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Future Prospects in Gravitational Waves: From Testing Fundamental Physics to Instruments beyond LIGO
No full textIn this thesis, we study the prospects for gravitational wave astronomy in the future. We focus on a couple of areas for gravitation waves beyond LIGO: improving measurement techniques of cosmological parameters, developing new waveforms for environmental effects, probing fundamental physics in waveforms, and high frequency gravitational wave detectors.
In the first part of this thesis, we develop two methods to constrain cosmological parameters using gravitational-wave observations. The first approach employs the statistical dark siren method, where the observed distribution of binary black hole events---whose luminosity distances are directly measured---is matched against astrophysical population models. By analyzing the Fisher information in the event distribution, we derive the Cram\'er-Rao bounds to quantify both statistical uncertainties and potential biases arising from unmodeled features in the merger rate and mass distribution. The second approach leverages the benefits of multiband observations with decihertz detectors, which dramatically improve host galaxy identification by refining source localization. This enhanced capability benefits reduces systematic errors in the measurement of the Hubble constant and other cosmological parameters. Together, these methods pave new pathways for precision cosmography using gravitational waves.
In the second part of the thesis, we investigate gravitational-wave signatures arising from binary black holes merging in the vicinity of supermassive black holes (SMBHs). One study focuses on hierarchical triple systems where the orbital motion around an SMBH imprints striking modulations on the gravitational waveforms. In our work, gravitational lensing is highlighted as a pivotal effect---alongside Doppler shifts and de Sitter precession---that is crucial for breaking parameter degeneracies. A complementary analysis considers eccentric orbits, incorporating orbital pericenter precession alongside Doppler and precession effects to further refine parameter estimation. Together, these investigations demonstrate that dynamic lensing and orbital modulations can be leveraged to probe SMBH properties and their environments with unprecedented precision, underscoring the importance of incorporating these environmental effects into waveform models.
In the third work, we explore inspiral tests of general relativity by examining the phase evolution of gravitational-wave signals from coalescing binary systems. First, we test Giddings' non-violent non-locality proposal, which posits that quantum information is transferred via a non-local interaction that generates metric perturbations around black holes by creating an effective-one-body waveform. We show that this can be captured by parameterized tests of general relativity waveforms. In the second half, we assess the robustness of post-Newtonian coefficients against unmodeled deviations by introducing parameterized tests that exploit the inherent geometry of the waveform. We show that the tests of general relativity are intimately related to the geometry of the signal manifold and propose a new singular value decomposition method to search for deviations for testing the predictions of general relativity and probing potential modifications to gravitational dynamics.
In the fourth part of this thesis, we explore optimizing the GEO600 detector for high-frequency gravitational wave detection. Although GEO600 is less sensitive than LIGO in the conventional 50–400 Hz band, we demonstrate that by detuning the signal-recycling mirror its sensitivity can be enhanced at tens of kHz. Using simulations with Finesse 3.0, we show that the sensitive point can be effectively scanned across various frequencies by adjusting the detuning angle. This tuning enables GEO600 to better target monochromatic sources, such as boson clouds arising from superradiance, thereby opening a promising new window for high-frequency gravitational wave astronomy.</p
Quantitative Nucleic Acid Measurements Inform Strategies to Mitigate Viral Outbreaks
No full textHumans have always been and continue to be at risk of infection by pathogens that surround us. However, recent advancements in quantitative nucleic acid technologies have allowed for more detailed study of these pathogens, how they spread among individuals, and how our immune systems respond to infection. In this thesis, I describe the design and execution of the Caltech COVID-19 Study, which used quantitative nucleic acid measurements to investigate the natural history of SARS-CoV-2 infection and inform strategies for diagnostics and vaccine development to reduce viral transmission. The Caltech COVID-19 Study enrolled participants in the Los Angeles area between September 2020 and April 2022 who were at risk of SARS-CoV-2 