Battelle Memorial Institute

National Institutes of Health, a Component of the US Dept. of Health & Human Services

Alexandre A Shvartsburg

Richard Dale Smith

Keqi Tang

Gordon A Anderson

Yehia M Ibrahim

Jon Gardner Wilkes

Dan Alexander Buzatu

Paul Chiarelli

Ricky D Holland

Michael A Beaudoin

A method for raising the resolving power, specificity, and peak capacity of conventional ion mobility spectrometry is disclosed. Ions are separated in a dynamic electric field comprising an oscillatory field wave and opposing static field, or at least two counter propagating waves with different parameters (amplitude, profile, frequency, or speed). As the functional dependencies of mean drift velocity on the ion mobility in a wave and static field or in unequal waves differ, only single species is equilibrated while others drift in either direction and are mobility-separated. An ion mobility spectrum over a limited range is then acquired by measuring ion drift times through a fixed distance inside the gas-filled enclosure. The resolving power in the vicinity of equilibrium mobility substantially exceeds that for known traveling-wave or drift-tube IMS separations, with spectra over wider ranges obtainable by stitching multiple segments. The approach also enables low-cutoff, high-cutoff, and bandpass ion mobility filters.

Method for enhancing the resolving power of ion mobility separations over a limited mobility range

Electrodynamic ion funnels confine, guide, or focus ions in gases using the Dehmelt potential of oscillatory electric field. New funnel designs operating at or close to atmospheric gas pressure are described. Effective ion focusing at such pressures is enabled by fields of extreme amplitude and frequency, allowed in microscopic gaps that have much higher electrical breakdown thresholds in any gas than the macroscopic gaps of present funnels. The new microscopic-gap funnels are useful for interfacing atmospheric-pressure ionization sources to mass spectrometry (MS) and ion mobility separation (IMS) stages including differential IMS or FAIMS, as well as IMS and MS stages in various configurations. In particular, 'wedge' funnels comprising two planar surfaces positioned at an angle and wedge funnel traps derived therefrom can compress ion beams in one dimension, producing narrow belt-shaped beams and laterally elongated cuboid packets. This beam profile reduces the ion density and thus space-charge effects, mitigating the adverse impact thereof on the resolving power, measurement accuracy, and dynamic range of MS and IMS analyzers, while a greater overlap with coplanar light or particle beams can benefit spectroscopic methods.

Microchip and wedge ion funnels and planar ion beam analyzers using same

A differential ion mobility spectrometry or field asymmetric waveform ion mobility spectrometry (FAIMS) platform is disclosed that utilizes both gas flow and electric field, consecutively or simultaneously, to move ions through the analytical gap. The consecutive combination of flow and field enables rapid and flexible switching of the FAIMS stage 'on' (for ion separation) and 'off' (for high non-selective transmission) with no hardware modifications. This capability is needed for effective use of multidimensional instrument systems that couple FAIMS to mass spectrometry and/or conventional ion mobility spectrometry. The joint application of flow and field allows controlling the discrimination against high-mobility ions, maximizing it to remove the chemical noise or minimizing it to make the analyses of complex samples more predictable and uniform.

Platform for field asymmetric waveform ion mobility spectrometry with ion propulsion modes employing gas flow and electric field

A method for reproducibly analyzing mass spectra from different sample sources is provided. The method deconvolutes the complex spectra by collapsing multiple peaks of different molecular mass that originate from the same molecular fragment into a single peak. The differences in molecular mass are apparent differences caused by different charge states of the fragment and/or different metal ion adducts and/or reactant products of one or more of the charge states. The deconvoluted spectrum is compared to a library of mass spectra acquired from samples of known identity to unambiguously determine the identity of one or more components of the sample undergoing analysis.

