Abstract
Table of Contents
List of Tables
List of Figures
Chapter 1. Introduction
1.1. High-Throughput Small-Volume Bioassays
1.1.1. Miniaturization Trends in Biochemical Screening Platform
1.1.2. Clinical Value of the Small-Volume HTS Platform
1.1.3. Lab-on-a-Chip Based HTS Platforms
1.2. Developmental Goal for the 'Pipetting-Free' HTS Platforms
1.2.1. Difficulties in Automation of Liquid Handling System
1.2.2. Previous Researches for 'Pipetting-Free' HTS Platforms from Other Groups
1.3. Main Concept: One-Step Generation of a Drug-Releasing Microarray-on-a-Chip by Self-Assembly of Drug-Laden Microparticles (DLPs)
1.3.1. Previous Works of Partipetting from Our Group and Their Limitations
1.3.2. My Works in This Dissertation
Chapter 2. System Development
2.1. Sealing-Film Assisted Seeding Method for Saving Cell Consumptions
2.2. Chip and Jig Development
2.2.1. Polystyrene-Poly(dimethylsiloxane) (PS-PDMS) hybrid Chip for Precise Alignment and Sealing
2.3. Preparation of DLPs Library
2.3.1. Microparticles as Drug Carriers and Requirements for Drug Loading
2.3.2. Strategies to Increase the Absorbing Amount of Drugs into Hydrogel Microparticles
2.3.3. Mixing Drug Solution with Prepolymer to Fabricate Microparticles
2.3.4. Drug Loading into Prefabricated Microparticles by Freeze-Drying
2.4. Decoding Microparticles
2.4.1. Design of Graphical Codes on the Microparticles
2.4.2. Decoding by Neural-Network-Based Recognition of Coding Components
2.4.3. Neural-Network-Based Decoding from an Image of a Whole Microparticle
2.5. Statistical Analysis for Duplications
2.5.1. Binomial Distribution Model for Random Assembly of Microparticles
2.5.2. Monte-Carlo Simulation for Statistical Analysis
Chapter 3. Application: Screening of Sequential Drug Combinations
3.1. Therapeutic Benefit of Sequential Drug Combination Based on Rewiring of Intracellular Pathways
3.2. Screening of Sequential Drug Combination Using a Partipetting Platform
3.3. Proof-of-Concept: Sequential Combinatorial Cell Staining Assay by Replacement of the Drug Chip
3.4. Screening of Sequential Combinatorial Drugs with EGFR Inhibitor Followed by Genotoxin against Triple Negative Breast Cancer (TNBC)
Chapter 4. Conclusion and Discussion
Bibliography
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