SERS-based miniaturized biosensors for alkaline phosphatase detection: Towards intelligent, real-time diagnostics in...

Alkaline phosphatase (ALP) is a clinically important hydrolase enzyme and a valuable biomarker for hepatobiliary diseases, metabolic bone disorders, and certain malignancies. Raman-based miniaturized sensors, particularly those employing surface-enhanced Raman scattering (SERS), have enabled ultrasensitive and selective ALP detection at femtomolar to picomolar levels in complex biological samples. This narrative review critically examines recent advances in SERS-enabled ALP sensors, highlighting hotspot engineering, nanozyme-assisted signal amplification, and microfluidic integration to achieve high-throughput, low-volume assays. It also explores the incorporation of artificial intelligence algorithms for real-time spectral interpretation and discusses the potential for integrating these systems with fifth and sixth generation (5G/6G) wireless networks for rapid, cloud-based diagnostics. In addition, this review outlines current challenges, including substrate reproducibility and standardization issues, and proposes strategies to enhance clinical translation. Collectively, these developments are transforming ALP sensing by enabling decentralized, intelligent, and personalized diagnostic platforms, which hold promise for advancing precision healthcare and improving patient outcomes.