SERS hydrogel pellets for highly repeatable and reliable detections of significant small biomolecules in complex samples without pretreatment

The detections of significant small molecules in biological fluids is always challenging due to the complicated sample pretreatment. Here, a universal SERS-hydrogel micropellet was developed for pretreatment-free, reliable detections of small molecules (glucose and melamine) in complex sample (whole blood and milk). The SERS-hydrogel micropellet has an adjustable pore size, which is acquired by the ultraviolet light solidification of the water-in-oil microdroplets in which the hydrogel monomers and the SERS-active metal nanoparticles (MNPs) were encapsulated. These micropellets have a pore size selectivity to allow small molecules to access in and exclude larger molecules, which is helpful for the highly selective, label-free/labeling SERS determinations of small molecules. This SERS substrate ensures high reproducibility of SERS detections since MNPs are uniformly dispersed in each micropellet. The hydrogel matrix can well protect MNPs from the surrounding environments to guarantee long-term stability. The lowest detectable concentration is 10 μM for glucose in whole blood and 10 nM for melamine in milk, and the linear ranges are 0.1-20 mM and 10^-8-10^-3 M, respectively. This method avoids the complicated preprocessing steps, requires a small volume of samples, has a fast response time and low-cost, which provides the possibility for multiplex SERS detections in liquid biopsy.