infection due to recent exposure to a household contact with acute infection. Participants collected paired upper respiratory specimens (saliva, nasal swabs, and throat swabs) daily or twice daily for approximately two weeks. These specimens underwent SARS-CoV-2 viral load quantification to assess transmission risk and determine whether to extend or terminate study enrollment. For participants who initially tested negative for SARS-CoV-2 RNA but later developed sustained infection, we tracked viral load from the very start of infection. These measurements were then used to evaluate the performance of various COVID-19 diagnostic tests. Our findings revealed a significant advantage of high-analytical-sensitivity tests over those with lower sensitivity, as well as the benefit of testing both the throat and nose rather than just the nose. In addition to viral load quantification, we sequenced human mRNA from these specimens to assess gene expression. Analyzing these changes allowed us to study how the mucosal immune system responds to acute viral infection across multiple anatomical sites over time, providing insights that could improve mucosal vaccine design. Notably, our data showed that, contrary to current models of localized paracrine interferon signaling, distinct compartments of the upper respiratory mucosa exhibited synchronized interferon stimulation during early infection—even in the absence of detectable local viral replication. Mucosal vaccines capable of triggering this coordinated interferon response, maintaining CD8+ T memory cells to rapidly execute effector functions upon viral exposure, may be key to achieving sterilizing immunity. Findings from quantitative nucleic acid measurements in this thesis inform strategies to more effectively mitigate viral outbreaks
Development and Characterization of a Table-Top Laser-Produced Plasma Source for In-Situ and Time-Resolved Soft X-Ray Absorption Spectroscopy
Get PDFX-ray absorption spectroscopy (XAS) has emerged as an indispensable tool in the fields of carbon capture and conversion, providing element-specific insights into electronic structure, oxidation states, and chemical bonding. Of particular interest are soft X-rays (SXRs), which can probe the X-ray water window, enabling detailed studies of carbon, nitrogen, and transition metal L-edges in aqueous environments. Traditionally, access to this technique and this energy range has been limited to large- scale facilities like synchrotrons and XFELs, which can only serve a small population of users in a given year. Furthermore, more complex techniques such as time-resolved and in-situ XAS are practically inaccessible to the majority of users. This thesis explores the development of a table-top laser-produced plasma (LPP) source based on a gaseous target to extend the reach of XAS techniques into laboratory settings. Such sources offer significant advantages in accessibility, flexibility, and cost, while advances in X-ray optics and detection systems have further enhanced their utility. The research presented here focuses on the utilization of gaseous LPP sources for both in-situ and time-resolved XAS, pushing the boundaries of table-top soft X-ray absorption capabilities.
Key achievements include exploration of the lower temporal limit of LPP sources for SXR emission, and the first demonstration of liquid-phase XAS measurements using a gaseous LPP source. Gas-phase measurements were also achieved using the system built in this work. Additionally, a novel UV-pump/SXR-probe technique was developed, enabling future time-resolved studies of charge transfer dynamics in transition metal oxides. These advances pave the way for detailed investigations of photodriven processes, interfaces, and catalytic mechanisms critical to carbon capture and conversion. By improving temporal resolution and expanding the scope of in-situ XAS techniques, this work addresses fundamental challenges in the field, bringing the power of synchrotron-like spectroscopy into everyday laboratories. Ultimately, the results presented here aim to democratize XAS, fostering a broader adoption of this technique in catalysis and materials research.</p
Atomically Thin Spatial Light Modulators with Excitonic Nanomaterials
Get PDFAchieving active control of light at the ultimate thickness limit—a single atomic layer—offers unprecedented opportunities for next-generation optoelectronic devices. The quest for ultrathin spatial light modulators has long relied on integrating tunable materials with plasmonic or high-index nanoantennas that serve as small, but three-dimensional optical resonators. As structures for controlling light become increasingly complex and compact, the geometrical constraints of these three-dimensional resonators will ultimately limit their scalability and versatility. A new avenue for device miniaturization emerges when harnessing electrically tunable resonances that are intrinsic to atomically thin materials.