Pattern recognition of whole cell mass spectra

Disclosed are a device and method for improved interfacing of differential mobility spectrometry (DMS) or field asymmetric waveform ion mobility spectrometry (FAIMS) analyzers of substantially planar geometry to subsequent or preceding instrument stages. Interfacing is achieved using curved DMS elements, where a thick ion beam emitted by planar DMS analyzers or injected into them for ion filtering is compressed to the gap median by DMS ion focusing effect in a spatially inhomogeneous electric field. Resulting thinner beams are more effectively transmitted through necessarily constrained conductance limit apertures to subsequent instrument stages operated at a pressure lower than DMS, and/or more effectively injected into planar DMS analyzers. The technology is synergetic with slit apertures, slit aperture/ion funnels, and high-pressure ion funnel interfaces known in the art which allow for increasing cross-sectional area of MS inlets. The invention may be used in integrated analytical platforms, including, e.g., DMS/MS, LC/DMS/MS, and DMS/IMS/MS that could replace and/or enhance current LC/MS methods, e.g., for proteomics research.

Hooked differential mobility spectrometry apparatus and method therefore

The present invention relates generally to separation of ions based on their transport properties. More particularly, the invention relates to separation of ionic mixtures and characterization of ions in gases using higher-order differential ion mobility spectrometry (HODIMS) enabled by asymmetric waveforms of fundamentally new types. The invention discloses a method and apparatus for separation of ionic mixtures and characterization, identification, or quantification of ions in a gas based substantially on the terms of third or higher order in a series expansion of ion mobility as a function of electric field intensity. This is achieved using a periodic, time-dependent electric field with novel waveform profiles that cancel or substantially reduce the contributions to time-averaged ion motion of the leading n (where n&#x2267;2) terms of that expansion, thereby achieving ion separations based substantially on the (n+1)th term. Separations using HODIMS with different n are expected to be highly orthogonal, enabling multidimensional separations employing HODIMS analyzers of different orders. The expected high orthogonality between HODIMS and mass spectrometry or ion mobility spectrometry would make HODIMS/MS and HODIMS/IMS combinations powerful analytical tools of broad utility.

Method and apparatus for high-order differential mobility separations

The invention discloses a new interface with non-circular conductance limit aperture(s) useful for effective transmission of non-circular ion beams between stages with different gas pressure. In particular, the invention provides an improved coupling of field asymmetric waveform ion mobility spectrometry (FAIMS) analyzers of planar or side-to-side geometry to downstream stages such as mass spectrometry or ion mobility spectrometry. In this case, the non-circular aperture is rectangular; other geometries may be optimum in other applications. In the preferred embodiment, the non-circular aperture interface is followed by an electrodynamic ion funnel that may focus wide ion beams of any shape into tight circular beams with virtually no losses. The jet disrupter element of the funnel may also have a non-circular geometry, matching the shape of arriving ion beam. The improved sensitivity of planar FAIMS/MS has been demonstrated in experiments using a non-contiguous elongated aperture but other embodiments (e.g., with a contiguous slit aperture) may be preferable, especially in conjunction with an ion funnel operated at high pressures.

Interface and process for enhanced transmission of non-circular ion beams between stages at unequal pressure

Techniques and instrumentation are described for analyses of substances, including complex samples/mixtures that require separation prior to characterization of individual components. A method is disclosed for separation of ion mixtures and identification of ions, including protein and other macromolecular ions and their different structural isomers. Analyte ions are not free to rotate during the separation, but are substantially oriented with respect to the drift direction. Alignment is achieved by applying, at a particular angle to the drift field, a much stronger alternating electric field that 'locks' the ion dipoles with moments exceeding a certain value. That value depends on the buffer gas composition, pressure, and temperature, but may be as low as &#x2dc;3 Debye under certain conditions. The presently disclosed method measures the direction-specific cross-sections that provide the structural information complementing that obtained from known methods, and, when coupled to those methods, increases the total peak capacity and specificity of gas-phase separations. Simultaneous 2-D separations by direction-specific cross sections along and orthogonally to the ion dipole direction are also possible.

