Early detection of various diseases is expected using surface-enhanced Raman scattering (SERS). For example, a method of labeling an antibody of a disease-related molecule on metal nanoparticles and detecting the SERS signals of the particles bound to the antigen is a promising approach. However, the problems of a slow antigen–antibody reaction and low sensitivity remain unsolved. In this study, we fabricated nanoparticles that can be freely moved using an external magnetic field for rapid antigen–antibody reaction and also nanoengineered the substrate to increase the density of hotspots required for SERS. Gold-coated magnetic nanoparticles (Au-MNPs) with a core–shell structure were prepared by applying multiple coatings of gold onto magnetic iron(II,III) oxide nanoparticles, which were used as the core. A neodymium magnet easily moved and converged the Au-MNPs in the solution within a few seconds. In addition, a silver nanoparticle substrate (Ag-NS) with a hexagonal close-packed structure fixed on a polydimethylsiloxane thin film was prepared, and the stable generation of SERS was confirmed over the entire substrate. Upon aggregation of the Au-MNPs onto Ag-NS using a neodymium magnet, the total SERS strength per unit area drastically increased, suggesting that the combination of Au-MNPs and Ag-NS increased the density of the generated hotspots. In future work, with the labeling of antibodies onto Au-MNPs, we expect the proposed method to be applied in the sensitive measurement of biomarkers associated with diseases.

Micro uidic devices are powerful bioapplication tools for cellular experiments in particular, as they can regulate physical and chemical parameters such as the ow rate, shear stress, oxygen, and molecular concentrations in a culture medium to mimic physiological and pathological microenvironments in vitro. However, as cell cultures take place in enclosed spaces, culture samples have to be removed repeatedly to monitor cell-derived metabolites and proteins in order to maintain the cellular microenvironment. We report a simple method for obtaining surface enhanced Raman scattering (SERS) spectra through self-assembly of a nanoparticle monolayer on polydimethylsiloxane (PDMS), which is commonly used in highly biocompatible micro uidic devices. Silica nanoparticles were stabilized as a hexagonal close packed structure on an O 2 plasma-processed PDMS membrane, and was coated with silver using vapor deposition to create an SERS plate. When this SERS plate was installed in a micro uidic device, the nanoparticles did not peel off even after long-term uid immersion. The SERS spectra exhibited stable SERS generation and an enhancement factor of more than 1.5 × 10 6 of the Raman signals from rhodamine 6G compared to the signals without nanoparticles. The SERS spectra of lactate and ATP were obtained, and Raman shifts due to the different masses of 12 C-and 13 C-lactate were observed, suggesting that the proposed method can be applied to determine the cellular metabolic ux in micro uidic devices. We also obtained cell membrane-derived SERS spectra by culturing murine mammary carcinoma 4T1 cells directly on the nanoparticle membrane. PDMS has high biocompatibility and is often used for fabricating micro uidic devices. Through tight binding of the nanoparticles to the O 2 plasma-treated PDMS, the chemical reaction products or the metabolites from cells can be measured for a long duration, while maintaining the microenvironment. We anticipate that this technology can be utilized as a useful tool for analyzing cellular metabolic functions and imaging cellular distributions without staining in various pathological models created in micro uidic devices.