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

Abstract

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 [...

Solvent vapor effects on planar high-field asymmetric waveform ion mobility spectrometry

“…Micromachined geometries, however, do not offer very high resolving powers due to the small size and short ion residence time. It has been shown that the resolving power of a FAIMS spectrometer, particularly planar geometries, increases as the residence time inside the cell increases [20,21]. Higher resolving power planar FAIMS spectrometers have been built by Smith and coworkers, showing resolving powers up to at least 40 [21].…”

Improved Differential Ion Mobility Separations Using Linked Scans of Carrier Gas Composition and Compensation Field

“…Increasing the applied dispersion field or increasing the separation time can result in improved separations [11][12][13][14]. Another method used introduces organic dopant vapors into the carrier gas as a means to take advantage of differences in ion-molecule interactions in the low and high fields [15][16][17][18].…”

Pushing the Frontier of High-Definition Ion Mobility Spectrometry Using FAIMS

“…14) With a gap of 1.9 mm width and ∼50 mm length, DV of 4 kV, and t=0.2 s, we obtained R ∼40 using the nitrogen gas and R ∼70 with 1 : 1 helium/N 2 mixtures (for multiplycharged peptides). 12,14) While the resolving power scales roughly as (DV) 3 and rapidly improves upon He addition because of increasing ion mobility in gases of lighter molecules, 15) the feasible combinations of DV and He fraction are limited by electrical (avalanche) breakdown across the gap. However, the breakdown threshold is materially greater for high-frequency rf than dc voltages, and a 1.9-mm gap can hold 16,17) DV= 4 kV with up to 75% He (rest N 2 ) or up to 5.4 kV at 50% He.…”

“…Operation in these regimes increases R (for peptides) up to ∼200, which compares with the metrics for the most advanced existing DTIMS systems. 18) The resolving power of separations in media, including FAIMS, is normally proportional 15,19) to t 1/2 because the positions of peaks scale as t while the widths, governed by diffusion, scale as t 1/2 . The ion filtering time in FAIMS is proportional to the inverse gas flow velocity and thus can be set by adjusting the volume flow rate, Q.…”

“…Whereas fundamentally the use of He is an effective path to elevated FAIMS resolution, the approach is severely constrained by He being about the easiest gas to break down. 20) The only gas lighter than He, thus supporting yet higher ion mobilities that lead to better resolution, 15) is hydrogen. Fortunately, H 2 has much higher breakdown threshold than He, 20) permitting up to 90% H 2 (vs. 50% for He) even at our maximum DV= 5.4 kV.…”