Ambient mass spectrometry

Ambient mass spectrometry involves the direct sampling and ionization of samples in their ambient states, followed by mass spectrometric (MS) analysis. It differs from the traditional MS analysis with in-vacuum ionization, such as electron impact (EI), chemical ionization (CI), or matrix-assisted laser desorption ionization (MALDI), in that the whole sample is not transferred into vacuum but sampling and ionization is performed at atmospheric pressure; it also differs from MS analysis using atmospheric pressure ionization, such as electrospray (ESI) or atmospheric pressure chemical ionization (APCI), in that the experiment can be performed without any sample preparation whatsoever, including simple dissolution. Because ambient ionization mass spectrometry is characterized by direct sampling/ionization of analytes from native samples its characteristics include high speeds for the total analysis process. Typical examples include the direct analysis of non-volatile compounds in complex matrices using solvent-based desorption methods such as desorption electrospray ionization (DESI) or plasma-based methods such as direct analysis in real time (DART).

The history of the development of MS technology is punctuated by the development of new types of ionization methods which have played an enabling role in the applications of mass spectrometry from atomic mass measurement to complex biological mixtures. EI and CI allowed the analysis of the volatile compounds and the masses of the identity of molecular and fragment ions could be inferred through mass analysis. With the selection of appropriate reagents, the internal energy of the ions from CI could be controlled and ion fragmentation minimized so that mass spectra recorded for mixtures could be highly simplified. Desorption ionization and spray ionization methods brought mass spectrometry to the analysis of non-volatile compounds present in condensed-phase samples. Many small molecules in solids and solutions could be desorbed and ionized with the aid of laser beams, heat or energetic ion impact, but additional effort was required to observe intact ions from large molecules such as peptides and proteins. This problem was initially addressed with fast atom bombardment (FAB) but most successfully using matrix-assisted laser desorption (MALDI) and electrospray ionization (ESI).

Mass spectrometry is generally recognized as the most sensitive, most specific general purpose analytical technology and its power is most vividly demonstrated in the analysis of complex mixtures and quantification at trace-level concentrations. However, mass spectrometry is also vulnerable to matrix effects. Thus, sample extraction, chromatographic separation and other purification processes are routinely used to deliver analytes in relatively uniform matrices for ionization and MS analysis. These procedures are implemented in sequence with a series of complex analytical instruments and in analytical laboratories staffed by experienced personnel to customize the experimental conditions to maximize the performance for the target compounds. An informing principle of ambient mass spectrometry is to develop direct sampling/ionization methods to allow desorption and ionization of analytes for MS analysis without any of these procedures, so the entire process of chemical analysis using mass spectrometry can be performed extremely fast and with minimum human intervention.

Since DESI and DART were reported in 2004 and 2005, respectively, more than 30 ambient ionization methods have been developed. Commercial versions of some of the ambient ionization sources have also become available. These methods have been applied for a wide variety of applications resulting in hundreds of publications. Significant effort has been expended on the development and optimization of several of the methods and some systematic comparison studies have also been conducted. Each of these ionization methods contributes an additional name and acronym, though some of them are similar in principle while differing in the implementation. The particular power of the ambient ionization methods has been effectively demonstrated in the desorption ionization of non-volatile analytes from untreated solid or liquid samples. Depending on the strategy adopted for each individual method, the desorption and ionization processes occur simultaneously or in two separate steps. The desorption mechanism varies: in some experiments it depends on solution–solid extraction, in others on energy deposition with photons or pneumatic desorption and transport, and in still others, on reactions with reactive gas-phase species. The ionization goes through either an ESI-like process with charged droplets or an APCI-like process with reactions involving highly reactive ions or excited neutrals. An important application of these methods is the imaging of plant, animal, and human tissues. In all cases, the sample is directly analyzed outside the mass spectrometer without applying a matrix, which speeds up the entire analysis process and minimizes the possibility of altering the chemical properties of the surface of interest.

The development of ambient mass spectrometry takes advantage of the knowledge and experience accumulated in mass spectrometry as well as other areas of chemistry, physics and engineering. As an example, while highly simplified processes are involved in ambient mass spectrometry, tandem MS analysis is essential for improving the signal-to-noise ratio as well as for confirmation of analyte identities in untreated samples. The fact that the samples need not be processed prior to analysis does not preclude the deliberate use of chemical reactions with high specificity to cause selective ionization or to improve the desorption and/or ionization efficiencies of particular compounds.

This themed issue includes 2 reviews and 18 papers. The reviews by Weston and by Cooks and co-workers, respectively, are complementary to each other, with one reporting the current status and the other previewing future trends in ambient mass spectrometry. The papers by Wiseman et al., Fernandez et al., Green et al., Elberlin et al., and Figueiredo et al. report studies using charged droplets from sprays for desorbing and ionizing analytes. In the studies done by Vertes et al., Shiea et al., and Loo et al., lasers are used for desorption while charged droplets generated by electrospray are used for ionization of the analytes in the gas phase. In the work of the Vertes group, reactants are added in the spray solution to facilitate a reactive ionization and to enhance the structure-specific fragmentation of lipid ions. The contributions of Zenobi et al. and Chen et al. report another hybrid method in which charged droplets bring about ionization while a high velocity gas is used for analyte desorption. The papers by Cody et al., Domin et al., Hieftje et al., Cooks et al., Fernandez et al., and Ding et al. cover the second main category of methods (the first being spray-based methods) in which plasmas are used to generate active species at atmospheric pressure for desorption ionization. In the work done by Corso et al. and Basile et al., thermal desorption is used for desorption while charged droplets and charged reagent ions, respectively, are used for the subsequent ionization of the desorbed analytes.

The focus of relentless efforts over the past 40 years to extend the scope of mass spectrometry has sought extension of the molecular weights of compounds that can be converted into gas-phase ions. In the course of this endeavour, sight has been lost of other extremely important characteristics – the speed of the experiment, the complexity of the instrumentation, the need for high quality technical personnel, and particularly the amount of work-up associated with preparation of the sample for MS analysis. All these are key components of ambient mass spectrometry and its rapid acceptance so quickly in so many various forms is testimony to the depth of this unmet need that it addresses. We see continued extremely rapid development in the subject, particularly as miniature mass spectrometers are combined with ambient ionization to provide truly portable in situ MS analysis capabilities.

Zheng Ouyang

Purdue University, West Lafayette, IN, USA

Xinrong Zhang

Tsinghua University, Beijing, China

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