Two-Dimensional Gas-Phase Separations Coupled to Mass Spectrometry for Analysis of Complex Mixtures

Tang, Keqi; Li, Fumin; Shvartsburg, Alexandre A.; Strittmatter, Eric F.; Smith, Richard D.

doi:10.1021/ac050871x

Cited by 131 publications

(207 citation statements)

References 76 publications

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“…There also is a significant orthogonality between FAIMS and IMS dimensions, 63,64 which enables 2-D separations by FAIMS/IMS coupling. 64 However, FAIMS is still substantially correlated to MS. For example, in FAIMS in N 2 or air buffer, small ions with masses up to several hundred Da (including monatomics, 30 all amino acid ions, 31 and other simple organic ions 33,54 ) are "A-type" 49 (i.e., have a positive a), while large ions (including all peptides 24,53,63,64 ) are "C-type" 48 (i.e., have a negative a). The inverse correlation between a and m is also found within many homologous series, e.g., for the previously introduced organophosphorus compounds, 54 ketones, 33 and aromatic amines, 55 halogenate anions, 65 and amino acids (below).…”

Section: Orthogonality To Msmentioning

confidence: 99%

Feasibility of Higher-Order Differential Ion Mobility Separations Using New Asymmetric Waveforms

2006

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Technologies for separating and characterizing ions based on their transport properties in gases have been around for three decades. The early method of ion mobility spectrometry (IMS) distinguished ions by absolute mobility that depends on the collision cross section with buffer gas atoms. The more recent technique of field asymmetric waveform IMS (FAIMS) measures the difference between mobilities at high and low electric fields. Coupling IMS and FAIMS to soft ionization sources and mass spectrometry (MS) has greatly expanded their utility, enabling new applications in biomedical and nanomaterials research. Here, we show that time-dependent electric fields comprising more than two intensity levels could, in principle, effect an infinite number of distinct differential separations based on the higher-order terms of expression for ion mobility. These analyses could employ the hardware and operational procedures similar to those utilized in FAIMS. Methods up to the 4 th or 5 th order (where conventional IMS is 1 st order and FAIMS is 2 nd order) should be practical at field intensities accessible in ambient air, with still higher orders potentially achievable in insulating gases. Available experimental data suggest that higher-order separations should be largely orthogonal to each other and to FAIMS, IMS, and MS.Approaches to separation of ion mixtures and characterization of ions in the gas phase based on ion mobility are becoming commonplace in analytical chemistry. The key advantage of gas-phase separations over condensed phase methods is the exceptional speed enabled by rapid molecular motion in gases. This inherent benefit is made increasingly topical by the growing focus of analytical technology on higher throughput. Since their first demonstration a decade ago, 1-3 instrumental platforms combining electrospray ionization (ESI) or matrixassisted laser desorption ionization (MALDI) sources with ion mobility separations and mass-spectrometry (MS) have undergone a sustained development that has improved their resolution and sensitivity to the levels demanded by practical applications. 4-10 Recent commercial introduction of such systems 11-14 is expanding interest in ion mobility/MS, particularly for analyses of complex biological samples such as proteolytic digests and lipids, nucleotides, and metabolites. [15][16][17][18][19][20][21][22][23][24] Single-stage ion mobility spectrometry (IMS) was investigated since the 1970s, 25-27 with a noteworthy development of ESI/IMS in 1980s. 28 In IMS, ions drift through a non-reactive buffer gas under the influence of a modest electric field. The drift velocity (v) in the field of intensity E is determined by ion mobility (K):(1)For consistency, measured mobilities are normally converted to reduced values K 0 by adjusting the buffer gas temperature (T, Kelvin) and pressure (P, Torr) to standard (STP) conditions:NIH Public Access

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Section: Orthogonality To Msmentioning

confidence: 99%

Feasibility of Higher-Order Differential Ion Mobility Separations Using New Asymmetric Waveforms

2006

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“…Under typical operating conditions, the spread of elimination rates for commonly analyzed ions is reduced from Ͼ5 times in flow-driven to 1.6 times in field-driven FAIMS while the difference in resolving power decreases from ϳ60% to ϳ15%. ield asymmetric waveform ion mobility spectrometry (FAIMS) has emerged as a powerful new analytical technique [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. All IMS methods separate ions using their transport in a gas under the influence of electric field [21]: conventional IMS is based on absolute ion mobility (K) at particular field intensity (E) and FAIMS works with the difference between K at high and low E. So FAIMS is also known as differential mobility spectrometry (DMS) [11,12].…”

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Scaling of the resolving power and sensitivity for planar FAIMS and mobility-based discrimination in flow- and field-driven analyzers

