Patent Application
20070278398
a) is longitudinal cross-sectional schematic diagram of a prior art FAIMS instrument having cylindrical electrodes.
Embodiments described herein provide a FAIMS apparatus with enhanced ion focusing and a method of using the apparatus for analysis of ionized samples. In one embodiment the apparatus has two cylindrical electrodes which include a hollow outer electrode and an inner electrode positioned in the central region of the outer electrode. The axes of cylindrical inner and outer electrodes are parallel but not coincident. Such positioning of the electrodes forms a non-uniform gap between the electrodes. Namely, the gap between the cylinders is narrower on one side of the apparatus and wider on the other side. An ion entrance aperture is placed near the wide gap region. The placement of the ion entrance aperture proximate the wide gap region may facilitate collection of ions from an ion source. An ion exit aperture is positioned proximate the narrow gap region. When an asymmetric waveform is applied to one electrode an asymmetric radio frequency field (e.g., a “dispersion field” or “field”) is formed in the gap. To transmit a selected ion species through the gap from the ion entrance aperture to the ion exit aperture in the presence of the dispersion field, a compensation voltage is applied to the other electrode which creates a compensation field in the gap. As ions propagate from the entrance aperture into the narrow gap region to the exit aperture, the ions experience an incremental increase in the dispersion and the compensation fields as they travel. The incremental increase in the dispersion and compensation fields serves to focus the ions into a narrowed ion beam as they are transmitted to the exit aperture.
The enhanced focusing of the apparatus enhances the sensitivity of the FAIMS apparatus. The apparatus and method have many applications and are particularly useful in applications in which a FAIMS apparatus is interfaced to a mass spectrometer or other second stage analyzer.
Cross-sectional schematic diagrams of prior art FAIMS spectrometers with cylindrical electrodes are shown in
Embodiments described herein provide an apparatus and method for enhanced focusing of ions in FAIMS. Enhanced focusing may improve sensitivity generally and is also useful if a second stage of analysis such as a second stage FAIMS apparatus, or a mass spectrometer, for example, is used in combination with the apparatus. When a second stage of analysis is employed, the apparatus not only provides for enhancing sensitivity, but also for facilitating efficient transfer of ions to the second analyzer. The enhanced ion focusing may be achieved at a manufacturing cost comparable to a conventional FAIMS instrument.
In the embodiment shown in
A non-uniform or asymmetrical gap 40 is formed between the inner electrode external surface 30 and the outer electrodes inner surface 32. As shown in
The apparatus 20 further includes an ion source 68 which provides ions that are transferred into the gap 40 (i.e., the ion channel) via the entrance aperture 44. Transfer of ions generated in the ion source 68 into the ion channel 40 is facilitated by applying a potential difference between the ion source 68 and one of the cylindrical electrodes 22. 24. Optionally, a lens system 50 may be used to direct ions from the ion source 68 into the entrance aperture 44 and the gap 40.
The carrier gas flows in the gap 40 in a direction from the entrance aperture 44 to exit aperture 46. The carrier gas is the gas in which the ion mobility is to be measured. The carrier gas may be admitted via a conventional valving system (not shown) or by any other system that permits reproducible regulation of the flow of the carrier gas. The carrier gas may be introduced at room temperature. Alternatively, in some embodiments the carrier gas may be heated prior to admission to the gap 40.
Carrier gases suitable for use in a conventional FAIMS system are likewise suitable for use in the enhanced focusing FAIMS system. For example, carbon dioxide, nitrogen, oxygen or mixtures of gases may be used. Defined identity of the gas composition as well as an apparatus for regulating and measuring flow rate of the carrier gas are desirable as such factors and parameters facilitate reproducibility of analyses.
The apparatus 20 further comprises a detection system 52 positioned adjacent exit aperture 46. The detection system 52 includes provision for detecting ions passing through gap 40 and exit aperture 46. The detection system 52 may directly detect ions and/or transfer ions for an additional stage of analysis. Suitable detectors for detecting ions include but are not limited to Faraday cups, Faraday cups with amplification systems, photomultipliers, diode arrays, and scintillation detectors, for example. Optionally, the detection system may collect ions for an additional stage of analysis such as a second stage of FAIMS or mass spectrometry. The subsequent analyses may provide further structural characterization of selected ion species and/or quantitative data, for example.
Referring again to
The apparatus 20 further comprises an outer electrode contact 60. The outer electrode contact 60 provides for the application of a compensation voltage from a compensation voltage source 54 to the outer electrode 24. The compensation voltage source 54 may be a power supply, for example. The compensation voltage should be controllable in magnitude and duration. Adjustment of the magnitude of the compensation voltage permits selection of the species of ion to be passed through the gap 40 from the entrance aperture 44 to the exit aperture 46. The compensation voltage can be set to pass a selected ion species through the gap 40 for a determined period of time. Alternatively, the compensation voltage may be adjusted in a predetermined systemic manner (scanned) to provide for sequential detection of a plurality of ion species (i.e., ion species from various components of the sample).
