Optofluidic waveguide sensors for point-of-care applications

This Ph.D. thesis is concerned with optofluidic waveguide sensors for point-of-care (PoC) applications. The main objective is to demonstrate a hemolysis sensor that shows the potential of integration into state-of-the-art PoC blood gas analyzers. This project is conducted in collaboration with Radiometer Medical ApS.
Hemolysis is the rupture of the red blood cells in blood and has been a long-lasting global healthcare issue in clinics worldwide. In vivo hemolysis is an indication of serious medical condition and in vitro hemolysis interferes with other important blood parameters such as K+ and bilirubin. Currently, there is no method to detect hemolysis in a fast and reliable way since the separation of red blood cells and plasma require time-consuming procedure such as centrifugation. The novel sensor developed in this thesis presents innovative nano-filters on a single-mode optical waveguide, which enables evanescent absorption of free hemoglobin and simultaneous filtering of red blood cells.
Thus, whole blood samples from patients can be directly measured with no sample preparation required. Sample volume of 65 μL is sufficient and measurement turn-around time of 1 minute is demonstrated. The sensor is successfully integrated in a modified PoC blood gas analyzer of Radiometer and shows excellent performance in repeatability, specificity, and long-term reliability. Furthermore, in this thesis, a waveguide interferometer sensor is demonstrated which is capable of simultaneous detection of liquid refraction and absorption. The interferometer sensor is composed of a sensing waveguide and a reference waveguide, from which an interferogram is generated by interference of the light. The change in the real part of the refractive index (refraction) causes phase shift of the interferogram, while the change in imaginary part of the refractive index (absorption) causes signal attenuation. Size-exclusion function is added to the interferometer by using nano-filters as demonstrated in the hemolysis sensor. Nano-beads with diameter from 100 nm to 500 nm are measured with regard to their refractive index, where large nano-beads are filtered out and cause no signal change. Evanescent fluorescent excitation experiments further confirm the size-exclusion functionality.