# Molecularly-Imprinted SERS: A Potential Method for Bioanalysis
## 4 Molecularly-Imprinted SERS Methods
### One Step MIP-SERS
MIP synthesis uses a com-bination of two functional monomers. The results showed that using SiO\({}_{2}\)/GO/Ag (SGA) nanocomposite as a substrate gave a better increase in SERS signal than using AgNPs alone. The addition of pDA on the nanocomposite surface also led to better substrate dispersion to increase the sensitivity and selectivity of this method [124]. [PERSON] et al. using Au nanocylinder to analyze paracetamol residues in water samples. By using the one-step MIP-SERS method, it is known that the analytical method provides good sensitivity and selectivity and can be used for routine analysis [125]. The one-step MIP-SERS method with core-shell type was applied by [PERSON] et al., for the analysis of pesticide residues (carbaryl and thiodicarb) in agricultural products. The uniqueness of this research is to compare the use of a single template and dual templates in MIP synthesis. This research also uses a computational approach to predict intermolecular interactions between templates and monomers using the molecular electrostatic potential (MEP) method. The results showed that the results were synchronous between the computational approach and those carried out in the laboratory. The use of dual templates in making MIP results in better selectivity than single templates [126]. [PERSON], et.al, used Ag@TiO\({}_{2}\) composite as a substrate in one-step MIP-SERS analysis for sulfamethazine compounds. Ag@TiO\({}_{2}\) is predicted to have the ability to clean the remnants of the template left by a photolytic mechanism. There were still about 5% of the template which was challenging to clean from the surface of the MIP cavity. Results showed that Ag-TiO\({}_{2}\)@MIP could be used for routine analysis in the laboratory [127]. [PERSON] et al., used a nanocomposite which is a combination of two semiconductors (ZnO and TiO\({}_{2}\)) with Ag as a substrate in one-step MIPSERS analysis. This nanocomposite is expected to improve the detection of SERS signals during analysis. The type used is the core-shell type. The results showed that ZnO@TiO\({}_{2}\)@Ag nanocomposite can be used as a substrate and has good sensitivity, selectivity, and accuracy for histamine analysis in food products [128]. [PERSON] et al., developed a tyrosine analysis method using SERS. The substrate was made in a composite between PVDF/pDA/Ag. PVDF (polyvinylidene fluoride) was chosen because it has a rough surface, so it is expected to increase the \"hotspot\" effect which plays a role in increasing the SERS signal. The PVDF/pDA/Ag composite formed was then surface modified with vinyl from methacryloxypropyl tri-methoxy silane (MPS). MIP is then printed to form a PDA/MIM on the modified surface. In this study, MIP was made with a two-stage precipitation polymerization reaction. This tyrosine detection method uses a sandwich type. The results show that this analytical method has a good recovery percentage, and the detection limit is equivalent to the previous method (\(10^{-9}\) mol/L), but with a shorter analysis time of only 1.0 min [129]. Analysis of p-nitroaniline in water samples can also be carried out using the MIP-SERS combination method. Ag substrate was made in the form of nanocomposite with graphene, then MIP was copolymerized on the surface of DG/Ag using p-nitroaniline as a template. The use of graphene as a supporting material because of its 2-dimensional morphology provides a large surface area, making it suitable for use in the sample preparation stage. Graphene morphology can protect Ag from oxidation. Graphene material can also increase the signal of Raman spectroscopy through chemical enhancement mechanism. The results showed that the combination of the MIP SERS method could be used for the analysis of p-nitroanaline in environmental samples [130]. [PERSON] et al., combined the technology of imprinting, membrane separation and detection with SERS for the analysis of enrofloxacin in water samples. A poly(vinylidene fluoride) (PVDF) membrane was used as a buffer. AgNPs are then dispersed on the membrane surface.