Browsing by Subject "Acoustics"
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Item Open Access Acoustic resonators with integrated microfluidic channels for ultra-high Q-factor: a new paradigm for in-liquid gravimetric detection(2023) Zhao, YichengBiosensing is a critical area of research that involves detecting and measuring biological molecules. Among the various types of biosensors, acoustic biosensors are attractive for their simplicity, robustness, and low cost, particularly in point-of-care (POC) applications. However, the quality factor (Q-factor) of acoustic biosensors is often low, limiting their sensitivity and accuracy in terms of in-liquid gravimetric detection for biosensing applications. In this dissertation, we present a novel approach that eliminates nearly all dissipation and damping from sample liquids, rendering a significant improvement in Q-factor for in-liquid gravimetric detection. We constructed rigid microfluidic channels to confine liquids and the associated acoustic energy, thereby eliminating acoustic radiation damping. We also used the channels' side walls to create pressure waves, confining the liquids within and suppressing acoustic damping due to the viscous layer. The quartz crystal microbalance (QCM) was selected as the model system for implementing the new paradigm due to its widespread usage in various applications, simplicity, cost-effectiveness, and relevance of its principles to other types of acoustic biosensors. We hypothesized that the ratio of the wavelength of the pressure wave to the width of the channels is a crucial determining factor for optimal performance. We then tested the hypothesis by building the microfluidic QCM (the µ-QCM) to improve the Q-factor of conventional QCM. The combination of experiments, simulations, and theoretical studies demonstrated a 10-fold improvement in the Q-factor. The new system offers many other advantages, including direct data interpretation, minimized sample volume requirement, and easier temperature control for in-liquid gravimetric detection. Additionally, the same principles can be applied to other acoustic biosensors, benefiting the entire field.
Item Embargo Acoustic-based automated manipulation of particles for biological applications(2023) Zhu, HaodongAcoustic-based techniques have emerged as a promising avenue for the precise manipulation of particles, combining the disciplines of acoustics, physics, and biotechnology. Utilizing sound waves, this method allows for the gentle, non-invasive movement and positioning of particles, from minute biological entities to larger synthetic materials. Such automated manipulation harnesses the intricacies of acoustic radiation forces and streaming, offering advantages in terms of scalability, precision, and integration into various systems. As biotechnological demands grow, the potential of acoustic-based platforms to influence fields like drug delivery, diagnostics, and cellular research becomes increasingly evident. This defense delves into the development of two platforms utilizing automated acoustic technologies for particle manipulation aimed at advancing biological applications. The first part showcases a digital piezoelectric-based platform, adept at dynamic particle manipulation through the modulation of acoustic streaming, enhanced with surrounding barrier structures. We built a programmable droplet-handling platform to demonstrate the basic functions of planar-omnidirectional droplet transport, merging droplets, and in situ mixing via a sequential cascade of biochemical reactions. The ensuing part unveils a novel platform tailored for the meticulous long-term observation of single cell physical attributes, founded on 2D acoustic patterning of single cell array and automatic phase modulation. By adaptively segmenting and fitting the movement, we are able to monitor the density, compressibility and size fluctuation of the sample at the same time. These innovations have the potential to revolutionize biological endeavors, notably in large-scale drug screening and the proactive surveillance of cellular responses to distinct environmental stimulations over extended periods.
Item Open Access Acoustics-induced Fluid Motions(2021) Chen, ChuyiAcoustic waves, as a form of mechanical vibration, not only induces the force directly on the object, but also induces the motion of the medium that propagates throughout the system. The study of acoustofluidic mainly focuses on the exploration of the underlying mechanism of the acoustic waves and fluid motion and the methodology of applying this technique to practical applications. Featuring its contactless, versatile, and biocompatible capabilities, the acoustofluidic method makes itself an ideal tool for biosample handling. As the majority of the bio-related samples (e.g., cell, small organism, exosome) possess their native environment within liquids, there is an urgent need to study the acoustic induced fluid motion in order to cooperate with the development of the acoustic tweezing technique. While both the theoretical study and application exploration have been established for the combination of acoustics and microfluidics, the fluid motion on a larger scale is still under-developed. One reason is that, although the acoustofluidic methods hold great potential in various biomedical applications, there is a limited way to form an organized motion in a larger fluid domain, which may lead to the imprecise manipulation of the target. On the other hand, the theoretical study for the microfluidic domain is on the basis of a simplified model with certain assumptions, when applying to the larger fluid area, and significantly influences both the accuracy and computation cost. In this dissertation, we have first developed a series of theoretical and numerical methods in order to provide insights into the acoustofluidic phenomenon in different domain scales. Specifically, we explored the non-linear acoustic dynamics in fluids with the perturbation theory and Reynolds’ stress theory. Then we presented that the vortex streaming can be predicted and designed with our theoretical and numerical study, which can be utilized for various fluid systems and expanded to practical biomedical applications. The boundary-driven streaming and Reynolds’ stress-induced streaming are studied and applied to the digital acoustofluidic droplet handling platform and droplet spinning system, respectively. We demonstrated that within the digital acoustofluidic platform, the droplet can be manipulated on the oil layer in a dynamic and biocompatible manner. Meanwhile, in the droplet spinning system, we can predict and guide the periodic liquid-air interface deformation, as well as the particle motion inside the droplet. We demonstrated that with the theoretical and experimental study, this platform can be utilized for the nanoscale particle (e.g., DNA molecule and exosome) concentration, separation, and transport. Next, based on our study of the acoustically induced fluid motion, we developed an integrated acoustofluidic rotational tweezing platform that can be utilized for zebrafish larvae rapid rotation (~1s/rotation), multi-spectral imaging, and phenotyping. In this study, we have conducted a systematic study including theory development, acoustofluidic device design/fabrication, and flow system implementation. Moreover, we have explored the multidisciplinary expansion combining the acoustofluidic zebrafish phenotyping device with the computer-vision-based 3D model reconstruction and characterization. With this method, we can obtain substantial information from a single zebrafish sample, including the 3D model, volume, surface area, and deformation ratio. Moreover, with the design of the continuous flow system, a flow-cytometry-like system was developed for zebrafish larvae morphological phenotyping. In this study, a standard workflow is established which can directly transfer the groups of samples to a statistical digital readout and provide a new guideline for applying acoustofluidic techniques to biomedical applications. This work represents a complete fusion of acoustofluidic theory, experimental function, and practical application implementation.