This thesis explores how exciton resonances, specifically in two-dimensional (2D) van der Waals materials, can serve as the central building blocks for future spatial light modulators that are as thin as atoms. We start by characterizing the gate-tunable optical properties of a monolayer molybdenum diselenide (MoSe₂), a 2D transition metal dichalcogenide. By tuning the exciton resonances with voltage, we demonstrate over 200% modulation in the real and imaginary part of the complex refractive index. We attribute this large tunability to the interplay between radiative and nonradiative decay channels of the excitons. The index modulation gives rise to amplitude and phase modulation of the scattered light, which is then used to engineer an electrically tunable phase gradient across a single monolayer MoSe₂ flake to dynamically steer the reflected beam.
Next, we present a theoretical analysis of the complex frequency response of a generalized excitonic heterostructure. We show how the spectral positions of the phase singularities, e.g. zeros and poles, can be dynamically controlled, their impacts on the real frequency phase response, and how they can be used in active metasurface design. Finally, we evaluate excitons in quantum dots as an alternative platform for room temperature optical modulators and show how they present different challenges in designing phase modulators.
Overall, our work highlights the novel functionalities enabled by exciton resonances for advanced light manipulation, underscoring their potential for atomically thin light modulators.</p
Bond-Selective Nonlinear Optical Microscopy: From Live Cells to Single- Molecule Imaging
Get PDFAdvances in optical microscopy have revolutionized cell biology, transforming our understanding of cellular processes from static structural observations to dynamic temporal and spatial insights at the single-molecule level. While fluorescence imaging remains the gold standard due to its high sensitivity, specificity, and versatile toolbox, it faces significant limitations, particularly in imaging small molecules that are not inherently fluorescent. Attaching fluorescent tags to these molecules often disrupts their physicochemical properties, highlighting the need for minimally invasive and intrinsic-contrast-based approaches.
Vibrational spectro-microscopy, which probes the intrinsic vibrational frequencies of chemical bonds, offers a promising solution. Stimulated Raman scattering (SRS) microscopy, a well-established vibrational imaging technique, enhances vibrational excitation by up 10⁸-fold through stimulated emission amplification, enabling rapid, label-free imaging of biological samples with high specificity.
In the first half of this thesis, we advance SRS microscopy to tackle specific biological challenges and explore new methodological possibilities. To visualize glycogen metabolism, we combined a stable isotope labeling strategy with SRS imaging, achieving high-specificity imaging of glycogen in live cells. This approach was further applied to metabolic phenotyping of patient-derived melanoma cell lines. Additionally, we investigated strategies to photoswitch electronic pre-resonance (epr) SRS probes, which are typically photostable. By inducing electronic transitions that modulate electronic-vibrational coupling, we developed the first genetically encodable photoswitchable epr-SRS probe using a near-infrared fluorescent protein, unlocking new possibilities in Raman imaging.
In the second half of this thesis, we address the limitations of SRS microscopy by developing a novel bond-selective nonlinear optical microscopy technique called bond-selective fluorescence-detected infrared-excited (BonFIRE). BonFIRE introduces a vibration-state-mediated two-photon process as a new vibrational contrast mechanism, overcoming key limitations in sensitivity and speed associated with SRS. By combining the high sensitivity and specificity of fluorescence with the rich chemical information provided by IR absorption-based vibrational contrast, BonFIRE offers a powerful platform for multidimensional insights into biological systems. We envision BonFIRE as a tool to tackle unique challenges that current technologies cannot address, representing a significant step forward in understanding the complex processes that define life.</p
Evaluation of the Generalizability of Machine Learning-Assisted Protein Engineering Methods
