JP6229797B2 - Ionizer - Google Patents

Description

  The present invention relates to an ionization apparatus for ionizing a liquid sample in a mass spectrometer such as a liquid chromatograph mass spectrometer.

  In a liquid chromatograph mass spectrometer (hereinafter referred to as “LCMS”) that combines a liquid chromatograph (hereinafter referred to as “LC”) and a mass spectrometer (hereinafter referred to as “MS”), the components in the liquid sample are timed by the LC column. Are separated and introduced into the ionization chamber of the MS in order to generate various ions. And the produced | generated ion is detected for every mass to charge ratio, and an objective component is identified and quantified. In LCMS, in order to accurately determine the mass-to-charge ratio of ions generated from each component, a standard sample having a known mass-to-charge ratio of generated ions is used.

  There are two methods for introducing a standard sample. One is a method in which a component (hereinafter referred to as “analysis target component”) eluted from the LC and a standard sample are simultaneously introduced into the ionization chamber and ionized, and the other is an analysis target component and standard. In this method, the sample is introduced into the ionization chamber at a different timing and ionized. In the former method, one having both a mass peak derived from an analysis target component and a standard sample is obtained on one mass spectrum (internal standard method), and in the latter method, the mass spectrum of the analysis target component and a standard sample are obtained. Are independently acquired (external standard method). In any method, the mass-to-charge ratio value of the mass peak derived from the analysis target component is calibrated based on the position of the mass peak derived from the standard sample.

  The standard sample is usually introduced into the ionization chamber from an ionization probe different from the ionization probe into which the analysis target component is introduced in order to prevent contamination. For example, Patent Document 1 discloses an ionization apparatus that includes a plurality of ionization probes and introduces a liquid analysis target component and a liquid standard sample independently from these probes into an ionization chamber. As an ionization probe for generating ions from a liquid sample, an ESI (electrospray ionization) probe or an APCI (atmospheric pressure chemical ionization) probe is used.

US Pat. No. 6,207,954

  Each of the ESI probe and the APCI probe includes a liquid sample supply pipe that supplies a liquid sample, and a nebulization gas supply pipe that is provided so as to cover the outer periphery of the liquid sample supply pipe. Nebulization gas such as nitrogen gas supplied to the nebulization gas supply pipe is sprayed onto the liquid sample at the outlet of the ionization probe to promote atomization of the liquid sample.

  In the ionization apparatus described in Patent Document 1, a mechanism for supplying a liquid sample (analysis target component or standard sample) and nebulization gas to each of a plurality of ionization probes is provided. As described above, when a mechanism for supplying a liquid sample and a nebulization gas to each of a plurality of ionization probes is provided, there is a problem that the configuration of the ionization apparatus becomes complicated.

  The problem to be solved by the present invention is to provide an ionization apparatus capable of introducing a liquid analysis target sample and a liquid standard sample into an ionization chamber with a simple configuration.

An ionization apparatus according to the present invention, which has been made to solve the above problems,
a) an ionization chamber;
b) an analyte sample supply pipe for delivering a liquid analyte sample to the ionization chamber;
c) an ionization promoting gas supply pipe for feeding a gas that promotes ionization of the sample to be analyzed;
d) a standard sample gas supply unit for supplying a standard sample gas generated by vaporizing a liquid standard sample to the ionization promoting gas supply pipe;
It is characterized by providing.

  As the ionization promoting gas supply pipe, for example, a nebulization gas supply pipe of an ESI ionization probe or an APCI probe can be used. In addition, a dry gas supply pipe that supplies a dry gas that promotes vaporization and ionization by drying the gas of the sample to be analyzed in the ionization apparatus may be used as the ionization promoting gas supply pipe.

  In the ionization apparatus according to the present invention, instead of providing an ionization probe independently for the standard sample, the standard sample vaporized through the existing ionization promoting gas supply pipe is introduced into the ionization chamber. Therefore, the liquid analysis target sample and the liquid standard sample can be introduced with a simple configuration.

The ionization promoting gas supply pipe is preferably a dry gas supply pipe.
The dry gas is a gas for promoting the ionization and vaporization of the liquid sample, and is usually fed by heating. Therefore, the drying gas supply pipe is provided with a drying gas heating mechanism and a temperature control mechanism. Therefore, by using the dry gas supply pipe as the ionization promoting gas supply pipe, the standard sample having a high boiling point can be supplied to the ionization chamber without condensing.

  The standard sample gas supply unit preferably includes a supply switching unit that switches between supply and non-supply of the standard sample gas. Thus, the standard sample gas can be introduced into the ionization chamber at a desired timing and used for analysis. As the supply switching unit, for example, a switching valve provided at a connection portion between the ionization promoting gas supply pipe and the standard gas supply unit can be used.

