DART and DESI

Two further techniques that can be included under the title of direct analysis ate DART and DESI. The focus of these two techniques is slightly different from those already presented in this chapter. What distinguishes DART and DESI is that they do not foctts on gas phase VOCs but instead extract or wipe off analyte mol-ecttles from samples by exposing the sttrface to the ionizing gas or aerosol. The ionization still occms at atmospheric pressure. This enables the direct examination of completely improcessed samples or even entire objects. Both DESI and DART 

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The IMS had a resolving power of about 25 in this design. One primary advantage of MALDI over DART and DESI is that the last two ion sources are continuous, and... 

Wells, J.M., et al. (2008) Implementation of DART and DESI ionization on a fieldable mass spectrometer. Journal of the American Society for Mass Spectrometry, 19,1419-1424. 

Two new ionization methods to appear recently are desorption ESI (DESI) and direct analysis in real time (DART). They are the first in a new area of ionization mechanisms that are collectively referred to as open-air ionization. Both DART and DESI form ions in an open atmosphere and sample the resulting plume through an entrance cone into the mass spectrometer. 

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. 

The stand-alone chapters cover various topics - from metabolite identification to fast chromatography with UPLC - and in a style that is understandable to experts and field newcomers alike. The second edition of this bestseller includes coverage of new instrumentation and software as well as a wealth of updated information on the latest findings surrounding biomarkers and metabolomics and new chapters on both UPLC and DESI/DART. 

Two new independently developed techniques called Dart ° (direct analysis in real time) and Desi (desorption electrospray ionisation) are making a huge impact on mass spectrometry. Together they remove the need for sample preparation and vacuum, speed up analysis time and can work in the open air. The sample is held in a gas or liquid stream at room temperature and the impact induces the surface desorption of ions. The ions then continue into the vacuum interface of the MS for analysis. Samples can be hard, soft or even liquid in nature. Ifa et al. have used Desi to image biological samples in two dimensions, recording images of tissue sections and the relative concentrations of molecules therein. Jeol have launched a commercial Dart ion source for non-contact analysis of materials in open air under ambient conditions. 

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. 

A somewhat similar but mechanistically different ion source from DART is DESI. DESI ionization is accomplished by directing electrosprayed charged droplets and ions of the solvent onto a surface of the sample. Eigure 3.15 provides a schanatic of the DESI process. 

All these methods have one inportant characteristic in common they direct a stream of ionizing or at least ion-desorbing fluid medium onto a sarrple surface from which analyte ions are withdrawn and transported through air into the mass analyzer via a standard API interface. The beauty of this approach lies in the fact that a sarrple needs just to be exposed to the ionizing medium imder ambient conditions. In other words, DESI, DART and those numerous related methods enable the detection of surface materials like waxes, alkaloids, flavors, or pesticides from plants as well as explosives, pharmaceuticals, or drugs of abuse from luggage or banknotes. These and many more analytical apphcations are readily accessible by... 

Note Although the features of DESI and DART are in many ways superior and revolutionary , one should be aware of intrinsic limitations. The detection of a compound largely depends on the matrix, e.g., whether it is on or eventually in skin, fruit, bark, stone etc. This also results in a lack of quantification abilities. However, also no other single ionization method, especially when used under just one set of conditions, can deliver ions of all constituents of a complex sample. Nonetheless, DESI, DART and related methods can deliver a wealth of chemical information with unprecedented ease. 

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. 

Over the past two decades, QMF-based quantification assays have become the technique of choice for quantification of drug candidates and their metabolites. Combining a mass spectrometer with LC provides an additional degree of selectivity and makes the combined technique the method of choice for quantitative bioanalysis of drugs and metabolites. Among the mass spectrometer types, QMF are ideal for coupling with LC and atmospheric pressure ionization sources (ESI, APCI, APPI, DART, DESI, etc.) because QMFs have the lowest voltage requirements and vacuum requirements. 

Besides AP-MALDI, already described earlier, electrospray (ESI), atmospheric pressure chemical ionization (APCI), atmospheric pressure photoionization ionization (APPI), DESI and DART are other examples of atmospheric pressure ionization (API) sources. 

DART produces relatively simple mass spectra characterized by the presence of two main types of ions of the molecular species M,+ or [M + H]+ in positive ion mode and M or [M - H] in negative ion mode. Fragmentation is observed for most of the compounds. These results appear similar to those obtained with DESI, but no multiply charged ions are... 

Recently, a new family of ionization techniques that are distinguished by their ability to ionize analytes from surfaces under ambient conditions have been developed.61 These methods are also characterized by the fact that no prior separation or extraction of the sample is required. Of these methods two have so far been well characterized, desorption electrospray ionization (DESI)62 and direct analysis in real time (DART).63... 

Figure 9 Approximate ranges of analyte polarity and size that may be suited to different ionization techniques. With respect to the surface desorption techniques, DESI and DART, they are comparable in their range of application to ESI and APCI, respectively.

Two Most Established Ambient Ionization Methods DESI and DART.378... 

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],... 

In this chapter, we first provide an introduction to DESI and DART as the two most established ambient ionization methods. We then review some details on the early applications of DESI and DART in ADME studies. We close this chapter with some perspectives on the future role of ambient ionization methods in ADME studies. 

TWO MOST ESTABLISHED AMBIENT IONIZATION METHODS DESI AND DART... 

Shortly after the report on the DESI technique, DART was reported as another ambient ionization method [5], In this method, a gas with a high ionization potential such as helium or nitrogen flows through a probe that contains multiple chambers. The gas first flows into a discharge chamber where electrical discharge occurs by applying a potential of several thousand volts across a cathode and an anode. The... 

Although still at a very early stage, ambient ionization methods, mostly DESI and DART, have been evaluated and used in the ADME studies for drug candidates. The fact that ambient ionization methods can analyze samples without sample preparation seems extremely attractive for bioanalysis as sample preparation is widely considered as the key bottleneck in bioanalysis. Also, the fact that samples can be analyzed... 

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