Charged aerosol detector

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The charged aerosol detector (CAD) is a 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).

Contents

History

The predecessor to the CAD, termed an evaporative electrical detector, was first described by Kaufman in 2002 at TSI Inc in US patent 6,568,245 [5] and was based on the coupling of liquid chromatographic approaches to TSI's electrical aerosol measurement (EAM) technology. [6] 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. [7] 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). [8] Continued research and engineering improvements in product design resulted in CADs with ever increasing capabilities. [9] The newest iterations of the CAD are the Thermo Scientific Corona Veo Charged Aerosol Detector, [10] Corona Veo RS Charged Aerosol Detector [11] and Thermo Scientific Vanquish Charged Aerosol Detectors. [12]

200520062009201120132015
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 [13] involves:

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. [14]

Performance and comparison to other aerosol detectors

Related Research Articles

In chemical analysis, chromatography is a laboratory technique for the separation of a mixture into its components. The mixture is dissolved in a fluid solvent called the mobile phase, which carries it through a system on which a material called the stationary phase is fixed. Because the different constituents of the mixture tend to have different affinities for the stationary phase and are retained for different lengths of time depending on their interactions with its surface sites, the constituents travel at different apparent velocities in the mobile fluid, causing them to separate. The separation is based on the differential partitioning between the mobile and the stationary phases. Subtle differences in a compound's partition coefficient result in differential retention on the stationary phase and thus affect the separation.

<span class="mw-page-title-main">High-performance liquid chromatography</span> Technique in analytical chemistry

High-performance liquid chromatography (HPLC), formerly referred to as high-pressure liquid chromatography, is a technique in analytical chemistry used to separate, identify, and quantify specific components in mixtures. The mixtures can originate from food, chemicals, pharmaceuticals, biological, environmental and agriculture, etc, which have been dissolved into liquid solutions.

<span class="mw-page-title-main">Ion source</span> Device that creates charged atoms and molecules (ions)

An ion source is a device that creates atomic and molecular ions. Ion sources are used to form ions for mass spectrometers, optical emission spectrometers, particle accelerators, ion implanters and ion engines.

<span class="mw-page-title-main">Gas chromatography</span> Type of chromatography

Gas chromatography (GC) is a common type of chromatography used in analytical chemistry for separating and analyzing compounds that can be vaporized without decomposition. Typical uses of GC include testing the purity of a particular substance, or separating the different components of a mixture. In preparative chromatography, GC can be used to prepare pure compounds from a mixture.

<span class="mw-page-title-main">Gas chromatography–mass spectrometry</span> Analytical method

Gas chromatography–mass spectrometry (GC–MS) is an analytical method that combines the features of gas-chromatography and mass spectrometry to identify different substances within a test sample. Applications of GC–MS include drug detection, fire investigation, environmental analysis, explosives investigation, food and flavor analysis, and identification of unknown samples, including that of material samples obtained from planet Mars during probe missions as early as the 1970s. GC–MS can also be used in airport security to detect substances in luggage or on human beings. Additionally, it can identify trace elements in materials that were previously thought to have disintegrated beyond identification. Like liquid chromatography–mass spectrometry, it allows analysis and detection even of tiny amounts of a substance.

<span class="mw-page-title-main">Column chromatography</span> Method to isolate a compound in a mixture

Column chromatography in chemistry is a chromatography method used to isolate a single chemical compound from a mixture. Chromatography is able to separate substances based on differential adsorption of compounds to the adsorbent; compounds move through the column at different rates, allowing them to be separated into fractions. The technique is widely applicable, as many different adsorbents can be used with a wide range of solvents. The technique can be used on scales from micrograms up to kilograms. The main advantage of column chromatography is the relatively low cost and disposability of the stationary phase used in the process. The latter prevents cross-contamination and stationary phase degradation due to recycling. Column chromatography can be done using gravity to move the solvent, or using compressed gas to push the solvent through the column.

<span class="mw-page-title-main">Liquid chromatography–mass spectrometry</span> Analytical chemistry technique

Liquid chromatography–mass spectrometry (LC–MS) is an analytical chemistry technique that combines the physical separation capabilities of liquid chromatography with the mass analysis capabilities of mass spectrometry (MS). Coupled chromatography – MS systems are popular in chemical analysis because the individual capabilities of each technique are enhanced synergistically. While liquid chromatography separates mixtures with multiple components, mass spectrometry provides spectral information that may help to identify each separated component. MS is not only sensitive, but provides selective detection, relieving the need for complete chromatographic separation. LC–MS is also appropriate for metabolomics because of its good coverage of a wide range of chemicals. This tandem technique can be used to analyze biochemical, organic, and inorganic compounds commonly found in complex samples of environmental and biological origin. Therefore, LC–MS may be applied in a wide range of sectors including biotechnology, environment monitoring, food processing, and pharmaceutical, agrochemical, and cosmetic industries. Since the early 2000s, LC–MS has also begun to be used in clinical applications.

