Liquid chromatograph/mass spectrometer and its ionization...

Radiant energy – Ionic separation or analysis – With sample supply means

Reexamination Certificate

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C250S281000, C250S294000

Reexamination Certificate

active

06646255

ABSTRACT:

The present invention relates to a liquid chromatograph/mass spectrometer (LC/MS), and particularly to an atmospheric pressure ionization interface of an LC/MS disposed between the liquid chromatograph (LC) part and the mass spectrometer (MS) part.
BACKGROUND OF THE INVENTION
In an LC/MS, a sample liquid is separated into components by the column in the LC part, and the components, flowing out of the column at different time points, are ionized by an ionization interface and introduced into the MS part. The ionization interface includes an ionizer first to change the sample liquid to mist by means of heat, high-velocity gas flow, high voltage electric field, etc, and then to produce gaseous ions from the mist. Some widely used ionizers utilize the so-called atmospheric ionization method, such as atmospheric pressure chemical ionization (APCI) or electrospray ionization (ESI). In an APCI, for example, a nozzle connected to the outlet of the column in the LC part is disposed with its exit port directed to the inside of the ionization chamber which is maintained substantially at the atmospheric pressure, and a needle-like discharging electrode is disposed ahead of the exit port of the nozzle. The sample liquid is heated into mist at the nozzle, and the droplets of the mist are brought into reaction with the solvent ions (or buffer ions) produced by corona discharge from the discharging electrode. Thus, the sample ions are produced. In an ESI, on the other hand, a high voltage of about several kilovolts is applied to the tip of the nozzle to produce a strong non-uniform electric field there. Due to the non-uniform electric field, electric charges in the sample liquid are separated, and the Coulomb force breaks the sample liquid into mist or droplets. The solvent contained in the droplets evaporates when they contact the ambient air. Thus, the gaseous ions are produced.
With the above-described ionizer, either a positive ionization, where electrons are stripped from the sample molecules, or a negative ionization, where electrons are donated to the sample molecules, is selected depending principally on the kinds of the sample components. In the case of APCI, the optimal position of the discharging electrode to maximize the ion-producing efficiency in the positive ionization is not always the same as that in the negative ionization. Therefore, in the conventional APCI type ionizer, if either positive or negative ions are to be produced, the discharging electrode is adjusted to the position where the ion-producing efficiency is maximized for the selected ionization method. A sample, however, is often a mixture of different components: some tend to become positive ions and others tend to become negative ions. When this type of sample is to be analyzed, a design which compromises the maximum efficiency in both cases has hithertofore inevitably been chosen such that the discharging electrode is disposed at an intermediate place where the ion-producing efficiency is not optimal either for the positive or negative ionization. This design decreases the number of ions introduced into the MS part, and deteriorates the accuracy and sensitivity of the analysis.
In order to solve the above problems, the present invention proposes an LC/MS constructed to present a maximized or almost maximized ion-producing efficiency of APCI, irrespective of whether the positive or negative ions are produced.
SUMMARY OF THE INVENTION
Thus, a liquid chromatograph/mass spectrometer (LC/MS) according to the present invention includes a liquid chromatograph part for separating a sample liquid into components according to their retention times, an ionizer for changing the components to ions by an atmospheric pressure chemical ionization method, and an interface for introducing the ions into a mass spectrometer part, wherein:
the ionizer includes a sprayer and a plurality of discharging electrodes disposed ahead of the sprayer, where the sprayer sprays the separated components of the sample liquid into a space at a substantially atmospheric pressure and the plurality of electrodes ionize molecules of a mobile phase solvent; and
one discharging electrode is disposed at a position optimal to a positive ion production, and another discharging electrode is disposed at a position optimal to a negative ion production.
FIG. 5
roughly shows the relationship between the ion-producing efficiency and the distance between the tip of the discharging electrode and the central axis C of the sprayer. FIG.
5
teaches that the optimal position of the discharging electrode for the positive ion production is closer to the central axis C than that for the negative ion production. Thus, in the LC/MS according to the present invention, one (or the first) discharging electrode is disposed at the position optimal to the positive ion production, and another (or the second) discharging electrode is disposed at the position optimal to the negative ion production, and a positive or negative high voltage is equally applied to all the electrodes according to whether positive or negative ions are to be produced. The application of the voltage generates corona discharge from both the first and second discharging electrodes, where the ions produced from the mobile phase solvent molecules by the corona discharge generated from one of the two discharging electrodes dominantly contribute to the ionization of the sample molecules, depending on whether positive or negative ions are produced.
Thus, with the LC/MS according to the present invention, the ion-producing efficiency is maintained at an almost maximized level irrespective of whether positive or negative ions are produced. As a result, a greater number of ions are introduced into the MS part, enhancing the accuracy and sensitivity of the analysis. Also, the present invention omits the conventional time-consuming work of adjusting the exact position of the discharging electrode, depending on whether positive or negative ions are to be produced. Thus, the analysis work can be carried out efficiently.


REFERENCES:
patent: 4888482 (1989-12-01), Kato
patent: 5726447 (1998-03-01), Aisawa et al.
patent: 6207954 (2001-03-01), Andrien et al.

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