JP2004185886A - Atmospheric pressure ionization mass spectroscope - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an atmospheric pressure ionization mass spectroscope switching ESI (electric spray ionization), APCI (atmospheric pressure chemical ionization), and APPI (atmospheric pressure photo-ionization) without taking much work, and obtaining each chromatogram by successively switching three kinds of ionization modes against one sample injection especially at an LC (liquid chromatograph) part. <P>SOLUTION: A discharge electrode 26 for APCI and a light source for APPI are arranged at the positions separated from each other around an axis S by about 90°, in front of a spray nozzle 22 spraying sample liquid in an atomizing chamber. A control part 40 makes a metal cylinder 22a packaged in the nozzle 22, the discharge electrode 26, and a light source 27 alternatively operate. Since the ionization modes are switched only by an electric control, the chromatogram can be made for every ionization mode by successively practicing respective modes in every short time, and by assorting samples of detection signals corresponding with respective modes. <P>COPYRIGHT: (C)2004,JPO&NCIPI

Description

[0001]
TECHNICAL FIELD OF THE INVENTION
According to the present invention, for example, a liquid sample whose components are separated by a liquid chromatograph (LC) is ionized by being sprayed into a substantially atmospheric pressure atmosphere, and the generated ions are introduced into a mass spectrometer (MS) for analysis. The present invention relates to a pressure ionization mass spectrometer.
[0002]
[Prior art]
FIG. 5 is a schematic configuration diagram showing an example of a conventionally known general LC / MS device (see, for example, Patent Document 1). The sample liquid which is temporally separated and eluted from the column 11 of the LC section 10 is introduced into an interface section (atmospheric pressure ionization interface) 20 and sprayed from a spray nozzle 22 into an atomization chamber (ionization chamber) 21. Ionized. The generated ions are sent to the MS section 30 through a small-diameter passage hole 24 drilled at the top of a conical sampling cone 23 located in front of the ion.
[0003]
The MS unit 30 includes three chambers, a first intermediate chamber 31, a second intermediate chamber 32, and an analysis chamber 33. The atomizing chamber 21 and the first intermediate chamber 31 are separated from the first intermediate chamber 31 by the passage holes 24. The second intermediate chamber 32 communicates with a small-diameter passage hole (orifice) 36 provided at the top of a conical skimmer 35. The interior of the atomization chamber 21 is maintained at approximately atmospheric pressure, the first intermediate chamber 31 is rotated up to about 1 Torr by a rotary pump, and the second intermediate chamber 32 and the analysis chamber 33 are each driven by a turbo molecular pump to about 10 ^-3 to 10 ^-4. The gas is exhausted to about Torr and about 10 ⁻⁵ to about 10 ⁻⁶ Torr, and the degree of vacuum is gradually increased from the atomization chamber 21 toward the analysis chamber 33 to maintain the analysis chamber 33 in a high vacuum state. I have.
[0004]
The ions that have passed through the passage holes 24 as described above are converged on the orifice 36 by the first ion lens 34, pass through the orifice 36, and are introduced into the second intermediate chamber 32. Then, it is converged and accelerated by the second ion lens 37 and sent to the analysis chamber 33, and only target ions having a specific mass number (mass / charge) are filtered by the quadrupole filter 38 disposed in the analysis chamber 33. It passes through the space in the long axis direction and reaches the ion detector 39. Then, in the ion detector 39, a current corresponding to the number of arrived ions is extracted as a detection signal.
[0005]
In the above configuration, the interface unit 20 ionizes various sample components contained in the sample liquid by atomizing the sample liquid by heating, a high-speed gas flow, a high electric field, and the like, and uses an electrospray ionization method (ESI = Electric spray ionization and atmospheric pressure chemical ionization (APCI) are most widely used.
[0006]
FIG. 6A is a configuration example of an ionization spray unit based on ESI. In the ESI, a high DC voltage of about several kV is applied to the tip of the spray nozzle 22 to generate a strong unequal electric field. The sample liquid that has reached the tip of the spray nozzle 22 is separated into charges by this electric field, and is finely charged with the help of a nebulizing gas ejected from a nebulizing tube (not shown) disposed coaxially with the spray nozzle 22. Forcibly sprayed as droplets. In the atomization chamber 21, the spray flow is exposed to a heating gas supplied by a heating gas supply path (not shown), whereby the evaporation of the solvent in the droplet proceeds, and the generation of gas ions is promoted.