<span class="mw-page-title-main">Solid-phase extraction</span> Process to separate compounds by properties

Solid-phase extraction (SPE) is a solid-liquid extractive technique, by which compounds that are dissolved or suspended in a liquid mixture are separated, isolated or purified, from other compounds in this mixture, according to their physical and chemical properties. Analytical laboratories use solid phase extraction to concentrate and purify samples for analysis. Solid phase extraction can be used to isolate analytes of interest from a wide variety of matrices, including urine, blood, water, beverages, soil, and animal tissue.

<span class="mw-page-title-main">Atmospheric-pressure chemical ionization</span> Ionization method

Atmospheric pressure chemical ionization (APCI) is an ionization method used in mass spectrometry which utilizes gas-phase ion-molecule reactions at atmospheric pressure (105 Pa), commonly coupled with high-performance liquid chromatography (HPLC). APCI is a soft ionization method similar to chemical ionization where primary ions are produced on a solvent spray. The main usage of APCI is for polar and relatively less polar thermally stable compounds with molecular weight less than 1500 Da. The application of APCI with HPLC has gained a large popularity in trace analysis detection such as steroids, pesticides and also in pharmacology for drug metabolites.

See Patented via Nth Cycle for metal electro-extraction process.

Reversed-phase liquid chromatography (RP-LC) is a mode of liquid chromatography in which non-polar stationary phase and polar mobile phases are used for the separation of organic compounds. The vast majority of separations and analyses using high-performance liquid chromatography (HPLC) in recent years are done using the reversed phase mode. In the reversed phase mode, the sample components are retained in the system the more hydrophobic they are.

<span class="mw-page-title-main">Hydrophilic interaction chromatography</span> Type of chromatography

Hydrophilic interaction chromatography is a variant of normal phase liquid chromatography that partly overlaps with other chromatographic applications such as ion chromatography and reversed phase liquid chromatography. HILIC uses hydrophilic stationary phases with reversed-phase type eluents. The name was suggested by Andrew Alpert in his 1990 paper on the subject. He described the chromatographic mechanism for it as liquid-liquid partition chromatography where analytes elute in order of increasing polarity, a conclusion supported by a review and re-evaluation of published data.

Supercritical fluid chromatography (SFC) is a form of normal phase chromatography that uses a supercritical fluid such as carbon dioxide as the mobile phase. It is used for the analysis and purification of low to moderate molecular weight, thermally labile molecules and can also be used for the separation of chiral compounds. Principles are similar to those of high performance liquid chromatography (HPLC); however, SFC typically utilizes carbon dioxide as the mobile phase. Therefore, the entire chromatographic flow path must be pressurized. Because the supercritical phase represents a state whereby bulk liquid and gas properties converge, supercritical fluid chromatography is sometimes called convergence chromatography. The idea of liquid and gas properties convergence was first envisioned by Giddings.

<span class="mw-page-title-main">Thermospray</span>

Thermospray is a soft ionization source by which a solvent flow of liquid sample passes through a very thin heated column to become a spray of fine liquid droplets. As a form of atmospheric pressure ionization in mass spectrometry these droplets are then ionized via a low-current discharge electrode to create a solvent ion plasma. A repeller then directs these charged particles through the skimmer and acceleration region to introduce the aerosolized sample to a mass spectrometer. It is particularly useful in liquid chromatography-mass spectrometry (LC-MS).

Sample preparation for mass spectrometry is used for the optimization of a sample for analysis in a mass spectrometer (MS). Each ionization method has certain factors that must be considered for that method to be successful, such as volume, concentration, sample phase, and composition of the analyte solution. Quite possibly the most important consideration in sample preparation is knowing what phase the sample must be in for analysis to be successful. In some cases the analyte itself must be purified before entering the ion source. In other situations, the matrix, or everything in the solution surrounding the analyte, is the most important factor to consider and adjust. Often, sample preparation itself for mass spectrometry can be avoided by coupling mass spectrometry to a chromatography method, or some other form of separation before entering the mass spectrometer. In some cases, the analyte itself must be adjusted so that analysis is possible, such as in protein mass spectrometry, where usually the protein of interest is cleaved into peptides before analysis, either by in-gel digestion or by proteolysis in solution.

A chromatography detector is a device that detects and quantifies separated compounds as they elute from the chromatographic column. These detectors are integral to various chromatographic techniques, such as gas chromatography, liquid chromatography, and high-performance liquid chromatography, and supercritical fluid chromatography among others. The main function of a chromatography detector is to translate the physical or chemical properties of the analyte molecules into measurable signal, typically electrical signal, that can be displayed as a function of time in a graphical presentation, called a chromatograms. Chromatograms can provide valuable information about the composition and concentration of the components in the sample.