Item Open Access Acoustofluidic Manipulation for Diagnosis and Drug Loading(2021) Wang, ZeyuShowing increased application in biological and medical fields, acoustofluidics is a combined technology between acoustics and microfluidics. The core function of acoustofluidics is a label-free and contact-free manipulation of particles in the fluid, which can be applied as active separation, active mixing, and active concentration. Since in therapeutic and diagnostic applications, contamination in the samples can significantly interference analysis results and treatment outcome, proper per-screening of the sample can significantly decrease the target detection threshold and avoiding interferences come from noise and misreading. The acoustofluidic technology derive a particle manipulation based on physical properties of the particles and fluids, specifically, the size of the particle, densities for the particles and fluid, and the viscosity of the fluid, which generate a screening system that can separate particles with different sizes and densities. By utilizing this property, acoustofluidics has been applied on separating multiple biological particles and objects including circulating cancer cells, red blood cells, and multiple populations of vesicles. These reagent-free and contact-free separations have been demonstrated biocompatible for cells and vesicles and can conserve the cell viabilities and vesicle cargoes including DNA, miRNA, and proteins. However, current achievements on acoustofluidic manipulation focus on general analysis of the separated components, which are not disease specific biomarkers, and the body fluid using for separation are limited to blood and artificial isotonic solutions including phosphate-buffered saline. Although these works demonstrated acoustofluidic technology is eligible for separating bio-particles that have diagnosis and therapeutic functions, lack of real cases related applications and diseases specific investigations still make the technology’s application abilities being restricted to possibilities but not promised functions. To deeply investigate and demonstrate the acoustofluidic technology’s potential on diagnostic application, the technology was evaluated by using samples related with multiple specific diseases. Since the acoustofluidic technology has been demonstrated eligible for isolating exosomes, which are 50-200 nm vesicles secreted from cells, pathology related exosomes were selected for diagnostic application investigation. Exosomes’ vesicle structures make them ideal candidate for diagnosis, since vesicles formed by lipid bilayer membrane contain both proteins or nucleic acids as cargoes inside and transmembrane or membrane proteins and polysaccharides on the surface. Furthermore, the forming and secreting pathologies of exosomes are highly dependent on endocytosis and exocytosis pathologies, which are influenced by cellular metabolism. Exosomes’ cargoes have been found specifically correlated with secreting cells populations, indicates depending on types of cells, like tumor cells or stem cells, the secreted exosomes will contain different molecules that can be used as biomarkers for reversed identifying secreting cells. Except high values on biological and medical research and applications, exosomes’ small size makes the vesicles difficult for isolation and increase the cost on both equipment and time aspects. Since acoustofluidics provides an active approach for separating nanometer sized particles and the isolation is a continuous procedure, the simple and rapid exosome isolation the acoustofluidics can provide makes the technology high valuable. Considering these improvements, the acoustofluidics can provide on exosome related fields, demonstrating acoustofluidic devices separated exosomes containing disease biomarkers and could be used for diagnostic applications become a necessary step for validating the technology’s ability. In this dissertation, the first attempt for validating acoustofluidic exosome separation’s diagnostic potential was made for isolating salivary exosomes aimed at human papillomavirus (HPV) induced oropharyngeal cancer diagnosis. Different with previous research that worked on blood exosome separation, a unique property of this study is achieving exosome separation from saliva, which is a more unstable system on components and physical properties than blood. By isolating salivary exosome using the acoustofluidic technology and processing down-stream digital droplet polymerase chain reaction (PCR) analysis, HPV-16 virus, which has been found can induce oropharyngeal cancer, was found majorly distributed in isolated exosome fractions. Since saliva has complex components that cause inaccuracy analysis result, the application of acoustofluidic technology can increase the diagnostic sensitive and enable saliva based liquid biopsy for early screening of oropharyngeal cancer. In the next work, we further demonstrate the acoustofluidic technology’s advantage on rapid isolation of exosomes benefits the time sensitive diagnosis. The acoustofluidic devices were applied for isolating exosomes from mice models that were induced to traumatic brain injury (TBI), which can develop to chronic diseases or deteriorate in short term. Since these outcomes induced by improper or untimely treatments, fast screening of TBI becomes critical for achieving ideal therapeutic outcomes. By collecting plasma from mice and deriving exosome isolation through the acoustofluidics devices, isolated exosome samples with less contamination were found compared with original plasma. Protein analysis further indicates isolated exosomes keeps several exosome specific and neuron damage specific proteins, indicates the acoustofluidic technology is biocompatible and low harmful for exosome structures and components. High isolation purity achieved by the acoustofluidic technology also benefits downstream analysis by decreasing detection noise. In flow cytometer analysis, the acoustofluidic devices isolated exosomes demonstrated TBI disease biomarker increasing in 24 h after the mice were induced to TBI, while the plasma sample cannot demonstrate this tendency. The success of revealing early stage TBI biomarker changes indicates the acoustofluidic technology not only can benefit diagnosis, but also eligible for achieving diagnosis in a very early stage of the pathology. Since the acoustofluidic technology had demonstrated a promising performance on biocompatibility and rapid separation, other time-sensitive samples, including live virus was applied for evaluating the device’s performance. To achieve better control and eliminate irrelevant