Sustainable analytical techniques: a closer look at supercritical fluid chromatography

The demand for sustainable analysis techniques is increasing and within chromatography, supercritical fluid chromatography (SFC) seems to be a suitable 'green' solution. Although this analytical method has been known since the 1960s, the technology has never made a major breakthrough. But what are the advantages compared to conventional separation techniques? Isabelle François, founder of Chromisa Scientific and product manager and business developer at TharProcess, is a big supporter of SFC. She explains why more analysts should work with this technique.

By: Eline te Velde

Like other chromatography techniques, SFC is a separation technique used to separate components in a mixture based on the differences in interactions with the stationary and mobile phases. In liquid chromatography (LC), a liquid is used as the mobile phase, but in SFC the mobile phase consists of a supercritical fluid. This is a substance that is above the critical temperature and pressure. François explains that SFC almost always uses CO2: “In principle you can use any substance, but in practice CO2 is used most often. CO2 is easy to bring under supercritical conditions, has no harmful disadvantages such as corrosiveness or explosion hazard, and it is easily available.”

Bad reputation

With her twenty years of experience in SFC, François sees interest in technology waxing and waning. “The technology never fully developed until about ten years ago and the main reason for this was the lack of robust equipment. This is directly linked to the interest of instrument suppliers in this technology.” In addition, SFC also suffers from a bad reputation. “When I started with SFC during my doctoral research in 2004, I saw that my divorces were impressive. But at the time it was completely unrepeatable and therefore not applicable for routine use. The sensitivity in UV detection was also insufficient compared to traditional LC. SFC has carried this bad connotation in the past and that has been a barrier for many to pick it up again.”

“SFC has carried a bad connotation in the past and that has been a barrier for many to pick it up again.”

Since the 2010s, Waters, Agilent and Shimadzu have introduced new generations of analytical SFC equipment. The quality and robustness of these systems are now at the level of LC and UHPLC. “Several interlaboratory studies have been conducted that have shown that this technology is reliable and can be implemented in routine labs.” In the past ten years, the combination with mass spectrometry (MS) has also been commercialized, and this has contributed to the increased interest in and applicability of the technique.

Another aspect that plays a role in the popularity of SFC is the willingness of laboratories to adapt their existing methods. “Companies have often been working with fixed SOPs for years. People generally have difficulty with change and it takes effort and budget to adapt an existing workflow. Knowledge of the technology is very important and I always have to explain the benefits thoroughly in every sales conversation.” In her role as a consultant, François also sees the dilemmas that laboratories struggle with when purchasing a system. “Companies feel a lot of uncertainty. They wonder whether they will still have service on the system in ten years. A fair question because there now appears to be a decline in interest in the technology among analytical instrument builders. But if you look at the facts in black and white, the benefits are very clear.”

A green alternative

The sustainable qualities in particular seem to be the reason for the increased interest, especially on an industrial scale. LC uses liquid solvents and after separation these substances must be disposed of in a safe and environmentally friendly manner. The CO2 used at SFC is seen as a green alternative: “If you remove the pressure restriction from CO2, it becomes gaseous again. For laboratories, this means a significant decrease in waste materials and therefore lower costs for waste processing. Moreover, the CO2 supplied is already a recycled product. This is especially an advantage on a large scale, because preparative LC uses enormous amounts of solvents. The green character is also mentioned on an analytical scale, but I think it is quite limited there. On this smaller scale, not much solvent is used anymore, especially since much smaller column diameters and particles are used in UHPLC equipment nowadays.”

Investing in equipment

According to François, the future of this technology largely depends on the instrument suppliers. “I see many opportunities to improve the equipment for SFC, but investments now seem to be declining slightly. SFC is always a bit like the little brother of liquid chromatography. There are a number of companies involved in development, but they mainly focus on large-scale application. But the analytical side is also very important. Everything we do on a large scale starts in the analytical lab.”

Isabelle François gives a lecture on supercritical fluid chromatography during the chromatography seminar at the LabNL trade fair. Together with three other experts, she shares her knowledge in the field of this separation technique. Read more about the chromatography seminar or Register for a free visit to the fair.