Microfluidic Technologies to Advance Antibody and Bacteriophage Discovery

Abstract

Antibody Discovery: This dissertation introduces a pioneering approach to antibody discovery that harnesses the power of advanced microfluidic technology. Our innovative methodology revolves around the isolation of singular antibody-producing B-cells, a feat accomplished through the encapsulation of individual B-cells and an oligo-dT gel within microdroplets. This cutting-edge technique enables the targeted capture of a single type of antibody, thereby streamlining the discovery process. Leveraging microfluidic systems, we have meticulously designed a microenvironment conducive to encapsulating a solitary B-cell alongside the oligo-dT gel. The microdroplets function as miniature reaction vessels, providing an isolated setting for antibody synthesis and capture. This microscale strategy not only enhances efficiency but also minimizes sample requirements. Furthermore, we have employed state-of-the-art DNA sequencing techniques to meticulously analyze and characterize the antibody library resulting from our microfluidic-assisted capture. The comprehensive DNA sequencing results have furnished invaluable insights into the diversity and specificity of the isolated antibodies. The pivotal findings of this research underscore the potential of our microfluidic-assisted method for expeditious and precise antibody discovery. By capturing antibodies at the single B-cell level, we have ushered in a new era of possibilities for generating targeted and highly specific antibodies. This work serves as a significant contribution to the advancement of antibody engineering and lays the groundwork for the development of therapeutic agents boasting enhanced efficacy and precision. Bacteriophage Development: This research explores an innovative system for phage therapy leveraging microfluidics to revolutionize the precision and efficacy of bacterial infection treatment. Through a startup experiment, we designed a microfluidic platform where bacterial cells were encapsulated in microdroplets, each serving as an independent microenvironment for targeted phage therapy. Confocal microscopy was employed to visualize and analyze the dynamic interactions within these microdroplets. Bacterial cells were introduced into microdroplets, creating a controlled environment where some droplets contained bacteriophages, while others did not. This experimental design facilitated real-time observation and quantification of the impact of phage therapy at the microscale. The use of microfluidics allowed for the encapsulation of individual bacterial cells, providing a unique perspective on the dynamics of phage-bacterium interactions. The success of this experimental setup demonstrates the potential of microfluidics in advancing phage therapy precision. The targeted nature of phage therapy, observed and quantified at the microscale, opens avenues for developing tailored and responsive treatments for bacterial infections. These findings underscore the transformative potential of microfluidic-enabled phage therapy in addressing antibiotic resistance challenges and enhancing treatment precision. The promising outcomes of this startup experiment pave the way for further exploration and refinement of microfluidic-assisted phage therapy. Future research endeavors may focus on scaling up the system, optimizing parameters for broader applications, and exploring the clinical translatability of this precision medicine approach.