# Molecularly-Imprinted SERS: A Potential Method for Bioanalysis
## 4 Molecularly-Imprinted SERS Methods
### One Step MIP-SERS
MIP is then superimposed on the surface of the support and AgNPs, thus forming a sandwich-like shape. The interaction between enrofloxacin and the substrate was estimated based on the \"gate\" effect. It was suspected that on the surface of the imprinting layer there was a channel that could connect the substrate with the compound to be analyzed. Therefore, the detection of SERS for enrofloxacin in this study was thought based on an electromagnetic enhancement mechanism [71]. MIP SERS application for antibiotic residue analysis was also developed using Fe\({}_{3}\)O\({}_{4}\)/Ag nanocomposite as a substrate. AgNPs are dispersed on the surface of Fe\({}_{3}\)O\({}_{4}\), then MIP will wrap the surface of the formed nanocomposite substrate. In this study the separation is also assisted magnetically. Poly-dopamine was used as a functional monomer as well as crosslinkers, while enrofloxacin was used as a template. The combination of Fe\({}_{3}\)O\({}_{4}\)/Ag is expected to increase the hotspot area during SERS analysis. [PERSON] et al. [131] also developed analytical methods for antibiotic analysis with MIP SERS using AgESM MIP, utilizing eggshell as a support material while [PERSON] et al., used GO/Ag composite as a substrate combined with PVDF membrane as a support. The results of research by [PERSON] et al., showed that the detection of illegal biguanide derivatives in pharmaceutical preparations circulating in the trade could be done using the MIP-SERS combination analysis method. This study used graphene oxide (GO) nanocomposites with gold nanoparticles (AuNPs) as substrates. AuNPs were immobilized on the GO surface with the help of p-aminothiophenol. Next, the MIP was encapsulated on the surface of the nanocomposite. The template used is metformin. The results show that MIP@Au-GO SERS can analyze metformin HCI and phenformin HCI in the pharmaceutical preparation. This method is expected to be used to analyze and detect active drug compounds in complex matrix [132]. Two different researchers developed the analytical method for the detection of malachite green. The difference lies in the substrate composition and the type of MIP-SERS used. [PERSON] et al. used Au@ AgNPs nanocomposite with single-stage MIP-SERS type [133], while [PERSON] et al., used AgNPs as substrate with two-stage MIP SERS type. [PERSON] et al., combined MIP with magnetic nanoparticles to increase the selectivity of the assay. Based on the study results, both methods can be used to detect malachite green on samples with complex matrix [134]. [PERSON] et al., developed an Ag/GO/MIP sandwich nanostructure to analyze propranolol in complex matrix. In this structure, AgNPs are placed in the top position, and can interact directly with the target compound molecules to produce the best increase in SERSsignal. This method can be applied to other target molecules and is used to detect various pollutants with high sensitivity [135]. [PERSON] et al., developed molecularly imprinted polymer coated gold nanoparticles (MIP-AuNPs) as a material for detect and quantify L-Phenylalanine in one-step approach. Gold nanoparticles were prepared by bottom up method using sodium citrate as a reductor. The MIP-AuNPs hybrids were prepared by combination of sol gel method and molecular imprinting technology. MIP was in-situ formed on AuNPs by sol gel methods. L-phenylalanine was used as a template, TEOS as a crosslinkers and phenyltrimethoxysilane as a functional monomer. The MIP-AuNPs showed a good linearity and limit of detection. This material also can detect L-phenylalanine in the presence of its analogue, D-Phenylalanine and bovine serum [140]. The selective and sensitive MIP-SERS detection was also developed for determination of bisphenol A (BPA). Silver nanoparticles were synthesize by in-situ preparation inside molecularly imprinted polymer matrix for BPA detection. The MIP was prepared by using BPA as a template, EGDMA as a crosslinker, and AIBN as an initititator. Then amount of silver nitrate as a AgNPs precursor were added to the mixture.