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A Bioengineering Approach to Develop New Technologies for Genomics-Based Healthcare

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Abstract:
Abstract of A Bioengineering Approach to Develop New Technologies for Genomics-Based Healthcare, by Olivia Ott, Sc.M. Brown University, May 2023. Genomics-based healthcare is a rapidly growing field, with use cases spanning molecular diagnostics and personalized medicine. Next-generation sequencing (NGS) is the underlying technology enabling innovations in genomics but remains limited by cumbersome and inefficient sample preparation. This thesis work explores an innovative bioengineering approach to develop cheaper and more accessible NGS sample preparation solutions by eliminating manual labor. The platform for automated NGS library preparation consists of a simplified mechanical design that exploits both macro- and microfluidic properties for optimizing heat transfer, reaction kinetics, mass transfer, fluid mechanics, adsorption-desorption rates, and molecular thermodynamics. The approach introduces a unique two-cannula cylindrical capillary system that integrates automatic reagent movement, mixing, and magnetic bead-based washing with capillary-based thermal cycling (capillary-PCR). The method was used to develop two library preparation assays, one incorporating mechanical and the other enzymatic DNA fragmentation. The platform successfully prepared eight libraries in parallel, generating sequencing data for both human and E. coli DNA libraries with negligible coverage bias compared to positive controls. The method achieved final library concentrations and size distributions comparable with the conventional manual approach, demonstrating compatibility with downstream sequencing and data analysis. This approach offers repeatability and consistency in the quality of DNA libraries, asserting the importance of mechanical design considerations that employ and optimize fundamental fluid mechanics and heat transfer properties.
Notes:
Thesis (Sc. M.)--Brown University, 2023

Citation

Ott, Olivia, "A Bioengineering Approach to Develop New Technologies for Genomics-Based Healthcare" (2023). Biomedical Engineering Theses and Dissertations. Brown Digital Repository. Brown University Library. https://repository.library.brown.edu/studio/item/bdr:yepy2bdu/

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