## 3 Advanced Multidimensional Techniques for Aerosol WSOM Analysis
### Application of Off-Line Multidimensional MS Methodologies for Water-Soluble OA Analysis
For example, GC \(\times\) GC-ToF-MS has been successfully applied to the separation and detection of more than 15,000 peaks in atmospheric OA samples, of which up to 200 organic compounds have been identified, including \(n\)-alkanes, \(n\)-alkan-2-ones, \(n\)-alkanoic acid methyl esters, acetic acid esters, \(n\)-alkanoic acid amides, nitriles, linear alkylbenzes and 2-alkyltoluenes, hopanes, polycyclic aromatic hydrocarbons (PAH), alkylated PAH and oxidized PAH [56]. As in GC separations, GC \(\times\) GC is of limited application for the analysis of very polar and low volatile water-soluble OA. Nevertheless, comprehensive 2D liquid chromatography (LC \(\times\) LC) can be a leading technique for attaining a suitable chromatographic resolution of such water-soluble organic compounds, allowing to overcome the lack of chromatographic resolution of the traditional one-dimensional LC separation of complex mixtures. These multidimensional separation techniques provide a characteristic 2D separation pattern of a specific class of compounds, and when coupled to MS detection, can be quite useful for associating sample fingerprinting with the different parameters causing aerosols variabilities, such as the aerosol sources and the actual meteorological conditions. For example, LC \(\times\) LC coupled to electrospray ionization ToF-MS (ESI-ToF-MS) has been applied for the identification and quantification of carboxylic acids in rural and urban aerosol samples [57]. LC \(\times\) LC has also been employed for unraveling the complexity of WSOM from fine urban atmospheric aerosols and identify its seasonal patterns [27; 58]. In these studies, LC \(\times\) LC, combining the use of two independent separation mechanisms (per aqueous liquid chromatography (PALC) vs. size-exclusion chromatography (SEC)), was coupled with a diode array (DAD) and fluorescence (FL) detectors to map the hydrophobicity vs. molecular weight distribution of the most hydrophobic acid fractions in WSOM and alkaline-soluble organic matter from fine urban aerosols collected over different seasons. As shown in Figure 2a,b for samples collected during summer and winter, the PALC \(\times\) SEC method allowed the separation of WSOM hydrophobic acid samples into several fractions, with the UV absorption contour plots displaying different elution patterns [27]. Apparently, the obtained fractions exhibit different molar mass distributions and chemical characteristics in terms of hydrophobicity between the two different seasons (Figure 2c,d). More recently, [PERSON] et al. [59] employed a 2D offline chromatographic method (also known as the heart-cutting approach, denoted as LC-LC) combining SEC and reversed-phase LC (RP-LC) to characterize the so-called HULIS in aerosol particles. This method involved the collection of five SEC fractions (first dimension (1D) effluent) and their subsequent injection into the RP column (second dimension (2D)) for further separation into 11 fractions with different polarities, after being concentrated and redissolved in a proper solvent for injection into the second separation dimension. In the following study, the same group of authors characterized those 11 fractions collected from the RP column by means of Fourier transform-ion cyclotron resonance mass spectrometry (FT-ICR MS) to resolve the high complexity of the aerosol organic material [60]. The authors reported that the number of assigned molecular formulas increased by a factor of 2.3 for the fractionated sample (18,144) compared to a bulk sample analysis without fractionation (7819), with more than 15,000 compounds being identified in the fractionated sample (including organosulfates, reduced N-containing compounds, and polyaromatic compounds) [60]. This 2D offline chromatographic approach coupled to an HR-MS detection method offers an astounding separation power, besides being a simple and easy implementation of 2D LC.