Optical Fiber Needle Probes for In Situ-Distributed Biosensing Based on Optical Frequency Domain Reflectometry

In situ detection is crucial for diagnosing lesions during surgery, endoscopy, or biopsy but has always been a challenge in medical diagnostics. Optical fiber biosensing needle probes, with their small size, can be nearly noninvasively guided to the lesion site for in situ detection. However, existing optical fiber biosensing probes are single-point sensors, unable to precisely locate lesions. We propose an optical fiber needle probe for in situ distributed sensing of hepatocellular carcinoma (HCC) biomarker GPC3 in soft matter based on optical frequency domain reflectometry (OFDR). The needle type probe is fabricated by integrating a polydopamine (PDA)-assisted anti-GPC3 antibody-functionalized micro/nano fiber into a metal needle with a lateral opening near the distal tip. Through differential-phase demodulation, calibration experiments with varying GPC3 concentrations reveal that the needle probe exhibits an 8 mm sensing length with a sensitivity of 0.0031 rad/(ng/mL). More importantly, the proposed needle probe achieves the precise spatial localization of both independent and simultaneous multiple 250-μm mimic lesions loaded by GPC3 in an agarose-glycerol hydrogel soft matter phantom with a spatial resolution of 25 μm and a limit of detection (LOD) of 3.23 ng/mL, which offers unparalleled advantages compared with existing biosensors. The proposed method provides a potential for in situ detection and localization of HCC or other lesions.