Radiant energy – Ionic separation or analysis – With sample supply means
Reexamination Certificate
2003-05-08
2004-09-21
Lee, John R. (Department: 2881)
Radiant energy
Ionic separation or analysis
With sample supply means
C250S281000, C250S297000, C250S42300F, C250S424000, C356S246000
Reexamination Certificate
active
06794646
ABSTRACT:
FIELD OF THE INVENTION
The present invention generally relates to atmospheric pressure chemical ionization (APCI) in preparation for mass analysis, as is performed in mass spectrometry (MS). More particularly, the present invention relates to an apparatus and method for improving ionization of sample molecules in an APCI source.
BACKGROUND OF THE INVENTION
Mass spectrometry is a highly sensitive method of molecular analysis. In general, mass spectrometry is a technique that produces a mass spectrum by converting the components of a sample into rapidly moving gaseous ions, and resolving the ions on the basis of their mass-to-charge (m/e or m/z) ratios. The mass spectrum can be expressed as a plot of relative abundances of charged components as a function of mass, and thus can be used to characterize a population of ions based on their mass distribution. Mass spectrometry is often performed to determine molecular weight, molecular formula, structural identification, and the presence of isotopes. The apparatus provided for implementing mass spectrometry, i.e., a mass spectrometer (MS) system, typically consists of a sample inlet system, an ion source, a mass analyzer, and an ion detection system, as well as the components necessary for carrying out signal processing and readout tasks. Many of these functional components of the mass spectrometer, particularly the mass analyzer, are maintained at a low pressure by means of a vacuum system. The ion source converts the components of a sample into charged particles. The negative particles are ordinarily removed from the process flow in positive ion mode when analyzing positive particles. In negative ion mode the positive ions are removed. The mass analyzer disperses the charged particles based on their respective masses, and then focuses the ions on the detector. The ion currents produced by the detector are then amplified and recorded as a function of spectral scan time. The designs of the components of the mass spectrometer, and the principles by which they operate, can vary considerably. Thus, components of differing designs have distinct advantages and disadvantages when compared to each other, and the desirability of any one design can depend on, among other factors, the nature of the sample to be analyzed.
The sample inlet system employed for mass spectrometry can be chromatographic. That is, the effluent from a chromatographic column can be utilized as the sample source for the MS system. The mass spectrometer in such cases can be considered as serving as the detector for the chromatographic apparatus. Such an arrangement is commercially available in systems in which a gas chromatographic (GC) apparatus is directly coupled to the mass spectrometer (GC/MS systems), or a liquid chromatographic (LC) apparatus is directly coupled to the mass spectrometer (LC/MS systems). These combined systems are particularly useful for deriving complex spectra from mixtures, as it is known that mass spectrometers alone are more or less limited to handling pure compounds and relatively simple mixtures.
An ion source commonly serving as the interface between an LC apparatus and the mass spectrometer operates according to the principle of atmospheric pressure ionization (API), a soft ionization technique in which ionization of a sample occurs outside of the vacuum region or regions associated with the mass spectrometer. An increasingly popular type of API technique is atmospheric pressure chemical ionization (APCI or APcI). Simply stated, APCI is a means for ionizing samples (e.g., analyte molecules) dissolved in a liquid (e.g., an excess of mobile-phase molecules such as solvent). The sample-containing liquid emitted from the LC apparatus is pneumatically nebulized into a fine dispersion of numerous small droplets, typically below 100 microns in diameter. Heat is applied to the droplets to vaporize the liquid and sample matrix. This nebulization/vaporization process, however, is gentle enough to preserve the molecular identity of the sample constituents at this stage. The resulting gas/vapor is subsequently passed into a chamber where electrons emitted from an electrode generate a low-current corona discharge in the ambient, atmospheric-pressure environment consisting of, for example, a background gas such as nitrogen or air. The corona discharge ionizes the mobile-phase molecules to form an energetic chemical reagent gas plasma. In the corona discharge, ion-molecule reactions occur between the charge-neutral sample and the reagent ions formed in the primary discharge. The dominant mechanisms for the ion-molecule reactions are collisions between the reagent ions and the sample molecules, enabled by the relatively high (atmospheric) pressure environment, and charge transfer reactions. The ion-molecule reactions cause the sample to become charged, and the resulting stable sample ions are passed through an opening in a vacuum chamber into the mass analyzer of the mass spectrometer for mass analysis. Unlike the API technique of electrospray ionization (ES), in which multiple-charged molecular ions [M+nH]
n+
are produced, in most applications APCI produces only single-charged molecular ions typically in the form of [M+H]
+
or [M−H]
−
as a result of protonation or deprotonation.
FIG. 1
illustrates an example of a conventional APCI source, generally designated
10
, utilized in, for example, an LC/MS system. In general terms, APCI source
10
comprises a sample introduction and nebulizing section, generally designated
20
; a vaporization section, generally designated
30
; an ionization section, generally designated
40
; and an ion inlet section, generally designated
50
. Ion inlet section
50
includes a front plate
52
having an ion inlet aperture
53
through which ionized products are directed into the mass analyzer of the mass spectrometer. For simplicity, the mass analyzer and other typical components of the mass spectrometer, such as its ion detection, signal processing and readout systems, are collectively designated as MS in FIG.
1
.
Nebulizing section
20
comprises a capillary tube
23
, typically a metal capillary, that serves as the sample inlet system of mass spectrometer MS. Capillary tube
23
conducts the LC column flow from a liquid chromatographic apparatus LC into vaporization section
30
. In addition, a length of conduit
27
for directing a suitable inert nebulizing gas such as nitrogen into vaporization section
30
is coaxially disposed about capillary tube
23
. Vaporization section
30
of APCI source
10
generally includes a vaporizing tube
33
and a heater
35
enclosed in a coaxial housing (not shown), and a conduit
37
for directing a suitable inert vaporizing (“auxiliary” or “make-up”) gas such as nitrogen into vaporizing tube
33
. Heater
35
is situated so as to ensure sufficient thermal contact with the wall of vaporizing tube
33
. The wall of vaporizing tube
33
is typically quartz, and can operate at temperatures ranging from about 200-600° C. to rapidly vaporize effluent from capillary tube
23
. While the thermal effect on typical samples is minimal, such a technique is not compatible with very thermally labile molecules. Capillary tube
23
is disposed along the central axis of vaporizing tube
33
and terminates at a capillary tube outlet
23
A within vaporizing tube
33
. A portion of vaporizing gas conduit
37
is coaxially disposed about nebulizing gas conduit
27
as well as capillary tube
23
.
Ionization section
40
of APCI source
10
generally includes an ionization chamber
42
defining an enclosed volume into which a corona needle or pin
43
is inserted. Capillary tube
23
and conduits
27
and
37
are often integrated in a manifold structure which, along with vaporization section
30
, is often structured as a probe that is mounted to ionization chamber
42
. Corona needle
43
typically operates at about 5-10 kV and 1-5 mA to strike a low-current corona discharge or electron cloud
45
within ionization section
40
. This
Schachterle Steven
Tong Roger
Wells Gregory
Fishman Bella
Gloekler David
Lee John R.
Leybouren James J.
Varian Inc.
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