Radiant energy – Ionic separation or analysis – With sample supply means
Reexamination Certificate
2000-08-23
2003-06-24
Lee, John R. (Department: 2881)
Radiant energy
Ionic separation or analysis
With sample supply means
C250S281000, C250S287000, C250S282000
Reexamination Certificate
active
06583407
ABSTRACT:
TECHNICAL FIELD
This invention relates generally to mass spectrometry and particularly to use of a dielectric conduit in combination with means for altering the motion of an ion to effect selective ion delivery to a mass analyzer.
BACKGROUND
Mass spectrometers have been shown to be particularly useful for analysis of liquid or gaseous samples, and have been coupled with gas chromatographs in gas chromatography (“GC”) or liquid chromatographs in liquid chromatography (“LC”), for analysis of substances having a wide range of properties. Considerable interest has developed in the pharmaceutical and medical diagnostic industries in employing mass spectrometers to analyze batch samples that contain defined analytes. Typically, the sources of the samples are biological fluids or crude extracts that contain significant interfering components to analysis. Therefore, sample treatment for removal of these confounding components constitutes a significant proportion of the cost of analysis. Efforts, therefore, have been directed toward reducing the extent of sample treatment prior to introduction into a mass spectrometer. For instance, tandem mass spectrometry (“MS/MS”) has been used to reduce the need for sample preparation during a simple target compound analysis. However, MS/MS systems are significantly more expensive than single MS systems. Therefore, it would be desirable to provide a method and/or apparatus that allows for inexpensive mass filtration in a MS system yet allows for improved and efficient analysis of specific target compounds.
Mass spectrometers operate by ionizing a sample and directing the ionized sample to a mass analyzer. There are many methods by which a sample may be ionized. For example, mass spectrometers employing atmospheric pressure ionization (“API”) techniques can be particularly useful for obtaining mass spectra from liquid samples, and MS systems employing such ion sources are frequently used in conjunction with high performance liquid chromatography (“HPLC”). Combined HPLC/MS systems are commonly used for analysis of polar and ionic substances, including biomolecular species. In API techniques, a liquid sample containing a mobile phase (e.g., solvent) and analytes is introduced into an ionization chamber and there converted to a charged dispersion or aerosol of fine droplets from which ions emerge as the liquid evaporates and the droplets shrink in size. The conversion of liquid to spray or aerosol can be accomplished by any of a variety of techniques. Evaporation of the liquid can be assisted, for example, by passing a flow of warm gas (“drying gas”) through the cloud of droplets.
In mass spectrometers, an interface may be provided between the ion source and the mass analyzer. In the API technique, a liquid sample is introduced into an ionization chamber that is at a relatively high pressure, e.g., at or near atmospheric pressure. Once ionized, the sample is conveyed through the interface to the mass analyzer. Typically, the mass analyzer is disposed in an enclosure at high vacuum or a very low pressure. A conduit having a lengthwise bore there through may serve as the interface for the ions. One end of the conduit opens into the ionization chamber, and the other end of the conduit opens into the enclosure containing the mass analyzer. As a result, a gas stream flows through the bore of the conduit from the ionization chamber to the enclosure containing the mass analyzer.
Various mass spectrometers employing a conduit interface between an API ion source and the mass analyzer have been described, for example, in U.S. Pat. No. 5,838,003 to Bertsch et al. relating to electrospray ionization (“ESI”), and U.S. Pat. No. 5,736,741 to Bertsch et al. relating to ESI and atmospheric pressure chemical ionization (“APCI”), U.S. Pat. No. 5,726,447 to Aisawa et al. relating to corona discharge ionization. None of these techniques and interfaces provides for mass selectivity or separation of components in a complex matrix.
Dielectric conduits are a means for providing direction and guidance of gas flow. Mass spectrometers often employ dielectric conduits in combination with electrodes disposed at each end of the conduit, wherein the electrodes are connected to a source of electrical potential. See, for example, U.S. Pat. No. 4,542,293 to Fenn et al. In conventional operation of such an apparatus, the electrode at the upstream end of the capillary, i.e., the end in the ion source, is held at a high electrical potential (typically in the range −3000 V to −5000 V for operation in a “positive ion” mode; the polarity is reversed for operation in a “negative ion” mode). The electrode at the downstream end of the capillary, i.e., the end in the vacuum chamber containing the mass analyzer, is held at a lower and oppositely charged electrical potential (typically in the range +50 V to +400 V for operation in a “positive ion” mode). As the gas stream flows through the bore of the conduit, the gas stream tends to entrain and carry ions generated in the ion source toward the mass analyzer. However, the opposing electric field generated by the electrodes hinders ion movement toward the mass analyzer. In conventional use of the conduit, the effect of the gas flow dominates over that of the opposing electric field, and the ion is moved from the entrance toward the exit of the conduit.
Techniques have been proposed for separating ions according to their mobility by a combination of gas flow and electric field. In ion mobility spectrometry (“IMS”), an accelerating electrical potential is employed to move ions with a drift velocity through a gas, in some cases against a counter current gas flow. In IMS, ions having higher mobility have higher drift velocities. In one approach as described in U.S. Pat. No. 5,936,242 to De La Mora et al., a laminar gas flow is established along an axis within an analytical chamber and an electric field is applied along a transverse axis to separate ions in a complex mixture according to their mobility. Although this technique provides separation of ions according to mobility, it provides no further analysis of the ions.
There is a need for a method and apparatus of mass selection that takes advantage of using a dielectric conduit and which does not suffer from the inherent limitation of being dependent on the polarity of the analyte ion. The invention addresses this need.
OBJECTS AND SUMMARY OF THE INVENTION
Accordingly, it is an object of the present invention to overcome the above-mentioned limitations of the prior art by providing a new and effective method for selectively delivering ions to a mass analyzer operating in a vacuum region through a dielectric conduit. Selective delivery of an ion is effected by altering the motion of the ion in a manner that does not substantially depend on the polarity of the ion.
It is still another object of the invention to provide such an apparatus that comprises a dielectric conduit and a velocity altering means for altering the velocity of the ion in the conduit in a manner that does not substantially depend on the polarity of the ion.
It is a further object of the invention to provide such an apparatus wherein the velocity altering means involves a gas temperature change or ion trapping in an alternating electric field.
Additional objects, advantages and novel features of the invention will be set forth in part in the description which follows, and in part will become apparent to those skilled in the art upon examination, or may be learned by practice of the invention.
Accordingly, in one general aspect, the invention features a method for selectively delivering ions to a mass analyzer operating in a vacuum region. In this method, a dielectric conduit is provided having an axial bore originating in an inlet opening in communication with an ion source and terminating in an exit opening within the vacuum region. An ion of either positive or negative polarity is entrained by a gas stream and exhibits a drift velocity through the conduit from the inlet opening toward the exit opening. The drif
Fischer Steven M.
Russ, IV Charles W.
Agilent Technologie,s Inc.
Fernandez K
Joyce Timothy H.
Lee John R.
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