| 22 Jul 2026
Coupling Liquid Chromatography with Aerosol Mass Spectrometry to Enhance Chemically Resolved Aerosol Analysis
Abstract. We present a novel analytical method that links liquid chromatography with aerosol mass spectrometry (LC-AMS) to separate and chemically characterize soluble constituents in atmospheric samples. This method is demonstrated here using ion chromatography (IC) to resolve ionic species prior to AMS detection. As the IC effluent is analyzed by the AMS, quantifiable ion signals and reproducible mass spectra are obtained every second throughout the chromatographic run. These chromatographically resolved AMS data yield quantitative information and chemical fingerprints for distinct and partially overlapping chromatographic features. The method was evaluated using standard mixtures of inorganic anions and cations, as well as atmospherically significant organic compounds (e.g., levoglucosan and organic acids). The IC-AMS chromatograms exhibited stable background signals, which permitted reliable integration of peak regions for quantification of the AMS-derived ions. Isotopically labeled ammonium sulfate ((NH4)234SO4) was used as an internal standard to account for variations in aerosol generation efficiency and AMS sensitivity. Low-volatility compounds, such as ammonium sulfate and sucrose, showed recoveries close to 100 %. Application to an ambient aerosol sample collected during a wildfire event demonstrated that LC-AMS offers improved chemical resolution that can better characterize aerosol sources, atmospheric processing, and climate- and health-relevant properties.
General comments
In this manuscript, Farley et al. describe a method for coupling ion chromatography (IC) with aerosol mass spectrometry (AMS). Because AMS employs electron ionization and operates under high-vacuum conditions, it is inherently incompatible with direct liquid sample introduction. The authors address this challenge by incorporating a nebulizer, cyclone, and diffusion dryer to convert the liquid effluent into an aerosol stream suitable for AMS analysis. Through this approach, they achieve substantially improved chemical resolution, particularly for organic compounds, compared with conventional AMS measurements, which are generally limited to providing bulk chemical composition or broad chemical class information. This development represents a potentially valuable advance in extending the molecular level characterization capabilities of AMS-based analyses. While the manuscript falls within the scope of AMT, several major issues need to be addressed before I can recommend its publication. Most importantly, the mechanism by which seemingly non-ionic organic compounds are retained and separated on the ion chromatography column requires a much clearer explanation. As outlined below, the current discussion does not adequately justify the reported separations or their underlying chemistry.
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Major comments
Line 203: I am a little surprised that the 14N15N+ ion can interfere with CHO+ ion at m/z 29, considering that the natural abundance of 15N is only about 0.37~0.38%. Where does it originate from? In my experience, column bleed typically produces a smoother and more consistent chromatographic background than the pulsed noise pattern shown in Fig. 4b, making quaternary ammonium groups derived from column materials a less likely source. Could the authors add a brief discussion of the possible origin of this interference and explain the observed background pattern?
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Line 225: I wonder what type of organic nitrate the authors have in mind when they attribute the higher than expected nitrate signal in the IC-AMS to the co-elution of organonitrates with inorganic nitrate. Unlike inorganic nitrate, organonitrates generally do not ionize in solution, which makes their separation on an IC column difficult. Even if organonitrates are somehow ionized, their retention times are likely to be very different from that of inorganic nitrate. Could the authors explain the mechanism by which organonitrates could increase the nitrate signal in IC-AMS? In particular, it would be helpful to clarify how co-elution with inorganic nitrate is expected to occur and whether there is experimental evidence supporting this interpretation.
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Line 239: I wonder how carbonyl compounds and esters can be separated using an anion-exchange column. Do these compounds form anionic species under the chromatographic conditions employed in this study? If so, could the authors clarify the chemical structures of the species being retained and separated?
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Line 265: The coupling of LC with EI-MS predates the development of the widely used atmospheric pressure ionization techniques such as ESI and APCI. However, coupling LC to an EI source is intrinsically challenging because the high eluent flow rates and the relatively low volatility of typical reversed-phase and HILIC eluent and additives are fundamentally incompatible with the high vacuum conditions required for EI operation. Considerable efforts were made to develop LC/EI-MS interfaces, particularly up to the early 2000s. Nevertheless, the technique has seen limited acceptance as a practical analytical tool, largely because its advantages over ESI and APCI are confined to relatively niche applications.
I therefore suggest that the authors either provide a more comprehensive historical perspective on LC/EI-MS, including a discussion of previously developed interfaces and a clear explanation of how the approach described in this manuscript overcomes their limitations, or omit this section altogether. Without such context, the significance and novelty of the method are difficult to assess.
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Technical corrections
Line 55: Electron Impact should be replaced with Electron Ionization, as the latter is the IUPAC-recommended term.
Line 149: A space is missing between "1" and "ppm" in NaBr (1ppm).
Line 196: It has one extra period.