SYNTHESIS AND MODIFICATION IN 2D NANOMATERIALS BASED COMPOSITES FOR CANCER DIAGNOSTIC APPLICATIONS

Abstract

This thesis has undertaken a systematic and in-depth exploration into the synthesis, characterization, and electrochemical applications of hexagonal boron nitride nanosheets (hBNNS) and their nano-hybrid composites with the overarching goal of developing ultrasensitive biosensors for the detection of carcinoembryonic antigen (CEA), a critical biomarker associated with several malignancies. The investigation addressed both the fundamental material challenges associated with pristine hBNNS and the engineering of innovative hybrid architectures capable of overcoming these intrinsic limitations to deliver enhanced electrochemical biosensing performance. Hexagonal boron nitride nanosheets, due to their atomically thin morphology, large specific surface area, superior physicochemical stability, and dielectric properties, have attracted significant attention as a next-generation nanomaterial platform. Their layered structure provides smooth, chemically robust surfaces that are highly desirable for biomolecule immobilization and interface engineering. However, unlike conductive counterparts such as graphene, pristine hBNNS possess inherent chemical inertness and poor charge-transfer capability, severely restricting their direct applicability in electrochemical devices. This limitation forms the central bottleneck in translating the theoretical advantages of hBNNS into practical biosensing platforms. To address these fundamental shortcomings, the present work systematically designed and fabricated hBNNS-based nano-hybrid composites through strategic integration with conductive, catalytically active, and structurally complementary materials. The rationale was to leverage synergistic effects wherein the weaknesses of pristine hBNNS are counterbalanced by the strengths of co-integrated nanostructures. Three representative material classes were employed: (i) reduced graphene oxide (rGO), a two-dimensional conductor with excellent electron mobility; (ii) copper/copper oxide (Cu/CuXO), a three-dimensional hierarchical material providing abundant catalytic and redox-active sites; and (iii) titanium dioxide (TiO2), a one-dimensional nanostructure renowned for its high surface area, photocatalytic activity, and electrochemical stability. Each of these hybrid interfaces was engineered under optimized synthesis conditions to ensure controlled morphology, strong interfacial bonding, and homogeneous dispersion on the hBNNS surface. For instance, the incorporation of rGO introduced highly conductive networks that drastically improved electron transport and minimized interfacial resistance. The Cu/CuXO component, synthesized into nanoflower and composite morphologies, imparted abundant catalytic sites and enhanced redox reactivity, thereby increasing charge transfer kinetics at the electrode interface. Similarly, TiO2 nanostructures provided chemically stable scaffolds with enriched surface area that supported efficient immobilization of bio-recognition elements, while also acting as electron mediators. Collectively, these integrations transformed inert hBNNS into multifunctional hybrid architectures possessing conductivity, catalytic activity, and structural robustness. Comprehensive physicochemical characterizations confirmed the successful formation of these hybrid systems. X-ray diffraction (XRD), Raman spectroscopy, FTIR, and UV–Visible spectroscopy validated structural integrity, phase purity, and bonding interactions. Microscopy analyses, including SEM and TEM, revealed the unique morphologies, ranging from layered nanosheets and hierarchical nanoflowers to well- distributed heterointerfaces, confirming the intended hybridization strategies. These VII characterizations provided the structural and morphological foundation upon which electrochemical evaluations were subsequently built. Electrochemical studies offered clear evidence of the enhanced performance delivered by hBNNS nano-hybrids. Cyclic voltammetry (CV) and differential pulse voltammetry (DPV) confirmed that hybrid electrodes demonstrated significantly improved electron transfer rates, lower charge-transfer resistance, and amplified current responses in comparison to pristine hBNNS. Furthermore, the reproducibility, selectivity, and stability studies highlighted the reliability of the fabricated immunoelectrodes. For instance, incorporation of rGO ensured superior conductivity and sensitivity, Cu/CuXO contributed strong catalytic activity and favorable redox reactions, while TiO2 offered chemical stability that enhanced long-term electrode performance. These synergistic effects collectively established hBNNS hybrids as versatile and high-performance electrochemical platforms. The practical utility of these hybrid materials was demonstrated through their application in CEA biosensing. CEA is a clinically relevant biomarker whose sensitive detection is crucial for the early diagnosis and monitoring of cancers, including colorectal, pancreatic, and lung cancers. The fabricated immunoelectrodes exhibited ultrasensitive detection capability with low detection limits, wide linear ranges, and robust selectivity against common interferents. Blocking agents such as BSA ensured suppression of nonspecific binding, further improving selectivity. Real-sample analysis in spiked serum confirmed the applicability of the developed biosensors in clinically relevant conditions, thereby bridging the gap between laboratory synthesis and practical diagnostic implementation. Importantly, the insights gained in this work extend beyond the development of CEA biosensors. The systematic demonstration of hybridization strategies provides a generalized framework for tailoring the properties of otherwise inert materials like hBNNS to suit diverse electrochemical applications. The ability to tune conductivity, generate defect-mediated active sites, and enhance biomolecule immobilization through rational material engineering opens new opportunities in multiple domains, including enzymatic and non-enzymatic biosensing, energy storage, catalysis, and environmental monitoring. Thus, this thesis establishes hBNNS-based nano-hybrids not merely as specialized materials for CEA detection but as a broader materials platform with multifunctional utility. From a scientific perspective, this work makes three key contributions. First, it provides a comprehensive understanding of how intrinsic limitations of pristine hBNNS can be systematically overcome through strategic hybridization with conductive, catalytic, and stable nanostructures. Second, it validates the importance of defect generation, interface engineering, and synergistic interactions in dictating the electrochemical behavior of hybrid nanomaterials. Third, it demonstrates the successful translation of these materials into practical biosensing devices with clinical relevance, thereby bridging the gap between fundamental material science and biomedical application. Looking forward, the findings of this thesis pave the way for future investigations in several directions. One promising avenue is the integration of hBNNS hybrids with emerging materials such as MXenes, metal–organic frameworks (MOFs), and covalent organic frameworks (COFs), which could further enrich electrochemical performance. Another potential direction involves exploring flexible and wearable biosensor architectures utilizing hBNNS hybrids, thereby advancing toward real-time, point-of- VIII care diagnostics. Additionally, coupling the developed biosensors with microfluidic platforms and smartphone-based readouts may provide cost-effective and accessible diagnostic technologies, particularly beneficial in resource-limited settings. In conclusion, this thesis has successfully established hBNNS nano-hybrid composites as a new class of multifunctional materials with exceptional promise for advanced biosensing applications. Through a combination of careful material design, detailed structural and electrochemical characterization, and practical demonstration in CEA biosensing, the work not only addressed the inherent limitations of pristine hBNNS but also advanced the broader field of hybrid nanomaterials in biomedical sensing.