Cavity‐Like Silver Aggregates‐Based Colloidal SERS Microfluidic Platform for Highly Reproducible Online Reaction Process Analysis

Abstract Process analytical technology (PAT) is a key tool in the chemical and biological production industry. However, it is still desirable to develop online PAT enabling rapid and sensitive detection of various reaction intermediates, to meet the requirements of precise and green chemistry. Here these challenges are addressed by developing a cavity‐like silver aggregate (Ag cavity)‐based colloidal surface‐enhanced Raman scattering (SERS) microfluidic platform, which exhibits a reproducible flow detection window, enabling sensitive online monitoring and identification of the organic reaction intermediates of the model flow photochemical reactions. The key element of the platform is the colloidal Ag cavity prepared through a template‐mediated method. Finite difference time domain (FDTD) simulation and molecular adsorption measurements indicate the increased electromagnetic field and the high surface area contribute to the high SERS sensitivity of the cavity‐like silver aggregates. Moreover, the Ag cavity shows a long‐term flow detection window in the microfluidic channel with high reproducibility (RSD = 3.72%). This platform is successfully used to monitor and analyze the photodegradation intermediates of the model antibiotics, indicating the promising practical applications. This study contributes to the advancement of online chemistry studies and provides an effective tool for online reaction monitoring across diverse organic production fields.