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Title:Design and application of multidentate polymers as quantum dot coatings
Author(s):Han, Zhiyuan
Director of Research:Smith, Andrew M
Doctoral Committee Chair(s):Smith, Andrew M
Doctoral Committee Member(s):Braun, Paul V; Selvin, Paul R; Evans, Christopher M; Zhang, Yingjie
Department / Program:Materials Science & Engineerng
Discipline:Materials Science & Engr
Degree Granting Institution:University of Illinois at Urbana-Champaign
Degree:Ph.D.
Genre:Dissertation
Subject(s):Quantum dot
Surface coating
Polymer Science
Molecular imaging
Abstract:Colloidal nanomaterials are being developed as analytical tools for unravelling the fundamentals in life science and for diagnostic tests in clinical medicine. Quantum dots (QDs) are florescent colloidal nanomaterials that are advantageous as molecular labels for single molecule imaging in cells and tissues. Multidentate polymers are enabling technologies as organic coatings for QDs which can make the products compact, stable, and inert toward nonspecific binding. Proof-of-concepts studies over the preceding decade have shown the potential of these materials, but rigorous structure-function relationships have not been reported, and further advances are needed to make these materials into versatile probes that are effective across diverse applications of fluorescent molecular labels. My PhD thesis is focused on the design and application of multidentate polymer as coatings for QDs. In Chapter 1, I investigate the trends in QD development as molecular probes, for which the applications in fixed cells and tissues declined in the last 5 years due to inadequacies in colloidal QDs quality control. To address this challenge, I introduce multidentate polymer coatings, which are advantageous in controlling QD colloidal properties compared with other types of coatings. In Chapter 2, I report design strategies of linear multidentate polymers to reduce the QD hydrodynamic size. The conformation of these polymers are controlled through their structural characteristics including anchoring group composition, backbone length, and side chain length. The QDs hydrodynamic diameter can be reduced from 10.8 to 5.7 nm by precise control of coating structure and QD core size. The smallest core/shell QD probes exhibit a near two-fold improvement in labeling specificity of cellular membrane receptors compared with previous QD generations (13.8 nm). In Chapter 3, I describe insights into controlling and minimizing QD nonspecific binding to proteins and cells using multidentate polymers with tunable hydrophilic functional groups that are cationic, anionic, zwitterionic (ZW), or non-ionic oligo(ethylene glycol) (OEG). I report an analytical workflow based on fluorescence correlation spectroscopy and flow cytometry to measure nonspecific interactions of QDs with proteins and cells. I find that there a substantial improvement in nonspecific binding resistance when surfaces are functionalized with a combination of ZW and OEG groups. The independent underlying effects of counterion adsorption and flexibility appear to synergistically resist protein adsorption on QDs when combined, particularly for applications in fixed cells. I further show that ZW-OEG QDs can be self-assembled with antibodies to specifically label surface receptors on living cells and cytoplasmic proteins in fixed cells. In Chapter 4, I study how the polymer coating structures affect the photophysical properties of QDs under different environmental stimuli and analyze the pH dependent photophysical properties of multidentate QDs and the mechanism behind their pH sensitivity. Finally, in Chapter 5, I summarize trends in multidentate polymer coatings and describe the future directions of QDs in life science application. As a whole, this thesis provides fundamental knowledge in structure-function relationships of multidentate coatings and QD colloidal properties, as well as design strategies for generating stable, small QDs that resist nonspecific binding for single molecule tracking and immunostaining in live and fixed cells. I expect these findings will be broadly applicable to other classes of polymers and nanoparticles, and further recommend a roadmap for coatings to refine QDs in analytical applications.
Issue Date:2021-12-02
Type:Thesis
URI:http://hdl.handle.net/2142/114090
Rights Information:Copyright 2021 Zhiyuan Han
Date Available in IDEALS:2022-04-29
Date Deposited:2021-12


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