Abstract

Biological systems exhibit hierarchical organization spanning molecular to tissue scales. Molecular orientation and supramolecular packing define nanoscale architecture, while collective organization of these constituents contributes to emergent mechanical and dynamical behavior at the tissue level. Although optical imaging provides access to both regimes, modalities are typically optimized for a single scale and often emphasize qualitative visualization rather than quantitative measurement. Establishing rigorous frameworks for extracting physical parameters from optical signals and articulating conceptual continuity across scales remains a central challenge. This dissertation advances optical imaging as a quantitative measurement technology through the development of complementary approaches at the nanoscale and microscale. At the single-molecule level, orientation-resolved fluorescence imaging is formulated within explicit detection and sensitivity limits. Detection-rate trade-offs for polarized single-molecule orientation-localization microscopy (SMOLM) are analyzed, and polarization-engineered dipole-spread functions are applied to resolve the supramolecular organization of β-sheet peptide assemblies under physiological conditions. Extensions to anisotropic rotational diffusion refine models of molecular wobble and quantify direction-dependent confinement, enabling more rigorous interpretation of nanoscale structural order. At the tissue scale, coherence-based imaging is developed for high-speed, phase-sensitive functional measurements. A photonic-chip-enabled space-division multiplexing optical coherence elastography (SDM-OCE) system employing eight parallel beams achieves an effective A-scan rate of 1 MHz while improving phase stability through a glass reference. Ex vivo biological tissue imaging demonstrates wide-field elastographic mapping and resolves subregional mechanical heterogeneity. Complementary investigations of photonic taper geometry reveal systematic control of anisotropic beam divergence in integrated circuits, linking chip-level design to imaging performance. Although the nanoscale and microscale systems developed in this dissertation are not integrated into a single experimental platform, they are unified by a common quantitative imaging perspective. Across these modalities, optical measurements are treated as forward models that encode physical parameters through orientation-dependent contrast, system response, noise, and bandwidth. By shifting the emphasis from qualitative visualization to quantitative parameter inference across spatial scales, this work establishes analytical foundations for future multiscale imaging strategies that connect molecular organization to emergent tissue-level behavior.

Committee Chair

Chao Zhou

Committee Members

Matthew Bersi; Matthew Lew; Quing Zhu; Song Hu

Degree

Doctor of Philosophy (PhD)

Author's Department

Electrical & Systems Engineering

Author's School

McKelvey School of Engineering

Document Type

Dissertation

Date of Award

6-4-2026

Language

English (en)

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