# Green Strategies for Molecularly Imprinted Polymer Development
## Green Strategies in MIP Development  
### Supercritical Fluid Technology  
Supercritical carbon dioxide (scCO\({}_{2}\)) is a green alternative to replace typical organic solvents used in polymerization reactions. Indeed, scCO\({}_{2}\) has several advantages, such as being inexpensive, non-toxic, non-flammable, inert, odorless, can be easily removed without any additional energy input, and can be recycled [4]. Moreover, CO\({}_{2}\) is available in high purity as a sub-product from industry, and also, the price of CO\({}_{2}\) is expected to decrease in the forthcoming years [5]. Thus, CO\({}_{2}\) is a sustainable solvent full of potential to be used either in research area or industry, with an easy scale up. Moreover, CO\({}_{2}\) properties can be easily tuned by simply adjusting pressure and temperature. CO\({}_{2}\) has an easily obtained critical point (\(p_{\rm C}\) = 73.8 bar; \(T_{\rm C}\) = 31.1 \({}^{\circ}\)C) above which there is no longer vapor-liquid equilibrium, becoming the so-called supercritical fluid. Here there is a significant change in density by tuning pressure and temperature, and therefore, in all the properties that are density dependent, such as solubility. Above its critical point, CO\({}_{2}\) combines the best properties of gas and a liquid, such as gas-like diffusivity and viscosity, and a liquid-like density, leading to a high mass transport capacity and a very high diffusion coefficient compared to the liquid [6]. scCO\({}_{2}\) is apolar and has a low dielectric constant, making it a suitable solvent not only for nonpolar molecules with low molecular weight, but also for small polar molecules such as methanol and vinyl monomers. A co-solvent can be added to tune its polarity. In addition, it has near-zero surface tension, which makes scCO\({}_{2}\) an excellent medium for cleaning/extraction without damaging the structures to be cleaned. Polymers, in particular with high molecular weight, have low solubility at mild conditions (<100 \({}^{\circ}\)C, <1000 bar) with the exception of fluoropolymers and polysiloxanes that show good solubility in scCO\({}_{2}\), due to weak dipole-induced dipole interactions and flexible backbones, respectively [7; 8]. Interestingly, the introduction of carbonyl groups on the polymer chains can increase, remarkably, the solubility of the polymer by weak interactions. Polymer synthesis in scCO\({}_{2}\) brings many advantages compared with traditional organic solvents, such as that scCO\({}_{2}\) is aprotic and has high mass transfer and diffusivity which is not achieved easily using organic solvents, polymers are obtained by simply depressurization, have low toxicity, and low cost of preparation, making scCO\({}_{2}\) an interesting solvent to replace commonly used organic solvents [9]. Another feature of scCO\({}_{2}\) is that it can induce plasticization or melting of polymers (homopolymers, copolymers, and polymer blends) under a much lower temperature than their glass transition (\(T_{\mathrm{g}}\)) and melting (\(T_{\mathrm{m}}\)) temperatures, which have a strong impact on their mechanical and thermophysical properties [10; 11; 12]. scCO\({}_{2}\) has already proved to be a versatile solvent reaction medium to produce polymers [13; 14; 15; 16; 17; 18; 19], as impregnation medium of polymers [20; 21; 22; 23], as anti-solvent to produce solvent-free 3D structures [19; 20; 21; 22], and as spray drying agent [23; 24], etc. Most commercially available monomers are soluble in scCO\({}_{2}\), namely those typically used in MIP synthesis. MIPs developed using this green solvent are typically obtained as dry free-flowing powders, pure, sterile, in high yield, with narrow particle size distribution, without the need of any further drying or purification steps, ready-to-use, and easy-to handle [18; 19], in opposition to traditional bulk methods, where MIPs need to be ground and sieved before use, leading to irregular particles and destruction of affinity sites [20].