## 3 Advanced Multidimensional Techniques for Aerosol WSOM Analysis
### Application of Off-Line Multidimensional MS Methodologies for Water-Soluble OA Analysis
However, this offline multidimensional separation method still has limitations in terms of the increased conceptual and instrumental complexity, the increased time of analysis when multiple fractions are selected for analysis in the 2D, phase-system incompatibility issues, and possibly reduced number of target unresolved analytes that can be addressed in the analysis [61]. On the other hand, in the LC \(\times\) LC approach, such as that applied by [PERSON] et al. [27] and [PERSON] et al. [58], all fractions are subjected to two different separations, thus providing a comprehensive characterization of the sample. The LC \(\times\) LC is a considerably faster  
Figure 2: Total sum of intensities for the per aqueous liquid chromatography (PALC) \(\times\) size-exclusion chromatography (SEC)–diode array (DAD) chromatogram of the water-soluble organic matter (WSOM) hydrophobic acids from (**a**) summer and (**b**) winter urban aerosol samples (color normalized to the intensity of the highest peak), and three-dimensional representation of the peak regional maxima location of the PALC \(\times\) SEC–DAD chromatograms of the WSOM hydrophobic acids from (**c**) summer and (**d**) winter samples. Reprinted with permission from the work of [PERSON] et al. [27]. Copyright © American Association for Aerosol Research, reprinted by permission of Taylor and Francis Ltd., www.tandfonline.com (accessed on 9 February 2021) on behalf of American Association for Aerosol Research, [[https://www.aaar.org/](https://www.aaar.org/)]([https://www.aaar.org/](https://www.aaar.org/)) (accessed on 9 February 2021). multidimensional separation method than LC-LC, with a high degree of orthogonality, thus proving a reliable fingerprint that allows an efficient comparison (often visual) of samples [27; 58]. Combined with HR-MS detection methods, LC \(\times\) LC is well suited for the untargeted analysis of the atmospheric WSOM samples, offering a thorough mapping of the complexity of these samples and enabling the identification of an unsurpassed number of organic compounds. In addition to the hyphenated approaches, there are other MS-based techniques that have also been used for acquiring detailed structural information on water-soluble OA. An example of this application is the development of a methodology using matrix-assisted laser desorption/ionization (MALDI) ToF-MS for the analysis of bioaerosol particles [62]. Nowadays, however, the most emerging systems based on MS for the analysis of aerosol WSOM is FT-ICR MS, with soft ionization techniques (e.g., ESI, MALDI) (e.g., references [26; 29; 63]). In such analytical systems, the soft ionization provides intact molecular ions, and the HR-MS can provide up to 25 billion theoretical plates of separation, thus allowing a rapid and definitive molecular mass determination of intact polar macromolecules that are difficult to analyze by the traditional hyphenated MS techniques [64]. The application of these HR-MS techniques has increased, mainly aiming at the identification of the molecular elemental composition of thousands of individual organic components for further investigations on the influence of the aerosol sources on the composition of OA [43; 45]. The detailed interpretation of these huge amounts of MS data generated by these HR-MS techniques requires data processing methods capable of handling all this information. Typically, the acquired data are represented in the form of van Krevelen diagrams, in which the H/C ratio is plotted as a function of the O/C ratio for each mass and corresponding molecular formula identified in a sample. As reviewed by [PERSON] et al. [22], these diagrams are plotted as three-dimensional figures with ion signal intensities included as an additional dimension, being often used to describe the evolution and differentiate potential sources of OA. Another approach to glean compositional information from HR-MS analysis of OA was introduced by [PERSON] et al. [64], who developed a framework to consider the chemical and physical evolution of OA.