A Microfluidics-Enabled Photonic Crystal Biosensor for Simplified, Point-of-Care Diagnosis of Blood Biomarker

Abstract

Point-of-care testing (POCT) aims to deliver laboratory-based analytical platform to resource-limited settings, yet its development is often hindered by cumbersome sample preparation and complex detection workflows. Here, we report an optical biosensing chip that integrates the fluorescence enhancement effect from photonic crystal arrays with the microfluidic automation for rapid and highly sensitive quantification of alpha-fetoprotein (AFP) in blood. The pre analytical process for serum separation is also simplified by replacing the conventional centrifugation with an on-chip membrane filtration step. After the optimization of the antibody modification parameters on the PC arrays and the hydrodynamic performance, the optical biosensor exhibits a detection limit as low as 0.1 ng·mL⁻¹ for AFP and a broad linear range from 1 to 1600 ng·mL⁻¹ via one-droplet blood. After conducting a double blinded comparison with the clinical golden standard ELISA using 70 clinical samples, the high accuracy and agreement was achieved with a Pearson correlation coefficient of R² = 0.981, and a mean bias of -5.15 ng·mL-¹ by Bland Altman analysis. The optical biosensor integrates the high sensitivity of photonic crystals, the automation of microfluidics, and the simplicity of membrane filtration for the development of next generation on site diagnostic devices, which offers a practical solution to the key challenges of simplified, point-of-care diagnosis of hepatic disease.