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Multicellular Control
Get PDFRobust control theory was developed in the late twentieth century as a mathematical framework to enable the principled incorporation of uncertainty into engineering design in applications like aerospace. However, engineered technologies that interface with living systems in applications like medicine and ecology must accommodate uncertainties and unmodeled dynamics far beyond what robust control theory has historically achieved. This thesis develops a robust control foundation for overcoming large-scale uncertainty and designing interfaces with living systems, through formal theory and three case studies: neural control of movement, immune control of viruses, and homeostatic control of neoplasia in the moon jellyfish.
The central argument of this thesis is that these three systems, along with many others, have two key properties that enable new approaches to the uncertainty intrinsic to their study: they are themselves control systems, and they are multicellular systems. These properties motivate new work in control theory, blending recent results in localized and distributed control with older results from robust and modern control. The resulting theory framework answers domain-specific questions, guides the design of new experiments and technologies, and enables a conceptual synthesis. By leveraging the fact that these are multicellular control systems, we are able to make progress in theory, basic science, and engineering.</p
Topics in Gravitational Wave Physics: Quantum Theory for Detector Improvement and High-Precision Modeling of Binary Black Hole Ringdown Waveform
Get PDFThis thesis covers topics in gravitational wave physics, including optomechanical measurement theory, novel detection schemes (PT-symmetric interferometer, matter-wave interferometer), and modeling of binary black hole ringdown waveform.
Measurements are accomplished through the interaction between signal and measurement devices. Identifying the nature of couplings is an important step in designing setups for specific applications. In Chapter II, we develop a general framework based on the system Hamiltonian to unambiguously classify optomechanical couplings. We add the new type, ``coherent coupling'', where the mechanical oscillation couples several non-degenerate optical modes supported in the cavity. We give examples of different couplings, discuss in detail one particular case of the coherent coupling, and demonstrate its benefits in optomechanical experiments. Our general framework allows the design of optomechanical systems in a methodological way, to precisely exploit the strengths of some particular optomechanical couplings.
Conventional resonant detectors are subject to bandwidth-peak sensitivity trade-off, which can be traced back to the quantum Cramer-Rao Bound. Chapters III and IV in this thesis are devoted to the study of PT-symmetric amplifier, which is a stable quantum amplification scheme enabled by two-mode non-degenerate parametric amplification. In Chapter III, we study stability and sensitivity improvements for laser-interferometric gravitational-wave detectors and microwave cavity axion detectors, under Hamiltonian formalism adopting single-mode and resolved-sideband approximations. In Chapter IV, we go beyond these approximations and consider realistic parameters in the optomechanical realization of PT-symmetric interferometer for gravitational detection. We show that the main conclusion concerning stability remains intact using Nyquist analysis and a detailed time-domain simulation.
The detection method of gravitational waves is developed with linear quantum measurement theory. In Chapter V, we extend the usage of this theory to another kind of measurement device — matter-wave interferometers, which have been widely discussed as an important platform for many high-precision measurements. This theory allows us to consider fluctuations from both atoms and light and leads to a detailed analysis of back-action (of light back onto the atoms) and its effect on dynamics and measurement noise in atom interferometry. From this analysis, we obtain a Standard Quantum Limit for matter-wave interferometry. We also give a comparison between the LIGO detector and matter-wave interferometer from the perspective of quantum measurement.
