Microscopic nucleic acid-to-protein ratio: A label-free approach for pancreatic cancer detection.

Accurate and timely diagnosis remains a major clinical challenge, hindered by the limitations of conventional histopathological methods, which often rely on labor-intensive staining protocols and subjective interpretation by specialized pathologists. These methods can fail to capture the full molecular and phenotypic heterogeneity of tumors, leading to increased diagnostic time, cost, and variability. To overcome these challenges, we developed a novel label-free ultraviolet (UV) microscopic imaging technique that exploits the intrinsic optical absorption properties of cellular nucleic acids and proteins. By modifying standard brightfield microscopes, our approach quantitatively measures the nucleic acid-to-protein ratio (NPr), enabling high-resolution visualization and discrimination between malignant and non-malignant cells without the need for exogenous labels or staining. We validated this technique using cultured pancreatic cell lines and tissue microarrays, demonstrating a significant elevation in NPr values in malignant samples. Diagnostic evaluation revealed a sensitivity of 82 % and specificity of 89 % for pancreatic cancer detection. This high-throughput, cost-effective, and minimally operator-dependent method offers a promising alternative to traditional histopathology, with potential applications in clinical diagnostics and cancer research. Our findings highlight the potential of UV NPr imaging to facilitate rapid, objective, and accurate cancer diagnosis, reducing reliance on subjective interpretation and complex sample preparation.