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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.

Since its introduction, the orbitrap has proven to be a robust mass analyzer that can routinely deliver high resolving power and mass accuracy. Unlike conventional ion traps such as the Paul and Penning traps, the orbitrap uses only electrostatic fields to confine and to analyze injected ion populations. In addition, its relatively low cost, simple design and high space‐charge capacity make it suitable for tackling complex scientific problems in which high performance is required. This review begins with a brief account of the set of inventions that led to the orbitrap, followed by a qualitative description of ion capture, ion motion in the trap and modes of detection. Various orbitrap instruments, including the commercially available linear ion trap–orbitrap hybrid mass spectrometers, are also discussed with emphasis on the different methods used to inject ions into the trap. Figures of merit such as resolving power, mass accuracy, dynamic range and sensitivity of each type of instrument are compared. In addition, experimental techniques that allow mass‐selective manipulation of the motion of confined ions and their potential application in tandem mass spectrometry in the orbitrap are described. Finally, some specific applications are reviewed to illustrate the performance and versatility of the orbitrap mass spectrometers. © 2008 Wiley Periodicals, Inc., Mass Spec Rev 27: 661–699, 2008

A major design objective of portable mass spectrometers is the ability to perform in situ chemical analysis on target samples in their native states in the undisturbed environment. The miniature instrument described here is fully contained in a wearable backpack (10 kg) with a geometry-independent low-temperature plasma (LTP) ion source integrated into a hand-held head unit (2 kg) to allow direct surface sampling and analysis. Detection of chemical warfare agent (CWA) simulants, illicit drugs, and explosives is demonstrated at nanogram levels directly from surfaces in near real time including those that have complex geometries, those that are heat-sensitive, and those bearing complex sample matrices. The instrument consumes an average of 65 W of power and can be operated autonomously under battery power for ca. 1.5 h, including the initial pump-down of the manifold. The maximum mass-to-charge ratio is 925 Th with mass resolution of 1-2 amu full width at half-maximun (fwhm) across the mass range. Multiple stages of tandem analysis can be performed to identify individual compounds in complex mixtures. Both positive and negative ion modes are available. A graphical user interface (GUI) is available for novice users to facilitate data acquisition and real-time spectral matching.

For field applications, "miniature" and "rapid" have become almost synonymous, yet these small mass spectrometers are not useful if performance is too severely compromised. (To listen to a podcast about this feature, please go to the Analytical Chemistry website at pubs. acs.org/journal/ancham.)MS is widely regarded as the gold standard for chemical analysis with respect to selectivity, detection limits, and broad applicability. However, mass spectrometers are comparatively delicate instruments, partly a consequence of the need for a vacuum system into which the sample is introduced. There have long been efforts at direct MS analysis of complex mixtures, 1 but extensive sample cleanup and increasingly sophisticated multianalyzers have been involved. These considerations have limited the applications of MS outside the laboratory. It is striking that although progress in many areas of technology is strongly associated with miniaturization, this correlation is barely evident in MS.Nevertheless, for many applications of MS, in situ experiments would have significant advantages over laboratory measurements, even if there are significant losses in analytical performance. Some applications of immediate interest include environmental monitoring (especially surveys that require large numbers of samples), quality control, food safety, forensics, security and public safety, and clinical diagnostics. The objective of this article is to summarize recent progress in developing handheld miniature mass spectrometers. Note that the focus is on complete systems, not particular components, even important ones like the mass analyzer. ON THE SMALL SIDEInterest in small mass analyzers stretches back several decades. For example, a hyperbolic ion trap analyzer the size of a quarter with a 2.5-mm radius and an m/z range of 70,000 was reported in 1991.2 A Mattauch-Herzog-type, nonscanning, double-focusing sector mass analyzer was reported in 1991, and a very small, double-focusing, crossed electric-and magnetic-field sector analyzer was described in 2001.3,4 Recent work by Ramsey, Austin, Short, and others has advanced small analyzers further, and the emphasis is increasingly turning to microelectromechanical systems (MEMS)-fabricated mass analyzers. [5][6][7][8] However, only in the past decadesand especially in the past 5 yearsshas significant progress been made in the development of small, low-power, portable, autonomous mass spectrometer systems; some have progressed to the point of commercialization. A review in 2000 summarized the mass analyzers used in miniature instruments, showing examples of virtually all the common types, including quadrupole mass filters, quadrupole ion traps, magnetic sector fields, TOF, and FT ion cyclotron resonance instruments. 9 More recent work has seen the commercialization of a novel toroidal ion trap system. 10 A website devoted to small instruments and a conference series on MS in harsh environments prominently features handheld mass spectrometers (www.gcms.