In Chapter VI, we switch focus from measurement to gravitational wave sources. Specifically, we study high-frequency gravitational radiation from the ringdown of a binary black hole merger. We study the high-precision modeling on both temporal and spatial features of ringdown wave to propose a more complete test of General Relativity. We show that spin-weighted spheroidal harmonics, rather than spin-weighted spherical harmonics, better represent ringdown angular patterns. We also study the correlation between progenitor binary properties and the excitation of quasinormal modes, including higher-order angular modes, overtones, prograde and retrograde modes. This chapter seeks to provide an analytical strategy and inspire the future development of ringdown tests using data from real gravitational wave events.</p
Advancement of Asymmetric Bipolar Membranes for Tailoring Chemical Environments in Electrochemical Systems
No full textUnder reverse bias, bipolar membranes (BPMs) enhance water dissociation (WD) at the junction between a cation exchange layer (CEL) and an anion exchange layer (AEL), often with additional improvement from an integrated WD catalyst. Recent research has shown promise for developing and implementing BPMs in renewable energy systems, such as carbon removal, water and CO₂ electrolysis, and energy storage. The economic feasibility of these carbon capture and conversion systems with incorporated BPMs, however, relies on BPMs to maintain stable operation at high current densities (>100 mA cm⁻²) and low overpotentials. Existing commercial BPMs are limited to current densities of ≤100 mA cm⁻² as water transport through the CEL and AEL cannot keep up with the increased rate of WD at the junction at higher current densities. In this work, we present a freestanding, high current density BPM (HCD-BPM) with a thin AEL (15 μm, PiperION 15R), a graphene oxide (GrOx) catalyst layer, and a mechanically supportive CEL (50 μm, Nafion 212) specifically designed to overcome water transport limitations. When tested under reverse bias in a custom electrodialysis cell with Luggin capillaries, this HCD-BPM demonstrates the lowest published overpotentials up to 1 A cm⁻². Furthermore, the HCD-BPM exhibits stabilities of >1000 hour at 80 mA cm⁻², >100 hours at 500 mA cm⁻², and >60 hours at 1 A cm⁻², Faradaic efficiencies for H⁺ and OH⁻ of >95%, and successful implementation into a multi-cell electrodialysis stack designed for integration into a DOC system. Additional characterization, such as SEM, Confocal microscopy, and titration, was performed to understand the structure and performance of the HCD-BPM. Additionally, the BPM was tested in forward bias to investigate its use for acid/base flow batteries. Overall, this thesis presents a novel BPM with record performance in multiple electrochemical systems that mitigate anthropogenic CO₂ emissions.</p
Enabling Robust and User-Customized Bipedal Locomotion on Lower-Body Assistive Devices via Hybrid System Theory and Preference-Based Learning
Get PDFPractical robotic assistive devices have the potential to transform many aspects of our society, from enabling locomotive autonomy to facilitating rehabilitation. However, as is typically the case when having autonomous systems interact closely with humans, one must simultaneously solve multiple grand challenges. My work focuses specifically on 1) leveraging hybrid system theory to achieve stable and robust walking that generalizes well across various human models and environmental conditions, and 2) developing an online learning strategy to customize the experimental walking for individual user comfort. The presented methodology is grounded in realizing lower-body exoskeleton locomotion for subjects with motor complete paraplegia, with extensions to other robotic applications. The contributions are broken down as follows.
First, by leveraging tools from nonlinear control theory, I propose techniques for systematically addressing locomotive robustness. These techniques include: using saltation matrices to generate robust gaits with experimental demonstrations on the Atalante lower-body exoskeleton; and developing an input-to-state stability perspective to certify robustness to uncertain impact events. Importantly, these methods aim to better understand the mathematical conditions underlying robust locomotion -- a necessary step towards realizing safe locomotion across varying human models and environmental conditions. Second, I develop a preference-based learning framework to explicitly optimize user comfort during exoskeleton locomotion (achieved using the aforementioned nonlinear control methodology) by learning directly from subjective feedback. This framework is implemented in real-world settings, including the clinical realization of user-preferred locomotion for two subjects with motor complete paraplegia.Third, the extensibility of this framework is demonstrated through three general robotic applications: tuning constraints of the gait generation optimization problem with demonstrations on a planar biped; tuning Lyapunov-based controller gains on a 3D biped; and tuning control barrier function parameters for performant yet safe exploration on a quadrupedal platform. Lastly, I discuss other relevant clinical considerations for lower-body assistive devices including how exoskeleton locomotion influences metabolic cost of transport, the study of latent factors underlying user-preferred walking, and embedding musculoskeletal models directly in the gait generation process.</p
