On-line supercritical fluid extraction-supercritical fluid chromatography (SFE-SFC) at a glance: A coupling story
Graphical abstract
Introduction
The first notion of supercritical fluid appeared in the XIXth century, with the experiments of the French scientist Charles Cagniard de la Tour [1], in 1822. At that time, he observed in sealed glass tube the shift from liquid to gaseous state of alcohol, ether, and water, due to temperature increase. During the 1860s, based on Faraday's results on chlorine liquification and other similar works, Andrews [2] added his piece to the puzzle through his experiments on the changing state of carbonic acid and the reversibility of the phenomenon. His results highlighted the impact of pressure and temperature on the physical state of carbonic acid, allowing him to determine the phase diagram of the molecule. He was the first one to name the critical point and to explain that these different states referred to a single chemical. A century later, Klesper et al. [3] used supercritical fluids (monochloro-difluoromethane and dichloro-fluoromethane) for chromatography in 1962, in an experiment called high-pressure gas chromatography (HPGC). In the years 1966–1967, Sie and coworkers published several papers [[4], [5], [6], [7]] using supercritical carbon dioxide (CO2) as mobile phase for HPGC. During the 1970s, the first extraction applications appear, notably for the decaffeination of coffee beans [8] and other purposes [9]. At the same time, supercritical fluids have more difficulties to establish in chromatography. Indeed, competition is stiff with the establishment of gas chromatography (GC) and the expansion of liquid chromatography (LC) applications. It took years for supercritical fluid chromatography (SFC) to finally emerge as a valuable technique, complementary to GC and LC [10,11].
However, supercritical fluids offer attractive possibilities. By applying adequate temperature and pressure values, as shown in Fig. 1 with the example of pure carbon dioxide, it is possible to reach the supercritical state either from gaseous or from liquid CO2. The density and diffusivity of supercritical fluids are close to those of liquids, allowing to maintain high chromatographic efficiency, while their viscosity is low, rather close to that of gases, permitting to work at high flow rate [12]. Moreover, supercritical fluids such as CO2 revert to gases at atmospheric pressure, thereby reducing drying steps in extraction and purification processes.
Over the past decades, various supercritical fluids were used either for chromatography or extraction, but also for other processes. Nitrous oxide was used as an alternative to carbon dioxide but Raynie [13] highlighted the risks associated with its use in supercritical fluid extraction (SFE). Indeed, extraction cells may explode during matrix extraction with high organic content, due to exothermic reaction and rapid sample oxidation. Supercritical carbon dioxide and trifluoromethane (CHF3) were both introduced in enhanced fluidity liquid chromatography mobile phases to investigate the separation of triazine herbicides [14]. Both fluids improved efficiency and reduced analysis time, but unfortunately, CHF3 is a strong greenhouse gas and its use has been abandoned. Subcritical (or superheated) water was also used for various applications. In such conditions, its polarity is much lower than in the liquid state, allowing to extract non-polar compounds [15]. Extraction yields of Soxhlet extraction, SFE with CO2 and superheated water extraction (SWE) at 150°C of eugenol, eugenyl acetate and caryophyllene were compared by Clifford et al. [16] in 1999. Both techniques using sub/supercritical fluids offered quicker processes with similar yields to Soxhlet. Subcritical water was used for the extraction of antioxidants and essential oils from rosemary plants and Thymbra spicata [17,18]. A better purity and a higher amount of antioxidants were obtained with sub/supercritical approaches than with Soxhlet. In addition, subcritical and supercritical water were used for hydrothermal liquefaction of wet algae in order to extract lipids and bio-crudes [19]. It avoided a drying step and yielded either wet or dry samples, with a higher yield observed in subcritical conditions. Supercritical methanol was also used for the synthesis of zinc oxide nanoparticles and biodiesel in a single process [20]. In summary, in general supercritical fluids offer significant advantages (i.e. increase yields and speed) for different processes, whatever the chemical nature of the fluid.
Nevertheless, carbon dioxide was one of the few to establish itself over time. With its low critical temperature and pressure (Tc = 31°C and Pc = 7.3 MPa), extraction or chromatography can be performed with CO2 in a supercritical state without the need of extreme temperature or pressure, as opposed to, e.g. water with much higher critical values (Tc = 374°C and Pc = 22.1 MPa) [21]. Furthermore, CO2 is enticing on many aspects: it is chemically inert, non-toxic, non-corrosive, non-flammable, inexpensive, available at high purity and abundant because it is mostly produced as a by-product of several industries. Even if its polarity is supposedly close to that of hexane, it is miscible with most co-solvents usually employed in the chromatography laboratory (e.g. methanol, ethanol, acetonitrile …). The co-solvents are often called modifiers. Mixtures of CO2 and a more polar solvent in all proportions offer a wide range of fluid polarity. In addition, the introduction of a third chemical in low proportion, often called additive (e.g. water, salts, small acids or bases …) permits further increases in the fluid polarity, and/or variation of the interaction properties of the fluid, which are useful for extracting or separating all sorts of molecules. In the end, because CO2 usually remains the major component of the fluid composition, the net cost and recycling costs are often reduced compared to conventional liquid solvents.
