Getting the most out of your charged aerosol detector - TECHNICAL GUIDE

Significance of the topic

Charged Aerosol Detection (CAD) has emerged as a universal, non-optical detection technique offering high sensitivity and uniform response for non-volatile and semi-volatile analytes. Unlike traditional UV/Vis detectors, CAD measures charged aerosol particles, making its performance strongly dependent on analyte volatility and mobile phase composition. Its versatility supports applications across pharmaceutical development, lipidomics, carbohydrate analysis and QA/QC workflows.

Objectives and study overview

This guide is divided into two main parts. Part A examines the fundamental factors affecting CAD performance, including scope of detection, key performance parameters (noise, drift, background current), system configuration, sources of contamination, and column behavior. Part B presents practical best practices for routine operation, covering instrument start-up and shutdown, mobile phase preparation, flow injection analysis (FIA) troubleshooting, calibration strategies, and maintenance protocols.

Methodology and instrumentation

Performance metrics were obtained by measuring aerosol particle number and size distributions (using a Scanning Mobility Particle Sizer), baseline noise and drift under default CAD settings (evaporation temperature, data collection rate, filter constant). Analyte volatility was correlated with boiling point, vapor pressure and enthalpy of vaporization cut-offs. The impact of mobile phase purity, solvent grade, additives, water quality and container leachables on background current was systematically assessed. Flow splitting approaches and inverse gradient compensation were evaluated for multi-detector setups. Column bleed and cleaning protocols were investigated to maintain low noise.

Instrumentation

• Thermo Scientific Corona Veo RS Charged Aerosol Detector
• Thermo Scientific Vanquish and Vanquish Horizon UHPLC systems with VWD/DAD and MS interfaces
• Scanning Mobility Particle Sizer (TSI Model 3938) for aerosol characterization
• Nitrogen supply by cylinder, dewar or generator with inline filtration

Main results and discussion

• Non-volatile compounds (boiling point>400 °C, ΔHvap>65 kJ/mol) exhibit uniform CAD response; semi-volatiles show reduced sensitivity at low mass loadings; true volatiles remain undetected.
• Background current and noise rise with formation of non-volatile salts (influenced by additive volatility and concentration, evaporation temperature).
• High-purity solvents (LC/MS grade) and ultrapure water are essential to minimize drift and baseline artifacts; glassware and vials must be triple-rinsed or pre-certified.
• Inverse gradient or post-column solvent addition compensates for viscosity and surface tension changes during gradients, stabilizing response.
• Static and adjustable flow splitters enable CAD–MS coupling; balancing backpressure and dispersion is critical for multi-detector configurations.
• Column bleed from stationary phase degradation and pH extremes contributes to background noise; smaller-bore UHPLC columns reduce bleed and enhance sensitivity.
• Routine flushing with high-purity solvent mixtures and periodic high-temperature cycles effectively restore detector performance; preventive maintenance is recommended for persistent noise.

Benefits and practical applications of the method

• Universal detection independent of chromophoric or ionization properties.
• Uniform response enables quantitation with a single calibration standard and estimation without individual analyte standards.
• Seamless integration with UV/Vis and MS detectors for comprehensive impurity profiling in pharmaceutical, biochemical and industrial analyses.
• Robust detection of low-level analytes in QA/QC, stability testing, lipid profiling and carbohydrate analysis.

Future trends and opportunities

• Adoption of sub-2 µm UHPLC columns and microflow CAD for enhanced sensitivity and reduced solvent consumption.
• Development of advanced volatility prediction models to guide evaporation temperature settings and method optimization.
• Automation of mobile phase screening and vial qualification workflows to accelerate method development.
• Software enhancements for dynamic power-function selection, real-time noise monitoring and integrated performance qualification.

Conclusion

Charged Aerosol Detection provides a powerful and versatile platform for detecting a broad range of analytes in liquid chromatography. Achieving reliable performance requires attention to analyte volatility, mobile phase purity, instrument configuration and regular maintenance. By following the outlined best practices, laboratories can ensure reproducible, high-quality results across diverse analytical applications.

References

• 1. Menz M, Eggart B, Lovejoy K, Acworth I, Gamache P, Steiner F. Charged aerosol detection: factors affecting uniform analyte response. Thermo Fisher Scientific Technical Note 72806.
• 2. Wang J, Liu G, Zhu B, Tang L. Universal quantification method of degradation impurities in 16-membered macrolides using HPLC-CAD and study on source of the impurities. J. Pharm. Biomed. Anal. 2020;184:113170.
• 3. Squibb AW, Taylor MR, Parnas BL, Williams G, Girdler R, Waghorn P, Wright AG, Pullen FS. Application of parallel gradient HPLC with UV, ELSD and ESI-MS for quantitative quality control of the compound library to support pharmaceutical discovery. J. Chromatogr. A. 2008;1189:101–108.
• 4. Meding S, Lovejoy K, Swart R, Steiner F, Ruehl M. A multi-detector platform comprising UV/Vis, charged aerosol and single quadrupole MS detection for comprehensive sample analysis. Thermo Scientific Application Note 72869.
• 5. Grosse S, Muellner T, Lovejoy K, Acworth I, Gamache P. Why use charged aerosol detection with inverse gradient? Thermo Scientific Technical Note 73449.
• 6. Plante M, Bailey B, Kusinitz F, Acworth I. Effect of mobile phase quality on analytical performance of CAD. Thermo Scientific Technical Note 159.
• 7. Neubauer M, Franz H. Optimizing and monitoring solvent quality for UV-Vis, fluorescence and CAD detectors. Thermo Scientific Technical Note 140.
• 8. Gamache PH, editor. Charged aerosol detection for liquid chromatography and related separation techniques. John Wiley & Sons, 2017.
• 9. Gamache P, Muellner T, Eggart B, Lovejoy K, Acworth I. Charged aerosol detection: use of the power function and robust calibration practices. Thermo Scientific Technical Note 73299.
• 10. Bailey P, Gamache P, Acworth I. Guidelines for method transfer and optimization—from earlier model Corona detectors to Corona Veo Detectors. Thermo Scientific Technical Note 71290.