S.P.E.C.T.R.A. - Spectral Protein Evaluation for Core Tissue Real-Time Analysis: A Multi-Modal Precision Biopsy System for AHSG-Driven Metabolic Hotspot Detection

Liver cancer, specifically Hepatocellular Carcinoma (HCC) and Intrahepatic Cholangiocarcinoma (iCCA), remains a leading cause of global cancer mortality, characterized by extreme tumor heterogeneity. Standard-of-care needle biopsies often suffer from sampling errors, missing aggressive metabolic hotspots and leading to incomplete molecular profiling. This study introduces a novel multi-modal system designed to transform the standard biopsy cannula into an active biochemical sensor for detecting Alpha-2-HS-glycoprotein (AHSG), a key driver of these malignant hotspots. The system utilizes a dual-approach: (1) a real-time intraoperative guidance tool using optical spectroscopy, and (2) an origami-based microfluidic paper analytical device (μPAD) for rapid biomarker verification. Statistical validation demonstrated high diagnostic sensitivity and accuracy in hotspot identification, even within high-noise biological environments. This framework provides a scalable, low-cost solution for precision oncology, potentially reducing the need for repeat biopsies and accelerating the transition to targeted anti-metabolic therapies in resource-limited settings.