  By using the ionization apparatus according to the present invention, it is possible to introduce a liquid analysis target sample and a liquid standard sample with a simple configuration.

The schematic block diagram of a liquid chromatograph mass spectrometer. 1 is a schematic configuration diagram of an ionization apparatus according to Embodiment 1. FIG. FIG. 3 is a schematic configuration diagram of an ionization apparatus according to Embodiment 2.

  An ionization apparatus according to the present invention is provided as an interface unit between a liquid chromatograph unit (LC) and a mass spectrometer unit (MS), for example, in a liquid chromatograph mass spectrometer (LCMS) described below. It is used as an apparatus for ionizing sample components separated temporally in a column and supplying them to MS.

  FIG. 1 is a schematic configuration diagram of an LCMS provided with an ionization apparatus of an embodiment described later. The sample to be analyzed introduced from the injector 13 of the LC 10 is introduced into the column 14 along the flow of the mobile phase supplied from the mobile phase vessel 11 by the pump 12 at a constant speed, and the components are separated. The eluate (mixed liquid of the separated sample component and LC mobile phase) from the column 14 is fed to the ionization probe 22 of the ionization apparatus 20 and sprayed into the ionization chamber 21 from the tip thereof to be ionized. Fine droplets containing the generated ions are transported to the MS 30 through a thin tube (desolvent tube) 23 heated by a heater (not shown).

  The MS 30 is discharged from the ion transport optical system 31 that converges ions introduced from the desolvation tube 23 and sends them to the subsequent stage, a three-dimensional quadrupole ion trap 32 that accumulates ions, and the ion trap 32. A time-of-flight mass analyzer (TOFMS) 33 that separates the various ions according to their time of flight, and a detector 34 that detects ions separated by the TOFMS 33.

Examples of the ionization apparatus according to the present invention will be described below.
FIG. 2 is a schematic configuration diagram of the ionization apparatus 20 according to the first embodiment.
This ionization apparatus 20 is an apparatus (ESI source) that ionizes sample components contained in the eluate (mixed liquid of separated sample components and LC mobile phase) from the column 14 of the LC 10 by an ESI (electrospray ionization) method. And an analysis target sample supply pipe 221 for feeding the eluate from the column 14 and a nebulization gas supply pipe 222 provided so as to cover the outer periphery of the analysis target sample supply pipe 221, with a few kV at the tip. An ESI probe 22 to which a DC high voltage is applied is provided. A nebulization gas supply line 50 for supplying a nebulization gas such as nitrogen gas is connected to the nebulization gas supply pipe 222.

  The eluate introduced into the analysis target sample supply pipe 221 of the ESI probe 22 is charged by a high voltage when reaching the tip of the supply pipe 221, and the nebulization gas discharged from the nebulization gas supply pipe 222 is sprayed to form a mist. Is released into the ionization chamber 21 and ionized.

  In the ionization apparatus 20 of the present embodiment, a standard sample gas supply line 40 is connected to a nebulization gas supply line 50 via a valve 43, and a standard sample container 41 heated by a heater 42 is disposed at the end. Has been. When the valve 43 is opened, the standard sample vaporized in the standard sample container 41 heated by the heater 42 is introduced into the nebulization gas supply line 50 through the standard sample gas supply line 40 and supplied to the nebulization gas supply pipe 222 together with the nebulization gas. Is done. The standard sample gas that has reached the tip of the nebulization gas supply pipe 222 is ionized by the high DC voltage applied to the tip of the ESI probe 22 and released into the ionization chamber 21.

  In the ionization apparatus 20 of the present embodiment, when a standard sample is introduced as an internal standard, the valve 43 is always opened, and the sample components eluted from the column 14 of the LC 10 and the standard sample are simultaneously ionized and sent to the MS 30. On the other hand, when introducing a standard sample as an external standard, the valve 43 is closed while the sample component is being eluted from the column 14 of the LC 10, and the valve 43 is opened while the sample component is not being eluted. The sample component and the standard sample are ionized and detected at different timings.

  In the ionization apparatus 20 of the first embodiment, the ionization probe for ionizing each of the sample components and the standard sample is not provided as in the prior art, but vaporization is performed through the nebulization gas supply line 50 and the nebulization gas supply pipe 222 included in the ESI source. Introduce a standard sample. Therefore, sample components and standard samples can be efficiently introduced with a simple configuration.

Next, the ionization apparatus of Example 2 is demonstrated.
FIG. 3 is a schematic configuration diagram of an ionization apparatus according to the second embodiment. The same components as those of the ionization apparatus of Embodiment 1 are denoted by the same reference numerals, and description thereof will be omitted as appropriate.