variable, we use cultured reverse transcription virus that is used for mammal cells transfection as target for isolation. The acoustofluidic technology showed reliable isolation of the murine leukemia virus and majority of the virus particles were separated out from the original sample. Virus viability was further validated robust based on the transfection experiments that using acoustofluidic separated virus and original virus samples demonstrated similar level transfection rates. This work indicates except vesicles like exosomes, the acoustofluidic technology is also eligible for isolating virus and keeping its viability, which significantly expands the application of the technology. Next, to expend the acoustofluidic technology’s functions, we utilized the concentration and manipulation ability of the device for deriving high efficiency membrane degradation. By generating strong microstreaming and microstreaming derived shear stress, the acoustofluidic devices can generate strong vertex flow fields in channel that can capture and lyse mammal cells. Since the acoustofluidic cell lysis is totally a physical process without participation of any chemical reagent and demonstrates a high lysis efficiency, this acoustofluidics application has potential for achieving high efficiency cell analysis. Since the acoustofluidic technology has demonstrated potential for concentration and lysis effect by generating high flow rate microstreaming vertex, we further investigated whether similar effect can derive exosome concentration and lysis. By generating acoustofluidic vertex in droplet containing exosome, nanoparticles, and small molecule drugs, exosome concentration and lysis effects were utilized for high efficiency drug loading and carrier encapsulation. Derived by the acoustofluidic concentration effect, the porous nanoparticles and drug molecules are concentrated in small area of the fluid system and this active concentration increasing induces a high drug loading rate. Simultaneously, the acoustofluidic vertex disrupts exosome membrane and concentrates exosomes with the nanoparticles, which induces exosome encapsulation. These exosome encapsulated drug-loaded nanoparticles demonstrate high intake rate of cells and derive more efficient drug delivery rate. Since the drug loading and exosome encapsulation are physical processes, the acoustofluidic technology derived particle manipulation has potential for deriving loading and encapsulation for large varieties of drugs, particles, and vesicles, which significantly expand the technology’s application.
Item Open Access Adaptable Design Improvements For Electromagnetic Shock Wave Lithotripters And Techniques For Controlling Cavitation(2012) Smith, Nathan BirchardIn this dissertation work, the aim was to garner better mechanistic understanding of how shock wave lithotripsy (SWL) breaks stones in order to guide design improvements to a modern electromagnetic (EM) shock wave lithotripter. To accomplish this goal, experimental studies were carefully designed to isolate mechanisms of fragmentation, and models for wave propagation, fragmentation, and stone motion were developed. In the initial study, a representative EM lithotripter was characterized and tested for in vitro stone comminution efficiency at a variety of field positions and doses using phantom kidney stones of variable hardness, and in different fluid mediums to isolate the contribution of cavitation. Through parametric analysis of the acoustic field measurements alongside comminution results, a logarithmic correlation was determined between average peak pressure incident on the stone surface and comminution efficiency. It was also noted that for a given stone type, the correlations converged to an average peak pressure threshold for fragmentation, independent of fluid medium in use. The correlation of average peak pressure to efficacy supports the rationale for the acoustic lens modifications, which were pursued to simultaneously enhance beam width and optimize the pulse profile of the lithotripter shock wave (LSW) via in situ pulse superposition for improved stone fragmentation by stress waves and cavitation, respectively. In parallel, a numerical model for wave propagation was used to investigate the variations of critical parameters with changes in lens geometry. A consensus was reached on a new lens design based on high-speed imaging and stone comminution experiments against the original lens at a fixed acoustic energy setting. The results have demonstrated that the new lens has improved efficacy away from the focus, where stones may move due to respiration, fragmentation, acoustic radiation forces, or voluntary patient movements. Using traditional theory of brittle fragmentation and newfound understanding of average peak pressure correlation to stone comminution, the entire set of stone comminution data for lens comparison was modeled using a Weibull-style distribution function. This model linked both the average peak pressure and shock wave dose to efficacy, including their respective threshold parameters, and demonstrated correlation of coefficients to cavitation activity. Subsequently, this model was used in prediction of stone comminution efficiency from mimicked respiratory motions in vitro, which compared favorably to actual simulated motion studies using both the new and original lenses. Under a variety of mimicked respiratory motions, the new lens produced statistically higher stone comminution efficiency than the original lens. These results were confirmed in vivo in a swine model, where the new lens produced statistically higher stone comminution after 1,000 and 2,000 shocks. Finally, a mechanistic investigation into the effects of cavitation with the original lens was conducted using an integrated, self-focusing annular ring transducer specially designed for tandem pulse lithotripsy. It was found that cavitation and stone comminution efficiency are progressively enhanced by tandem pulsing as source energies of both the primary LSW and trailing pressure pulse increase, which suggests cavitation and stress waves act synergistically enhance the efficacy in kidney stone fragmentation.
Item Open Access Adaptive Discontinuous Galerkin Methods Applied to Multiscale & Multiphysics Problems towards Large-scale Modeling & Joint Imaging(2019) Zhan, QiweiAdvanced numerical algorithms should be amenable to the scalability in the increasingly powerful supercomputer architectures, the adaptivity in the intricately multi-scale engineering problems, the efficiency in the extremely large-scale wave simulations, and the stability in the dynamically multi-phase coupling interfaces.
