Engineered molecular diagnostic strategies for hepatocellular carcinoma: Integrating flexible photonic barcodes, liquid biopsies, and AI‐enhanced sensing platforms

Abstract Early diagnosis of hepatocellular carcinoma (HCC) remains challenging because conventional serum biomarkers, especially alpha‐fetoprotein (AFP), show limited sensitivity for early‐stage disease. Recent progress in engineered molecular diagnostics provides new opportunities to improve HCC detection through integrated material, molecular, and computational strategies. In this review, we summarize current AFP‐based diagnostic approaches and discuss their major limitations. We then focus on emerging flexible biosensing platforms, particularly hydrogel photonic barcodes, for multiplexed biomarker detection. Further integration with exosome‐based liquid biopsy, clustered regularly interspaced short palindromic repeats‐assisted nucleic acid amplification, and artificial intelligence may enhance detection sensitivity, signal interpretation, and individualized risk assessment. Potential applications include point‐of‐care testing, longitudinal surveillance, and personalized clinical management. Key challenges still need to be addressed, such as material standardization, scalable fabrication, device reproducibility, and multicenter validation. Overall, integrated flexible biosensing systems may offer a promising direction for earlier and more precise HCC diagnosis.