gas may be automatically selected by the apparatus or arbitrarily selected by the user. The cleaning gas is not limited to a basic gas or an acid gas, and may be an alcohol.

After cleaning, measure the blank sample again to confirm the contamination level of the device (S14). If the contamination is eliminated by washing, the next sample is measured. If the contamination is not gone, wash again. When the contamination level can be confirmed while washing, it is not always necessary to measure the blank sample after washing. Normally, cleaning gas is introduced into the apparatus during cleaning, and the apparatus is operated in the cleaning mode. For example, the degree of contamination reduction of the device can be confirmed by shifting from the cleaning mode to the sample measurement mode temporarily every 10 times of opening and closing the valve and acquiring the mass spectrum. In this way, there is an operation method in which the degree of contamination is periodically checked and the cleaning mode is continued until it is sufficiently reduced.

FIG. 11 is an explanatory diagram showing an example of a screen displayed on the data display 9 of the portable mass spectrometer 26. During sample measurement, the time until completion of measurement is displayed. If there is a suspicion of contamination from the measurement results, request the user to perform a cleaning operation. During cleaning, the time until the completion of the cleaning operation is displayed. After cleaning is completed, the user is required to measure a blank sample in order to examine the degree of contamination reduction. If a blank sample is measured and it can be confirmed that there is no contamination, the process proceeds to the next sample measurement. You may lock the software so that sample measurement is not possible until it is confirmed that there is no contamination. As shown in Fig. 2, when using a sample vial, the shape of the vial for sample measurement and the vial for washing can be changed, and if it is not the designated vial, it can be locked so that the measurement is not started.

¡Gas cylinders, vials containing liquids and solids, etc. can be considered as the supply source of the cleaning gas. In the case of liquid or solid, the gas evaporated from them is used as cleaning gas. A liquid or solid may be heated to increase the amount of gas generated. As shown in FIG. 12, a gas can be generated by reacting a liquid and a solid. For example, a method of generating a cleaning gas by reacting a strongly basic or strongly acidic liquid 28 with a salt 30 of the cleaning gas is effective. A label 29 describing the type of gas and the expiration date may be attached to the cylinder or vial 31 for storing the cleaning gas supply source.

If the cleaning gas supply source is a vial containing a liquid or solid, the internal pressure of the vial should be reduced from atmospheric pressure in order to increase the cleaning efficiency. The vapor pressure of the molecules contained in the liquid or solid is not affected by the internal pressure of the vial. For example, if the internal pressure is 100,000 Pa and the vapor pressure of the cleaning gas molecules is 1 Pa, the cleaning gas molecules are 0.00001% of the gas in the vial headspace. On the other hand, when the internal pressure of the vial is reduced to 1000 Pa, the cleaning gas molecules are 0.001% of the gas in the vial headspace. That is, the ratio of cleaning gas molecules is increasing. Therefore, if the flow rate of the gas introduced into the apparatus is the same, the cleaning efficiency is improved because the absolute amount of the cleaning gas molecules introduced into the apparatus increases when the internal pressure of the vial is reduced.

There are no restrictions on the type of cleaning gas in places where exhaust gas can be managed, such as in laboratory laboratories. On the other hand, when considering on-site analysis, toxic gas cannot be used as cleaning gas. Odor is also a problem. The odor can be avoided from the user before toxicity to the body. Since alcohol gas is less toxic, odorless and has a cleaning effect, it is desirable to use alcohol gas for on-site analysis.

[Example 2]
FIG. 13 is a schematic configuration diagram showing an embodiment of a mass spectrometer according to the present invention. The difference from the first embodiment is that the valve 3 is disposed between the ion source 2 and the vacuum chamber 4. Neutral molecules in the sample gas are ionized by the ion source 2 and are introduced into the vacuum chamber 4 through the ion introduction pipe 12 and the pulse valve 3. Similarly, neutral gas and cleaning gas that have not been ionized are introduced through the pulse valve 3. In this configuration, the ion source 2 is generally arranged under atmospheric pressure. For this reason, the ion source 2 can be disassembled, cleaned, remodeled, etc. without breaking the vacuum of the mass spectrometer, and handling of the ion source is easier than in the first embodiment. However, since ions are introduced into the vacuum chamber 4 from atmospheric pressure, the ion loss in the piping is large, and the device sensitivity is often better in the first embodiment.

FIG. 14 is a schematic configuration diagram showing another form of the mass spectrometer of the second embodiment. When the sample is a liquid rather than a gas, electrospray ionization is generally used as shown in FIG. The sample solution 11 is fed to the electrospray probe 10 and ionized. However, the present invention is not limited to electrospray, and there is a method in which a gas heater 33 is used to heat and vaporize a liquid in the ion source 2 and the vaporized gas is ionized by atmospheric pressure chemical ionization, and various ionization methods can be used. Even in the apparatus configuration of this embodiment, there is a problem that the inside of the apparatus is contaminated when a high concentration sample is measured. In order to clean the apparatus, it is effective to introduce the cleaning gas in the form of pulses as in the first embodiment. In the method of continuously introducing the cleaning gas without using the valve 3, it is necessary to keep the vacuum chamber at a high vacuum due to the characteristics of the pump 5, and a large amount of cleaning gas cannot be introduced. On the other hand, if the gas is introduced in a pulse form using the valve 3, a larger amount of cleaning gas can be introduced than in the continuous introduction system, and the inside of the apparatus can be efficiently cleaned. It is possible to perform cleaning more effectively by extending the valve opening time in a state in which the occurrence of electric discharge in the apparatus is prevented by lowering the voltage inside the apparatus than when measuring the sample. In addition, since it is not necessary to stop the pump 5, quick cleaning is possible.