In this study, I will present a multi-scale \& multi-physics 3D wave propagation simulator to tackle these grand scientific challenges. This simulator is based on a unified high-order discontinuous Galerkin (DG) method, with adaptive nonconformal meshes, for efficient wave propagation modeling. This algorithm is compatible with a diverse portfolio of real-world geophysical/biomedical applications, ranging from longstanding tough problems: such as arbitrary anisotropic elastic/electromagnetic materials, viscoelastic materials, poroelastic materials, piezoelectric materials, and fluid-solid coupling, to recent challenging topics: such as fracture-wave interactions.
Meanwhile, I will also present some important theoretical improvements. Especially, I will show innovative Riemann solvers, inspired by physical meanings, in a unified mathematical framework, which are the key to guaranteeing the stability and accuracy of the DG methods and domain decomposition methods.
Item Open Access An Analysis of the Potential Acoustic Effects of Cape Wind's Offshore Wind Farm on Marine Mammal Populations(2010-04-29T02:06:38Z) Burgman, JennyOffshore wind farms are an appealing form of renewable energy that are common in Europe but have yet been developed fully in the United States. The Cape Wind project in Massachusetts has proposed the construction of 130 turbines in the Horseshoe Shoal of Nantucket Sound. Despite the potential local benefits of the development, many Cape Cod residents oppose construction of the wind farm. Opposition to this development includes concerns that the noises emitted during all phases of the wind farm’s life cycle will adversely affect populations of marine mammals. In my Master’s project I review and analyze information regarding the acoustic effects of offshore farms and other relevant anthropogenic sound sources. It is difficult to predict fully what effects the Cape Wind project will have on marine mammals in Nantucket Sound. Nevertheless, it is clear that the construction phase would have the greatest potential acoustic impact, including possible displacement; operational sounds are less intense and more likely to result in habituation. Ultimately, however, marine mammals within Horseshoe Shoals do not face any greater risk from Cape Wind than from other anthropogenic sound source in the region.Item Open Access Analytical Models for the Structural-Acoustic Response of Elastic Barriers Subject to Acoustic Forcing(2019) Villa, MauricioAnalytical models are developed for the structural-acoustic response of flexible panels to obliquely incident, planar harmonic acoustic waves. These models provide a detailed understanding of the complex effects of structural discontinuities on the reflection and transmission from both isolated and periodically connected panels bounded by two fluid half-spaces. This investigation demonstrates that boundaries and spatial discontinuities redirect part of the structural energy into reverberant structural waves having flexural wavenumbers different from the oblique wave forcing, creating deviations from specular reflection. The dominant mechanisms that characterize the acoustic scattering from the vibrating panels depend on the Mach regime of the structure-to-fluid in vacuo wave speed ratio. Super-critical reverberant flexural waves act as surface radiators that result in pronounced radiation lobes centered at the Mach Angles with localized spreading. The scattering from baffled sub-critical panels exhibit directivities that can be predicted by distributions of acoustic edge radiators, with significant energy redistribution occurring at structural resonances. These insights are both derived from and used to refine the analytical models developed for membranes and 2D plates.
The periodically connected panels interfaced with discrete discontinuities, and modeled by various boundary conditions, are analyzed with the method of Analytical Numerical Matching (ANM). The method is advanced to more efficiently model the influence of the structural discontinues and it is demonstrated that it improves the numerical accuracy and convergence rate of the structural-acoustic response. The ANM approach includes a novel way to handle difficulties associated with coincidence frequencies. The periodic configuration exhibits acoustic cut-off and a finite set of radiation angles dependent on structural and fluid properties.
In the pursuit of models suitable for broadband energy intensity based methods, radiation models for the baffled finite panels are developed by approximate means. The dominant effects of the fluid loading are characterized and introduced as modifications to the in vacuo flexural wavenumber of the structures. Simple, closed-form, far-field acoustic intensity directivity patterns and the corresponding power spectrums are analytically expressed for high frequencies. These approximate models are compared to the periodic configuration, and exhibit considerable agreement for limited fluid loadings and boundary conditions that eliminate structural coupling across bays. The approximate sub-critical models are refined using insight from the radiation mechanisms to improve the agreement to the periodic panels.
An exact benchmark solution for the structural-acoustic response of the acoustically driven baffled finite structure over a full range of parameters is developed and interpreted utilizing a new approach which is largely analytical. This hybrid modal-analytical solution is developed for homogeneous Dirichlet boundary conditions, and then generalized to arbitrary impedance conditions by isolating the influence of the boundaries. In addition to their availability for quantitative use, the benchmark solution offers a high degree of physical insight, and is used for verification and refinement of the approximate high frequency methods developed. Remarkable agreement between the approximate high frequency models and the benchmark solutions is demonstrated for both light and heavy fluid loading cases.
Item Open Access APPLICATION OF ACOUSTIC METAMATERIALS IN AUDIO SYSTEMS(2023) Peng, XiuyuanAudio systems have become an integral part of our daily lives, transforming the way we hear sound in a myriad of applications, including TV, cinema, laptops, mobile phones, and even AR/VR sets. However, although there have been significant technological advancements in recent years, nearly all of these applications still rely on the same century-old electrodynamic transducer technology. This technology operates based on the fundamental principle of an AC motor, where the electrical signal generates a magnetic field that interacts with a permanent magnet. This interaction produces a force that moves the attached diaphragm back and forth, creating sound waves that propagate through the air. Over the years, the electrodynamic transducer has proven to be an effective technology, and its implementation in loudspeakers has become a ubiquitous component of modern audio systems.