[0007]
FIG. 6B shows an example of the configuration of an ionization spray unit based on APCI. In the APCI, a needle-shaped discharge electrode 26 is arranged in front of the spray nozzle 22, and sample molecules generated by heating the spray flow with a heater 28 provided so as to surround the tip of the spray nozzle 22 include: Carrier gas ions (buffer ions) generated by corona discharge from the discharge electrode 26 are chemically reacted to perform ionization.
[0008]
Generally, APCI is effective for ionization of low to medium polarity compounds, and ESI is effective for ionization of medium to high polarity compounds. In addition, since ESI generates polyvalent ions in the process of ionizing a substance represented by a protein, a compound having a molecular weight exceeding the upper limit of the mass range of the apparatus and having a molecular weight of tens of thousands can be measured. Therefore, the ionization method is properly used depending on the type of the sample to be analyzed and the purpose of the analysis. Conventionally, in a general LC / MS apparatus, the spray section for ESI and the spray section for APCI are configured to be interchangeable, and the analyst exchanges the spray section appropriately according to the ionization method ( For example, see Non-Patent Document 1). However, such an exchange operation is troublesome, which is one of the causes of lowering the analysis efficiency. Therefore, an apparatus aiming to save the trouble of such replacement has been conventionally proposed.
[0009]
For example, in the device described in Patent Document 3, an ESI spray unit and an APCI spray unit are provided side by side, and a sample liquid is selectively supplied to one of the spray units by a flow path switching valve. In addition, an inlet for taking in ions is provided independently in front of the spray part for ESI and the spray part for APCI, and an ion transport pipe connected to the two inlets joins in the middle, and only the latter one is provided. It is configured to transport ions to the analysis chamber. However, such a configuration is complicated, costly and the device itself becomes large. On the other hand, in the apparatus described in Patent Document 4, for example, the spray nozzle itself is common to the ESI and the APCI, and a mechanism for mechanically switching the positional relationship between the heater and the nozzle is provided, so that the ESI mode and the APCI mode are switched. Switching has been achieved.
[0010]
In recent years, as an ionization method for an LC / MS interface, an atmospheric pressure photoionization method (APPI = Atmospheric Pressure Photo-Ionization) has been proposed in addition to the above-described ionization method (for example, see Patent Document 5). . FIG. 6C is a configuration example of an ionization spray unit using APPI. APPI irradiates light from a light source 27 which is a krypton lamp to sample molecules generated by heating by a heater 28 in the same manner as APCI, and is ionized by the photon energy hν. This APPI can ionize polycyclic aromatics, fat-soluble vitamins, etc., which are hardly ionized by ESI or APCI, and is superior in quantitative analysis because the linearity between component concentration and detection output is wider than APCI. There are features.
[0011]
[Patent Document 1]
JP 2000-214149 A (paragraph 0003, paragraph 0004, and FIG. 6)
[Patent Document 2]
JP 2001-272375 A [Patent Document 3]
JP-A-8-297112 [Patent Document 4]
JP-A-8-236064 [Patent Document 5]
US Patent No. 6211516 [Non-Patent Document 1]
“Desktop, simple, high-performance LCMS system LCMS-QP8000α”, “ESI, APCI standard equipment”, [Online], Shimadzu Corporation, [Search November 18, 2002], Internet <URL: http: // www. an. shimadzu. co. jp / products / lcms / qp8000. htm>
[0012]
[Problems to be solved by the invention]
In recent years, samples analyzed by LC / MS have become more complicated and diversified, and opportunities for measuring a sample in which various components are mixed in a complicated manner are increasing. Therefore, when analyzing a certain sample, all the components contained in the sample cannot be sufficiently captured by only one type of ionization method, and the results of analysis using a plurality of ionization methods are collected and qualitatively analyzed. Analysis and various analyzes are often performed. In such a case, it is troublesome and troublesome to replace with an ionization spray unit corresponding to each ionization mode as in the related art, or to perform some sort of mechanical switching. In addition, since it is necessary to perform the analysis a plurality of times while changing the ionization mode, the analysis takes a long time. Further, when the amount of the sample is very small, such an analysis may be difficult even in a plurality of times.
[0013]
The present invention has been made in view of the above points, and a main object thereof is to appropriately switch a plurality of ionization modes without any troublesome work according to the type of sample and the purpose of analysis. An object of the present invention is to provide an atmospheric pressure ionization mass spectrometer that can perform analysis by switching.
