Xiuli Gao

Droplet microfluidics has been widely used in biological, chemical, and medical research owing to its advantages of miniaturization, high throughput, and low reagent consumption. However, limited sensitivity and optical path length in on-chip absorbance detection remain major challenges for droplet-based microfluidic analysis. Traditional absorbance detection suffers from low sensitivity due to the extremely short optical path in microfluidic channels, while existing optical path extension methods have drawbacks such as complex fabrication, easy droplet rupture, or strict incident angle requirements. To address these issues, this study developed a droplet microfluidic absorbance detection platform integrating optical fibers, on-chip micromirrors, external fluidic actuation, and an absorbance detection module. Microchannel sidewalls filled with low-melting-point metal act as mirrors; the multi-reflection optical path, combined with optical fibers and micromirrors, compensates for insufficient light manipulation and effectively extends the absorption path length, improving sensitivity and accuracy. Using this method, the detection limit for methylene blue solution was 20 μM, and the sensitivity for Escherichia coli (E. coli) suspension was doubled compared with traditional Nanodrop OD600 measurement. This device features low fabrication difficulty and cost and stable detection, providing a proof-of-concept strategy for enhanced absorbance detection in droplet microfluidic systems.

The demand for rapid and highly sensitive sensing technologies is increasing across diverse fields, including precise disease diagnosis, early-stage screening, and real-time environmental monitoring. Field-effect transistor (FET)-based sensing platforms have shown tremendous potential for detecting target molecules at extremely low concentrations, owing to their ultrahigh sensitivity, label-free and amplification-free operation, and rapid response. In recent years, the rapid advancement of nucleic acid probe design and interfacial engineering has markedly accelerated the development of FET sensors, leading to the emergence of nucleic acid-based FET (NA-FET) biosensors. Beyond their fundamental role in nucleic acid detection, the integration of nucleic acid aptamers and framework nucleic acids has greatly expanded NA-FET biosensors’ applicability to a wide range of analytes and multiplexed detection. At the same time, advances in semiconductor materials have endowed the NA-FET biosensor with highly efficient signal transduction and diverse device architectures, enabling successful proof-of-concept demonstrations for various clinically and environmentally relevant molecular biomarkers. Furthermore, the integration into portable, wearable, and implantable devices has laid a solid foundation for their future development into real-world applications. This review summarizes recent cutting-edge progress in NA-FET biosensors, highlights key design strategies and performance improvements, and discusses current challenges, future development directions, and their prospects for practical applications.