Ultrasensitive Label-Free Biomarker Detection Utilizing a Large-Core Biconical Fiber-Embedded Optofluidic Biochip with Optimized Optical Architecture and Multimodal Signal Amplification

Label-free detection technologies, such as surface plasmon resonance (SPR), have emerged as powerful tools for biomarker detection due to their unique capabilities. However, their widespread adoption has been hindered by challenges such as complex biochip fabrication, cumbersome optical systems, and limited sensitivity. To address these limitations, we present a novel large-core biconical-fiber embedded optofluidic biochip (LBOB) that innovatively integrates multimode interference (MMI), Fresnel reflection, and a large-core biconical fiber biosensor. The LBOB eliminates complex noble-metal coatings and precise optical alignment in traditional label-free biosensors through employing a large-core biconical fiber sensor and all-fiber optical architecture. These advancements confer exceptional sensitivity, superior biocompatibility, facile functionalization, cost-effectiveness (<$0.25 per sample), and portability. Leveraging multimodal signal enhancement mechanisms, the LBOB achieves an outstanding sensitivity of 1.8 × 10-6 RIU. The use of the large-core biconical fiber biosensor significantly increases the number of biomolecules immobilized on the biosensing surface and enhances light-matter interactions, further boosting sensitivity. Beyond biomolecular interaction analysis, the LBOB demonstrates remarkable utility in the rapid (<10 min) and ultrasensitive detection of hepatitis biomarkers, achieving detection limits of 0.0008 IU/mL for HBsAg and 0.12 ng/mL for cholyglycine in serum. The LBOB represents a transformative tool for biomarker detection, establishing a novel paradigm for label-free biomolecular detection and interaction analysis.