Direct Analysis in Real Time DART

A gas (usually helium) flows through a corona discharge where it can be ionized or form excited (metastable) atoms. 

The ions are removed from the gas stream and the remaining excited atoms, heated as necessary, are directed onto the sample. 

Energetic atoms generate ions directly at the sample surface by causing ejection of an electron to form [M] ions, or alternatively, ambient water is ionized and forms a cluster with the analyte where proton transfer yields [M + Hj ions. 

A competing process that ionizes oxygen leads to negatively charged species, e.g., [M - H] ions. 

Heat from the helium flow, combined with like-charge repulsion of ionized sample, evaporate the analyte ions. The desorbed ions enter the mass analyzer via a skimmer cone. 

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A new family of ionization techniques allows ions to be created under ambient conditions and then collected and analyzed by MS. They can be divided into two major classes desorption electrospray ionization (DESI) and direct analysis in real time (DART). 

Direct analysis in real time DART Discharge Nonvolatile molecular ions Direct, preparation-free analysis of samples... 

Direct analysis in real time (DART) was introduced in 2005 by Cody et al. [109]. Similarly to DESI samples can be analyzed directly without preparation. While analytes in the small protein range can be analyzed by DESI, DART is in practice limited to analysis of ions in the region below 1 kDa or slightly above. However, as in SIMS, for example, fragment spectra of larger componds can be acquired, which can provide useful information, although the molecular ion cannot be observed. 

API offers unique opportunities for the implementation of new sources or to develop new applications. Atmospheric pressure matrix assisted laser desorption (AP-MALDI) [21] can be mounted on instruments such as ion traps which were originally designed only for electrospray and LC-MS. New API desorption techniques such as desorption electrospray (DESI) [22] or direct analysis in real time (DART) [23] have been described and offer unique opportunities for the analysis of surfaces or of solid samples. 

DART Direct analysis in real time (DART) is an analogous technique to DESI that does not require the electrospray solvent (Cody et al., 2005 McEwen et al., 2005 Williams et al., 2006). 

A new ion source has been developed for rapid, non-contact analysis of materials at ambient pressure and at ground potential [8,9], The new source, termed direct analysis in real time (DART), is based on the atmospheric pressure interactions of long-lived electronic excited-state atoms or vibronic excited-state molecules with the sample and atmospheric gases. Figure 5 shows a schematic diagram of the DART ion source. 

Fig. 5. Schematic diagram of direct analysis in real time (DART) ion source. Reproduced with permission from Cody et al. [9]. Copyright 2005 American Chemical Society.

The direct analysis in real time (DART) method has been described by Cody et al. [88] and commercialized by JEOL. This method allows direct detection of chemicals on surfaces, in liquids and in gases without the need for sample preparation. All of these analyses take place under ambient conditions in a space just in front of the inlet of the mass spectrometer. The sample is not altered because no exposure to high voltage or to vacuum is required. 

Seemingly, the next frontier for fast bioanalysis is the removal of the column altogether. Techniques such as direct analysis in real time (DART) and desorption electrospray ionization (DESI) have shown great potential. These techniques are discussed in more detail in Chapter 13. 

One of the most significant developments in mass spectrometry in the recent years is the introduction of a new class of ionization methods where samples in either solid or liquid state can be directly ionized in their native environment under ambient conditions (rather than inside a mass spectrometer) without any sample preparation. This new class of ionization methods is often referred to as ambient ionization methods [1,2], Because these methods generally ionize analytes on the surface or near the surface of the samples at atmospheric pressure, they have also been called atmospheric pressure surface sampling/ionization methods or direct/open air ionization methods [3], Since the first reports on ambient ionization with desorption electrospray ionization (DESI) [4] and direct analysis in real time (DART) [5], numerous reports have been published on the applications of these new ionization methods as well as the introduction of many related ambient ionization methods such as desorption atmospheric pressure chemical ionization (DAPCI) [6], atmospheric solid analysis probe (ASAP) [7], and electrospray-assisted laser desorption/ionization (ELDI) [8], Recently, two reviews of the various established and emerging ambient ionization methods have been published [2,3],... 

Pierce, C.Y. et al., Ambient generation of fatty acid methyl ester ions from bacterial whole cells by direct analysis in real time (DART) mass spectrometry, Chem. Commun., (8), 807, 2007. 

A new generation of mass spectrometer inlets allow for direct sampling of a substrate under ambient conditions. Theoretically, this eliminates the need for any sample preparation. Examples include direct analysis in real time (DART) and desorption electrospray ionization (DESI), as well as desorption atmospheric-pressure chemical ionization (DAPCI) and atmospheric solids analysis probe (ASAP). These techniques utilize a source of energy interacting directly with a sample surface at ambient pressure, causing molecules of interest to desorb, ionize, and be sampled by a mass spectrometer. 

Atmospheric pressure ionization (API). The need to analyze polar componnds and the necessity to interface LC with MS led to the development of techniqnes where the ionization occurs at atmospheric pressure outside the vacuum chamber, and the resulting ions are transferred directly into the mass analyzer. Electrospray ionization (ESI) is the most successful of the API methods because of the range of molecular masses to which it can be applied, from small molecules to proteins. Other API methods include atmospheric pressure chemical ionization (APCI) and atmospheric pressure photo-ionization (APPI), and also the recently developed surface ionization methods such as desorption electrospray ionization (DESI) and direct analysis in real time (DART) (see below and Sections 2.2.2 and 2.2.3). 

FIGURE 2.18 Direct analysis in real time (DART) source. 

Methods Ambient ionization methods, of which there are now over 20, e.g., desorption electrospray ionization (DESI), desorption atmospheric pressure chemical ionization (DAPC), desorption atmospheric pressme photo-ionization (DAPPI), and direct analysis in real time (DART), are now joined by paper spray, a method where ESI is initiated at the pointed tip of a piece of filter paper. A drop of blood ( 15 pi) is dried on the paper, and then the paper is moistened with 25 pi of a solvent suited to both the extraction of the analytes from the blood and the ESI process (e.g., 90% methanol 10% water with either 100 ppm acetic acid or 200 ppm sodium acetate). When the paper is exposed to high voltage (3-5 kV) while held close ( 5 mm) to the entrance of the mass analyzer, a spray (similar to electrospray) is induced at the tip of the paper as capillary action carries extracted compounds through the paper (Figure 4.5). The spray is maintained for 30-90 s at a flow rate comparable to that used in nano-electrospray. 

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