SERS-based biosensing platform using shape-coded hydrogel microparticles incorporating silver nanoparticles

•Suspension array of hydrogel microparticles with different shapes were preparedas new substrates for SERS-based biosensing.•Incorporation of silver nanoparticles into hydrogel microparticles generated strong SERS signals for the target detection.•Simultaneous immunoassay was possible using shape-coded hydrogel microparticles and SERS nanotags. Biosensors based on surface-enhanced Raman scattering (SERS) represent an efficient tool that can quickly detect even very low concentrations of the target molecule. Recent SERS-based biosensing has been moving toward a multiplex detection platform to analyze samples containing a variety of molecules, such as blood and urine. In this study, shape-coded suspension arrays have been developed for SERS-based multiplex biosensing. The suspension microarrays were fabricated using different shapes of poly(ethylene glycol) (PEG)-based hydrogel microparticles, which were prepared by a simple photopatterning process. The resultant hydrogel particles were coated with silver nanoparticles by a silver mirror reaction and then divided into two groups depending on the shape. As a proof of concept, square-shaped particles were coated with 4-mercaptophenylboronic acid by self-assembly to detect glucose, while circular particles were functionalized with anti-human serum albumin (HSA) to detect HSA. The assay was performed in the concentration range of 1 pg/mL to 1 μg/mL for both glucose and HSA without crosstalk. Target selectivity was also confirmed from Raman mapping, which shows that each group of particles reveals a different pattern. Moreover, we verified the potential of our method in multiplex immunoassays by quantifying two different antigens using SERS nanotags. The performance of the developed SERS-based multiplex immunoassay platform was demonstrated by the detection of a very low concentration of biomolecules with excellent selectivity.