Satendra Prasad

Simulation of Ion Motion in FAIMS through Combined Use of SIMION and Modified SDS

A key application of field asymmetric waveform ion mobility spectrometry (FAIMS) has been in selectively transmitting trace analyte ions that are present in a complex ion mixture to a mass spectrometer (MS) for identification and quantification. The overall sensitivity of FAIMS-MS, however, still needs to be significantly improved through the optimization of ion transmission into FAIMS and at the FAIMS-MS interface. Processes that cause ion losses include diffusion, space charge, separation field in the FAIMS and fringe fields around the edges of the FAIMS electrodes. These were studied here by first developing an algorithm using SIMION as its core structure to compute ion trajectory at different ratios of electric field to buffer gas number density (E/N). The E/N was varied from a few Td to approximately 80 Td by using an asymmetric square waveform. The algorithm was then combined with statistical diffusion simulation (SDS) model, columbic repulsion, and a parabolic gas flow profile to realistically simulate current transmission and peak shape. The algorithm was validated using a FAIMS model identical to the Sionex Corporation SVAC model. Ions modeled included low mass ions with K(o) in the range of 2.17 (m = 55) to 1.39 cm(2) x V(-1) x s(-1) (m = 368). Good agreement was achieved between simulated and experimental CV (peak maxima) values, peak width (fwhm), and transmitted ion current I(output). The model was then used to study fringe fields in a simple arrangement where a 0.5 mm (w) gap was created between the FAIMS exit and a capillary inlet (i.d. = 0.5 mm). At an optimum CV (11.8 V), only approximately 17% (1.3 pA) of the total ion current that correlate to CV = 11.8 V, entered the capillary; bulk of the ion loss was caused by the fringe fields. Current transmission into the capillary was improved, however, by applying a 500 V DC bias across w (0.5 mm).

Pulsed multiple reaction monitoring approach to enhancing sensitivity of a tandem quadrupole mass spectrometer.

Liquid chromatography (LC)-triple quadrupole mass spectrometers operating in a multiple reaction monitoring (MRM) mode are increasingly used for quantitative analysis of low-abundance analytes in highly complex biochemical matrixes. After development and selection of optimum MRM transitions, sensitivity and data quality limitations are largely related to mass spectral peak interferences from sample or matrix constituents and statistical limitations at low number of ions reaching the detector. Herein, we report on a new approach to enhancing MRM sensitivity by converting the continuous stream of ions from the ion source into a pulsed ion beam through the use of an ion funnel trap (IFT). Evaluation of the pulsed MRM approach was performed with a tryptic digest of Shewanella oneidensis strain MR-1 spiked with several model peptides. The sensitivity improvement observed with the IFT coupled in to the triple quadrupole instrument is based on several unique features. First, ion accumulation radio frequency (rf) ion trap facilitates improved droplet desolvation, which is manifested in the reduced background ion noise at the detector. Second, signal amplitude for a given transition is enhanced because of an order-of-magnitude increase in the ion charge density compared to a continuous mode of operation. Third, signal detection at the full duty cycle is obtained, as the trap use eliminates dead times between transitions, which are inevitable with continuous ion streams. In comparison with the conventional approach, the pulsed MRM signals showed 5-fold enhanced peak amplitude and 2-3-fold reduced chemical background, resulting in an improvement in the limit of detection (LOD) by a factor of ∼4-8.