Although a cylindrical electrode embodiment of the apparatus has been described in detail herein, it is not required that the geometry of the electrodes be cylindrical or that both electrodes have the same shape. For example, any geometry of inner and outer electrodes may be used so long as the gap between the electrodes is wider at the ion entrance than in the region near the ion exit. Furthermore, the electrodes do not have to have the same shape. For example, a combination of cylindrical inner electrode and elliptical outer electrode or visa versa could be used so long as the gap between the electrodes was wider proximate the ion entrance than proximate the ion exit.
As to construction, the electrodes may be constructed from a conductive material or non-conductive material with conductive plating or some combination thereof. The electrodes can be made as an integrated structure so long as the conductive region that forms one electrode is electrically isolated from the conductive region that forms the other electrode. Micro-machining may be employed to facilitate construction of the electrically isolated electrodes.
To analyze a sample, a plurality of ion species from the ion source are introduced into the gap 40 via the entrance aperture 44 (e.g., into the region between the inner electrode 22 and outer electrode 24). An ion species is an ion with recognizable distinctive or characteristic features of composition and/or charge.
Ions may be derived from a variety of ion sources 68, including but not limited to ionization of a sample in a device such as an electrospray ionization source, an atmospheric pressure chemical ionization source (APCI), an atmospheric pressure ionization source (API), an atmospheric pressure MALDI (matrix assisted laser desorption ionization) source, a discharge source, and a radioactive ionization source. The sample may be introduced into the ion source 68 by direct probe or infusion pump, for example. Alternatively, the sample may be introduced into the ion source 68 as effluent from a gas chromatograph, a liquid chromatograph or capillary electrophoresis or as ions transported in a gas stream from an environmental or process monitoring sample.
Typically the ions introduced into the FAIMS apparatus 20 are a mixture of ion species. A potential differential between the ion source 68 and the inner electrode 22 facilitates transfer of ions. The plurality of ion species are introduced into a stream of carrier gas which is admitted to the ion channel or gap 40. Typically, nitrogen, oxygen or carbon dioxide is used as the carrier gas. However, other gases or gas mixtures may be used. Typically, a gas with a low propensity for chemical reaction with the ions of interest is preferred. As the ions travel in the stream of carrier gas in the gap 40 from the entrance aperture 44 to the exit aperture 46, the asymmetrical waveform generator 56 applies an asymmetric high voltage waveform to the cylindrical inner electrode 22 via contact 58, generating a time dependant high field (e.g., typically greater than 5000 V/cm). The high field causes ions traveling in the gap 40 to drift towards the opposite electrode (e.g., outer electrode 24). Absent other forces, ions will collide with the outer electrode 24 and fail to pass through the gap 40 to exit aperture 46.
The degree of drift depends on the mobility character of a particular ion species in the carrier gas. Ion size, chemical composition and charge are exemplary of the factors that determine the ion mobility characteristic of a specific species of ions and accordingly degree of drift. If a DC voltage (e.g., compensation voltage or CV) is applied to the electrode opposite the electrode to which the asymmetric waveform is applied (e.g., electrode 24 in the example of
The selected ion species travels to the exit aperture 46 and is transferred to the detector system 52. The detector system may directly collect data or transfer the ions to a second stage of analysis such as another stage of ion mobility spectrometry or mass spectrometry. The detector system 52 is positioned to receive the focused beam of ions that passes though the exit aperture 46.
Typically, when a beam of a mixture of ion species is introduced into the FAIMS spectrometer from the ion source 68, either the compensation voltage is set to transmit a selected ion species of interest and monitor that ion species for a period of time or the compensation voltage is varied with time (scanned) so that ions of different compounds sequentially pass through the gap 40 between the inner and outer cylindrical electrodes 22, 24 to the detector system 52. In principle, for a given compensation voltage only a single ion species with a specific particular ion mobility characteristic can pass through the gap 40 and be detected at a given time. Other species of ions in the sample fail to pass through the gap and become discharged. As indicated, the compensation voltage may be adjusted in a predetermined systematic manner (e.g., scanned) to provide for sequential detection of a plurality of ion species. Detecting ions sequentially yields an ion mobility spectrum as a function of compensation voltage.
The foregoing discussion discloses and describes many exemplary methods and embodiments of the present invention. As will be understood by those familiar with the art, the invention may be embodied in other specific forms without departing from the spirit or essential characteristics thereof. Accordingly, the disclosure of the present invention is intended to be illustrative, but not limiting, of the scope of the invention which is set forth in the following claims.
