# Molecularly-Imprinted SERS: A Potential Method for Bioanalysis
## 4 Molecularly-Imprinted SERS Methods
### One Step MIP-SERS
In addition, in the manufacture of MIP, a combination of two functional monomers, i.e., methacrylic acid and acrylamide, was used to increase the potential for template recognition to the formed cavity. This is expected to increase the selectivity and sensitivity of the MIP-SERS method. The use of SGA MIP SERS for the detection of 2,6-dichlorphenol in river water samples, showed a good recovery value (98.74-104.75%) and a linear range from 100-1.0 mmol/L [56]. [PERSON] et al. conducted research to develop patulin analysis methods on fruit products. Patulin is a secondary metabolite produced by fungi that often contaminate fruit products. The developed method is a one-step MIP, in which AuNPs as a substrate is then coated with MIP, which is synthesized using patulin as a template. MIP synthesis was carried out using the free-radical polymerization method. The analysis results using the MIP-SERS method showed the same good results as the previous method (MIP coupled with quantum dots, MIP-EC, LC-MS, and conductometric methods). This method also provides good selectivity in the presence of analytical confounders such as OXD (oxindole) and 5-HMF (5-hydroxymethylfurfural) [119]. Bisphenol A analysis method was also developed using the MIP-SERS method. Ag@MIP synthesis begins with the synthesis of silver nanoparticles ( AgNPs). MIP-SERS was carried out by a one-step method, where AgNPs as substrates acted as cores, while MIPs were superimposed on the surface of AgNPs and acted as shells. The formed AgNPs were then surface modified with the addition of APTES. Furthermore, MIP was synthesized by the  
Figure 4: Example of MIP SERS scheme application for analysis (**a**). 2,4-dichlorophenoxyylacetic acid; (**b**). caffeine; (**c**). L-Phenylalanine; and (**d**) Bisphenol A. Reuse with permission from [142, 137, 51, 128]. non-covalent method on the surface of the modified AgNPs. The mechanism of the one-step MIP-SERS analysis is thought to be the same as that of the Rhodamine 6G analysis, namely through the \"gate effect\" mechanism. The analysis results show an excellent detection limit value, but it has a drawback that not all BPA used in the MIP synthesis process can be released at the binding site of MIP. Therefore, in the subsequent development, it is hoped that dummy templates can be used to improve the performance of this method [120]. [PERSON] et al., developed the one-step MIP-SERS method. In this study, a combination of ZnO/Ag was used as a substrate, then MIP was coated on the nanocomposite surface for further use in the analysis of rhodamine 6G. This research involves a different mechanism with hotspots, where the substrate must be at a certain distance from the analyte to be analyzed. The mechanism that occurs in this study is the \"gate effect\", where the substrate coated with MIP can still detect the presence of the analyte, through a channel that connects the analyte to the substrate. The detection response produced by using ZnO/Ag as a substrate is better than using ZnO or Ag alone as a substrate [121]. Different mechanisms are shown by the analytical method developed by [PERSON] et al. This analytical method was used to detect carcinoembryonic antigen (CEA) from serum. The single-stage MIP-SERS mechanism used is the sandwich type. This study used nanotags composed of AuNPs that have been modified with the addition of MPBA (4-mercaptophenylboronic acid) on the surface. The results show that further development is needed. From the analysis results using Raman spectroscopy, it is known that template leaks are still detected through the background of the spectrum. This causes a low value of the signal-to-noise ratio. Therefore, this method still requires further development [122]. The exact mechanism is also suspected to occur in using SiO\({}_{2}\)/GO/Ag nanocomposite as a substrate in the analysis of \(\lambda\)-cyhalothrin in water samples. SiO\({}_{2}\)/GO/Ag then acts as a core which will be coated on the surface by MIP. Previously, the nanocomposite surface was modified with polydopamine (pDA).