Shvartsburg

Smith

2007

J. Am. Soc. Mass Spectrom.

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Continuing development of the technology and applications of field asymmetric waveform ion mobility spectrometry (FAIMS) calls for better understanding of its limitations and factors that govern them. While key performance metrics such as resolution and ion transmission have been calculated for specific cases employing numerical simulations, the underlying physical trends remained obscure. Here we determine that the resolving power of planar FAIMS scales as the square root of separation time and sensitivity drops exponentially at the rate controlled by absolute ion mobility and several instrument parameters. A strong dependence of ion transmission on mobility severely discriminates against species with higher mobility, presenting particular problems for analyses of complex mixtures. While the time evolution of resolution and sensitivity is virtually identical in existing FAIMS systems using gas flow and proposed devices driven by electric field, the distributions of separation times are not. The inverse correlation between mobility (and thus diffusion speed) and residence time for ions in field-driven FAIMS greatly reduces the mobility-based discrimination and provides much more uniform separations. Under typical operating conditions, the spread of elimination rates for commonly analyzed ions is reduced from Ͼ5 times in flow-driven to 1.6 times in field-driven FAIMS while the difference in resolving power decreases from ϳ60% to ϳ15%. ield asymmetric waveform ion mobility spectrometry (FAIMS) has emerged as a powerful new analytical technique [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. All IMS methods separate ions using their transport in a gas under the influence of electric field [21]: conventional IMS is based on absolute ion mobility (K) at particular field intensity (E) and FAIMS works with the difference between K at high and low E. So FAIMS is also known as differential mobility spectrometry (DMS) [11,12]. The value of K for all ions increases or decreases at sufficiently high E, depending on the interaction potentials with gas molecules. As those potentials differ for different ions, the K(E) function is characteristic of the species and, in principle, any two could be distinguished by FAIMS.Separation parameters in FAIMS are largely independent of the ion mass/charge state (m/z) ratio, which renders FAIMS substantially orthogonal to mass spectrometry (MS) and makes FAIMS/MS a powerful method of broad utility. The separation power of FAIMS/MS could be augmented by coupling to conventional IMS providing 2-D separations [17,18] before MS and/or pre-ionization stages such as liquid or gas chromatography (LC [14,16,20] or GC [5,8,9]) or capillary electrophoresis (CE) [10]. The operational simplicity, small size, and low cost make FAIMS attractive for field analyses that require rugged, portable, inexpensive sensors. Recent commercialization of FAIMS technology, alone and in conjunction with LC/MS or GC, has enabled its expansion into proteomics [15][16][17], structural biology [...

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“…Consequently, by fixing the CV value, a subset of ions is allowed to pass through the FAIMS, whereas other ions are lost to the walls of the device. FAIMS is readily coupled between an atmospheric pressure ionization source and a mass spectrometer [12][13][14][15][16] and, because of its unique ion-separation mechanism [17], FAIMS offers additional selectivity for bioanalytical applications. Indeed, FAIMS has been previously interfaced to atmospheric pressure ionization sources such as ESI [12] and APCI [8] operating at low liquid flow rates (and thus low temperatures) and has been found to significantly lower detection limits by reducing background ion current without sacrificing absolute signal intensity [18 -20].…”

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Characterization of a temperature-Controlled FAIMS system

Barnett

Belford

Dunyach

et al. 2007

J. Am. Soc. Mass Spectrom.

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High-field asymmetric waveform ion mobility spectrometry (FAIMS) focuses and separates gas-phase analyte ions from chemical background, offering substantial improvements in the detection of targeted species in biological matrices. Ion separations have been typically performed at atmospheric pressure and ambient temperature, although routine small molecule quantitation by LC-MS (and thus LC-FAIMS-MS) is generally performed at liquid flow rates (e.g., in excess of 200 L/min) in which atmospheric pressure ionization sources (e.g., APCI and ESI) need to be run at elevated temperatures to enhance ion desolvation. Heat from the ionization source and/or the mass spectrometer capillary interface is shown to have a significant impact on the performance of a conventional FAIMS electrode set. This study introduces a new FAIMS system that uses gas heating/cooling to quickly reach temperature equilibrium independent of the external temperature conditions. A series of equations and balance plots, which look at the effect of temperature and other variables, on the normalized field strength (E/N), are introduced and used to explain experimental observations. Examples where the ion behavior deviates from the predicted behavior are presented and explanations based on clusters or changes in ion-neutral interactions are given. Consequences of the use of temperature control, and in particular advantages of using different temperature settings on the inner and outer electrodes, for the purpose of manipulating ion separation are described. ecause of its high sensitivity and selectivity, liquid chromatography combined with tandem mass spectrometry (LC-MS/MS) has become the method of choice for quantitation of bioorganic compounds in biological matrices such as urine or blood plasma [1][2][3]. To preserve LC conditions and flow rates typically used with LC-UV (e.g., 1 mL/min), mass spectrometer manufacturers needed to adapt electrospray ionization (ESI) sources, which were initially operated at much lower liquid flow rates [4,5], to achieve sufficient ion desolvation. Consequently, sources that use the addition of heat to accelerate ion desolvation were created [6,7] and further developed into the commercial sources that are used today (e.g., Heated Electrospray; H-ESI™ and TurboIonSpray; TIS™). Despite the widespread utility offered by LC-MS/MS, because of the complexity of biological matrices, in many instances (e.g., high background [8], co-eluting interferences [9]) additional selectivity in an analysis is still required.High-field asymmetric waveform ion mobility spectrometry (FAIMS) is a gas-phase ion-separation technique that is based on compound-dependent differences in an ion's mobility at high field (K h ) relative to low field (K) [10,11]. With FAIMS, deviations in ion mobility resulting from the high electric fields are reflected experimentally by the compensation voltage (CV) of transmission for a particular analyte. Consequently, by fixing the CV value, a subset of ions is allowed to pass through the FAIMS, whereas other i...

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Two-Dimensional Gas-Phase Separations Coupled to Mass Spectrometry for Analysis of Complex Mixtures

Cited by 131 publications

References 76 publications

Feasibility of Higher-Order Differential Ion Mobility Separations Using New Asymmetric Waveforms

Feasibility of Higher-Order Differential Ion Mobility Separations Using New Asymmetric Waveforms

Scaling of the resolving power and sensitivity for planar FAIMS and mobility-based discrimination in flow- and field-driven analyzers

Characterization of a temperature-Controlled FAIMS system

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