Microfluidic SERS chip for quantitative detection of weak surficial affinity molecules

Microfluidic SERS chip has become increasingly attractive in sensitive chemical and biomolecular analysis. However, microfluidic SERS chip is substantially limited when detecting weakly adsorbed molecules in fluids, let alone achieving quantitative analysis that is vital for biochemical applications. Herein, a microfluidic SERS chip that can achieve quantitative analysis of weak affinity molecules is developed. By "direct-laser-writing", silver aggregates inherently modified with citrate are facilely fabricated in microfluidic channel. We demonstrate that the surficial citrate can not only "detain" analytes on plasmonic surface by multi-hydrogen bonding, but also serve as a stable internal-standard, which well solves the two challenges. It shows that the relative standard deviation of melamine SERS intensity at 701 cm-1 can be effectively reduced from about 20% to less than 10% by normalization using the citrate band at 1370 cm-1. Quantification of melamine in aqueous and milk samples down to 10-7 M are achieved, respectively. And the recoveries are in the range 95%-115%. Moreover, the detection of a kind of hypoglycemic drug (rosiglitazone) is also performed. This microfluidic SERS chip capable of robust quantification of weak affinity molecules would certainly extend the application scenarios of microfluidic SERS, especially for low dose, high efficiency and real time liquid analysis.