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Designing Functional Nanocultures for Controlled Microbial Dynamics

Davidson, Shanna-Leigh (2023) Designing Functional Nanocultures for Controlled Microbial Dynamics. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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While new techniques and platforms have advanced rapidly to enhance our understanding of complex microbial dynamics utilizing culture-independent methods, the same cannot be said for wet-lab culturing techniques. In fact, developments in meta-omics have revealed large bottlenecks in cell-culturing; omics methods can quickly reveal a myriad of information on microbial populations, yet, recapitulating those same microbial populations in a controlled environment is a non-trivial task. Therefore, there is a critical need to understand how the local milieu of microorganisms facilitates their growth in natural environments. Miniaturized cell-culturing techniques and novel microsystems can facilitate the interrogation of microorganisms and their local milieu in well-defined environments. Innovatively designed micro-technologies have shifted the paradigm in conventional microbial culturing. However, many of these technologies do not provide robust platforms for long-term studies, and are further limited by singular application; therefore, do not translate well from lab to clinical applications. Aspiring to design a novel tool for these purposes, our team has developed Nanocultures: nanolitre-sized, double-emulsion, polymeric microcapsules to sequester and cultivate microbial consortia. The nanocultures provide a robust, optically transparent, and high-throughput tool to study cell dynamics. As semi-permeability is a key design parameter, we can manipulate the chemistry of the nanoculture shell to achieve desired functionalities, such as for high-throughput screening and the development of biotherapeutics to reconstitute a disturbed microflora. As such, this thesis aims to explore I) transport and II) mechanical properties of a newly designed polymer, providing a highly functionalized shell with advantageous semi-permeability properties to the encased bacteria, as well as beneficial mechanical properties that allow for targeted lysis of the polymeric shell. Thirdly, this thesis discusses the design of a novel co-culturing platform to enable the growth of mammalian and bacterial cells together and allows for the assessment of cell-cell interactions in a first attempt, and proof-of-concept design of clinically applicable biotherapeutics. Together, these data will pave the way in our understanding of designing optimal nanocultures for applications-based functionality.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Davidson, Shanna-Leighshd73@pitt.edushd730000-0002-9820-7397
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Thesis AdvisorNiepa, Tagbo Herman
Committee MemberBanerjee,
Committee MemberLittle, Steven
Committee MemberSant,
Committee MemberCooper, Vaughn
Date: 14 September 2023
Date Type: Publication
Defense Date: 5 May 2023
Approval Date: 14 September 2023
Submission Date: 24 July 2023
Access Restriction: 2 year -- Restrict access to University of Pittsburgh for a period of 2 years.
Number of Pages: 175
Institution: University of Pittsburgh
Schools and Programs: Swanson School of Engineering > Chemical and Petroleum Engineering
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: micro-culturing, micro-technology, droplet Microfluidics, double-emulsion, Flory-Huggins, interaction parameter, small molecule diffusion, mechanical disruption, multimodal -omics platform, co-culture, Caco-2
Date Deposited: 14 Sep 2023 13:43
Last Modified: 14 Sep 2023 13:43


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