Dynamics of Time-Varying and Nonlinear Phononic Lattices
Get PDFThe control of waves and vibrations in materials and structures underpins both the most common and the most advanced technologies. Spatially structured and periodic media have been widely studied and applied to signal processing, vibration mitigation, focusing, and other applications beyond the capabilities of bulk materials. Recently, interest has grown in the effects of temporal variation of material and medium properties on wave propagation. Temporal variations serve as an additional dimension for the design and structure of materials, further expanding potential functionalities and performance. Many of the concepts of waves in time-varying media have been developed in photonics and other electromagnetic systems, but the same fundamental dynamics govern acoustic and elastic systems, which provide alternative opportunities for implementation and new applications of time-varying media. In this thesis, we employ a one-dimensional phononic lattice composed of repelling ring magnets with electromagnetic coils that act as time-dependent grounding stiffness. The lattice provides an excellent platform for studying waves in time-varying media, with implementation and modeling of time-variation of elastic properties made simple by its discreteness. In addition, the repelling force between the magnets allows not only for the study of the linear dynamics of time-varying systems for small displacements but also for the exploration of the interaction between time-variation and nonlinear effects. We first present novel demonstrations of two types of time-varying wave phenomena in acoustic or elastic systems. First, the measurement of the propagation of waves across a temporal discontinuity in elastic properties demonstrates the temporal analog to refraction across a spatial boundary. Second, the experimental reconstruction of the dispersion relation of a time-periodic periodic medium shows the opening of wavenumber band gaps. We then characterize the dynamic stability of the time-periodic lattice and consider the role of nonlinearity. Finally, we investigate the possible existence of wavenumber gap breathers, temporally localized solutions of the discrete, nonlinear system.</p
Cryo-ET Reveals Molecular Details of Multi-Megadalton Bacterial Protein Complexes
Get PDFCryo-electron tomography (cryo-ET) is a powerful method for investigating the 3D structure of intact cells, organelles, and complex protein macromolecules that cannot be crystallized or are too heterogenous for single-particle cryo-electron microscopy (cryo-EM). However, obtaining high- resolution cryo-ET structures for many biologically important targets is still a challenge. To address this challenge, cryo-ET can be combined with other methods, including X-ray crystallography, single-particle cryo-EM, structure predictions, cross-linking mass spectrometry, biochemistry, and evolutionary analysis to produce integrative models. Recently, with the development of AI-based tools such as AlphaFold2, structure prediction has played an increasingly important role in integrative modeling. The combination of cryo-ET and structure prediction in particular has provided unprecedented insights into the ultrastructure of cellular components. This thesis focuses on two bacterial multi-megadalton protein complexes which are difficult to study by classical structural biology approaches: gas vesicles (GVs) and the Legionella pneumophila Dot/Icm type IV secretion system (T4SS). GVs are gas-filled protein nanostructures that regulate the position of certain microorganisms in water and consequently their access to sunlight and nutrients. Here, we investigate the mechanical properties of GVs and reveal the molecular structure of GVs and its implication for the assembly mechanism. The Dot/Icm T4SS is a macromolecular complex formed by approximately 27 proteins, utilized by L. pneumophila to hijack the host cell's biology for its replication purposes. A nearly-complete integrative model of this complex provides crucial insights into its structural organization and its evolution from conjugation to secretion, as well as the transportation of substrates into the host cell.</p
Engineering Cytochrome P450BM3 for Oxidation and Silicon–Carbon Bond Cleavage of Volatile Methylsiloxanes
