# Microsphere Polymers in Molecular Imprinting: Current and Future Perspectives
## 3 Preparation of Molecularly Imprinted Microspheres
### Controlled/Living' Radical Precipitation Polymerisation (CRPP)
#### 3.2.1 Atom Transfer Radical Precipitation Polymerisation (ATRP)
R-X, dormant species; \(\mathrm{M_{t}^{n}}\), transition metal in its lower oxidation state; \(\mathrm{M_{t}^{n+1}}\), transition metal in its higher oxidation state; Y, may be another ligand or the counterion; \(\mathrm{M_{t}^{n}}\)-Y/Ligand, transition metal complex; \(k_{\mathrm{act}}\), rate constant of activation; \(k_{\mathrm{deact}}\), rate constant of deactivation; \(k_{\mathrm{p}}\), rate constant of propagation; \(k_{\mathrm{t}}\), rate constant of termination; ATRPP initiators, alkyl halide/CuCl/Ligand in normal ATRP or AIBN/CuCl\({}_{2}\)/Ligand in reverse ATRP. further surface modification. The ability to modify the surface of MIMs to achieve better compatibility in various solvent systems has made them immensely applicable in different fields. [PERSON] et al. [1] proposed the incorporation of the ATRP system into precipitation polymerisation to form MIMs with a surface consisting of reactive halogen groups. This study demonstrated the use of 4-vinylpyridine (4-VP) as the monovinyl functional monomer, ethylene glycol dimethacrylate (EGDMA) as the crosslinking monomer, ethyl 2-chloro-propionate as the initiator, CuCl as the transition metal salt, \(N\),\(N\),\(N^{\prime}\)\(N^{\prime}\),\(N^{\prime}\)-pentamethyldiethylenetriamine (PMDETA) as the ligand and acetonitrile divinyl as the solvent for ATRPP and compared it with TRPP using 4-VP, EGDMA, AIBN and acetonitrile. The processes were executed in acetonitrile (97% of the total volume) at 60 \({}^{\circ}\)C.  
The diameters of the MIMs produced via TRPP were 10 times smaller than those produced via both normal and reverse ATRPP (2-5 \(\upmu\)m vs. 200-430 nm), implying that the combined system in ATRPP significantly affects the particle size of the obtained MIMs. This relatively larger MIMs were useful in diverse applications, for example in HPLC as the stationary phase. Furthermore, the equilibrium loading capacities of the MIMs obtained by normal and reverse ATRPP systems were identical, yet higher than the MIMs obtained by TRPP. Another difference was shown regarding high-affinity site densities in which MIMs prepared by ATRPP had significantly higher high-affinity site densities on their surfaces compared to those obtained by TRPP [1]. [PERSON] et al. [126] investigated some polymerisation parameters in ATRPP systems that could impact the morphologies and yields of the MIMs. The outcomes indicated that the MIM particles prepared without magnetic stirring were relatively polydisperse, while monodisperse MIMs were acquired by applying suitable stirring rates (around 90-180 rpm) under similar conditions. As for the effect of monomer loading, both the yields and sizes of the MIMs increased along with increasing the monomer loading, similarly as observed in TRPP. The polymerisation rates were additionally found to increase with increasing both the initiator and catalyst concentrations, which is reasonable in such a highly diluted polymerisation system. To demonstrate its general applicability, [PERSON] et al. [126] also performed ATRPP with the use of hydrophilic functional monomers (i.e., 2-hydroxyethyl methacrylate (HEMA) and acrylamide (AAm)) to produce highly crosslinked copolymer microspheres. The 'livingness' of the MIMs was also shown by the ability to perform surface modification with hydrophilic functional monomers (i.e., \(N\)-isopropylacrylamide (NIPAAm) and HEMA) via the surface-initiated ATRP, producing polymer brush-grafted MIMs with significantly improved water dispersion stability and surface hydrophilicity. To create a more versatile methodology of ATRPP that can perform under mild reaction conditions, [PERSON] et al. [127] conducted the first ambient temperate MIM synthesis without any external initiators, which is of great environmental and commercial significance and highly applicable for monomers that are sensitive to high temperatures.