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The analyte detection challenge
One of the biggest challenges liquid chromatographers currently face with analyte detection is no single method can reliably measure all compounds. Often, analytes respond more strongly to one form of detection than another, like UV versus MS, or do not respond at all.
What is most needed is the ability to detect a wide range of analytes—from small molecules to antibodies—with a response that delivers accurate quantitation.
For complex separations where multiple analytes in a sample are incompatible with UV and MS detectors, like when compounds lack a chromophore or cannot ionize, liquid chromatographers can turn to a universal detection approach called Charged Aerosol Detection (CAD).
The Charged Aerosol Detector provides a uniform analyte response and standard relative quantitation capable of detecting all non-volatile and many semi-volatile compounds irrespective of the chemical structure.
By meeting the flexibility and performance needs for analytical R&D studies and the simplicity and reproducibility demands for manufacturing quality control in QA/QC studies, CAD gives chromatographers more confidence in every LC analysis.
The CAD can measure all analytes in the two samples shown above. Other detectors are more limited in scope. For example, mass spectrometry (MS) requires that analytes form gas phase ions (A) while response by a UV detector depends upon the nature of the chromophore (A and B).
Charged aerosol detection
Related resources
How Charged Aerosol Detection works
Charged Aerosol Detectors utilize evaporative technology. The conversion of an analyte to a detectable signal involves the same successive steps:
Schematic of CAD technology
Nebulization
Charged Aerosol Detection begins by nebulizing the column eluent into droplets and subsequently drying the droplets into particles. The particle size increases with the amount of analyte.
Charging
A stream of ionized nitrogen gas collides with the analyte particles in the mixing chamber. The charge transfers from the ionized gas to the analyte particles—the larger the particle, the greater the charge.
Detection
The charged particles transfer to a collector, where an extremely sensitive electrometer measures the aggregate charge. This process generates a signal directly proportional to the mass of the analyte present.
CAD history
Before the invention of CAD, liquid chromatographers relied on detectors such as refractive index, low wavelength UV absorbance, and evaporative light scattering for quantitative analyses.
While these HPLC detection methods helped analyze compounds incompatible with traditional UV-Vis detectors, they were also limited because of low sensitivity and quantitation challenges, severely impacting method development and research progression.
The first Charged Aerosol Detector, the Thermo Scientific Corona CAD, was introduced to the scientific community at the Pittsburgh Conference in 2005 and became commercially available soon after. The Corona CAD received both the Pittsburgh Conference Silver Pittcon Editor’s Award and the R&D 100 award in recognition of its potential.
CAD is now a preferred universal LC detector for both routine and complex analyses, driven by the need for sensitive, near-universal analyte response and standard-free quantitation.
Advancing CAD technology
The most impactful technology advancement happened in 2013 when the detector was fully redesigned and introduced by Thermo Scientific as the Thermo Scientific Corona Veo RS Charged Aerosol Detector, and later the Thermo Scientific Vanquish Charged Aerosol Detectors.
These major redesigns markedly improved the detector performance and user-friendliness in a few ways:
- Added sensitivity—chromatographers can routinely detect sub-nanogram analyte levels with confidence.
- Better versatility—the evaporation temperature is controllable and, as part of method development, used to improve the analyte response.
- Operational convenience—liquid waste drains freely like all other liquid chromatography detectors, along with active monitoring of the detector status to ensure optimal performance.
CAD benefits
The CAD shows uniform response (<5% RSD variation) among all non-volatile analytes (0.5 μg; flow injection analysis).
More information can be found in Technical Note TN72806.
The most desired feature of a near-universal detector like CAD is the ability to both quantitatively measure compounds incompatible with UV-Vis and MS detection and relative amounts of compounds when certified standards are not available for a single calibrant quantification.
The Charged Aerosol Detector also increases the efficiency of existing analytical operations and may open up entirely new possibilities by exploiting a range of analytes unseen by other detection methods.
Major benefits of using CAD include:
- An accurate response for all non-volatile compounds independent of analyte structure
- Excellent sub-nanogram sensitivity coupled with a wide dynamic range for unrivaled performance
- Single calibrant for the quantification of multiple analytes when individual standards are not available
- Full compatibly with gradient runs—the impact of gradient elution on uniform response is minimized using the Thermo Scientific Vanquish Duo UHPLC System
CAD publications
This collection of publications is a resource to demonstrate the analytical capabilities of CAD by highlighting the breadth and scope of the different analytical applications found in the literature.
