Development of 3D Printing Enabled Methodologies for Microfluidic Cell Analysis and Surface Plasmon Resonance Sensing Enhanced by Nanoconjugates
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Development of 3D Printing Enabled Methodologies for Microfluidic Cell Analysis and Surface Plasmon Resonance Sensing Enhanced by Nanoconjugates

Abstract

Understanding biomolecular interactions and cellular activities based on these interactions are important research topics in bioanalytical chemistry that can have a large impact on key fields such as drug discovery, biomedical sciences, and environmental monitoring. High performing biosensors are an essential part for this task. Effective sensing platforms with improved analytical performance and reduced cost are actively sought after and remain a major area of intense research endeavors. The goal of this thesis is to develop novel biosensing systems enabled by 3D printing technology and nanoscience for probing biochemical interactions and achieving cell lipidomic analysis.Surface plasmon resonance (SPR) biosensors have been wildly applied for biomolecular assays in a label-free fashion. The sensitivity of SPR sensors, however, still needs signal enhancement when dealing with trace amounts of analytes. Chapter 2 describes the fabrication and application of gold nanoparticles-coupled POPC liposomes nanoclusters for signal amplification for SPR sensors and the study of protein-membrane recognition on a biomimetic interface. By combining the large mass of liposomes and plasmonic coupling of the noble metal nanoparticles, the highly stable POPC-gold nanoparticles showed a large amplification effect and a 0.1 ng/mL LOD was achieved for cholera toxin detection. 3D printing technology has greatly impacted the bioanalytical fields by providing the fabrication capability with almost no geometric restriction, rapid prototyping, and low cost. Chapter 3 describes the design and fabrication of a Dove prism by 3D printing with transverse micropatterns for multiplexed sensing with SPR imaging. The sensitivity of the system was evaluated by bulk refractive index change and protein binding assays; both showed similar performance as compared to the SPR configuration using high end glass optics. 3D printing technology has been further applied to fabricating microfluidic chips for cell analysis. Chapter 4 demonstrates the design and fabrication of a 3D printed microfluidic device for on-chip cell lysis, lipid extraction and phase separation for lipidomic study of algae C. reinhardtii cells by the microchip enhanced MALDI-MS. Compared with conventional bulk methods, extraction by the microfluidic device showed higher efficiency and cell lysis capability.

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