Radiant energy – Ionic separation or analysis – With sample supply means
Reexamination Certificate
2001-09-20
2003-11-18
Lee, John R. (Department: 2881)
Radiant energy
Ionic separation or analysis
With sample supply means
Reexamination Certificate
active
06649908
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to an interface for transferring fluid streams into a mass spectrometer system. In particular, the present invention relates to a transfer capillary that allows multiple fluid streams to be monitored by a single mass analyzer.
2. Description of the Background
The combination of mass spectrometry (MS) and liquid chromatography (LC) is one of the most powerful methods available for analysis of chemical compounds and is widely used in chemical, environmental, pharmaceutical, and biological research. In a liquid chromatograph, a sample containing a mixture of compounds is pumped through a separation column in a liquid mobile phase. The components of the sample mixture are separated as they pass through the column, and the separated components emerge from the column one after another. A detector is connected to the fluid stream at the column exit to detect the components as they leave the column.
In a mass spectrometer, compounds are positively or negatively charged in an ionization source. The masses of the resultant ions are determined in a vacuum by a mass analyzer that measures the mass/charge (m/z) ratio of the ions. When used as a detector for a liquid chromatograph, a mass spectrometer can provide information on the molecular weight and chemical structure of each compound separated by the chromatograph, allowing identification of each of the components of the mixture.
FIG. 1
illustrates a conventional LC/MS instrument
100
. The mass spectrometer
105
contains a special interface
107
to connect the MS
105
to the LC
110
. Interface
107
is required because compounds exiting the LC column
112
are dissolved in a liquid solvent and are at atmospheric pressure, whereas the mass analyzer is operated under high vacuum and requires the compounds to be in the gas phase. The interface
107
includes an atmospheric pressure ionization chamber
120
, a first stage vacuum chamber
123
, and a second stage vacuum chamber
127
. The first stage vacuum chamber
123
is typically held at a pressure around two orders of magnitude less than the atmospheric pressure chamber
120
, and the second stage vacuum chamber
127
is typically held at a pressure two to four orders of magnitude less than the first stage chamber
123
. Effluent leaving column
112
enters the atmospheric pressure chamber
120
through sprayer
130
, which nebulizes and ionizes compounds as they exit the column.
Ions leaving sprayer
130
are directed or, depending on the orientation of sprayer
130
, attracted toward an ion transfer capillary
132
, which is positioned between the atmospheric pressure chamber
120
and a first stage vacuum chamber
123
. Ions that enter the transfer capillary
132
are swept into the first vacuum chamber
123
in a stream of gas due to the pressure difference between chambers
120
and
123
. The ions leave the transfer capillary
132
and pass through skimmer
140
or other equipment within the second vacuum
127
to focus and direct the ions to the mass analyzer
115
. Mass analyzer
115
determines the m/z ratio of each ion.
In many instances, it is desirable to be able to use a singe mass spectrometer to analyze multiple inlet streams coming from multiple LC columns or other liquid phase sample sources. Mass spectrometers are typically more expensive than liquid chromatographs, and thus it is cheaper to use a single mass spectrometer as a detector for multiple LC systems. Furthermore, particularly if the mass analyzer is a time-of-flight instrument, mass spectral acquisition is much faster than LC separation. Therefore, it is possible for multiple LC systems, or multiple parallel streams from a single LC system, to be monitored by a single mass spectrometer effectively simultaneously. This approach is referred to as multiplexing analysis.
Multiplexing analysis for LC/MS has been accomplished by altering interface
107
to allow ions generated from each of the multiple inlet streams to sequentially enter the transfer capillary
132
. Designs for such interfaces are described, for example, in Bateman et al., “Multiple LC/MS: Parallel and Simultaneous Analyses of Liquid Streams by LC/TOF Mass Spectrometry Using a Novel Eight-Way Interface,” Proceedings of the 47
th
ASMS Conference on Mass Spectrometry and Allied Topics, Jun. 13-18, 1999, Dallas Tex., pp 2216-2217; Analytical Chemistry, 2000, volume 72, p. 22A; and Analytical Chemistry, 2000, volume 72, pp. 20-24. These interfaces may suffer from problems such as cross-contamination and possible cross-reaction between samples from different fluid streams; mechanical complexity that causes the interface to be expensive and fragile; and slow switching between fluid streams that prevents the effectively simultaneous monitoring of multiple streams.
SUMMARY
The embodiments of the present invention provide a transfer capillary and mass spectrometer interface that allow samples from multiple fluid streams to be introduced into a single mass analyzer and multiplexing analysis to be conducted. Switching between ionized samples generated by the different fluid streams is accomplished by the transfer capillary, which allows for fast switching between the fluid streams and reduces the possibility of cross-contamination between ionized samples.
The mass spectrometer interface includes a first chamber through which the multiple fluid streams enter and a second chamber that is in fluid communication with a mass analyzer. The interface includes ionizers connected to the multiple fluid streams. The ionizers generate ionized sample from each fluid stream within the first chamber and direct the ionized sample toward the inlets of a transfer capillary.
The transfer capillary forms a passageway between the first and second chambers. In one embodiment the transfer capillary has two or more inlets, each connected to inlet channels. The inlet channels merge into a single outlet channel that is connected to an outlet. The inlets of the transfer capillary are positioned within a first chamber and the outlet positioned within a second chamber. In another embodiment the transfer capillary has multiple channels, and each channel has an inlet located within the first chamber and an outlet located within the second chamber.
The transfer capillary includes a multiplex selector that allows ions to flow through a selected subset of the channels while retarding the flow of ions through the non-selected channels. The multiplex selector is capable of changing which of the channels are in the selected subset through which ions are allowed to flow. The multiplex selector may be a mechanical gate placed across the channels, a set of conductors that electrostatically control the ion flow, a skimmer with multiple openings surrounded by conductors which electrostatically control which skimmer opening is active, or a pair of electrodes placed between the channel outlets and a skimmer which electrostatically control which stream is directed into the skimmer opening.
The second chamber of the interface is held at a lower pressure than the first chamber. Ions pass through the transfer capillary under the control of the multiplex selector into the second chamber and on into the mass analyzer. The interface may also include a controller for synchronizing the operation of the mass analyzer and the multiplex selector.
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Richard D. Ol
Apffel, Jr. James A.
Doherty Thomas P.
Yin Hongfeng
Agilent Technologie,s Inc.
Johnston Phillip
Lee John R.
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