Engineering polymeric materials to elucidate structure-property relationships and improve biomedical applications
Abstract/Contents
- Abstract
- Diagnostics and personalized therapeutics have seen a growing demand in recent years, driving the need for medical devices that respond to an individual's therapeutic needs. The production of such devices would have great implications, leading to early stage detection of viruses and diseases, improvement in the precision of drug dosing, and significantly reduced healthcare practitioner and patient burden. Towards this aim, biosensors have been developed that can respond to specific molecules in a complex biological environment. These biosensors detect specific analytes and produce a quantitative output (i.e. kinetic parameters, signal intensity), which provides precise information tailored to an individual and overcome limitations of other detection methods that are costly and require time-intensive sample preparation and processing. Continuous monitoring of analytes across a dynamic range of molecules and detection limits has led to significant advancements in the form of wearables and stretchable electronics, though adoption of implantable biosensors has been challenging. These limitations often stem from biofouling, which begins with non-specific protein adsorption in the body that accelerates the degradation of device performance that eventually renders them ineffective. A description and current state of biodevices and materials to combat biofouling is surveyed in Chapter 1. The choice of material for these biosensors is carefully curated to each application. Mechanical, chemical, and physical properties dictate how the body responds to these implanted devices and thus, affect device performance. Thus, there is pressing need for a deep understanding of these properties that leads to precision in the tuning of the materials. In Chapter 2, mechanical and chemical effects from the introduction of dangling chains in elastomeric systems are explored. Further, we develop a single-chain polymeric nano-carrier platform that offers highly controlled and precise properties (i.e. size, stability, cargo delivery), making it desirable as a drug delivery system. As these devices and platforms are translated to clinical applications, limitations from output quality, lifetime, and specificity have prevented widespread adoption and implementation of implantable biosensors. However, accompanying the rise of these devices is the introduction and development of materials that exhibit anti-biofouling properties. Biomaterials, specifically hydrogels, can be applied as coatings as they exhibit highly tunable properties that provide efficacy against fouling and the immune response, offering the potential to drive clinal translation of implanted devices to drive personalized, point-of-care diagnostics. In Chapter 3, we develop a library of acrylamide-based materials that can be used for their anti-blood biofouling properties and subject them to severe fouling conditions to screen their function and to select a top performing material. We explore the molecular features of the monomers underlying their performance and assess the mechanical properties of this material that allow it to serve as a soft materials interface with the body. In Chapter 4, we apply our top performing hydrogel to a selection of electrochemical biosensors to improve signal intensity in vitro and in vivo in whole blood conditions. In Chapter 5, translation to subcutaneous biocompatibility is explored. Through the use of insulin infusion pumps, we explore the translation of anti-biofouling materials to mitigate the foreign body response. Finally, towards future work of refining and expanding our material library, we develop a barcoded micro-particle system that can be delivered to the inter-peritoneal space for extensive material library screening.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2020; ©2020 |
| Publication date | 2020; 2020 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Chan, Doreen Chung-Yue |
|---|---|
| Degree supervisor | Appel, Eric (Eric Andrew) |
| Thesis advisor | Appel, Eric (Eric Andrew) |
| Thesis advisor | Bertozzi, Carolyn R, 1966- |
| Thesis advisor | Heilshorn, Sarah |
| Degree committee member | Bertozzi, Carolyn R, 1966- |
| Degree committee member | Heilshorn, Sarah |
| Associated with | Stanford University, Department of Chemistry. |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Doreen C. |
|---|---|
| Note | Submitted to the Department of Chemistry. |
| Thesis | Thesis Ph.D. Stanford University 2020. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2020 by Doreen Chung-Yue Chan
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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