イオン Ions may be introduced into the apparatus simultaneously with the cleaning gas. Sputtering occurs when ions collide with the inner wall of the apparatus. Contaminants jump out of the inner wall along with the adsorption sites by sputtering, and desorb from the adsorption sites by colliding with cleaning gas molecules. Since the probability of collision with cleaning gas molecules is higher when the gas is ejected into the gas than when it is present on the inner wall, the cleaning efficiency is improved.

In addition, the operation method shown in FIG. 10, the display of the data display shown in FIG. 11, the supply source of the cleaning gas, etc. can be the same as in the first embodiment.

[Example 3]
FIG. 15 is a schematic configuration diagram showing an embodiment of a mass spectrometer according to the present invention. The difference from the first embodiment is that the pulse valve 3 is not disposed between the gas inlet 1 and the vacuum chamber 4. However, a pulse valve 3 was installed between the cleaning gas inlet 13 and the vacuum chamber 4. That is, in this embodiment, the sample gas and the cleaning gas are introduced from different pipes into the apparatus. The measurement sequence is obtained by omitting the opening and closing of the valve from FIG. If there is no problem with plasma light entering the detector, there is no need to turn on / off the barrier discharge voltage. In Examples 1 and 2, ions could not be introduced into the apparatus unless the valve was opened, and the throughput for detecting ions was poor. On the other hand, in this embodiment, since ions are continuously introduced, the throughput is high. However, in the case of the continuous introduction system, since a large amount of ions cannot be introduced into the apparatus, the sensitivity is lower than in Examples 1 and 2. The cleaning effect is the same as in Examples 1 and 2, and the inside of the apparatus can be quickly cleaned by introducing a large amount of cleaning gas into the apparatus in a pulsed manner using the valve 3. In the example of FIG. 15, the cleaning gas is introduced between the ion source 2 and the vacuum chamber 4, but the cleaning gas may be directly introduced into the vacuum chamber 4.

FIG. 16 is a schematic configuration diagram showing another embodiment of the mass spectrometer of the third embodiment. The difference from FIG. 15 is that a valve 3 is arranged between the ion source 2 and the gas inlet 1. However, sample gas and cleaning gas are introduced from different pipes as in FIG. In the configuration of FIG. 16, since the sample gas is introduced in pulses, the sensitivity is high as in Examples 1 and 2. In the configuration of FIG. 16, the sample measurement mode and the cleaning mode are alternately repeated to perform cleaning while measuring the sample. For example, the sample gas side valve 3 is opened and closed to introduce and analyze the sample gas, and then the cleaning gas side valve 3 is opened and closed to clean the apparatus. Thus, by continuously performing sample measurement and cleaning, the inside of the apparatus can always be kept clean. It is not always necessary to alternately introduce the sample gas and the cleaning gas once, and the balance of the number of times can be changed, for example, the cleaning gas is introduced once every five times the sample gas is introduced.

FIG. 17 is also a schematic configuration diagram showing another form of the mass spectrometer of the third embodiment. Unlike FIG. 16, the pulse valve 3 on the sample gas side is arranged between the ion source 2 and the vacuum chamber 4. As in FIGS. 15 and 16, the sample gas and the cleaning gas are introduced from different pipes. In the configuration shown in FIG. 17, similarly to the configuration in FIG. 16, sample measurement and cleaning can be alternately repeated, and the apparatus can always be kept in a healthy state. In the configuration of FIG. 17, an atmospheric pressure ion source can be used.

FIG. 18 is also a schematic configuration diagram showing another form of the mass spectrometer of the third embodiment. The pipe for introducing the sample gas and the pipe for introducing the cleaning gas are joined before the ion source. The sensitivity is high because the sample gas is pulsed. Also, the cleaning gas is pulsed, so the cleaning efficiency is high. Unlike FIGS. 15 to 17, since the cleaning gas is introduced into the vacuum chamber 4 after passing through the ion source 2, the ion source 2 is also cleaned, and the robustness of the apparatus is high.

In addition, this invention is not limited to the above-mentioned Example, Various modifications are included. For example, the above-described embodiments have been described in detail for easy understanding of the present invention, and are not necessarily limited to those having all the configurations described. Further, a part of the configuration of one embodiment can be replaced with the configuration of another embodiment, and the configuration of another embodiment can be added to the configuration of one embodiment. In addition, it is possible to add, delete, and replace other configurations for a part of the configuration of each embodiment.

