Smartphone-based molecular imprinting electrochemiluminescence microscope for non-invasive alpha-fetoprotein visual...

Alpha-fetoprotein (AFP) is a marker of liver cancer. Patients are harmed by the blood sample collection. Saliva samples are painless, safe, and easy to collect. The development of detecting AFP in saliva is important. Electrochemiluminescence (ECL) has low background signal, a wide dynamic range, and high sensitivity, but traditional ECL methods use a photomultiplier tube as a detector, which is bulky and delicate, and limits the spatial and temporal resolution of ECL. ECL microscopy (ECLM) is a new imaging technique that combines ECL with optical microscopy and makes up for the shortcomings of traditional ECL.

In this study, we developed a smartphone-based electrochemiluminescence microscope (SECLM), utilizing a gold nanorods@polyethyleneimine@ferrocene composite as a quencher and Ru-bpy as the emitter. The SECLM was integrated with molecular imprinting and an immunological technique for the quantitative visual detection of AFP in saliva samples. The method's detection sensitivity was significantly enhanced by the presence of multiple quenching mechanisms, including a blocking effect, inner filter effect, and electron transfer. This study presents a novel strategy to improve the sensing performance of molecular-imprinted ECL sensors. The method demonstrated a linear detection range of 0.01-100 pg/mL, with a limit of detection of 4.5 fg/mL. Comparative analyses with existing techniques indicated that this method achieves a low limit of detection, high sensitivity, and excellent stability, comparable to traditional ECL sensors.

This novel quantitative visual technique may enhance biomarker detection, and offer a reliable means for disease diagnosis and screening, and open new avenues for the development of sensing methodologies. This expands the application scope of ECLM and is expected to realize the rapid and sensitive biomarker detection for point-of-care and on-site detection. MI-ECLM provides a new tool for disease diagnosis, physiological activity exploration, pathogenesis and molecular biology researches.