A Compact Prism-Based Microscope for Highly Sensitive Measurements in Fluid Biopsy

The increasing demand for sensitive, portable, and affordable disease detection methods has spurred the development of advanced biosensors for rapid early-stage diagnosis, population mass screening, and bed-monitoring. Current high-sensitivity devices face hurdles such as high production costs and challenges in multiplexed signal detection. To address these, we developed a prism-based total internal reflection system which, in combination with surface functionalization techniques of gold nanoparticles, enables evanescent wave scattering for highly sensitive and rapid detection of specific analytes in both synthetic and human liquid samples. To validate its efficacy, we conducted scattering experiments in synthetic and human serum samples, exploiting functionalized AuNPs to recognize bacterial lipopolysaccharides as biomarkers for sepsis disease. We demonstrate a remarkable sensitivity in the femtogram per mL concentration range for this specific pathological biomarker. Based on this result we envisage the potential adoption of our technique for liquid biopsy in the clinical scenario.