No full textEngineered proteins can carry out a vast array of functions and have become indispensable across numerous industrial applications. To accelerate wet-lab protein engineering efforts, machine learning-based methods have advanced rapidly. However, a gap remains between state-of-the-art machine learning methods and their practical adoption. A key factor contributing to this disconnect is the lack of application-relevant benchmarking and generalizable insights across protein engineering tasks. This thesis evaluates machine learning-assisted protein engineering approaches to identify generalizable strategies. The central problem considered is learning the mapping from protein sequence to function—known as the fitness landscape—to enable the prediction of unseen variant fitness. Chapter 1 introduces the background and context for machine learning-assisted protein engineering and highlights the practical constraint of limited experimental budgets. Chapter 2 investigates transfer learning, which leverages models pretrained on large protein sequence databases to generate informative representations for modeling task specific sequence-function relationships. Evaluation across ten diverse tasks shows that while transfer learning is effective in structure prediction, it underperforms in variant fitness prediction—a key objective in protein engineering. Chapter 3 evaluates alternative strategies with a focus on combinatorial fitness landscapes, a common setting in protein engineering. Across 16 diverse landscapes, focused training improves the performance of various machine learning approaches by strategically selecting training variants using zero-shot predictors, which estimate variant fitness from auxiliary information without relying on experimental data. Building on these insights, Chapter 4 addresses the specific challenge of engineering enzymes—proteins that convert substrates into products—for novel chemistries. While six general zero-shot predictors without substrate information can predict enzyme activity on non-native substrates, they fail on more out-of-distribution, new-to-nature chemistries. Incorporating substrate information into zero-shot predictors leads to more generalizable performance across all tested chemistries, spanning 22 substrates. Overall, this thesis identifies generalizable strategies for machine learning-assisted protein engineering by systematically evaluating and improving how sequence-to-function relationships are modeled across diverse tasks
Asymmetric Transformations from Palladium Enolates and Progress Toward the Total Synthesis of Hypermoin A
No full textResearch in the Stoltz group is centered around developing new methodologies for the asymmetric formation of stereocenters and the application of these technologies in complex natural product total synthesis. Herein we describe the development of new enantioselective transformations from Pd enolate intermediates and efforts toward the total synthesis of hypermoin A. Chapter 1 reports the development of an asymmetric intramolecular decarboxylative [4+2] cycloaddition from a catalytically generated chiral Pd enolate, forging four contiguous stereocenters in a single transformation. Mechanistic studies including quantum mechanics calculations, Eyring analysis, and KIE studies offer insight into the reaction mechanism. Appendix 2 discloses efforts toward the development of an asymmetric intermolecular decarboxylative double Michael addition. Chapter 2 describes an enantioselective cyclization of Pd enolates and isocyanates to form spirocyclic γ-lactams. This reaction proceeds under mild reaction conditions and utilizes a novel Meldrum’s acid derivative to achieve catalyst turnover, delivering enantioenriched products in up to 97% yield and 96% ee. Chapter 3 outlines the ongoing progress toward the total synthesis of hypermoin A. A [4+2] cycloaddition and ring expansion strategy has been developed in a model system to form the key [3.2.2] bicycle and current efforts are dedicated to the application of this sequence in a more complex setting
Illuminating Molecular Spin Relaxation Mechanisms through Ligand Field Theory and Physical Inorganic Spectroscopy
Get PDFElectron spin relaxation is a fundamental process in paramagnetic molecules, and successful development of molecular quantum bits (qubits) for quantum information science hinges on suppressing the rate of spin relaxation. While the relaxation process has been studied since the early 20th century, no consensus has been reached regarding the physical relaxation mechanism in S = 1/2 transition metal molecules. Practical guidelines for designing molecules with slow spin relaxation have likewise remained obscure. This thesis describes the use of ligand field theory and physical inorganic spectroscopy techniques to shed new light on molecular spin relaxation mechanisms, connecting relaxation rates to chemical bonding and transition metal electronic structure. Part 1 (Chapters 2-4) details the use of electron paramagnetic resonance (EPR), magnetic circular dichroism (MCD), and resonance Raman (rR) to interrogate the origins of spin relaxation. Experimental spectroscopic results are analyzed within the context of a model based on group theory, yielding a paradigm referred to as ligand field spin dynamics. Part 2 (Chapters 5-7) describes the development of a new experimental observable, T1 anisotropy, as a novel approach for distinguishing between competing theoretical spin relaxation models. Part 3 (Chapters 8-10) shows how the insights of ligand field spin dynamics and T1 anisotropy have been leveraged to rationally design molecules with slow spin relaxation and other desirable spin dynamics properties. This thesis establishes a framework for controlling the physical process of spin relaxation through distinctly chemical molecular design principles