Despite the electrodynamic loudspeakers' ability to reproduce high-fidelity sound at a relatively low cost, the physical design of audio systems has remained largely unchanged since the 1970s, leading to many unresolved problems. Although electrodynamic loudspeakers are commonly used in modern audio systems, their dimensions and directional characteristics are not satisfactory. This can result in poor sound quality, uneven distribution of sound, and the inability to deliver sound to certain areas effectively. As a result, listeners may not be able to fully appreciate the intended audio experience.
Acoustic metamaterials offer a promising solution to the growing need to improve the physical design of audio systems. These complex physical structures are intentionally formulated to engineer the propagation of sound, and over the past two decades, they have demonstrated remarkable capabilities to steer and shape sound fields into various patterns, introducing exotic physical phenomena to an otherwise ordinary system. Compared to traditional methods like digital signal processing (DSP) and multi-element arrays, acoustic metamaterials offer several advantages, including passivity, compactness, and cost-effectiveness. Furthermore, with the advent of 3D printing technology, producing acoustic metamaterial structures that work with airborne audible sound has become much easier, as they can be made of essentially rigid plastic that divides air into different compartments. This facilitates the rapid prototyping of novel metamaterial designs for audio systems, accelerating the pace of progress.
In this dissertation, we explore the use of innovative acoustic metamaterial design principles to address the persistent issues associated with electrodynamic loudspeaker-based audio systems and to elevate the user experience. Specifically, we examine how passive metamaterial structures can be used to modulate the frequency response and provide broadband directivity control of these systems. To achieve our objectives, we use a modeling approach that incorporates the entire sound path, balancing accuracy with computational cost. Additionally, we utilize a computerized algorithm to generate inverse designs that help us achieve our desired outcomes. By leveraging these techniques, we aim to design audio systems that provide users with high-quality sound and an optimal listening experience.
Item Open Access Automatic word count estimation from daylong child-centered recordings in various language environments using language-independent syllabification of speech(Speech Communication, 2019-10-01) Räsänen, O; Seshadri, S; Karadayi, J; Riebling, E; Bunce, J; Cristia, A; Metze, F; Casillas, M; Rosemberg, C; Bergelson, E; Soderstrom, M© 2019 The Authors Automatic word count estimation (WCE) from audio recordings can be used to quantify the amount of verbal communication in a recording environment. One key application of WCE is to measure language input heard by infants and toddlers in their natural environments, as captured by daylong recordings from microphones worn by the infants. Although WCE is nearly trivial for high-quality signals in high-resource languages, daylong recordings are substantially more challenging due to the unconstrained acoustic environments and the presence of near- and far-field speech. Moreover, many use cases of interest involve languages for which reliable ASR systems or even well-defined lexicons are not available. A good WCE system should also perform similarly for low- and high-resource languages in order to enable unbiased comparisons across different cultures and environments. Unfortunately, the current state-of-the-art solution, the LENA system, is based on proprietary software and has only been optimized for American English, limiting its applicability. In this paper, we build on existing work on WCE and present the steps we have taken towards a freely available system for WCE that can be adapted to different languages or dialects with a limited amount of orthographically transcribed speech data. Our system is based on language-independent syllabification of speech, followed by a language-dependent mapping from syllable counts (and a number of other acoustic features) to the corresponding word count estimates. We evaluate our system on samples from daylong infant recordings from six different corpora consisting of several languages and socioeconomic environments, all manually annotated with the same protocol to allow direct comparison. We compare a number of alternative techniques for the two key components in our system: speech activity detection and automatic syllabification of speech. As a result, we show that our system can reach relatively consistent WCE accuracy across multiple corpora and languages (with some limitations). In addition, the system outperforms LENA on three of the four corpora consisting of different varieties of English. We also demonstrate how an automatic neural network-based syllabifier, when trained on multiple languages, generalizes well to novel languages beyond the training data, outperforming two previously proposed unsupervised syllabifiers as a feature extractor for WCE.Item Open Access Beamforming of Ultrasound Signals from 1-D and 2-D Arrays under Challenging Imaging Conditions(2015) Jakovljevic, MarkoBeamforming of ultrasound signals in the presence of clutter, or partial aperture blockage by an acoustic obstacle can lead to reduced visibility of the structures of interest and diminished diagnostic value of the resulting image. We propose new beamforming methods to recover the quality of ultrasound images under such challenging conditions. Of special interest are the signals from large apertures, which are more susceptible to partial blockage, and from commercial matrix arrays that suffer from low sensitivity due to inherent design/hardware limitations. A coherence-based beamforming method designed for suppressing the in vivo clutter, namely Short-lag Spatial Coherence (SLSC) Imaging, is first implemented on a 1-D array to enhance visualization of liver vasculature in 17 human subjects. The SLSC images show statistically significant improvements in vessel contrast and contrast-to-noise ratio over the matched B-mode images. The concept of SLSC imaging is then extended to matrix arrays, and the first in vivo demonstration of volumetric SLSC imaging on a clinical ultrasound system is presented. The effective suppression of clutter via volumetric SLSC imaging indicates it could potentially compensate for the low sensitivity associated with most commercial matrix arrays. The rest of the dissertation assesses image degradation due to elements blocked by ribs in a transthoracic scan. A method to detect the blocked elements is demonstrated using simulated, ex vivo, and in vivo data from the fully-sampled 2-D apertures. The results show that turning off the blocked elements both reduces the near-field clutter and improves visibility of anechoic/hypoechoic targets. Most importantly, the ex vivo data from large synthetic apertures indicates that the adaptive weighing of the non-blocked elements can recover the loss of focus quality due to periodic rib structure, allowing large apertures to realize their full resolution potential in transthoracic ultrasound.