[0014]
[Means for Solving the Problems]
The present invention has been made to solve the above-described problems. The present invention provides a large-scale method in which a sample solution is sprayed from a spray nozzle into an ionization chamber at substantially atmospheric pressure, and component molecules contained in the sample solution are ionized to mass analyze the ions. In a pressure ionization mass spectrometer,
a) charge applying means for applying a high voltage to the tip of the spray nozzle in the ESI mode to charge the spray droplets;
b) a hot-air supply unit that blows a heating and drying gas onto a spray flow sprayed from the spray nozzle, or a spray-flow heating unit that is a heater disposed around the spray flow;
c) a discharge means provided in front of the spray nozzle and including a discharge electrode for generating a corona discharge in the APCI mode;
d) light source means provided in front of the spray nozzle and at a position that does not physically and functionally interfere with the discharge electrode, and irradiates the spray flow with light in an APPI mode;
e) Charge application for selectively applying high voltage to the spray nozzle tip, corona discharge from the discharge electrode, or irradiating light to the spray flow according to each ionization mode of ESI, APCI or APPI. Means, control means for controlling the discharging means and the light source means,
It is characterized by having.
[0015]
Here, the state in which the discharge electrode and the light source unit do not “functionally interfere” specifically means, for example, when a discharge voltage is applied to the discharge electrode, between the discharge electrode and the light source unit. This is a state in which an undesired situation, such as the occurrence of a discharge and an inadequate corona discharge in a space, does not occur.
[0016]
Embodiments and effects of the present invention
In the atmospheric pressure ionization mass spectrometer according to the present invention, when the control means activates the charge applying means, the control means is in the ESI ionization mode, when the discharge means is activated, the APCI ionization mode is in effect, and when the light source means is activated. The mode becomes the APPI ionization mode. The spray nozzle and the spray flow heating means are commonly used for both ionization modes, and the change of the ionization mode is achieved by the above-described electrical switching by the control means. Therefore, unlike the conventional case, the analyst does not need to replace the ionization spray unit when performing an analysis in a different ionization mode, and does not require any troublesome work. Further, since a mechanical switching mechanism is not required, the size of the apparatus is not increased, and the increase in cost can be suppressed to a minimum.
[0017]
Furthermore, high-speed switching is possible because the ionization mode is electrically switched. Therefore, in the case of introducing the sample liquid whose components have been separated by liquid chromatography into the atmospheric pressure ionization mass spectrometer according to the present invention, the control means performs one sample injection in liquid chromatography. It is possible to adopt a configuration in which the ionization mode of ESI, APCI and APPI is sequentially switched, and chromatogram data corresponding to each ionization mode is collected.
[0018]
According to this configuration, three types of chromatograms with different characteristics can be acquired for one sample injection, so that analysis of a sample with a complicated component composition can be completed in a short time. Can be. Further, even when the amount of the sample is small and it is difficult to perform the analysis a plurality of times, it is possible to obtain a sufficiently accurate analysis result.
[0019]
【Example】
Hereinafter, an embodiment of the atmospheric pressure ionization mass spectrometer according to the present invention will be described with reference to FIGS. FIG. 1 is a schematic configuration diagram of an ionization interface section of the atmospheric pressure ionization mass spectrometer according to the present embodiment, FIG. 2 is an electrical schematic configuration diagram of main parts of the apparatus, and FIG. 3 shows an example of a control operation of the apparatus. It is a timing chart. The basic configuration other than the above is the same as that of the conventional general MS apparatus described with reference to FIG.
[0020]
As shown in FIG. 1, a needle-like discharge electrode 26 is disposed in front of the spray nozzle 22 in the ionization interface portion (in FIG. 1, extends in a direction perpendicular to the paper surface). A krypton lamp or the like is located at a position about 90 ° in the rotational direction from the discharge electrode 26 around the central axis (that is, the central axis of the spray flow) S and slightly displaced in the extending direction of the central axis S. A light source 27 for APPI is arranged. The reason why the discharge electrode 26 and the light source 27 are separated from each other in the rotation direction is to keep the distance from each other sufficiently in the S-axis direction and to secure a sufficient distance between them. If the distance between them is not sufficiently ensured, a discharge is generated between the light source 27 when a high voltage is applied to the discharge electrode 26 as described later, and the surrounding carrier gas molecules are sufficiently ionized. You can't do that. Therefore, the angular distance between the discharge electrode 26 and the light source 27 in the rotation direction is not necessarily 90 °, and can be appropriately determined under the condition that the occurrence of the above-described undesired discharge can be avoided.
[0021]
The ionization interface is configured to selectively execute any one of the ionization modes of ESI, APCI and APPI. That is, as shown in FIG. 2, a first voltage source 42 capable of generating a high voltage of several kV or more by changing the voltage is provided by a switch 41 (SW1) by a metal tube housed in the discharge electrode 26 or the spray nozzle 22. 22a is alternatively connected. On the other hand, the second voltage source 44 is selectively connected to the light source 27 by the switch 43 (SW2). The switching operation of the switches 41 and 43 and the output voltage of the first voltage source 42 are controlled by a control unit 40 that controls the overall operation of the MS unit. The output signal of the ion detector 39 (not shown) is converted into a digital signal by the A / D converter 50 and then input to the data processing unit 51, where characteristic data processing described later is executed. .