No full textDirected evolution of enzymes can reveal activities that do not occur in the natural world. While most examples of directed evolution of new-to-nature chemistry have been applied in a synthetic direction, enzymatic biodegradation typically relies on wild-type enzymes. This thesis posits that directed evolution can generate enzymes capable of degrading non-biodegradable anthropogenic compounds, focusing on efforts to break silicon–carbon bonds, which are not known to be cleaved by enzymes in Nature. Chapter I establishes background on how enzymes evolve to catalyze degradation of compounds over long timescales in Nature, highlighting the enzymatic depolymerization of lignocellulosic biomass. This sets the stage for a case study of rapid enzyme evolution in response to anthropogenic molecules such as plastics and agrochemicals. With this background, directed evolution of new-to-nature synthetic activities is presented to demonstrate how new enzymatic activities can be evolved in the laboratory. In Chapter II, the state of the art for biocatalytic reactions involving organosilicon compounds is reviewed, starting with a description of how biology uses silicon and concluding with a perspective on future opportunities in this nascent field. Finally, Chapter III describes the engineering of a novel siloxane oxidase based on a cytochrome P450, which conducts two reaction steps in tandem to cleave silicon–carbon bonds. First, it hydroxylates the C–H bonds of siloxanes—the anthropogenic building blocks of silicone polymers—to yield a carbinol species, an activity reminiscent of the parent enzyme’s native hydroxylation of fatty acids. Via a function entirely different than its native activity, the enzyme converts this carbinol to a silanol species. In performing both of these steps, this is the first known enzyme that can cleave Si–C bonds, an activity which is the first step toward enzymatic degradation of these persistent, man-made compounds. In sum, this thesis demonstrates that directed evolution can reveal enzymatic degradation chemistries that are not known in Nature by establishing new-to-nature Si–C cleavage of siloxanes
Quantum States: With a View Toward Homological Algebra
Get PDFThe thesis comprises three papers covering different topics in quantum many-body physics. The first paper examines translationally invariant Pauli stabilizer codes, introducing invariants called charge modules and discussing their properties. The second paper explores invertible (G-invariant) states of 1D bosonic quantum lattice systems (or spin chains), demonstrating a full classification using group cohomology. The third paper analyzes the relation between ordinary correlators and Kubo's canonical correlators for thermal states of systems with short-range interactions. Overall, the thesis highlights the power of mathematics, especially homological methods, in understanding quantum states.</p
Low-Power and Miniaturized Medical Electronics for In-Vivo Localization and Tracking
Get PDFMedical electronic devices are an integral part of the healthcare system today. Significant advances have been made over the past few decades to yield highly miniaturized and low-power medical devices that are suitable for implantable, ingestible, or wearable applications. A key feature of medical devices that is central to their use in many applications is the capability to locate them precisely inside the body, and quite a lot of research effort has been expended in this direction. Location sensing is crucial for several applications: tracking pills in the GI tract, navigation during precision surgeries, endovascular procedures, robotic and minimally invasive surgery, and targeted therapy. The current gold-standard solutions for these procedures include invasive techniques such as endoscopy, or procedures that require repeated use of potentially harmful X-ray radiation such as CT scans. These techniques also require repeated evaluation in a hospital setting and are not conducive for non-clinical environments. While there are several alternative non-ionizing methods for imaging and localization based on electromagnetic tracking, radio-frequency, ultrasound, and optical tracking, none of them are able to simultaneously achieve a high field-of-view of tracking, high spatiotemporal resolution, fully wireless operation and miniaturization of the sensing devices, and system scalability with the number of devices. In this dissertation, we present a radiation-free system for high-precision localization and tracking of miniaturized wireless devices in vivo, using harmless magnetic field gradients.
First, we demonstrate our system for precision surgery applications. We designed highly miniaturized, wireless and battery-less microdevices, capable of measuring and transmitting their local magnetic field. One such device can be attached to an implant inside the body and another to a surgical tool, such that both can simultaneously measure and communicate the magnetic field at their respective locations to an external receiver. The relative location of the two devices on a real-time display can enable precise surgical navigation without using X-ray fluoroscopy. The prototype device consists of a micro-chip fabricated in 65nm CMOS technology, a 3D magnetic sensor and an inductor-coil. The chip performs wireless power management, wireless bi-directional data-telemetry, and I2C communication with the sensor. Planar electromagnetic coils are designed for creating monotonically varying magnetic fields in the X, Y, and Z directions, resulting in field gradients that encode each spatial point with a unique magnetic field value. The concept of gradient-based spatial encoding is inspired by MRI. The system is tested in vitro to demonstrate a localization accuracy of <100µm in 3D, the highest reported to the best of our knowledge.
