Charged aerosol detector
The Charged Aerosol Detector (CAD) is a universal detector used in conjunction with high-performance liquid chromatography (HPLC) and ultra high-performance liquid chromatography (UHPLC) to measure the amount of chemicals in a sample by creating charged aerosol particles which are detected using an electrometer.[1][2][3][4] It is commonly used for the analysis of compounds that cannot be detected using traditional UV/Vis approaches due to their lack of a chromophore. The CAD can measure all non-volatile and many semi-volatile analytes including, but not limited to, antibiotics, excipients, ions, lipids, natural products, biofuels, sugars and surfactants.[4] The CAD, like other aerosol detectors (e.g., evaporative light scattering detectors (ELSD) and condensation nucleation light scattering detectors (CNLSD)), falls under the category of destructive general-purpose detectors (see Chromatography Detectors).
History
The predecessor to the CAD, termed an evaporative electrical detector, was first described by Kaufman at TSI Inc in US patent 6,568,245 and was based on the coupling of liquid chromatographic approaches to TSI’s electrical aerosol measurement (EAM) technology.[5] At around the same time Dixon and Peterson at California State University were investigating the coupling of liquid chromatography to an earlier version of TSI’s EAM technology, which they called an aerosol charge detector.[6] Subsequent collaboration between TSI and ESA Biosciences Inc. (now part of Thermo Fisher Scientific), led to the first commercial instrument, the Corona® CAD®, which received both the Pittsburgh Conference Silver Pittcon Editor’s Award (2005) and R&D 100 award (2005). Continued research and engineering improvements in product design resulted in CADs with ever increasing capabilities. The newest iterations of the CAD are the Thermo Scientific Corona™ Veo™ Charged Aerosol Detector and Corona™ Veo™ RS Charged Aerosol Detector and Thermo Scientific Vanquish™ Charged Aerosol Detectors.
2005 | 2006 | 2009 | 2011 | 2013 | 2015 |
---|---|---|---|---|---|
ESA Biosciences, Inc.
Corona™ CAD |
ESA Biosciences, Inc.
Corona™ PLUS |
ESA Biosciences, Inc.
Corona™ ultra |
Dionex™
Corona™ ultra RS |
Thermo Scientific™
Dionex™ Corona™ Veo |
Thermo Scientific™
Vanquish™ Charged Aerosol Detector |
•First commercial CAD
•Designed for near-universal detection on any HPLC •Isocratic or gradient separations |
•Expanded solvent compatibility
•Heated nebulization •External gas conditioning module for improved precision |
•UHPLC compatible
•Stackable design •Enhanced sensitivity •Incorporated precision internal gas regulation system |
•Unified with Dionex™
UltiMate™ 3000 UHPLC+ system •Added on-board diagnostics/monitoring •Automated flow diversion capability •Selection of linearization parameters |
•Extended micro flow
rate range •Total redesign with concentric nebulization and optimized spray chamber •Heated evaporation and electronic gas regulation |
•Full integration with Thermo
Scientific™ Vanquish™ UHPLC platform •Slide-in module design •Reduced flow path for optimum operation |
Principles of Operation
The general detection scheme involves:
- Pneumatic nebulization of mobile phase from the analytical column forming an aerosol.
- Aerosol conditioning to remove large droplets.
- Evaporation of solvent from the droplets to form dried particles.
- Particle charging using an ion jet formed via corona discharge.
- Particle selection - an ion trap is used to excess ions and high mobility charged particles.
- Measurement of the aggregate charge of aerosol particles using a filter/electrometer.
The CAD like other aerosol detectors, can only be used with volatile mobile phases. For an analyte to be detected it must be less volatile than the mobile phase.
More detailed information on how CAD works can be found on the Charged Aerosol Detection for Liquid Chromatography Resource Center.
CAD Performance and Comparison to Other Aerosol Detectors[4]
- The CAD and evaporative light scattering detector (ELSD) are mass-flow sensitive detectors (response is proportional to mass of analyte reaching the detector per unit time) as opposed to concentration sensitive (response is proportional to analyte concentration within the eluent at a particular time) detectors such as UV detectors.
- The CAD and ELSD are non-linear detectors. The shape of the response curves are different between the two detectors and this has major impact on their performance e.g., sensitivity, dynamic range, and precision.[5]
Charged Aerosol Detector (CAD) | Evaporative light scattering detector (ELSD) |
---|---|
• Detection limits extend to lower mass levels
• Wider quasi-linear and dynamic range (~ 104 to 105). • Gradual changes in slope = better precision |
• Exponential signal drop at low mass range
• Narrow quasi-linear and smaller dynamic range102 to 103) • Large changes in slope = poorer precision |
- The CAD shows better analyte response uniformity than ELSD and CNLSD. Analyte response uniformity can be defined as the same response factor (signal/amount) for all components i.e., response that is independent of analyte properties. The CAD’s response exhibits a minor dependence on such properties and consistently provides more uniform response than ELSD and CNLSD where the properties can have much more of an impact (e.g., wettability and solubility of the particle (CNLSD), refractive index, UV absorption and fluorescence (ELSD and CNLSD)).[4] For example, when quantifying a series of compounds differing in their physicochemical properties, the CAD showed a 8% RSD variation in response among non-volatile analytes. The CNLSD, however, showed a 39% RSD variation in response for the same suite of compounds.[5]
- The CAD typically shows better LODs and LOQs than ELSD.[4]
- The CAD consistently shows significantly better intra- and inter-day precision/ reproducibility than ELSD.[4]
References
- ↑ Gamache P. (2005) HPLC analysis of nonvolatile analytes using charged aerosol detection retrieved September 17, 2015.
- ↑ "Dionex - Charged Aerosol Detectors". www.dionex.com. Retrieved 2016-01-21.
- ↑ Vehovec, Tanja; Obreza, Aleš (2010-03-05). "Review of operating principle and applications of the charged aerosol detector". Journal of Chromatography A. 1217 (10): 1549–1556. doi:10.1016/j.chroma.2010.01.007.
- 1 2 3 4 5 6 Acworth, Ian N.; Kopaciewicz, William (2017). Gamache, Paul H., ed. Charged Aerosol Detection for Liquid Chromatography and Related Separation Techniques. John Wiley & Sons, Inc. pp. 67–162. doi:10.1002/9781119390725.ch2/summary. ISBN 9781119390725.
- 1 2 3 Gamache, Paul H.; Kaufman, Stanley L. (2017). Gamache, Paul H., ed. Charged Aerosol Detection for Liquid Chromatography and Related Separation Techniques. John Wiley & Sons, Inc. pp. 1–65. doi:10.1002/9781119390725.ch1/summary. ISBN 9781119390725.
- ↑ Dixon, Roy W.; Peterson, Dominic S. (2002-07-01). "Development and testing of a detection method for liquid chromatography based on aerosol charging". Analytical Chemistry. 74 (13): 2930–2937. doi:10.1021/ac011208l. ISSN 0003-2700. PMID 12141649.