1 ... Gas inlet, 2 ... Ion source, 3 ... Valve, 4 ... Vacuum chamber, 5 ... Pump, 6 ... Ion detector, 7 ... Control circuit, 8 ... Control computer, 9 ... Data display, 10 ... Electrospray 11 ... Sample solution, 12 ... Ion introduction pipe, 13 ... Cleaning gas introduction port, 14 ... Silicon tube, 15 ... Pinch valve, 16 ... Sample molecule, 17 ... External winding electrode, 18 ... Glass tube, 19 ... Internal electrode for discharge, 20 ... In cap, 21 ... Rod electrode, 22 ... End cap, 23 ... Sample vial, 24 ... Sample solution, 25 ... High-voltage AC power source, 26 ... Portable mass spectrometer, 27 ... Portable Data display of mass spectrometer, 28 ... strongly basic or acidic liquid, 29 ... label, 30 ... cleaning gas salt, 31 ... cleaning gas supply vial, 32 ... pressure gauge, 33 ... gas heater

Claims

An ion source for ionizing the sample, a chamber having a mass separation unit for separating the ionized sample at a mass-to-charge ratio, a detector for detecting ions separated by the mass separation unit, and a cleaning gas are introduced into the chamber An analysis method using a mass spectrometer having a piping to be opened, an opening / closing mechanism provided in the piping, and a control unit,
A sample measurement step of introducing a sample into the ion source and ionizing the sample, introducing the ionized sample into the chamber, separating the sample in the mass separation unit, and detecting the sample with the detector;
A cleaning step of introducing the cleaning gas into the chamber,
The control unit controls the opening / closing mechanism so that a maximum value of the chamber pressure in the cleaning step is larger than a maximum value of the chamber pressure in the sample measurement step. .
2. The analysis method according to claim 1, wherein the control unit controls the opening / closing mechanism so that a pressure change of the cleaning gas in the chamber becomes a pulse shape.
The analysis method according to claim 1, wherein, in the cleaning step, the pressure in at least one place in the chamber changes by 10 times or more.
The analysis method according to claim 1, wherein, in the cleaning step, the pressure in at least one place in the chamber changes 100 times or more.
The analysis method according to claim 1, wherein, in the cleaning step, the control unit controls the opening / closing mechanism so that the opening time of the opening / closing mechanism is within one second.
The opening / closing mechanism is provided between the ion source and the chamber or between a sample inlet to the ion source and the ion source,
In the sample measurement step, sample ions are introduced into the chamber with the open / close mechanism open, and sample ions are separated by the mass separation unit and detected by the detector with the open / close mechanism closed. The analysis method according to claim 1.
A second opening / closing mechanism is further provided between the ion source and the chamber or between the sample inlet to the ion source and the ion source,
In the sample measurement step, sample ions are introduced into the chamber with the second opening / closing mechanism open, and the sample is separated by the mass separation unit with the opening / closing mechanism closed and detected by the detector. The analysis method according to claim 1, wherein:
The analysis method according to claim 6 or 7, wherein the cleaning process takes a longer time to open the opening / closing mechanism than the sample measurement process.
The analysis method according to claim 6 or 7, wherein in the sample measurement step, the opening / closing mechanism is controlled to be within one second.
8. The analysis method according to claim 6, wherein the pressure fluctuation in the chamber in the cleaning step is larger than the pressure fluctuation in the chamber in the sample measurement step by the control of the opening / closing mechanism.
The analysis method according to claim 1, wherein at least one voltage in the chamber is lower in the cleaning step than in the sample measurement step.
The analysis method according to claim 1, wherein the ion source is a discharge ion source.
The discharge ion source has an electrode pair and a power source provided across a part of an ionization chamber formed of a dielectric, and is generated by applying a voltage to the electrode pair in the sample measurement step. 13. The analysis method according to claim 12, wherein discharge plasma is generated by dielectric barrier discharge to generate sample ions.
13. The analysis method according to claim 12, wherein a discharge is generated in the discharge ion source in the sample measurement step and the cleaning step, and the discharge time is longer in the sample measurement step than in the cleaning step. .
13. The analysis method according to claim 12, wherein a discharge is generated in the discharge ion source in the sample measurement step and the cleaning step, and the discharge voltage is higher in the cleaning step than in the sample measurement step.
The cleaning gas is supplied from a cleaning gas generating liquid contained in a sealed container, and the cleaning gas is introduced in a state where the internal pressure of the container is reduced from the atmospheric pressure. The analysis method according to claim 1.
The cleaning gas is supplied from a state stored as a salt. In the cleaning step, the cleaning gas is generated by a salting-out effect by reacting the salt with a strongly acidic liquid or a strongly basic liquid. The analysis method according to claim 1, wherein the analysis method is introduced.
The analysis according to claim 1, further comprising a step of measuring a contamination confirmation substance, wherein the contamination state of the mass spectrometer is determined based on a measurement result of the sample or the contamination confirmation substance, and the cleaning step is performed. Method.