Bakshi, Shrishty (2024) Development of Biological Interfaces for Photonic Biosensors. PhD thesis, University of York.
Abstract
Biosensors can play a crucial role in biomedical diagnosis, benefiting point-of-care monitoring and the guided treatment of diseases. In addition to biomedical diagnosis, biosensing devices can contribute to environmental monitoring, drug discovery, and food quality monitoring. A wide range of biosensors, such as optical, electrochemical, etc., are being developed. Photonic biosensors appear to be a good candidate for wide-scale commercialisation and deployment because of their high sensitivity, the possibility of cost-effective large-scale fabrication, and easy miniaturisation. One of the significant obstacles in the wide-scale deployment of silicon nitride photonic biosensors is the lack of a robust surface functionalisation method to immobilise receptors on the sensor's surface to capture the target analyte. In this thesis, I have studied the analytical performance of bioinspired polydopamine-based surface chemistry for the immobilisation of bioreceptors on the surface of guided-mode resonance-based silicon nitride photonic biosensors and observed that this protocol provides high bioreceptor immobilisation density that, in turn, enhances the signal observed for antigen binding. A detection limit of 10 pg/mL and a wide dynamic range (10 pg/mL-10 µg/mL) was achieved for Immunoglobulins (IgG), C-Reactive Protein (CRP,) and Matrix Metalloproteinase-9 (MMP-9) antigens detection, using polydopamine functionalised guided mode resonance based photonic sensors. Moving forward, I studied polydopamine surface chemistry optimised guided mode resonance-based sensing platform for detecting inflammatory wound biomarkers Tumor Necrosis Factor- (TNF-α) and Interleukin-6 (IL-6) in hydrogel-based wound dressings absorbed with human matrix and clinical wound exudate. Additionally, I further studied the suitability of the photonic biosensing device for trypsin enzyme detection in human urine, an essential biomarker for pancreatic diseases, by developing the biological interface using beta-casein as the substrate for trypsin. Our platform can detect trypsin with high sensitivity and wide dynamic range in human urine. In brief, this thesis describes an optimisation of biological interfaces for guided mode resonances-based silicon nitride photonic sensors using a polydopamine layer. The sensor achieves sensitive detection of protein-based biomarkers in complex human fluids such as 10 % human serum, wound fluid-absorbed hydrogel, and human urine in label-free manner.
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