Item Open Access Boosting the Sensing Granularity of Acoustic Signals by Exploiting Hardware Non-linearit(2023) Chen, XiangruAcoustic sensing is a new sensing modality that senses the contexts of human targets and our surroundings using acoustic signals. It becomes a hot topic in both academia and industry owing to its finer sensing granularity and the wide availability of microphone and speaker on commodity devices. While prior studies focused on addressing well-known challenges such as increasing the limited sensing range and enabling multi-target sensing, we propose a novel scheme to leverage the non-linearity distortion of microphones to further boost the sensing granularity. Specifically, we observe the existence of the non-linear signal generated by the direct path signal and target reflection signal. We mathematically show that the non-linear chirp signal amplifies the phase variations and this property can be utilized to improve the granularity of acoustic sensing. Experiment results show that, by properly leveraging the hardware non-linearity, the amplitude estimation error for sub-millimeter-level vibration can be reduced from 0.137 mm to 0.029 mm.
Item Embargo Cellular Droplet Sorting and Manipulation for Immunity Analysis via Acoustofluidics(2024) Zhong, RuoyuDroplet microfluidics technology holds immense potential for single-cell level biomedical engineering studies, motivating the study of cellular immunotherapy, cell interactions, drug screening, and single-cell dynamics. However, existing droplet microfluidics have limited pairing efficiency, complex manual operation procedures, and low in-droplet cell manipulation capacity, which hinder their potential application in single-cell analyses with high sample purity or uniformity requirements. Several efforts, such as electrophoretic, magnetic, and optical droplet sorters, have been used to overcome some limitations. Still, they need the all-powerful capability of acoustics to solve all the problems. As a dynamic, precise, contact-free, and biocompatible force, acoustics can improve pairing efficiency in droplets and provide an ideal tool for active droplet manipulation. In this dissertation, I demonstrate the reinvention of droplet microfluidics, reporting the multifunctionality of acoustics for high throughput, high-precision droplet sorting, and active droplet manipulation. I propose a modular acoustofluidics platform designed for the streamlined sorting and collection of effector-target (i.e., NK92-K562) cell pairs, facilitating efficient monitoring of the real-time dynamics of immunological response formation. Coupled with transcriptional and protein expression analyses, I evaluated the synergistic effect of doxorubicin on the cellular immune response. In addition, because of the non-contact nature of acoustics, I can actively and simultaneously manipulate multiple cell-encapsulated droplets, which other methods cannot achieve. The proposed acoustofluidic platform can provide promising building blocks for high-throughput quantitative single-cell level coculture to understand intercellular communication while empowering immunotherapy through precision manipulation and analysis of immunological synapses.
Item Open Access Coherent flow power Doppler imaging(2017) Li, YouUltrasonic flow detection is a widely used technique to detect vessel, measure blood flow velocities, and monitor perfusion. Conventional techniques include color Doppler imaging and power Doppler (PD) imaging. These methods depend on either the measurement of phase change or the detection of the power of backscattered echoes from blood. Both techniques are susceptible to noise. Common noise sources include thermal noise and clutter. The noise significantly deteriorates the performance of color Doppler imaging, because color Doppler imaging estimates the axial blood velocity from temporal changes in the echo phase, and phase change measurement is sensitive to noise. Power Doppler imaging measures the power of the temporal differences in backscattered echoes, and can provide higher sensitivity with small vessel and slow flow detection than color Doppler imaging at the expense of direction and velocity information. However, it requires a large ensemble length, limiting the frame rate to a few frames per second. The limitations of color Doppler imaging and power Doppler imaging are more severe in deep body vessel imaging due to depth dependent attenuation of the ultrasound waves. Therefore, for deep body vessel imaging, including liver vessel imaging and placental spiral artery imaging, better vessel detection techniques are desirable.
Coherent flow power Doppler (CFPD) imaging was proposed as a sensitive flow detection and imaging technique for slow flow and small vessels. In this work, we present the study on CFPD from principles to clinical evaluation.
The CFPD imaging technique detects blood flow from the spatial coherence of the blood signal. The short-lag spatial coherence (SLSC) beamformer is used for the measurement of spatial coherence. Because blood signals and common noise sources, including thermal noise reverberation clutter, have different spatial coherence properties, CFPD can suppress the noise.
The performance of CFPD in flow detection was evaluated with simulations and flow phantom experiments under various imaging conditions, and compared with the performance of PD. It is found that CFPD provides an improvement of Doppler signal-to-noise ratio (SNR) of 7.5-12.5 dB over PD in slow flow and small vessel imaging. The improvement in SNR translates to higher Doppler image contrast, faster frame rate, or lower limit-of-detection (LOD). In similar imaging conditions of slow flow, CFPD may detect up to 50% slower flow than PD.
The CFPD imaging technique was also implemented with novel pulse sequences, including plane-wave synthetic transmit aperture imaging, and diverging-wave synthetic transmit aperture imaging. For plane-wave synthetic transmit aperture imaging, the angular coherence theory was proposed to describe the coherence of backscattered waves corresponding to plane wave transmits at different steering angles. In addition, we also propose the coherent Kasai and Loupas estimators, which utilizes the coherence information of flow signals to provide velocity estimates with reduced uncertainty.
