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

• Published in: Biosensors & bioelectronics Vol. 288; p. 117793
• Main Authors: Dhal, Ajitesh, Aviña, Ana Elena, Chang, Cheng-Jen, Chen, Chang-I, Yang, Tzu Sen
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 15.11.2025
• Subjects: Alkaline phosphatase (ALP); Alkaline Phosphatase - analysis; Alkaline Phosphatase - isolation & purification; Artificial Intelligence (AI); Biosensing Techniques - instrumentation; Biosensing Techniques - methods; Humans; Miniaturization; Miniaturized sensors; Point-of-care diagnostics; Precision healthcare; Precision Medicine - instrumentation; Precision Medicine - methods; Spectrum Analysis, Raman - instrumentation; Spectrum Analysis, Raman - methods; Surface-Enhanced Raman Scattering (SERS); Miniaturized sensors; Point-of-care diagnostics; Artificial Intelligence (AI); Precision healthcare; Surface-Enhanced Raman Scattering (SERS); Alkaline phosphatase (ALP)
• ISSN: 0956-5663; 1873-4235; 1873-4235
• DOI: 10.1016/j.bios.2025.117793

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. Fig. Schematic illustration of a SERS-based miniaturized sensor for alkaline phosphatase (ALP) detection. ALP activity in a blood sample is quantified by monitoring ALP-catalyzed reactions on a plasmonic substrate, enabling generation of distinct Raman spectral fingerprints. The resulting data provide sensitive and selective information on ALP levels, which are critical for monitoring liver, bone, kidney, and placental health, supporting early diagnosis and personalized disease management. [Display omitted] •SERS-based miniaturized sensors enable ultrasensitive ALP detection in femtomolar to picomolar levels in biofluids.•Microfluidic integration facilitates high-throughput, low-volume ALP assays, enhancing point-of-care applicability and sample handling efficiency.•Artificial intelligence algorithms are being leveraged for real-time spectral analysis, improving detection accuracy and decision-making in clinical settings.•Future integration with 5G/6G networks supports the development of cloud-connected ALP diagnostic systems, promoting decentralized and personalized healthcare.