## 6 Molecular Imprinting by Phase-Inversion
Thereby, the phase inversion method is appealing; yet, it is somehow limited by the fact that it usually applies for functional (co)polymer and templates, for which a common solvent can be found, to prepare the precursor solution. Another issue encountered when approaching the WPI is the medium-high solubility of the template in the coagulation bath, which leads to low specificity of the  
Figure 7: Synthesis of molecular imprinted membranes by phase inversion. prepared MIM. In this case, to avoid the diffusion of the template during the imprinting process, the DPI can be applied. On the other hand, if the polymer is susceptible to degradation during DPI and an adequate non-solvent for the polymer and template can be found, the preferred method to prepare MIMs is the WPI. The copolymers of acrylonitrile (AN) with acrylic acid (AA) or MAA are often used for membrane preparation by phase inversion for sensor application [168; 169; 170]. AN is used as a structural monomer, due to cyan polar groups that render stability to the imprinted cavities via strong hydrogen bonding, while AA or MAA are chosen as functional monomers due to their ability to interact with polar compounds. For instance, [PERSON] and his group [171] were the first to develop a quartz-crystal microbalance (QCM) sensor employing a PAN copolymer imprinted membrane for the detection of the stimulant drug caffeine. The authors used the phase inversion precipitation method to prepare two imprinted PAN copolymers membranes. A typical preparation of an electrochemical sensor by WPI is described by [PERSON] et al. [172]. In this respect, a molecularly imprinted film (MIF) was deposited on the surface of a Ti/TiO\({}_{2}\) electrode and used as recognition element of an electrochemical sensor with high selectivity and sensitivity for bisphenol A (BPA). In a first step, p(AN-co-AA) was synthesized according to solution radical copolymerization method using AN and AA in dimethyl sulfoxide (DMSO) with radical initiator AlBN. Step two referred to preparing the precursor solution of p(AN-co-AA) in DMSO, containing BPA as template molecule, followed by casting it directly onto the pretreated Ti/TiO\({}_{2}\) electrode. The MIF resulted after precipitation in the coagulation bath and the sensor assembly was kept in ultrapure water. Maintaining the membrane in the wet form after template removal is necessary, in order to preserve the imprinted network. If the membrane is dried by conventional methods, the shrinkage affects drastically the shape and size of the imprinted cavities which may collapse during this procedure. The Ti/TiO\({}_{2}\)/MIF sensor showed a linearity within the range 4.4 nM-0.13 mM, and a very low detection limit of 1.3 nM. Additionally, the sensor presented excellent recognition selectivity for BPA in competition with analogue compounds. This sensor was applied to detect BPA in paper cup samples and seawater, with high recoveries of 86-110% and with low relative standard deviations of 1.3-3.2%. Table 5 summarizes different methods via phase inversion applied for the preparation of MIP-based layers for sensors. Another paper describing the use of PAN copolymers in the WPI process is that of [PERSON] et al. [168], where the preparation of a MIM that may be applied for preparing sensors for epherrine detection is depicted. In this approach, two copolymers of AN and MAA with different weight rations (80:20 and 75:25) were prepared by emulsion polymerization and used to obtain two membrane variants, using ephedrine chlorohydrate as template. The membranes were tested by batch adsorption measurements in the attempt of finding the optimum recipe for preparing a film with affinity for ephedrine. In this regard, the MIMs with 20 wt% MAA were found to be more adequate to retain ephedrine with an adsorption capacity of 122 mg ephedrine/g polymer and an imprinting factor of 3.4. Furthermore, this same group [173] also used similar copolymer precursors to prepare sensitive membranes for the detection of explosives, more precisely, trinitrotoluene (TNT).