On-line supercritical fluid extraction-supercritical fluid chromatography (SFE-SFC) at a glance: A coupling story

https://doi.org/10.1016/j.trac.2021.116433Get rights and content

Highlights

  • Supercritical fluid extraction hyphenated to gas, liquid or supercritical fluid chromatography.

  • Compressible fluids set particular challenges compared to liquids.

  • Comparison of different hyphenation devices.

Abstract

The development of automatized hyphenated systems is attractive to avoid sampling error, save time and reduce costs. Among these systems, on-line SFE-SFC allows the extraction, the separation, and the detection of molecules in an efficient, quick and eco-friendly way. After a historical introduction and explanation on the use of supercritical fluids for extraction or analysis, principles of supercritical fluid extraction (SFE) and supercritical fluid chromatography (SFC) will be presented. Partially-supercritical on-line systems (e.g. SFE-liquid chromatography) will be compared before discussing about the evolution of on-line SFE-SFC over the past decades. Given the significance of the hyphenation between SFE and SFC to achieve a successful transfer, different devices will be examined to gain a better understanding of the coupling challenges and to determine the most advantageous configuration.

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).

References (108)

  • M.M.R. de Melo et al.

    Supercritical fluid extraction of vegetable matrices: applications, trends and future perspectives of a convincing green technology

    J. Supercrit. Fluids

    (2014)
  • T. Lefebvre et al.

    Selective extraction of bioactive compounds from plants using recent extraction techniques: a review

    J. Chromatogr. A

    (2021)
  • K. Hartonen et al.

    Detection of β-blockers in urine by solid-phase extraction-supercritical fluid extraction and gas chromatography-mass spectrometry

    J. Chromatogr. B Biomed. Sci. Appl.

    (1996)
  • J. Pól et al.

    Determination of lycopene in food by on-line SFE coupled to HPLC using a single monolithic column for trapping and separation

    J. Chromatogr. A

    (2004)
  • M.A. Stone et al.

    Quantitative coupling of supercritical fluid extraction and high-performance liquid chromatography by means of a coated open-tubular interface

    J. Chromatogr. A

    (2001)
  • R.M. Smith et al.

    Application of packed column supercritical fluid chromatography to the analysis of barbiturates

    J. Pharmaceut. Biomed. Anal.

    (1988)
  • J.R. Perkins et al.

    Analysis of sulphonamides using supercritical fluid chromatography and supercritical fluid chromatography—mass spectrometry

    J. Chromatogr. A

    (1991)
  • S. Khater et al.

    Development and validation of a supercritical fluid chromatography method for the direct determination of enantiomeric purity of provitamin B5 in cosmetic formulations with mass spectrometric detection

    J. Pharmaceut. Biomed. Anal.

    (2015)
  • J. Duval et al.

    Hyphenation of ultra high performance supercritical fluid chromatography with atmospheric pressure chemical ionisation high resolution mass spectrometry: Part 1. Study of the coupling parameters for the analysis of natural non-polar compounds

    J. Chromatogr. A

    (2017)
  • C. West

    Recent trends in chiral supercritical fluid chromatography

    TrAC Trends Anal. Chem. (Reference Ed.)

    (2019)
  • M. Saito

    History of supercritical fluid chromatography: instrumental development

    J. Biosci. Bioeng.

    (2013)
  • D. Guillarme et al.

    What are the current solutions for interfacing supercritical fluid chromatography and mass spectrometry?

    J. Chromatogr. B

    (2018)
  • J.M. Płotka et al.

    Pharmaceutical and forensic drug applications of chiral supercritical fluid chromatography

    TrAC Trends Anal. Chem. (Reference Ed.)

    (2014)
  • E. Lemasson et al.

    Comparison of ultra-high performance methods in liquid and supercritical fluid chromatography coupled to electrospray ionization – mass spectrometry for impurity profiling of drug candidates

    J. Chromatogr. A

    (2016)
  • M.A. Khalikova et al.

    Development and validation of ultra-high performance supercritical fluid chromatography method for quantitative determination of nine sunscreens in cosmetic samples

    Anal. Chim. Acta

    (2018)
  • L. Nováková et al.

    Ultra high performance supercritical fluid chromatography coupled with tandem mass spectrometry for screening of doping agents. I: investigation of mobile phase and MS conditions

    Anal. Chim. Acta

    (2015)
  • V. Cutillas et al.

    Evaluation of supercritical fluid chromatography coupled to tandem mass spectrometry for pesticide residues in food

    J. Chromatogr. A

    (2018)
  • K. Takahashi

    Polymer analysis by supercritical fluid chromatography

    J. Biosci. Bioeng.

    (2013)
  • Q. Gros et al.