<span class="mw-page-title-main">Direct electron ionization liquid chromatography–mass spectrometry interface</span>

A direct electron ionization liquid chromatography–mass spectrometry interface is a technique for coupling liquid chromatography and mass spectrometry (LC-MS) based on the direct introduction of the liquid effluent into an electron ionization (EI) source. Library searchable mass spectra are generated. Gas-phase EI has many applications for the detection of HPLC amenable compounds showing minimal adverse matrix effects. The direct-EI LC-MS interface provides access to well-characterized electron ionization data for a variety of LC applications and readily interpretable spectra from electronic libraries for environmental, food safety, pharmaceutical, biomedical, and other applications.

<span class="mw-page-title-main">Capillary electrochromatography</span> Method of separating components of a mixture via electro-osmosis

In chemical analysis, capillary electrochromatography (CEC) is a chromatographic technique in which the mobile phase is driven through the chromatographic bed by electro-osmosis. Capillary electrochromatography is a combination of two analytical techniques, high-performance liquid chromatography and capillary electrophoresis. Capillary electrophoresis aims to separate analytes on the basis of their mass-to-charge ratio by passing a high voltage across ends of a capillary tube, which is filled with the analyte. High-performance liquid chromatography separates analytes by passing them, under high pressure, through a column filled with stationary phase. The interactions between the analytes and the stationary phase and mobile phase lead to the separation of the analytes. In capillary electrochromatography capillaries, packed with HPLC stationary phase, are subjected to a high voltage. Separation is achieved by electrophoretic migration of solutes and differential partitioning.

Ion suppression in LC-MS and LC-MS/MS refers to reduced detector response, or signal:noise as a manifested effect of competition for ionisation efficiency in the ionisation source, between the analyte(s) of interest and other endogenous or exogenous species which have not been removed from the sample matrix during sample preparation. Ion suppression is not strictly a problem unless interfering compounds elute at the same time as the analyte of interest. In cases where ion suppressing species do co-elute with an analyte, the effects on the important analytical parameters including precision, accuracy and limit of detection can be extensive, severely limiting the validity of an assay's results.

An evaporative light scattering detector (ELSD) is a destructive chromatography detector, used in conjunction with high-performance liquid chromatography (HPLC), ultra high-performance liquid chromatography (UHPLC), purification liquid chromatography such as flash or preparative chromatography, countercurrent or centrifugal partition chromatography and supercritical fluid chromatography (SFC). It is commonly used for analysis of compounds that do not absorb UV-VIS radiation significantly, such as sugars, antiviral drugs, antibiotics, fatty acids, lipids, oils, phospholipids, polymers, surfactants, terpenoids and triglycerides.

References

  1. Gamache P. (2005) HPLC analysis of nonvolatile analytes using charged aerosol detection retrieved September 17, 2015.
  2. "Dionex - Charged Aerosol Detectors". www.dionex.com. Retrieved 2016-01-21.
  3. 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. PMID   20083252.
  4. 1 2 3 4 5 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. ISBN   9781119390725.
  5. https://www.google.com/patents/US6568245
  6. 1 2 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. ISBN   9781119390725.
  7. 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.
  8. http://www.bionity.com/en/news/48452/esa-corona-cad-wins-2005-r-d-100-award.html
  9. https://www.thermofisher.com/us/en/home/industrial/chromatography/chromatography-learning-center/liquid-chromatography-information/liquid-chromatography-innovations/charged-aerosol-detection-liquid-chromatography.html?cid=fl-cmd-cad
  10. https://www.thermofisher.com/order/catalog/product/5081.0010?SID=srch-srp-5081.0010
  11. https://www.thermofisher.com/order/catalog/product/5081.0020?SID=srch-srp-5081.0020
  12. https://www.thermofisher.com/order/catalog/product/VF-D20-A?SID=srch-srp-VF-D20-A
  13. https://www.youtube.com/watch?v=utseMBL1fTQ
  14. https://www.thermofisher.com/us/en/home/industrial/chromatography/chromatography-learning-center/liquid-chromatography-information/liquid-chromatography-innovations/charged-aerosol-detection-liquid-chromatography.html Charged Aerosol Detection for Liquid Chromatography Resource Center]
  15. 1 2 3 Russell, JJ (2015). "Performance of charged aerosol detection with hydrophilic interaction chromatography". Journal of Chromatography A. 1405: 72–84. doi: 10.1016/j.chroma.2015.05.050 . PMID   26091786.
  16. Hutchinson, JP (2012). "Investigation of polar organic solvents compatible with Corona Charged Aerosol Detection and their use for the determination of sugars by hydrophilic interaction liquid chromatography". Analytica Chimica Acta. 750: 199–206. doi:10.1016/j.aca.2012.04.002. PMID   23062441.