Paper-based short-wave infrared spectroscopy for glucose quantification with human serum

Accurate glucose monitoring is essential for diabetes management and clinical diagnostics. We present a paper-based assay utilizing a short-wave infrared (SWIR) spectroscopy for glucose quantification at the 6599 cm⁻¹ (1515 nm) absorption peak, while minimizing the water interference. Our study investigates two structural forms of glucose, α-D-glucose and β-D-glucose (anomers), tracking their ratio in glucose solutions with phosphate-buffered saline (PBS), pure human serum, and their mixtures. While the β/α D-glucose ratio remains stable across all measured glucose concentrations in PBS, human serum induces a shift favoring α-D-glucose at higher concentrations, due to glucose interactions with other biomolecules. Our findings may have implications for glucose transport, enzymatic processing, metabolic assessment and understanding nutrient uptake in the body. While SWIR glucose spectroscopy has been explored in prior studies, our work integrates anomeric equilibrium shifts, protein-glucose binding effects, and paper-based sensing into a unified analytical framework, providing an effective approach for glucose quantification with wide-ranging applications in human health. This study explores a simpler, accurate and cost-effective method to test glucose with human serum using infrared light. • Paper-based SWIR assay enables water-free glucose quantification in human serum • Measures glucose at 6599 cm⁻¹ with linear correlation across biological samples • Anomeric β/α glucose ratio shifts in serum, indicating α-D-glucose preference • Reveals glucose-protein binding effects using SWIR absorbance ratio dynamics • Applicable in clinical diagnostics, gut health, and food quality assessment