Physics Commons^™

Information-Rich 6d Single-Molecule Imaging Design Using Optimization, Tingting Wu

McKelvey School of Engineering Theses & Dissertations

When studying biochemical processes, localizing the targets alone will not paint a complete picture. We also need techniques to probe how biomolecules interact with one another, including how molecules are organized into larger structures, how they are oriented with respect to surrounding molecules, and how local chemical parameters, like pH and hydrophobicity, vary spatially and temporally. My dissertation focuses on single-molecule orientation localization microscopy (SMOLM, Chapter 1). The objective is to develop imaging techniques for measuring how molecules are oriented with respect to their surrounding molecules, namely, 3D orientation. Achieving optimal imaging performance requires careful design of both the forward …

Non-Hermitian Physics And Engineering In Whispering Gallery Mode Microresonators, Changqing Wang

McKelvey School of Engineering Theses & Dissertations

Non-Hermitian physics describes the behaviors of open systems which have interactions with the environment. It can be applied to a wide range of classical and quantum systems. Exotic physical phenomena are unveiled in such non-Hermitian systems, especially around a singular point in the parameter space, i.e., the exceptional point (EP), where the eigenvalues and the associated eigenvectors are degenerate. A plethora of demonstrations have been found in optics and photonics, where the non-Hermitian effects are ubiquitous due to the existence of optical dissipation or amplification. In particular, whispering gallery mode (WGM) resonators are ideal candidates for studying light-matter interactions in …

Assessment And Diagnosis Of Human Colorectal And Ovarian Cancer Using Optical Imaging And Computer-Aided Diagnosis, Yifeng Zeng

McKelvey School of Engineering Theses & Dissertations

Tissue optical scattering has recently emerged as an important diagnosis parameter associated with early tumor development and progression. To characterize the differences between benign and malignant colorectal tissues, we have created an automated optical scattering coefficient mapping algorithm using an optical coherence tomography (OCT) system. A novel feature called the angular spectrum index quantifies the scattering coefficient distribution. In addition to scattering, subsurface morphological changes are also associated with the development of colorectal cancer. We have observed a specific mucosa structure indicating normal human colorectal tissue, and have developed a real-time pattern recognition neural network to localize this specific structure …

Mutual Interaction Induced Multi-Particle Physics In Qed Systems – Cooperative Spontaneous Emission And Photonic Dimer Enhanced Two-Photon Excitation, Yao Zhou

McKelvey School of Engineering Theses & Dissertations

In recent years, the study of quantum electrodynamics (QED) in light-matter interactions has discovered various interesting phenomenons that orient many applications. However, due to the ambient entanglement among photons and atoms, few-particle dynamics remains challenging to analyze precisely and limits the progress in several fields. In few-particle systems, different number of atoms interacting with the light field generates drastically different results, even when there is only a single photon involved in the system. The interference between individual atom’s spontaneous emission wavefunctions can cooperatively alter the effective atom-light coupling strength. Depending on the spatial distance between individual of atoms and the …

Structural Organization And Chemical Activity Revealed By New Developments In Single-Molecule Fluorescence And Orientation Imaging, Tianben Ding

McKelvey School of Engineering Theses & Dissertations

Single-molecule (SM) fluorescence and its localization are important and versatile tools for understanding and quantifying dynamical nanoscale behavior of nanoparticles and biological systems. By actively controlling the concentration of fluorescent molecules and precisely localizing individual single molecules, it is possible to overcome the classical diffraction limit and achieve 'super-resolution' with image resolution on the order of 10 nanometers.

Single molecules also can be considered as nanoscale sensors since their fluorescence changes in response to their local nanoenvironment. This dissertation discusses extending this SM approach to resolve heterogeneity and dynamics of nanoscale materials and biophysical structures by using positions and orientations …

Biomedical Applications Of Polarimetry, Nathaniel Owen King

McKelvey School of Engineering Theses & Dissertations

Non- or minimally-invasive data collection is highly desirable for gathering the broad base of information that facilitates moving technology to the point of care. Polarimetry has been making this transition for years. Early forms of polarization-sensitive optics involved custom multiplexing a series of images to generate a single image, but today’s snapshot polarimeters are readily commercially available.

