Engineering nanostructured interfaces for sensing and capturing bionanoparticles

Abstract

Recently, the nanostructured interface has emerged as a topic of significant interest, offering the potential for biological applications. The research work presented in this thesis falls into two sections: (1) a comprehensive investigation of the mechanism of an imaging-based sensing platform utilizing a gradient nanostructured interface and optimization of the main influencing factors to enhance overall performance based on the numerical simulation and experiment validation; (2) the development and study of 3D nanogap electrodes in the vertical direction for capturing nanoparticles using electrophoresis (DEP) force below 1 Vpp. The first part of this thesis presents an imaging-based sensing strategy for biological applications, along with an innovative processing and fabrication method for creating gradient nanostructures in such biosensors. Firstly, we propose large-area spatially varying nanostructures using an innovative two-beam fiber-optic interference lithography (2-FOIL) method. These non-uniform nanopatterns can be then transferred onto glass slides with remarkable fidelity and quality through a low-cost nanoimprint technique. By employing a smaller aptamer and an optimal algorithm, we achieve highly sensitive and selective detection of tumor-derived extracellular vesicles (EVs). Secondly, in order to improve the performance of imaging-based biosensor, AuNPs are introduced for a one-step rapid detection of coronavirus disease 2019 (COVID-19) nucleic acids. The design of three-element molecular probes could enable AuNPs to be brought into the sensing area of the LSPR nanostructure through the highly specific hybridization reaction. This platform demonstrates high sensitivity for COVID-19 sequence detection, with a limit of detection (LOD) of 77.22 pM, and it distinguishes the target sequence from similar symptomatic diseases. Thirdly, we successfully construct a mathematical model and derive the influencing factors. To optimize the main factor (the gradient change of the nanostructure diameter), we present a double exposure approach for fabricating a spatially varying nanostructure. The fabrication results of the gradient nanostructure mold are consistent with MATLAB simulations, and the variation in nanostructure diameter is reduced by a factor of 3, resulting in improved physical performance in refractive index solutions. The second part of this thesis is dedicated to the capture and manipulation of nanoparticles based on an engineering nanostructured interface. To overcome the fabrication constraints of horizontal plane nanogap electrodes, a vertical nanogap electrode fabrication strategy is employed, which enables the manipulation of AuNPs and bioparticle model PS spheres at a voltage of 1 Vpp. The mechanism of this platform is deeply investigated through numerical simulation and experimental verification. The findings of this work are essential for the enrichment of biomarker extracellular vesicles and provide a promising avenue for downstream analysis inside them.