To demonstrate the clinical relevance of CFPD, we built a real-time CFPD imaging system and conducted a pilot clinical study with it. In the system, the CFPD technique was implemented on a Verasonics Vantage 256 research scanner. The software beamformer and CFPD processing were implemented on the graphics processing unit (GPU). The Doppler frame rate of the system is 10 frames per second for a field-of-view (FOV) of 10 cm axially and 4 cm laterally.
In the pilot clinical study, the liver vasculatures of 15 healthy human volunteers were imaged by a trained sonographer using the real-time CFPD system. The raw data corresponding to a 132 Doppler videos were captured and processed offline. The SNR of the vessels in the CFPD and PD images were measured and analyzed. In all of the 132 data sets, CFPD provides higher SNR than PD. The average improvement in SNR is 8.6 dB. From the visual analysis of the images, it can be seen that the improvement in SNR leads to more sensitive detection of small vessels in deeper parts of the liver.
Item Open Access Design and Experimental Applications of Acoustic Metamaterials(2013) Zigoneanu, LucianAcoustic metamaterials are engineered materials that were extensively investigated over the last years mainly because they promise properties otherwise hard or impossible to find in nature. Consequently, they open the door for improved or completely new applications (e.g. acoustic superlens that can exceed the diffraction limit in imaging or acoustic absorbing panels with higher transmission loss and smaller thickness than regular absorbers). Our objective is to surpass the limited frequency
operating range imposed by the resonant mechanism that s1ome of these materials have. In addition, we want acoustic metamaterials that could be experimentally demonstrated and used to build devices with overall performances better than the previous ones reported in the literature.
Here, we start by focusing on the need of engineered metamaterials in general and acoustic metamaterials in particular. Also, the similarities between electromagnetic metamaterials and acoustic metamaterials and possible ways to realize broadband acoustic metamaterials are briefly discussed. Then, we present the experimental realization
and characterization of a two-dimensional (2D) broadband acoustic metamaterial with strongly anisotropic effective mass density. We use this metamaterial to realize a 2D broadband gradient index acoustic lens in air. Furthermore, we optimize the lens design by improving each unit cell's performance and we also realize a 2D acoustic ground cloak in air. In addition, we explore the performance of some novel applications (a 2D acoustic black hole and a three-dimensional acoustic cloak) using the currently available acoustic metamaterials. In order to overcome the limitations of our designs, we approach the active acoustic metamaterials path, which offers a broader range for the material parameters values and a better control over them. We propose two structures which contain a sensing element (microphone) and an acoustic driver (piezoelectric membrane or speaker). The material properties are controlled by tuning the response of the unit cell to the incident wave. Several samples with interesting effective mass density and bulk modulus are presented. We conclude by suggesting few natural directions that could be followed for the future research based on the theoretical and experimental results presented in this work.
Item Open Access Detection and Classification of Whale Acoustic Signals(2016) Xian, YinThis dissertation focuses on two vital challenges in relation to whale acoustic signals: detection and classification.
In detection, we evaluated the influence of the uncertain ocean environment on the spectrogram-based detector, and derived the likelihood ratio of the proposed Short Time Fourier Transform detector. Experimental results showed that the proposed detector outperforms detectors based on the spectrogram. The proposed detector is more sensitive to environmental changes because it includes phase information.
In classification, our focus is on finding a robust and sparse representation of whale vocalizations. Because whale vocalizations can be modeled as polynomial phase signals, we can represent the whale calls by their polynomial phase coefficients. In this dissertation, we used the Weyl transform to capture chirp rate information, and used a two dimensional feature set to represent whale vocalizations globally. Experimental results showed that our Weyl feature set outperforms chirplet coefficients and MFCC (Mel Frequency Cepstral Coefficients) when applied to our collected data.
Since whale vocalizations can be represented by polynomial phase coefficients, it is plausible that the signals lie on a manifold parameterized by these coefficients. We also studied the intrinsic structure of high dimensional whale data by exploiting its geometry. Experimental results showed that nonlinear mappings such as Laplacian Eigenmap and ISOMAP outperform linear mappings such as PCA and MDS, suggesting that the whale acoustic data is nonlinear.
We also explored deep learning algorithms on whale acoustic data. We built each layer as convolutions with either a PCA filter bank (PCANet) or a DCT filter bank (DCTNet). With the DCT filter bank, each layer has different a time-frequency scale representation, and from this, one can extract different physical information. Experimental results showed that our PCANet and DCTNet achieve high classification rate on the whale vocalization data set. The word error rate of the DCTNet feature is similar to the MFSC in speech recognition tasks, suggesting that the convolutional network is able to reveal acoustic content of speech signals.