During the past decade, there has been a significant regain of interest for the use of supercritical fluids in chromatography, in light of the development of modern analytical systems by the manufacturers [22]. Although SFE and SFC are mostly employed separately, dedicated on-line SFE-SFC systems have emerged, in addition to the customized systems already used. On-line analytical systems are attractive as they save time, reduce sample-handling, limit molecules degradation and increase reproducibility. However, hyphenating the two may be challenging due to the many parameters to consider [23]. In this review, after detailing SFE and its principle, previously described partially-supercritical on-line systems (e.g. SFE-LC, SFE-GC …) are examined. After that, the principle of SFC is explained before we introduce on-line SFE-SFC, a fully supercritical hyphenated system. Initial attempts and modern approaches are discussed, to compare the advantages and drawbacks of the different set-ups, before concluding on the future of the method.
Section snippets
Supercritical fluid extraction (SFE)
In the 1970s, the first applications of SFE were developed in the food industry, as related by King [24]. Thanks to the technological evolution over the years, SFE enables both the isolation of compounds of interest through the collection of extracted fractions, or the removal of unwanted compounds from a matrix. In addition, CO2 returns to a gas at atmospheric pressure, thus no solvent is remaining in the collected fraction or recovered matrix when CO2 alone is employed. Being particularly
Partially-supercritical on-line systems
Here we will refer to partially-supercritical on-line systems using SFE for the extraction step, coupled with a non-supercritical chromatographic system (e.g. LC, GC …). Following its expansion at the end of the XXth century, various innovative on-line systems appeared using SFE. However, supercritical fluid can cause some issues during on-line approaches, depending on the connection type between the two systems and on the nature of the chromatographic system used.
In this context, SFE-GC is
Supercritical fluid chromatography
Decades after Klesper's first chromatographic use of supercritical fluids [3], SFC failed to impose itself, long remaining in the shadow of GC and HPLC. However, some progress was made first with the introduction of capillary SFC (cSFC) by Novotny et al. [42], in 1981. In addition, Hewlett-Packard developed a kit to turn an HPLC system into an SFC system, which would be mostly used with packed columns (pSFC). pSFC allows high efficiency at high flow rate, highlighted by more favourable van
Early approaches (1980s–2000s)
Despite the limited popularity of SFC at the end of the XXth century, on-line SFE-SFC approaches were developed during the 1980s, when cSFC- and pSFC-dedicated systems were introduced. As for partially-supercritical on-line systems, the way of coupling SFE and SFC is important for the success of the on-line system. If loop injection or trapping (with a trapping column or a cryofocusing jacket) were privileged at the beginning, various configurations were tried over the years.
The terms of
Summary and outlook
SFE and SFC offer alternative solutions to extract and separate molecules. The use of a low-viscosity fluid like supercritical CO2 allows shorter runs, a great versatility, and safer and greener experiments. Similar to other hyphenated techniques, on-line SFE-SFC has a strong potential, due to its automatization reducing the chance for human error, but also due to limited degradation of the samples (less oxidation and exposure to UV light) and its eco-friendly aspect. The possibility to
Funding
This work was supported by the French ANRT through a CIFRE grant (n°2019/0092) to Quentin Gros.
CRediT author statement
Quentin Gros: Investigation, Writing – Original Draft, Visualization. Johanna Duval: Writing – Review & Editing, Supervision. Caroline West: Writing – Review & Editing, Supervision. Eric Lesellier: Investigation, Writing – Original Draft, Supervision.
Declaration of competing interest
The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Quentin Gros reports financial support was provided by Shimadzu Corporation. Johanna Duval reports financial support was provided by Shimadzu Corporation. Eric Lesellier reports a relationship with Shimadzu Corporation that includes: non-financial support. Caroline West reports a relationship with Shimadzu Corporation that includes: non-financial support.
Acknowledgment
ICOA is supported by the University of Orléans, the National Centre for Scientific Research, the Labex programs SynOrg (ANR-11-LABX-0029) and IRON (ANR-11-LABX-0018-01), the FEDER programs CHemBio (FEDER-FSE 2014-2020-EX003677) and Techsab (FEDER-FSE-2014-2020-EX011313) and the RTR Motivhealth (2019-00131403).
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