## 2 Supercritical Fluids Technology: Challenges and Limitations
Extending catalyst lifetimes using SCF carbon dioxide reaction media, apart from the convenience of keeping the catalytic system running longer, also provides other potentially important economic benefits [16]. For example, due to its low viscosity and high diffusivity, scCO\({}_{2}\) affords an effective and \begin{table}
\begin{tabular}{l c c c} \hline
**Fluid** & **T\({}_{\epsilon}\) (\({}^{\circ}\)C)** & **P\({}_{\epsilon}\) (MPa)** & **Density (g/L)** \\ \hline Methane (CH\({}_{4}\)) & \(-\)82.6 & 4.60 & 162 \\ Fluoroform (CHF\({}_{3}\)) & 26.2 & 4.85 & 516 \\ Carbon dioxide (CO\({}_{2}\)) & 31.3 & 7.29 & 469 \\ Ethane (C\({}_{2}\)H\({}_{6}\)) & 32.3 & 4.88 & 203 \\ Sulfur hexafluoride (SF\({}_{6}\)) & 45.5 & 3.77 & 755 \\ Propane (C\({}_{3}\)H\({}_{8}\)) & 96.7 & 4.25 & 217 \\ Butane (C\({}_{4}\)H\({}_{10}\)) & 152.0 & 3.75 & 230 \\ Methanol (CH\({}_{4}\)O) & 239.6 & 8.09 & 272 \\ Ethanol (C\({}_{2}\)H\({}_{6}\)O) & 240.9 & 6.14 & 276 \\ Acetone (C\({}_{3}\)H\({}_{6}\)O) & 235.1 & 4.70 & 278 \\ Water (H\({}_{2}\)O) & 374.3 & 22.12 & 348 \\ \hline \end{tabular}
\end{table} 
Table 1: Fluids used in near-critical or supercritical conditions for (bio)catalysis and their critical parameters [14]. continuous cleaning within the porous catalyst structures. This good performance of heterogeneous chemical catalysts under supercritical conditions has been observed in many catalytic reactions, e.g., Fisher-Tropsh, hydroformylation, hydrogenation, Heck, Suzuki, oxidations and alkylations, even including continuous operation [17]. As regards biocatalysis, proteins are noticeably insoluble in all SCFs, allowing easy recovery and reuse, while the gas-like diffusivity and low viscosity of SCFs enhance reactant mass-transport rates to the active site of enzymes [18]. Lipases and esterases in scCO\({}_{2}\) are the most widely studied systems, due to the catalytic promiscuity of these enzymes towards hydrophobic substrates and the ability of this SCF to dissolve and transport hydrophobic compounds [19]. The synthesis of aliphatic esters of different alkyl chain lengths by esterification and/or transesterification (e.g., by alcoholysis, acidosis or inter-esterification) is a common approach to the production of terpenic flavour compounds (e.g., geranyl acetate) [20], and the valorisation of oils and fats (e.g., enrichment of acylglycerols with polyunsaturated fatty acids [21]). Currently, the use of lipases for the asymmetric synthesis of esters is one of the most important tools for organic chemists, whereby the combination of the unique properties of scCO\({}_{2}\) with the catalytic excellence of lipases allows the kinetic resolution (KR) or (dynamic) kinetic resolution (DKR) of a large number of racemates (e.g., 1-phenylethylanol [22], glycolidol [23], _etc._). However, it must be taken into account that CO\({}_{2}\) cannot be considered completely inert with regards to its interaction with proteins. The CO\({}_{2}\) forms carbamates with \(\varepsilon\)-amino groups of lysine residues placed on the enzyme surface, and lowers the pH of the aqueous layer around the enzyme, which can result in a significant decrease in the enzyme activity [24, 25]. The appropriate design of SCF (bio)reactors involves controlling mass-transfer limitations, environmental conditions (pressure and temperature) and product recovery. For example,  
Figure 2: **(A)** High-pressure packed bed enzyme-reactor with recirculation, equipped with high pressure pump (HPP), separators (S), heaters (H), pressure (P) and temperature control (T), and flowmeter (F) for Lipozyme®-catalyzed ethyl oleate synthesis in scCO\({}_{2}\)[26]; **(B)** High-pressure enzymatic membrane reactor with recirculation (B) for biotransformations in scCO\({}_{2}\)[27]. [PERSON] _et al._[26] developed a recycling packed bed enzyme reactor at pilot scale for Lipozyme(r)-catalyzed ethyl oleate synthesis through oleic acid esterification with ethanol in scCO\({}_{2}\) [see Figure 2(A)].