    Characterization of stationary phases in supercritical fluid chromatography including exploration of shape selectivity

    J. Chromatogr. A

    (2021)
  • T.A. Berger et al.

    Role of additives in packed column supercritical fluid chromatography: suppression of solute ionization

    J. Chromatogr. A

    (1991)
  • T.A. Berger

    Separation of polar solutes by packed column supercritical fluid chromatography

    J. Chromatogr. A

    (1997)
  • R. Bennett et al.

    Gradient separation of oligosaccharides and suppressing anomeric mutarotation with enhanced-fluidity liquid hydrophilic interaction chromatography

    Anal. Chim. Acta

    (2017)
  • R. Bennett et al.

    Protein separations using enhanced-fluidity liquid chromatography

    J. Chromatogr. A

    (2017)
  • K. Taguchi et al.

    Simultaneous analysis for water- and fat-soluble vitamins by a novel single chromatography technique unifying supercritical fluid chromatography and liquid chromatography

    J. Chromatogr. A

    (2014)
  • V. Desfontaine et al.

    Applicability of supercritical fluid chromatography – mass spectrometry to metabolomics. I – optimization of separation conditions for the simultaneous analysis of hydrophilic and lipophilic substances

    J. Chromatogr. A

    (2018)
  • K. Sugiyama et al.

    New double-stage separation analysis method

    J. Chromatogr. A

    (1985)
  • M.E.P. McNally et al.

    Supercritical fluid extraction coupled with supercritical fluid chromatography for the separation of sulfonylurea herbicides and their metabolites from complex matrices

    J. Chromatogr. A

    (1988)
  • T. Lefebvre et al.

    Sequential extraction of carnosic acid, rosmarinic acid and pigments (carotenoids and chlorophylls) from Rosemary by online supercritical fluid extraction-supercritical fluid chromatography

    J. Chromatogr. A

    (2021)
  • W.M.A. Niessen et al.

    Phase-system switching as an on-line sample pretreatment in the bioanalysis of mitomycin C using supercritical fluid chromatography

    J. Chromatogr. A

    (1988)
  • A. Matsubara et al.

    High-accuracy analysis system for the redox status of coenzyme Q10 by online supercritical fluid extraction–supercritical fluid chromatography/mass spectrometry

    J. Chromatogr. A

    (2012)
  • T. Uchikata et al.

    High-throughput phospholipid profiling system based on supercritical fluid extraction–supercritical fluid chromatography/mass spectrometry for dried plasma spot analysis

    J. Chromatogr. A

    (2012)
  • M. Sakai et al.

    Development of a practical online supercritical fluid extraction–supercritical fluid chromatography/mass spectrometry system with an integrated split-flow method

    J. Chromatogr. A

    (2019)
  • A.P. Wicker et al.

    On-line supercritical fluid extraction—supercritical fluid chromatography-mass spectrometry of polycyclic aromatic hydrocarbons in soil

    J. Chromatogr. B

    (2018)
  • S. Tanaka et al.

    A simple and rapid method to simultaneously analyze ciclesonide and its impurities in a ciclesonide metered-dose inhaler using on-line supercritical fluid extraction/supercritical fluid chromatography/quadrupole time-of-flight mass spectrometry

    J. Pharmaceut. Biomed. Anal.

    (2021)
  • D. Giuffrida et al.

    Comparison of different analytical techniques for the analysis of carotenoids in tamarillo ( Solanum betaceum Cav.)

    Arch. Biochem. Biophys.

    (2018)
  • M. Zoccali et al.

    Apocarotenoids profiling in different Capsicum species

    Food Chem.

    (2021)
  • M. Zoccali et al.

    Carotenoids and apocarotenoids determination in intact human blood samples by online supercritical fluid extraction-supercritical fluid chromatography-tandem mass spectrometry

    Anal. Chim. Acta

    (2018)
  • C. Cagniard de Latour

    Exposé de quelques résultats obtenus par l’action combinée de la chaleur et de la compression sur certains liquides, tels que l’eau, l’alcool, l’éther sulfurique et l’essence de pétrole rectifiée

    Ann. Chem. Phys.

    (1822)
  • T. Andrews

    Bakerian lecture: on the continuity of the gaseous and liquid states of matter

    Proc. R. Soc. Lond. Publ. R. Soc.

    (1869)
  • E. Klesper et al.

    High-pressure gas chromatography above critical temperature

    J. Org. Chem.

    (1962)
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