Whispering gallery mode microtube sensor for real-time microfluidic monitoring of the coagulation process

Thrombin time is an important coagulation indicator reflecting the function of the terminal common pathway of the coagulation cascade, and it holds significant clinical value in anticoagulation therapy monitoring and the assessment of hemorrhagic and thrombotic diseases. In this paper, an optical sensor based on whispering-gallery-mode microtube resonator is proposed for real-time and label-free monitoring of plasma thrombin time. The core element of the sensor is a silica microtube fabricated by HF etching of a hollow-core fiber. The wall thickness is optimized via simulation to maximize the evanescent field energy at the liquid core–inner wall interface. By covalently immobilizing thrombin on the inner wall of the microtube, local refractive index changes induced by fibrin deposition during the coagulation reaction can be sensitively captured by the evanescent field and converted into real-time shifts of the resonant wavelength. Experimental results show that the sensor exhibits good repeatability for plasma thrombin time measurement, with a standard deviation of 2.67 ms. The influence of anticoagulant drugs on thrombin time was further investigated. Thrombin time was prolonged as the concentration of heparin sodium increased, and a good linear relationship ( R ²=0.94) was obtained between heparin sodium concentration (in the range of 0∼0.3 U/mL) and thrombin time, indicating that the response of the coagulation process to anticoagulant drugs can be well monitored by the proposed method. The sensor features simple fabrication, low sample and reagent consumption, resistance to external environmental contamination, and ease of storage, providing a promising optical detection platform for point-of-care monitoring of the coagulation process.