[0022]
Next, an example of the operation of the present apparatus will be described with reference to FIG. 3 in addition to FIGS. Here, taking advantage of the feature that the switching of ESI, APCI and APPI is performed only electrically rather than mechanically, analysis by the ionization mode of each of ESI, APCI and APPI for one injection of the sample in the LC unit 10 is performed. Is repeatedly executed for a short time, and an operation of acquiring analysis results in the respective ionization modes in a time sharing manner is performed.
[0023]
As shown in FIGS. 3A to 3D, the control unit 40 executes control so as to sequentially switch the ESI mode, the APCI mode, and the APPI mode by 100 msec each. In the ESI mode, the switch 41 is switched to select the A side, the switch 43 is turned off, and the voltage of the first voltage source 42 is set to V1 (for example, about 4 kV). In the APCI mode, the switch 41 is switched to select the B side, the switch 43 is turned off, and the voltage of the first voltage source 42 is set to V2 (for example, about 4 kV). Further, in the APPI mode, the switch 41 selects the side B (or the side A), the switch 43 is turned on, and the voltage of the first voltage source 42 is set to 0V.
[0024]
The operation in each ionization mode will be described in detail. In the ESI mode, the high voltage V1 generated by the first voltage source 42 is applied to the metal tube 22a of the spray nozzle 22. Since the metal tube 22a surrounds the capillary tube through which the sample solution flows, the sample solution that has reached the end of the capillary tube by the high voltage applied to the metal tube 22a is strongly charged positively, and the outer tube of the capillary tube With the help of the nebulizing gas ejected from the nebulizing tube, the liquid is forcibly sprayed into the atomizing chamber 21 as positively charged droplets. A heating gas blown from the heating gas supply pipe 25 hits the spray flow, the solvent in the droplets evaporates rapidly, and as the droplet size decreases, gas ions are generated by Coulomb repulsion. The ions and minute charged droplets thus generated are sucked into the first intermediate chamber 31 through the passage hole 24 by the pressure difference between the atomizing chamber 21 and the first intermediate chamber 31. In the meantime, the evaporation of the solvent from the droplet further progresses, and the ions are focused by the first ion lens 34.
[0025]
In the APCI mode, the high voltage V2 generated by the first voltage source 42 is applied to the discharge electrode 26. The fine droplets sprayed from the spray nozzle 22 are exposed to a heated gas as in the ESI mode, and the solvent in the droplets evaporates rapidly. At this time, since no electric charge is applied to the droplet, gas ions are not generated, and instead, sample molecules pop out. The LC mobile phase of the preceding stage is also sprayed into the atomization chamber 21 at the same time, and the molecules of the vaporized mobile phase are ionized by corona discharge generated from the discharge electrode 26, and the sample molecules are reacted by the molecular ions. Ionize. The ions thus generated are sucked into the first intermediate chamber 31 through the passage hole 24 by the pressure difference between the atomizing chamber 21 and the first intermediate chamber 31.
[0026]
In the APPI mode, power is supplied from the second voltage source 44 to the light source 27, and the light source 27 emits light. As in the case of the APCI mode, the fine droplets sprayed from the spray nozzle 22 are exposed to a heating gas, and the solvent in the droplets evaporates rapidly and the sample molecules fly out. When light from the light source 27 shines on such a spray flow, sample molecules are ionized by the photon energy hν. The ions thus generated are sucked into the first intermediate chamber 32 through the passage hole 24 by the pressure difference between the atomizing chamber 21 and the first intermediate chamber 31.
[0027]
The ionization in each of the ionization modes of ESI, APCI, and APPI as described above is sequentially repeated, and various ions characteristic of each ionization mode are introduced into the MS unit 30. Therefore, of the various ions generated in each ionization mode, only ions having a specific mass number selected by the quadrupole filter 38 sequentially reach the ion detector 39. The detection signal of the ion detector 39 is sampled at certain fixed time intervals in the A / D converter 50, and each sample is converted into a digital signal. Accordingly, the detection signal is input to the data processing unit 51 embodied by a personal computer or the like as a digital signal data sequence (see FIG. 3E).
