Development of Multi-ESI-Sprayer, Multi-Atmospheric-Pressure-inlet Mass Spectrometry and Its Application to Accurate Mass Measurement Using Time-of-Flight Mass Spectrometry

Abstract

The atmospheric pressure sampling nozzle (orifice, heated capillary, or inlet) of a high mass accuracy time-of-flight mass spectrometer (TOF-MS) was modified by replacing its single nozzle with multiple atmospheric pressure nozzles. This allowed multiple streams of liquids to be introduced into the MS in parallel (an electrosprayer for each nozzle), with minimum analyte interactions between the streams. The chemical contents of all liquid streams were analyzed concurrently using a single mass spectrometer. To obtain a higher mass accuracy by providing internal reference on each scan (acquisition) and to evaluate the suitability of TOF-MS for molecular-formula confirmation, a dual-ESI-sprayer, dual-nozzle version of this design was used. The accurate masses of tens of organic compounds in the mass range of 200-3000 Da were measured, and the results were compared with those obtained using dual-sprayer, single-nozzle TOF-MS. A significant improvement in mass accuracy was observed when the former technique was used. Comparison between the mass accuracy using dual-ESI-sprayer, dual-nozzle TOF-MS and that obtained using a double-focusing mass spectrometer operating under chemical ionization (CI) and fast atom bombardment (FAB) shows the suitability of the technique for elemental-composition confirmation. Approximately 85% of samples analyzed had mass errors of less than 5 ppm, and the other 15% had mass errors less than 8 ppm. Using a high-performance liquid chromatography (HPLC) as a device for introduction of one liquid stream (sample) and a syringe pump as a device for introduction of the second liquid stream (reference standard), the accurate mass of a tryptic digest of cytochrome c was measured. The range of mass errors was from -6.1 ppm to +3.6 ppm, a significant improvement over our previously reported mass accuracy for this digest using single-nozzle TOF-MS. The interactions between analytes in the liquid streams also were investigated using a variety of sample-introduction and nozzle-design combinations, including single-ESI-sprayer, single-nozzle; dual-ESI-sprayer, single-nozzle; dual-ESI-sprayer, Y-shaped inlet; and dual-ESI-sprayer, dual-inlet. The results demonstrated that the dual-ESI-sprayer, dual-inlet design provides reference peaks on every acquisition with minimum analyte-reference interaction and, therefore, higher consistent mass accuracy.

Toxicological screening of urine for drugs by liquid chromatography/time‐of‐flight mass spectrometry with automated target library search based on elemental formulas

“…This low accuracy is a consequence of temperature changes during the day, which effect the flight tube length and applied voltages. In a recent study, 6 the calibration standard and samples were introduced in parallel by using a dual-nozzle design to minimize mixing of sample and reference standard. However, introducing the internal calibrant to the interface before every sample injection through a 10-port valve not only provided the internal reference peak on every acquisition, but also prevented any suppression or other analyte-internal standard interactions in the interface.…”

Pulsed dual electrospray ionization for In/In reactions

“…However, MS n experiments involving ion/ion reactions between stages of MS are not possible with this arrangement. Dual ESI sources or multiple sprayer systems have also been described and studied by different groups to improve electrospray sensitivity [35], to increase sample throughput [36], and to improve mass measurement accuracy in time-offlight (TOF), Fourier transform ion cyclotron resonance (FTICR), and sector mass spectrometry by providing a reference spray for internal mass calibration [37][38][39]. The dual or multiple sprayer systems usually operate in one of two ways.…”

“…In one mode, all sprayers are active simultaneously and ions from all sprayers are sampled into the mass spectrometer. Under such a condition, depending upon the design, the simultaneous operation of two or more sprayers may lead to instabilities due to the interference of adjacent sprays [40], and the interaction of ions in the ESI interface can significantly reduce MS sampling efficiency [37,41]. In the other typical operation mode, ions from distinct sprayers can be sampled sequentially by utilizing a rotatable plate [42] or rotor [43], which allow ions from a specific sprayer to enter the mass spectrometer sequentially.…”

Accurate mass measurements by Fourier transform mass spectrometry

“…It is well known that the major problems associated with the first procedure are analyte-signal suppression, ionization discrimination, and adduct formation (McLuckey & Stephenson, 1998;Jiang & Moini, 2000;Hannis & Muddiman, 2000;Belov et al, 2001;Wolff et al, 2001;Tang et al, 2002;Zhou et al, 2002; Reprinted by permission of the American Chemical Society from Mize & Amster (2000). et al, 2003).…”

“…To overcome these problems, researchers have focused on developing dual electrospray sources to obtain accurate mass measurements (Belov et al, 2001;Flora, Hannis, & Muddiman, 2001;Hannis & Muddiman, 2000;Nepomuceno et al, 2003;Tang et al, 2002). To our knowledge, Andrien, Whitehouse, & Sansone in 1998 first introduced a dual electrospray ionization source, and Jiang & Moini (2000), Wolff et al (2001), and Zhou et al (2002) further developed and applied it in ESI-TOF mass-spectrometry measurements.…”