# Surface Plasmon Resonance-Based Fiber Optic Sensors Utilizing Molecular Imprinting
## 5 Molecular Imprinting
### MIP Fundamentals  
The MIP synthesis procedure demands the polymerization of functional monomer and the cross-linker around a template [68]. In the first step, template-monomer complexes are prepared with the reaction between a specific template and corresponding required monomer. This step is followed by the cross-linking polymerization reaction around the template-monomer complex. After polymerization, the template is unbound/removed from the achieved complex polymer with the help of the required remover. It may be noted that after the extraction of template molecules from the polymer, the template leaves its complementary imprint in the polymer. These imprints are usually known as the imprinted sites of the template and they contains a three-dimensional network with complementary shape and size to the template, which make the MIPs highly selective for the template molecule.  
According to the synthesis procedure and the interaction between template and the functional monomer, molecular imprinting is characterized in two different categories: covalent imprinting and non-covalent imprinting. The first approach of molecular imprinting was developed by [PERSON] and co-workers [69]. In this process of molecular imprinting, a pre-polymerized compound is prepared between the template and functional monomer by a covalent interaction which is followed by polymerization. The covalent interaction usually occurs between pairs like diol:ketone, amine:aldehyde and acid:amine. Thus, the imprinting of ketals/acetals [70], boronate esters [71] and Schiff's bases [72] follow the covalent approach. As the interaction between template and functional monomers is of a covalent nature, the porogen (solvent) may be polar [73] for the polymerization process. However, the strong covalent approach results in the slow binding and dissociation of the template [13] which limits the analytical applications of these MIPs. Moreover, this approach is limited due to its template:functional monomers specificity. [PERSON] and co-workers pioneered the non-covalent approach for the synthesis of MIPs around the 1990s [74; 75]. The method can be processed by non-covalent interactions such as hydrogen bonding, ionic interactions, \(\pi\)-\(\pi\) interactions and Van der Walls forces between the template and functional monomer. The most dominant interaction used for molecular imprinting is hydrogen bonding, which usually occurs between primary amines and functional monomers of methacrylic acid (MAA) groups in a non-polar solvent [17]. Due to its easy synthesis process and quick removal/rebinding of template, non-covalent molecular imprinting has become the most general and popular method of the preparation of MIPs. However, in case of this imprinting approach, the bonds are less selective, non-directional and heterogeneous [76]. A schematic diagram of the synthesis of MIPs is shown in Figure 4. To combine the stability of the covalent method and the rapid removal/unbind of the non-covalent method, a combined method has been developed named semi-covalent imprinting [15]. In this method, the template:functional monomers interact covalently while the rebinding is due to a non-covalent interaction.