Augmenting Ion Trap Mass Spectrometers Using a Frequency Modulated Drift Tube Ion Mobility Spectrometer

Abstract

Historically, high pressure ion mobility drift tubes have suffered from low ion duty cycles and this problem is magnified when such instrumentation is coupled with ion trap mass spectrometers. To significantly alleviate these issues, we outline the result from coupling an atmospheric pressure, dual-gate drift tube ion mobility spectrometer (IMS) to a linear ion trap mass spectrometer (LIT-MS) via modulation of the ion beam with a linear frequency chirp. The time-domain ion current, once Fourier transformed, reveals a standard ion mobility drift spectrum that corresponds to the standard mode of mobility analysis. By multiplexing the ion beam, it is possible to successfully obtain drift time spectra for an assortment of simple peptide and protein mixtures using an LIT-MS while showing improved signal intensity versus the more common signal averaging technique. Explored here are the effects of maximum injection time, solution concentration, total experiment time, and frequency swept on signal-to-noise ratios (SNRs) and resolving power. Increased inject time, concentration, and experiment time all generally led to an improvement in SNR, while a greater frequency swept increases the resolving power at the expense of SNR. Overall, chirp multiplexing of a dual-gate IMS system coupled to an LIT-MS improves ion transmission, lowers analyte detection limits, and improves spectral quality.

Separation of biologically relevant isomers on an Orbitrap mass spectrometer using high‐resolution drift tube ion mobility and varied drift gas mixtures

“…The ion mobility stage contains two Bradbury‐Nielsen type ion gates which enable operation in various IMS‐MS modes; these include open mode (no IMS separation), Faraday mode (IMS‐only spectrometry using a built‐in Faraday detector), gated mode (select introduction – or exclusion – of one or several compounds into the mass spectrometer based on their mobility) and scan mode (creation of two‐dimensional IMS‐MS maps through a series of gated mode measurements with increasing drift time) . Frequency‐modulate operation for increased duty cycle has been reported as an additional mode of operation to increase the duty cycle but was not used for the present study focusing on individual isomer pairs …”

“…DTIMS couplings for the Orbitrap have been presented for both the low-pressure regime, 18,19 as well as the atmospheric-pressure (AP) regime, including the MA3100 as described in previous papers [20][21][22] and in this study.…”

“…FAIMS and DTIMS are thus best seen as complimentary techniques when combined with trap‐based mass spectrometers, enabling the solution of different analytical problems. DTIMS couplings for the Orbitrap have been presented for both the low‐pressure regime, as well as the atmospheric‐pressure (AP) regime, including the MA3100 as described in previous papers and in this study.…”

The Ims Paradox: A Perspective on Structural Ion Mobility‐mass Spectrometry

“…Current commercial IM‐MS instruments suffer from low MS resolution ( R m / z ) in the TOF with only recent implementations of high‐resolution TOFs (e.g., Waters SELECT Series Cyclic IMS or Agilent 6545XT Q‐TOF MS, but the latter lacks IM capabilities) (Giles et al, 2019). Alternatively, IM can be coupled to a high‐resolution orbitrap platform, but this introduces a duty‐cycle mismatch since the orbitrap operates on a timescale of hundreds of milliseconds (Clowers & Hill, 2005; Szumlas, Ray, & Hieftje, 2006; Morrison, Siems, & Clowers, 2016; Poltash et al, 2018). This problem may be mitigated by supplementing the gate at the entrance of the DT with a second gate implemented post‐IM to isolate a single drift time of interest to be transferred for mass analysis; this process is then iterated over the entire drift time window.…”

Development of an Ion Mobility Spectrometry-Orbitrap Mass Spectrometer Platform

“…The IMS duty cycle can be improved by applying Hadamard-based multiplexing or frequency modulations schemes, 28–30 which can provide duty cycles as high as 50%. 26,28 Our laboratory has also introduced a modified pseudorandom sequence that incorporates a trapping stage before the IMS separation, and was shown to further improve the duty cycle for an IMS-TOF MS platform to beyond 50%. 30,31 …”