The research presented in this dissertation advances three areas of polarimetric imaging: First, this research develops a reflectance-based measurement for tracking changes in the alignment of dynamically loaded soft tissue, specifically tendon. This work highlights a range of mounting angles across which signal …

Development Of High-Speed Photoacoustic Imaging Technology And Its Applications In Biomedical Research, Yun He

McKelvey School of Engineering Theses & Dissertations

Photoacoustic (PA) tomography (PAT) is a novel imaging modality that combines the fine lateral resolution from optical imaging and the deep penetration from ultrasonic imaging, and provides rich optical-absorption–based images. PAT has been widely used in extracting structural and functional information from both ex vivo tissue samples to in vivo animals and humans with different length scales by imaging various endogenous and exogenous contrasts at the ultraviolet to infrared spectrum. For example, hemoglobin in red blood cells is of particular interest in PAT since it is one of the dominant absorbers in tissue at the visible wavelength.The main focus of …

Polarization Division Multiplexing For Optical Data Communications, Darko Ivanovich

McKelvey School of Engineering Theses & Dissertations

Multiple parallel channels are ubiquitous in optical communications, with spatial division multiplexing (separate physical paths) and wavelength division multiplexing (separate optical wavelengths) being the most common forms. In this research work, we investigate the viability of polarization division multiplexing, the separation of distinct parallel optical communication channels through the polarization properties of light. We investigate polarization division multiplexing based optical communication systems in five distinct parts. In the first part of the work, we define a simulation model of two or more linearly polarized optical signals (at different polarization angles) that are transmitted through a common medium (e.g., air), filtered …

In Vivo Vascular Imaging With Photoacoustic Microscopy, Hsun-Chia Hsu

McKelvey School of Engineering Theses & Dissertations

Photoacoustic (PA) tomography (PAT) has received extensive attention in the last decade for its capability to provide label-free structural and functional imaging in biological tissue with highly scalable spatial resolution and penetration depth. Compared to modern optical modalities, PAT offers speckle-free images and is more sensitive to optical absorption contrast (with 100% relative sensitivity). By implementing different regimes of optical wavelength, PAT can be used to image diverse light-absorbing biomolecules. For example, hemoglobin is of particular interest in the visible wavelength regime owing to its dominant absorption, and lipids and water are more commonly studied in the near-infrared regime.

In …

Developing Wavefront Shaping Techniques For Focusing Through Highly Dynamic Scattering Media, Ashton Hemphill

McKelvey School of Engineering Theses & Dissertations

One of the prime limiting factors of optical imaging in biological applications is the diffusion of light by tissue, which prevents focusing at depths greater than the optical diffusion limit of ~1 mm in soft tissue. This greatly restricts the utility of optical diagnostic and therapeutic techniques, such as optogenetics, microsurgery, optical tweezing, and phototherapy of deep tissue, which require focused light in order to function. Wavefront shaping extends the depth at which optical focusing may be achieved by compensating for phase distortions induced by scattering, allowing for focusing through constructive interference.

However, due to physiological motion, scattering of light …

Developing Photoacoustic Tomography Devices For Translational Medicine And Basic Science Research, Tsz Wai Wong

McKelvey School of Engineering Theses & Dissertations

Photoacoustic (PA) tomography (PAT) provides volumetric images of biological tissue with scalable spatial resolutions and imaging depths, while preserving the same imaging contrast—optical absorption. Taking the advantage of its 100% sensitivity to optical absorption, PAT has been widely applied in structural, functional, and molecular imaging, with both endogenous and exogenous contrasts, at superior depths than pure optical methods. Intuitively, hemoglobin has been the most commonly studied biomolecule in PAT due to its strong absorption in the visible wavelength regime.