The Chared Aerosol Detector delivers versatility and allows chromatographers to use traditional HPLC, UHPLC, and nano-flow separations. In many cases, CAD can eliminate the need for derivatization or sample pretreatment, providing dilute-and-shoot simplicity.
Scientists in diverse areas like pharmaceuticals, food and beverage, natural products, fundamental research, and environmental testing rely on this detection method for complete analyses.
Pharma and biopharma
Pharmaceutical · biopharmaceutical · biotechnology
These publications cover analysis of small and large APIs, counterions, excipients and adjuvants, liposome characterization, QC library measurement, degradants/impurities, analyte purity, and stability.
Biochemical research
Biochemical research · life science
These articles cover many disciplines relevant to the study of living organisms including the fields of biochemistry, biology, microbiology, and physiology.
Natural products
Botanicals · herbals · natural products · traditional medicines
Articles include the measurement of different classes of compounds found in plant extracts, many of which are used in traditional medicines. Some highlight CAD for analyte quantitation when reference standards are unavailable.
Food and nutrition
Foods · supplements · functional foods · consumer products
Includes publications describing the use of the CAD for measurement of analytes like carbohydrates and lipids, plus metabolomic approaches for determining product authenticity and adulteration.
Industry and environment
Industrial · environmental · agricultural · fuels sector
This section spans many industries including agriculture and farming, petrochemical, environmental, and the production and use of plastics and polymers.
Clinical research
Health · disease
Includes topics such as tissue drug measurement in fresh and post-mortem samples, effects of drugs, and how disease progression affects metabolism.
HPLC & UHPLC analysis
Chromatography · method development · detector performance
Articles include fundamentals, operating principles, detector optimization, detector comparison, method development, and evaluation of columns.
Thermo Scientific Charged Aerosol Detectors
Cutting-edge detection technology combined with modern instrumentation empowers liquid chromatographers to measure the previously unmeasurable and deliver results without compromise.
Our Thermo Scientific Charged Aerosol Detectors seamlessly combine with Thermo Scientific HPLC and UHPLC systems, leading column technologies, and advanced data handling to help you:
- Characterize versatile classes of compounds
- Analyze a broad range of samples
- Profile or quantify substances
Vanquish Charged Aerosol Detectors and Corona Veo Charged Aerosol Detectors provide:
- Simple, intuitive operation
- Wide linear and dynamic range
- Sub-nanogram sensitivity
- Method flexibility covering micro-flow HPLC and UHPLC applications with a single nebulizer
- Adjustable evaporation temperature to optimize signal-to-noise ratio
Thermo Scientific Vanquish Flex UHPLC System
with Vanquish Charged Aerosol Detector
More information: Discover what you’re missing with Thermo Scientific Charged Aerosol Detectors, Brochure BR70735
CAD testimonials
Dive into the technical capabilities of our unique HPLC/UHPLC detector. Hear from industry experts in pharma/biopharma and food/beverage how you can easily apply the CAD in your analyses along with tips, tricks, pointers, and advice from our guest speakers.
Access our full CAD symposium webinar series on-demand here.
“The Vanquish CAD system is intuitive to work with and requires minimal maintenance, which gives it potential to be used by industry for in-house testing.”
– Hilary G.| UC Davis Olive Oil Center
“We are living a love story with Vanquish Duo + CAD. In addition to sensitivity, its robustness and reliability keep our relationship secure. Coupled with CAD, we go further with this love story that reveals precisely unknown compounds … streamlining processes, reducing costs with maximum quality.”
– Emilia G. | GM Regulatórios
Additional resources
Charged Aerosol Detection - factors affecting uniform analyte response
HPLC-Charged Aerosol Detection for excipients
Getting the most out of your Charged Aerosol Detector
FAQ
Charged Aerosol Detectors utilize evaporative technology. The conversion of an analyte to a detectable signal involves (i) nebulization of the eluent stream, (ii) drying of the nebulized droplet aerosol into analyte particles, (iii) transfer of positive charge from ionized gas to the evaporated analyte particles, and, (iv) detection of the charged analyte particles.
Both CAD and ELSD are evaporative aerosol detectors able to detect non-volatile and many semi-volatile compounds. But how the particles are detected differs between the two technologies. CAD measures particle charge while ELSD measures the ability of the particle to scatter light.
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CMD Wide-format style fixes