[0028]
In the data processing unit 51, each sample belonging to the signal data sequence can be separated into ones corresponding to each ionization mode of ESI, APCI, and APPI by a control signal given from the control unit 40. FIG. 3F conceptually shows such data classification. After each sample is classified into three groups in this manner, each sample data is appropriately processed, for example, by performing a process of correcting data corresponding to a time position that is short due to being allocated to another ionization mode, thereby performing chromatographic processing. Get gram data. If chromatograms are created based on these, three types of chromatograms corresponding to each ionization mode of ESI, APCI, and APPI can be obtained. That is, a single sample injection in the LC unit 10 can create chromatograms corresponding to three different ionization modes. Thereby, for example, even if a component does not generate a sufficient amount of ions in one ionization mode, if a sufficient amount of ions is generated in another ionization mode, this is caught and the component 1 is reliably determined. One can be detected and even quantified.
[0029]
In any of the ionization modes of ESI, APCI, and APPI, it is necessary to dry the droplets in the spray flow. In the above-described embodiment, the heating gas ejected from the heating gas supply pipe 25 is used for this purpose. This is because the amount of heat that can be given to the droplet per unit time is relatively small, and is optimal for ESI. However, it is not always optimal for APCI and APPI. In other words, in terms of ionization efficiency, it can be said that the configuration of the above embodiment is optimized for ESI, not for APCI or APPI.
[0030]
On the contrary, FIG. 4 shows an example of a configuration in which the ionization efficiency is considered to be optimal in APCI or APPI instead of ESI. That is, in this example, the heater 28 is provided so as to surround the tip of the spray nozzle 22 in place of the heating gas supply pipe 25, thereby heating the droplet sprayed from the nozzle 22 more efficiently. Like that.
[0031]
It should be noted that the above embodiment is merely an example, and it is apparent that changes and modifications can be made as appropriate within the scope of the present invention.
[Brief description of the drawings]
FIG. 1 is a schematic configuration diagram of an atmospheric pressure ionization interface section of an atmospheric pressure ionization mass spectrometer according to one embodiment of the present invention.
FIG. 2 is an electrical schematic configuration diagram of a main part of the atmospheric pressure ionization mass spectrometer of the present embodiment.
FIG. 3 is a timing chart showing an example of a control operation in the atmospheric pressure ionization mass spectrometer of the present embodiment.
FIG. 4 is a schematic configuration diagram of an atmospheric pressure ionization interface unit of an atmospheric pressure ionization mass spectrometer according to another embodiment of the present invention.
FIG. 5 is a schematic configuration diagram showing an example of a conventionally known general LC / MS device.
FIG. 6 is a schematic view showing a configuration example of various conventional ionization methods.
[Explanation of symbols]
10 LC part 20 Interface part 21 Atomization room (ionization room)
22 Spray nozzle 22a Metal tube 23 Sampling cone 24 Passing hole 25 Heating gas supply tube 26 Discharge electrode 27 Light source 28 Heater 30 MS part 31 First intermediate chamber 32 Second intermediate chamber 33 Analysis chamber 34 first ion lens 35 skimmer 36 orifice 37 second ion lens 38 quadrupole filter 39 ion detector 40 control units 41 and 43 switches 42 first voltage source 44 second Voltage source 50 A / D converter 51 Data processing unit

Claims (2)

In an atmospheric pressure ionization mass spectrometer that sprays a sample liquid from a spray nozzle into an ionization chamber at substantially atmospheric pressure, ionizes component molecules contained in the sample liquid, and mass-analyzes the ions,
a) charge applying means for applying a high voltage to the tip of the spray nozzle in the ESI mode to charge the spray droplets;
b) a hot-air supply unit that blows a heating and drying gas onto a spray flow sprayed from the spray nozzle, or a spray-flow heating unit that is a heater disposed around the spray flow;
c) a discharge means provided in front of the spray nozzle and including a discharge electrode for generating a corona discharge in the APCI mode;
d) light source means provided in front of the spray nozzle and at a position that does not physically and functionally interfere with the discharge electrode, and irradiates the spray flow with light in an APPI mode;
e) Charge application for selectively applying high voltage to the spray nozzle tip, corona discharge from the discharge electrode, or irradiating light to the spray flow according to each ionization mode of ESI, APCI or APPI. Means, control means for controlling the discharging means and the light source means,
An atmospheric pressure ionization mass spectrometer characterized by comprising: An atmospheric pressure ionization mass spectrometer for performing mass spectrometry by introducing a sample liquid separated by liquid chromatography, wherein the control means controls ESI, APCI and ACI for one sample injection in liquid chromatography. The atmospheric pressure ionization mass spectrometer according to claim 1, wherein each ionization mode of the APPI is sequentially switched to repeatedly collect chromatogram data corresponding to each ionization mode.

Images