One of the main focuses of this dissertation is to investigate an underexplored wavelength regime—ultraviolet (UV), which allows us to image …

Fluorescence Guided Tumor Imaging: Foundations For Translational Applications, Jessica P. Miller

McKelvey School of Engineering Theses & Dissertations

Optical imaging for medical applications is a growing field, and it has the potential to improve medical outcomes through its increased sensitivity and specificity, lower cost, and small instrumentation footprint as compared to other imaging modalities. The method holds great promise, ranging from direct clinical use as a diagnostic or therapeutic tool, to pre-clinical applications for increased understanding of pathology. Additionally, optical imaging uses non-ionizing radiation which is safe for patients, so it can be used for repeated imaging procedures to monitor therapy, guide treatment, and provide real-time feedback. The versatile features of fluorescence-based optical imaging make it suited for …

Novel Sensing Mechanisms For Chemical And Bio-Sensing Using Whispering Gallery Mode Microresonators, He Huang

McKelvey School of Engineering Theses & Dissertations

Due to their ultra-high quality factor and small mode volume, whispering gallery mode (WGM) microresonators have proven to have exceptional sensing capabilities, with single particle level sensitivity to virions, proteins, and nucleic acids. Current sensing mechanisms rely on measuring the changes in the transmission spectrum of the resonator upon adsorption of the analyte on the surface of the resonator, appearing as either shift, splitting, or broadening of the resonance mode, all of which measure the polarizability of adsorbed analytes. In this dissertation, we present two new sensing mechanisms for WGM microresonators: the measurement of a dynamic chemical reaction around the …

Multiscale Imaging Of The Mouse Cortex Using Two-Photon Microscopy And Wide-Field Illumination, Jonathan Richard Bumstead

McKelvey School of Engineering Theses & Dissertations

The mouse brain can be studied over vast spatial scales ranging from microscopic imaging of single neurons to macroscopic measurements of hemodynamics acquired over the majority of the mouse cortex. However, most neuroimaging modalities are limited by a fundamental trade-off between the spatial resolution and the field-of-view (FOV) over which the brain can be imaged, making it difficult to fully understand the functional and structural architecture of the healthy mouse brain and its disruption in disease. My dissertation has focused on developing multiscale optical systems capable of imaging the mouse brain at both microscopic and mesoscopic spatial scales, specifically addressing …

Measuring Molecular Orientation And Rotational Mobility Using A Tri-Spot Point Spread Function, Oumeng Zhang

McKelvey School of Engineering Theses & Dissertations

Single molecules have become a powerful tool for biophysicists since they were first optically detected 28 years ago. Understanding molecular orientation can not only improve the accuracy of single-molecule localization, but it can also provide insight into biochemical behaviors at the nanoscale. In this thesis, I present a method to measure the molecular orientation and rotational mobility of single-molecule emitters by designing and implementing a tri-spot point spread function. The point spread function is designed so that it is capable of measuring all degrees of freedom related to molecular orientation and rotational mobility. Its design is optimized by maximizing the …

Goggle Augmented Imaging And Navigation System For Fluorescence-Guided Surgery, Suman Bikash Mondal

McKelvey School of Engineering Theses & Dissertations

Surgery remains the only curative option for most solid tumors. The standard-of-care usually involves tumor resection and sentinel lymph node biopsy for cancer staging. Surgeons rely on their vision and touch to distinguish healthy from cancer tissue during surgery, often leading to incomplete tumor resection that necessitates repeat surgery. Sentinel lymph node biopsy by conventional radioactive tracking exposes patients and caregivers to ionizing radiation, while blue dye tracking stains the tissue highlighting only superficial lymph nodes. Improper identification of sentinel lymph nodes may misdiagnose the stage of the cancer. Therefore there is a clinical need for accurate intraoperative tumor and …

Optical Resonators And Fiber Tapers As Transducers For Detection Of Nanoparticles And Bio-Molecules, Huzeyfe Yilmaz

McKelvey School of Engineering Theses & Dissertations

In recent years, detection of biological interactions on single molecule level has aspired many researchers to investigate several optical, chemical, electrical and mechanical sensing tools. Among these tools, toroidal optical resonators lead the way in detection of the smallest particle/molecule with the real time measurements. In this work, bio-sensing capabilities of toroidal optical resonators are investigated. Bio-sensing is realized via measuring the analyte-antigen interaction while the antigen is immobilized through a novel functionalization method.

Not long ago, detection of single nanoparticles using optical resonators has been accomplished however the need for cost-effective and practical transducers demands simpler tools. A tapered …