Elucidating the Role of Transition Metal Electronic Structure in Catalysis and Spin Relaxation
Get PDFTransition metal complexes are the workhorses of physical inorganic chemistry and have diverse applications in catalysis and quantum information science, especially. The primary descriptor of transition metal complexes, and a good predictor of their utility, is their electronic structure. Notably, rigorous characterization of the spin states, oxidation states, excited states, and magnetic properties of these complexes is necessary to gain mechanistic detail for these applications; this thesis focuses on elucidating the role of transition metal electronic structure in catalysis and spin relaxation. Chapter 1 introduces important transition metal electronic structure considerations and motivates these studies. Part I includes Chapters 2–4 and considers complexes relevant for CO₂ reduction chemistry and cross-coupling reactivity. Chapter 2 investigates the conditions under which a CO₂ reduction catalyst, Fe-p-TMA, undergoes speciation changes and characterizes its excited-state identities and lifetimes. Chapter 3 considers the electrochemical conditions under which highly reduced CO reduction products are generated in an iron porphyrin system, and important connections to photocatalysis are made. Chapter 4 compares the excited-state identities and reactivities of prototypical and tethered Ni(II)–bpy aryl halide complexes. Part 2 includes Chapters 5–6 and focuses on spin relaxation, a key figure of merit in quantum information science. Chapter 5 investigates the effect of structural distortions in S = ½ copper porphyrin systems on their spin-lattice relaxation times, and Chapter 6 moves to identifying the mechanism of spin relaxation in an S = 1 Cr(o-tolyl)₄ system. Together, these compiled studies reveal the nuanced roles of transition metal electronic structure in catalysis and spin relaxation and highlight the importance of their characterization for developing optimized systems
Crystal Chemistry and Seismic Wavespeeds of Dense Oxyhydroxides: Hydrogen Transport in Earth's Lower Mantle
Get PDFIn this thesis, I perform a thorough investigation of the electronic and elastic properties of the dense oxyhydroxide (Al,Fe)-phase H (Al0.84Fe3+0.07Mg0.02Si0.06OOH). This phase represents a realistic composition in a solid solution which has been hypothesized to carry 'water', in the form of hydrogen, to the lowermost depths of Earth's mantle. Its propensity for water storage and elastic properties are affected by hydrogen bond symmetrization and a high-low spin crossover of Fe3+ atoms, respectively. In order to determine changes in hydrogen bonding environment, I use synchrotron infrared spectroscopy and Raman spectroscopy, which identify O-H vibrational modes in the crystal structure and changes in their frequencies with pressure. These vibrational modes indicate that (Al,Fe)-phase H likely stores additional hydrogen as defects and that hydrogen bonds are disordered at ambient pressure due to the substitution of cations of different valence states. I find that hydrogen atoms become dynamically disordered across sites at 10 GPa and conclude that hydrogen bond symmetrization in (Al,Fe)-phase H takes place at 35 GPa. I use powder X-ray diffraction to constrain the equation of state of this phase, providing fundamental constraints on its incompressibility and density at high pressures. I complement this equation of state with study of the electronic environment around the Fe atoms via nuclear resonant forward scattering in order to constrain the spin crossover of Fe3+ atoms between 48 and 63 GPa. I use nuclear resonant inelastic X-ray scattering measurements to determine the seismic wavespeeds of (Al,Fe)-phase H to 120 GPa, the base of the lowermost mantle. The measured seismic wavespeeds are incorporated into whole-rock models which suggest that (Al,Fe)-phase H contributes to seismic heterogeneity in the mid-mantle and that hydrous metabasalt containing (Al,Fe)-phase H could contribute to seismic anomalies associated with the edges of large, low, shear velocity provinces in the lowermost mantle as it heats during descent in the lowermost mantle. The combined results of this thesis elucidate a complete compression pathway during transport of a dense oxyhydroxide into the lower mantle in the context of changes in its electronic and elastic properties. I offer several observables which may be used to detect the presence of this phase in subducted metabasalt and comment on the implications for hydrogen storage in the deep Earth