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Automated Fluidic Platforms for Protein Purification and Molecular Diagnostics
- Puccinelli, Robert Russell
- Advisor(s): DeRisi, Joseph
Abstract
The implementation of laboratory automation systems has yielded significant benefits in life science research settings due to reductions in operator induced errors and improvements in assay reproducibility; however, commercial platforms often impose substantial barriers that limit adoptability due to their prohibitive costs and black box ecosystems. In particular, current systems for protein purification and microfluidic control often lack the adaptability and extensibility required to broadly enable high throughput research. Consequently, there remains a critical need for accessible instrumentation that can bridge the gap between complex, labor intensive protocols and standardized, automated workflows. The work described here details the development of several fluidic platforms designed to facilitate laboratory automation and streamline molecular diagnostics. One system is a four-channel parallel fast protein liquid chromatography system capable of parallelized milligram scale purification of proteins, a capability that was leveraged for rapid SARS-CoV-2 protein production during the COVID-19 pandemic. Another system is a compact, low-cost microfluidic control platform that utilizes a multithreaded and modular software framework to flexibly control diverse device architectures. This work further explores methods to automate phage immunoprecipitation sequencing (PhIP-seq) protocols for the detection of autoantibodies and also explores spatially multiplexed CRISPR-Cas assays designed to bypass the spectral limitations of traditional fluorescence-based nucleic acid diagnostics. Collectively, these platforms lower the barriers to advanced instrumentation, enabling broader participation in cutting-edge biological research and accelerating the development of next-generation diagnostics.