The Orbitrap: a new mass spectrometer

Abstract

Research areas such as proteomics and metabolomics are driving the demand for mass spectrometers that have high performance but modest power requirements, size, and cost. This paper describes such an instrument, the Orbitrap, based on a new type of mass analyzer invented by Makarov. The Orbitrap operates by radially trapping ions about a central spindle electrode. An outer barrel-like electrode is coaxial with the inner spindlelike electrode and mass/charge values are measured from the frequency of harmonic ion oscillations, along the axis of the electric field, undergone by the orbitally trapped ions. This axial frequency is independent of the energy and spatial spread of the ions. Ion frequencies are measured non-destructively by acquisition of time-domain image current transients, with subsequent fast Fourier transforms (FFTs) being used to obtain the mass spectra. In addition to describing the Orbitrap mass analyzer, this paper also describes a complete Orbitrap-based mass spectrometer, equipped with an electrospray ionization source (ESI). Ions are transferred from the ESI source through three stages of differential pumping using RF guide quadrupoles. The third quadrupole, pressurized to less than 10(-3) Torr with collision gas, acts as an ion accumulator; ion/neutral collisions slow the ions and cause them to pool in an axial potential well at the end of the quadrupole. Ion bunches are injected from this pool into the Orbitrap analyzer for mass analysis. The ion injection process is described in a simplified way, including a description of electrodynamic squeezing, field compensation for the effects of the ion injection slit, and criteria for orbital stability. Features of the Orbitrap at its present stage of development include high mass resolution (up to 150,000), large space charge capacity, high mass accuracy (2-5 ppm), a mass/charge range of at least 6000, and dynamic range greater than 10(3). Applications based on electrospray ionization are described, including characterization of transition-metal complexes, oligosaccharides, peptides, and proteins. Use is also made of the high-resolution capabilities of the Orbitrap to confirm the presence of metaclusters of serine octamers in ESI mass spectra and to perform H/D exchange experiments on these ions in the storage quadrupole.

Parts-Per-Billion Mass Measurement Accuracy Achieved through the Combination of Multiple Linear Regression and Automatic Gain Control in a Fourier Transform Ion Cyclotron Resonance Mass Spectrometer

“…These calibration laws should also translate to improving MMA on the LTQ-Orbitrap. 40 We are currently working on extending these findings to intact proteins, and protein fragments in MS n data, which should both benefit from the extended dynamic range which these calibration laws and procedures provide. The experimental design is shown, which starts with the calibration of the instrument.…”

Phase-enhanced selective ion ejection in an orbitrap mass spectrometer

“…The Orbitrap mass spectrometer used in these experiments is a prototype of the commercial Thermo Orbitrap°and°is°described°in°detail°elsewhere° [3].°An°elec-trospray source creates ions, which are accumulated (100 -400 ms), energized (1300 V), and bunched into a small ion packet with a spatial spread of a few millimeters. The ion packet is then accelerated and deflected into the Orbitrap for mass analysis.…”

“…The Orbitrap, a new mass analyzer, provides high mass resolution (up to 100,000), high mass accuracy (2 ppm) [2], a mass/charge ratio range of at least 6000 [3], and a linear dynamic range of Ͼ5000 within a mass spectrum [4]. In the Orbitrap, the mass-to-charge ratio is obtained from the frequency of harmonic ion oscillations of the orbitally trapped ions along the axis of the electric field.…”

Recent developments in qualitative and quantitative analysis of phytochemical constituents and their metabolites using liquid chromatography–mass spectrometry

“…In respect to LC-MS applications, many types of mass analyzers including the single quadruple (Q), time-of-flight (TOF), ion trap (IT) and Fourier transform ion cyclotron resonance (FT-ICR) can be used as on-line analyzer [35][36][37][38]. Currently, because tandem combination of same or different mass analyzers results in a top level mass spectrometry solution, tandem mass spectrometry (coupling of mass analyzers in space) has been becoming a routinely analytical technique for structural elucidation and quantitative analysis of natural products.…”