Development of an optical cavity-based biosensor for point-of-care diagnostics.


An optical cavity-based biosensor (OCB) has been developed using a differential detection method towards point-of-care (POC) diagnostic applications. The optical cavity consisting of two partially reflective surfaces with a small gap was designed and optimized using a simulation tool, FIMMWAVE/FIMMPROP. The optical cavity samples were fabricated in the cleanroom by using simple and inexpensive processes. Lights from low-cost laser diodes pass through the fabricated cavity and reach a CMOS camera. As proof-of-concept tests, the refractive index measurements and the detection of biotinylated bovine serum albumin (BSA) were performed. Standard refractive index fluids were introduced to the cavity, then the changes in intensities of transmitted lights were measured by the camera. The measurement results matched up well with the simulation results. After the refractive index measurements, spin-on-glass layers were added for the surface functionalization, and the detection of biotinylated BSA with a concentration of 3 µM was performed in real-time. The detection results matched well with the simulation results, and the multiplexability of the OCB was discussed. To demonstrate the biosensing capability and experimentally determine the limit-of-detection (LOD) of the OCB, streptavidin and C-reactive protein (CRP) detections were performed. The optical cavity design was optimized further, and the surface functionalization process was improved. The polymer swelling was effectively utilized to fine-tune the cavity width and increase the success rate in producing measurable samples. Four different concentrations of streptavidin were measured in triplicate with a LOD of 1.35 nM. Based on the streptavidin detection, biotinylated CRP antibody is employed as the receptor molecules, and the OCB successfully detected three different concentrations of human CRP with a LOD of 377 pM. By reducing the sensing area, improving the functionalization and passivation process, and increasing the sample volume, the LOD of the OCB can be further improved into the femto-molar range. The portability of the OCB was also demonstrated by building a stand-alone system and performing refractive index measurements. To improve the fabrication tolerance, the three-laser system was proposed and validated through refractive index measurements. Overall, the demonstrated capabilities and characteristics of the OCB in this dissertation show great potential to be used as a promising POC biosensor.

Biosensor. Optical cavity-based biosensor. Point-of-care.