Microparticles with size/charge selectivity and pH response for SERS monitoring of 6-thioguanine in blood serum

Surface-enhanced Raman scattering (SERS) spectroscopy is an ultrasensitive analytical technique with high specificity, making it an ideal candidate for therapeutic drug monitoring. However, SERS measurement of drugs in biological samples is inevitably affected by the proteins adsorbed nonspecifically on metal nanoparticles, so the drugs usually require separation before SERS detection. In this work, semipermeable alginate microparticles containing gold nanoparticles were fabricated via a centrifugal microfluidic chip, and served as a reliable substrate for SERS detection of 6-thioguanine in serum without protein removal. In comparison with the conventional microfluidic methods using oil for droplet generation, this oil-free method can fabricate more clean and versatile microparticles. The microparticles were characterized by size/charge selectivity and pH response, which effectively improved anti-interference ability and SERS sensitivity for 6-thioguanine detection in serum. The microparticles were further endowed with magnetic property and SERS activity simultaneously by forming Janus structures embedded with magnetic nanoparticles and gold nanoparticles separately in independent hemispheres, which was convenient for manipulation in SERS detection. More broadly, the microparticles are potentially applicable for SERS detection of other small molecules in complex real samples.