Method and apparatus for ion mobility spectrometry with alignment of dipole direction (IMS-ADD)

The present invention relates to a device for separation and characterization of gas-phase ions. The device incorporates an ion source, a field asymmetric waveform ion mobility spectrometry (FAIMS) analyzer, an ion mobility spectrometry (IMS) drift tube, and an ion detector. In one aspect of the invention, FAIMS operating voltages are electrically floated on top of the IMS drift voltage. In the other aspect, the FAIMS/IMS interface is implemented employing an electrodynamic ion funnel, including in particular an hourglass ion funnel. The present invention improves the efficiency (peak capacity) and sensitivity of gas-phase separations; the online FAIMS/IMS coupling creates a fundamentally novel two-dimensional gas-phase separation technology with high peak capacity, specificity, and exceptional throughput.

Device for two-dimensional gas-phase separation and characterization of ion mixtures

A method and apparatus enabling increased sensitivity in ion mobility spectrometry/mass spectrometry instruments which substantially reduces or eliminates the loss of ions in ion mobility spectrometer drift tubes utilizing a device for transmitting ions from an ion source which allows the transmission of ions without significant delay to an hourglass electrodynamic ion funnel at the entrance to the drift tube and/or an internal ion funnel at the exit of the drift tube. An hourglass electrodynamic funnel is formed of at least an entry element, a center element, and an exit element, wherein the aperture of the center element is smaller than the aperture of the entry element and the aperture of the exit elements. Ions generated in a relatively high pressure region by an ion source at the exterior of the hourglass electrodynamic funnel are transmitted to a relatively low pressure region at the entrance of the hourglass funnel through a conductance limiting orifice. Alternating and direct electrical potentials are applied to the elements of the hourglass electrodynamic funnel thereby drawing ions into and through the hourglass electrodynamic funnel thereby introducing relatively large quantities of ions into the drift tube while maintaining the gas pressure and composition at the interior of the drift tube as distinct from those at the entrance of the electrodynamic funnel and allowing a positive gas pressure to be maintained within the drift tube, if desired. An internal ion funnel is provided within the drift tube and is positioned at the exit of said drift tube. The advantage of the internal ion funnel is that ions that are dispersed away from the exit aperture within the drift tube, such as those that are typically lost in conventional drift tubes to any subsequent analysis or measurement, are instead directed through the exit of the drift tube, vastly increasing the amount of ions exiting the drift tube.

High performance ion mobility spectrometry using hourglass electrodynamic funnel and internal ion funnel

A method and apparatus enabling increased sensitivity in ion mobility spectrometry/mass spectrometry instruments which substantially reduces or eliminates the loss of ions in ion mobility spectrometer drift tubes utilizing an hourglass electrodynamic ion funnel at the entrance to the drift tube and/or an internal ion funnel at the exit of the drift tube. An hourglass electrodynamic funnel is formed of at least an entry element, a center element, and an exit element, wherein the aperture of the center element is smaller than the aperture of the entry element and the aperture of the exit elements. Ions generated in a relatively high pressure region by an ion source at the exterior of the hourglass electrodynamic funnel are transmitted to a relatively low pressure region at the entrance of the hourglass funnel through a conductance limiting orifice. Alternating and direct electrical potentials are applied to the elements of the hourglass electrodynamic funnel thereby drawing ions into and through the hourglass electrodynamic funnel thereby introducing relatively large quantities of ions into the drift tube while maintaining the gas pressure and composition at the interior of the drift tube as distinct from those at the entrance of the electrodynamic funnel and allowing a positive gas pressure to be maintained within the drift tube, if desired. An internal ion funnel is provided within the drift tube and is positioned at the exit of said drift tube. The advantage of the internal ion funnel is that ions that are dispersed away from the exit aperture within the drift tube, such as those that are typically lost in conventional drift tubes to any subsequent analysis or measurement, are instead directed through the exit of the drift tube, vastly increasing the amount of ions exiting the drift tube.

Growing community of inventors

Richland, WA, United States of America

Alexandre A Shvartsburg