  The ionization apparatus of Example 2 is an apparatus (APCI source) that ionizes the eluate (mixed liquid of separated sample components and LC mobile phase) from the column 14 of the LC 10 by the APCI (atmospheric pressure chemical ionization) method. And an APCI probe 24 having an analysis target sample supply pipe 241 and a nebulization gas supply pipe 242, and a corona needle 25 disposed in the vicinity of the tip of the APCI probe 24. A high voltage is supplied to the corona needle 25 from a power source (not shown). The sample components in the eluate are ionized by exchanging charges with the mobile phase ionized by corona discharge in the corona needle 25.

In addition, the ionization apparatus according to the second embodiment includes a dry gas supply pipe 26 that supplies a dry gas (for example, nitrogen gas) heated to several hundred degrees C. near the tip of the APCI probe 22.
A nebulization gas supply line 50 for supplying nebulization gas is connected to the nebulization gas supply pipe 222, and a dry gas supply line 60 for supplying dry gas is connected to the dry gas supply pipe 26. The drying gas supply pipe 26 and the drying gas supply line 60 are provided with a temperature control mechanism (not shown) for maintaining the temperature of the heated drying gas.

  In the ionization apparatus of Embodiment 2, the standard sample gas supply line 40 is connected to the dry gas supply line 60 via the valve 43, and the standard sample container 41 is disposed at the tip. Similarly to the first embodiment, the standard sample container 41 is provided with a heater 42 for heating the container 41. When the valve 43 is opened, the standard sample vaporized through the standard sample gas supply line 40 is introduced into the dry gas supply line 60 and supplied to the dry gas supply pipe 26 together with the dry gas. The standard sample gas discharged from the dry gas supply pipe 26 is ionized by corona discharge in the corona needle 25 located near the tip thereof.

  In the ionization apparatus of Example 2, the standard sample is introduced using the dry gas supply line 60 and the dry gas supply pipe 26 that supply the dry gas heated to several hundred degrees Celsius. Therefore, even when the boiling point of the standard sample is high, the standard sample can be supplied to the ionization chamber 21 without being condensed and ionized.

  The above-described embodiment is an example, and can be appropriately changed in accordance with the gist of the present invention. For example, a standard sample vaporized from a dry gas supply pipe may be supplied to an ESI source equipped with a dry gas supply pipe, or a vaporized standard sample may be supplied from a nebulization gas supply pipe at an APCI source. In the second embodiment, the dry gas supply pipe 26 is arranged so as to supply the heated dry gas at the outer peripheral portion of the APCI probe 24. However, the heated dry gas (and the vaporized standard sample) is supplied to It can also be configured to supply in the vicinity.

DESCRIPTION OF SYMBOLS 10 ... Liquid chromatograph part 11 ... Mobile phase container 12 ... Pump 13 ... Injector 14 ... Column 20 ... Ionizer 21 ... Ionization chamber 22, 24 ... Ionization probe 221, 241 ... Analyte sample supply pipe 222, 242 ... Nebulization gas supply pipe 23 ... Desolvation tube 25 ... Corona needle 26 ... Dry gas supply tube 30 ... Mass analyzer 31 ... Ion transport optical system 32 ... Ion trap 33 ... TOFMS
34 ... Detector 40 ... Standard sample gas supply line 41 ... Standard sample container 42 ... Heater 43 ... Valve 50 ... Nebulization gas supply line 60 ... Dry gas supply line

Claims (6)

a) an ionization chamber;
b) an analyte sample supply pipe for delivering a liquid analyte sample to the ionization chamber;
c) an ionization promoting gas supply pipe for feeding a gas that promotes ionization of the sample to be analyzed;
d) a standard sample gas supply unit for supplying a standard sample gas generated by vaporizing a liquid standard sample to the ionization promoting gas supply pipe;
An ionization apparatus comprising:   The ionization apparatus according to claim 1, wherein the ionization promoting gas supply pipe is a dry gas supply pipe.   The ionization apparatus according to claim 1, wherein the standard sample gas supply unit includes a supply switching unit that switches between supply and non-supply of the standard sample gas.   4. The ionization apparatus according to claim 1, wherein the liquid analysis target sample is sprayed from the tip of the analysis target sample supply pipe into the ionization chamber. 5.   The ionization apparatus according to claim 1, wherein the gas that promotes ionization of the analysis target sample is a gas that is inert to the analysis target sample.   further,
  e) Standard sample heating section for vaporizing the liquid standard sample
  The ionization apparatus according to any one of claims 1 to 5, further comprising:

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