Integrated, locally-synthesized, and genetically-targeted polymer systems in neural tissue

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Abstract/Contents

Abstract
Recent advancements in the development of implantable brain-machine interfaces have bridged the communication gap between the brain and modern electronics. While much work has been done to optimize the electrode-tissue interface of these devices, a bioelectronic system that can reliably interact with and identify genetically-specific neural circuits within whole, intact 3D volumes of tissue is yet to be realized. Therefore, novel approaches for building seamlessly integrated tools that are more intimately connected to biological elements in tissue are highly desirable. An alternative to pre-fabrication and subsequent implantation of small-scale, mechanically compliant electronic devices is locally-performed synthesis that directly integrates material with cells and soft tissue, for which there has been little precedence. In this work, the mechanical and chemical properties of polymer-brain hybrid materials synthesized directly inside of rodent brains using CLARITY were obtained to more deeply understand the interactions amongst polymer precursor reagents and tissue, which can significantly alter optical properties of tissue while preserving molecular structure. Next, a novel strategy was developed to generate functional organic materials directly on specific neurons and their subcomponents using a genetically-encoded enzyme to trigger polymerization. Quantitative analysis of the resulting material verified the genetically-specific and enzyme-mediated synthesis of a conductive polymer layer proximal to the surface of neurons. Furthermore, whole-cell patch clamp and extracellular electrical recording measurements indicated that this polymerization strategy did not have short-term cytotoxic effects in cultured unfixed neurons and acute mouse brain slices. These studies demonstrate the feasibility of new methodologies for in situ polymer synthesis to maintain intimate connections with biological targets in the brain, and inspire next-generation bioelectronic tissue-device interfaces that can enhance our study of intact, whole-tissue dynamics with exceptional control and spatial resolution.

Description

Type of resource text
Form electronic; electronic resource; remote
Extent 1 online resource.
Publication date 2017
Issuance monographic
Language English

Creators/Contributors

Associated with Tom, Ariane
Associated with Stanford University, Department of Bioengineering.
Primary advisor Bao, Zhenan
Primary advisor Deisseroth, Karl
Thesis advisor Bao, Zhenan
Thesis advisor Deisseroth, Karl
Thesis advisor Heilshorn, Sarah
Advisor Heilshorn, Sarah

Subjects

Genre Theses

Bibliographic information

Statement of responsibility Ariane Tom.
Note Submitted to the Department of Bioengineering.
Thesis Thesis (Ph.D.)--Stanford University, 2017.
Location electronic resource

Access conditions

Copyright
© 2017 by Ariane Claire Tom

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