Second, we demonstrate our system for localization and tracking of ingestible microdevices in the GI tract, which is valuable for the diagnosis and treatment of GI disorders. We designed highly miniaturized, low-power, and wireless ingestible devices to sense and transmit their local magnetic field as they travel through the GI tract. These devices consist of a 3D magnetic sensor, a Bluetooth microprocessor and a 2.4GHz Bluetooth antenna for wireless communication, all packaged into a 000-size capsule. The magnetic field sensed by the devices is created by using high-efficiency planar electromagnetic coils that encode each spatial point with a distinct magnetic field magnitude, allowing us to track the location of the devices unambiguously. The system functionality is demonstrated in vivo in large animals under different chronic conditions and disease models to show 3D localization and tracking in real time and in non-clinical settings, with mm-scale spatial resolution, and without using any X-ray radiation. This has the potential for significant clinical benefit for quantitative assessment of GI transit-time, motility disorders, constipation, incontinence, medication adherence monitoring, anatomic targeting for drug delivery, and targeted stimulation therapy.
Third, in order to further miniaturize the devices developed for the above two applications and to make them even more low-power, we present a monolithic 3D magnetic sensor in 65nm CMOS technology that measures <5mm² in area and consumes 14.8µW in power while achieving <10μTrms noise. Our novel 3D magnetic sensor overcomes the challenges faced by traditional magnetic sensors by being fully CMOS compatible and achieving high sensitivity with only µW-level power, which is in sharp contrast with Hall and Fluxgate sensors. The sensor is comprised of three orthogonal and highly dense metal coils implemented in the 65nm node, which generate a voltage signal in response to AC magnetic fields by electromagnetic induction. The EMF voltage signal is processed by on-chip circuitry that performs low-noise amplification, filtering, peak detection, and 12-bit digitization. Though the sensor can be used for a variety of applications that require AC field sensing, it is particularly useful for biomedical applications—tracking catheters and guidewires during endovascular procedures, minimally invasive surgeries, targeted radiotherapy, and for use as fiducial markers during preoperative planning. The proposed magnetic sensor is demonstrated for use in 3D tracking of catheters using the magnetic-field gradient-based spatial encoding scheme, and achieves 500µm of mean 3D localization accuracy.</p
Next-Generation Technologies for Gravitational Wave Detectors
Get PDFSince the first detection of gravitational waves (GW) in 2015, gravitational wave detectors have continually been improved. Now, a compact binary coalescence (CBC) is detected once a week in a full sensitivity observation run of the Advanced Laser Interferometric Gravitational-wave Observatory (LIGO) detectors. This thesis describes research on a collection of projects aimed at developing next-generation of technologies for future gravitational wave detectors. In the first part, I describe my research on directly measuring the coatings Brownian noise of high-reflectivity coatings made out of crystalline AlGaAs. It is a part of the larger effort to reduce the classical noise limit in the 30 Hz to 300 Hz band in the current generation of detectors. The second part describes the Balanced Homodyne Readout (BHR) upgrade that was performed at the 40m prototype at Caltech. This new readout method would be instrumental in reducing excess noise at the lower frequencies in GW detectors. With several future detectors planned with an order of magnitude improvement in sensitivity, the parameter estimation about the merging bodies would be limited by the calibration uncertainty if the calibration method is not updated. In the third part of the thesis, I describe our work on developing a systematic-free absolute calibration of the detector. In this scheme, we refer the calibration to the ultra-stable optical common length mode of the arm cavities in the detectors. In the final part, I describe four new arm length stabilization schemes for the proposed cryogenic upgrade of Advanced LIGO detectors into Voyager