Item Open Access Differences in mismatch responses to vowels and musical intervals: MEG evidence.(PLoS One, 2013) Bergelson, Elika; Shvartsman, Michael; Idsardi, William JWe investigated the electrophysiological response to matched two-formant vowels and two-note musical intervals, with the goal of examining whether music is processed differently from language in early cortical responses. Using magnetoencephalography (MEG), we compared the mismatch-response (MMN/MMF, an early, pre-attentive difference-detector occurring approximately 200 ms post-onset) to musical intervals and vowels composed of matched frequencies. Participants heard blocks of two stimuli in a passive oddball paradigm in one of three conditions: sine waves, piano tones and vowels. In each condition, participants heard two-formant vowels or musical intervals whose frequencies were 11, 12, or 24 semitones apart. In music, 12 semitones and 24 semitones are perceived as highly similar intervals (one and two octaves, respectively), while in speech 12 semitones and 11 semitones formant separations are perceived as highly similar (both variants of the vowel in 'cut'). Our results indicate that the MMN response mirrors the perceptual one: larger MMNs were elicited for the 12-11 pairing in the music conditions than in the language condition; conversely, larger MMNs were elicited to the 12-24 pairing in the language condition that in the music conditions, suggesting that within 250 ms of hearing complex auditory stimuli, the neural computation of similarity, just as the behavioral one, differs significantly depending on whether the context is music or speech.Item Open Access Digital Acoustofluidics Based Contactless and Programmable Liquid Handling(2020) Zhang, PeiranHandling of fluids is essential for a majority of applications involving liquid phase reactions in chemistry, biology, and biomedicine. In contrast to manual pipetting in conventional small workshops, automated liquid handling techniques have brought unrivaled accuracy, precision, speed, and repeatability to modern biomedical researches and pharmaceutical industries. Despite their benefits, most advanced liquid handling techniques (e.g., microfluidics and micro-plates) lack fluidic rewritability due to surface-adsorption-induced contaminations on solid-liquid interfaces, limiting their capability of performing complex cascade reactions or high-content combinatorial screening on reusable fluid carriers. To date, the lack of fluidic rewritability still remains as a challenge for engineering scientists to achieve the automated processing of ‘fluidic bits’ in a manner similar to ‘electronic bits’ within a miniature chip. In this work, we approach the fluidic rewritability by contactlessly manipulating aqueous droplets floating on a dense, immiscible carrier fluid layer using acoustic-streaming-induced hydrodynamic gradients. The presented acoustic streaming-based liquid handling (i.e., digital acoustofluidics) devices can be categorized into three versions. (1) The first version of digital acoustofluidic devices actuate floating droplets and small objects by actively propelling them along a straight path following the horizontal direction of acoustic wave propagation. (2) In contrast, the second version employs acousto-hydrodynamic potential traps on the surface of the carrier fluid layer to attract and capture the floating droplets at the equilibrium position of the triggered butterfly-shaped streaming pattern. By selectively exciting the immersed interdigital transducers and sequentially triggering the localized acousto-hydrodynamic traps, the floating droplets can be transported, merged, mixed, split, and generated in a contact-free and programmable manner. (3) The third version of digital acoustofluidic devices is built upon the second version by integrating additional channel-shaped acoustic streaming vortices under high-amplitude excitations, enabling dual-mode manipulation using a single unit transducer. Furthermore, based on the scalable feature of the channel-shaped acoustic streaming vortices, fundamental droplet logic control can be achieved without solid-liquid interactions.
Altogether, this article summarizes the trials-and-errors, working mechanism, design principle, controlling strategy, and potential improvement directions of our digital acoustofluidics platform to facilitate the future development of compact liquid handling workstation with fluidic rewritability. Furthermore, it is our hope that our results and efforts can benefit the explorations in acoustic streaming and associated meso-/micro-manipulation techniques. Lastly, we hope the concept of fluidic rewritability in digitized liquid handling may motivate future microfluidic engineers to develop real Lab-on-a-Chip devices to enable high-speed automation of reactions with dynamic reconfigurability and controllability.
Item Open Access Effect of lithotripter focal width on stone comminution in shock wave lithotripsy.(J Acoust Soc Am, 2010-04) Qin, Jun; Simmons, W Neal; Sankin, Georgy; Zhong, PeiUsing a reflector insert, the original HM-3 lithotripter field at 20 kV was altered significantly with the peak positive pressure (p(+)) in the focal plane increased from 49 to 87 MPa while the -6 dB focal width decreased concomitantly from 11 to 4 mm. Using the original reflector, p(+) of 33 MPa with a -6 dB focal width of 18 mm were measured in a pre-focal plane 15-mm proximal to the lithotripter focus. However, the acoustic pulse energy delivered to a 28-mm diameter area around the lithotripter axis was comparable ( approximately 120 mJ). For all three exposure conditions, similar stone comminution ( approximately 70%) was produced in a mesh holder of 15 mm after 250 shocks. In contrast, stone comminution produced by the modified reflector either in a 15-mm finger cot (45%) or in a 30-mm membrane holder (14%) was significantly reduced from the corresponding values (56% and 26%) produced by the original reflector (no statistically significant differences were observed between the focal and pre-focal planes). These observations suggest that a low-pressure/broad focal width lithotripter field will produce better stone comminution than its counterpart with high-pressure/narrow focal width under clinically relevant in vitro comminution conditions.Item Open Access Efficient Spatial Coherence Estimation for Improved Endocardial Border Visualization in Real-Time(2017) Hyun, DongwoonCoronary heart disease contributed to approximately one in four deaths in the United States in 2014, and is caused by a restriction of blood flow to myocardial tissue. Stress echocardiography is a clinical technique used to assess myocardial ischemia by observing changes (or lack thereof) in ventricular wall motion in response to cardiac stress. The American Society of Echocardiography (ASE) recommends that left ventricle functionality be quantified using a 16 or 17 segment model of the left ventricle (LV). To properly assess the function of the ventricle, clear endocardial border delineation is necessary.
However, an increasing prevalence of obesity has been linked to a rise in the number of unreadable ultrasound scans. Image degradation is attributed to tissue inhomogeneities and subcutaneous fat layers, giving rise to phase aberration errors and acoustical clutter from near-field reverberation. In the event that two or more segments are inadequately visualized, the ASE recommends the use of contrast agents. Though contrast agents are effective, they are invasive and increase the procedure time and costs.
Recent work has shown that clutter can be suppressed using a novel image reconstruction technique based on the second order statistics of ultrasound echoes called short-lag spatial coherence (SLSC). Unlike conventional B-mode imaging, which forms images of the echo magnitude, SLSC forms images of the spatial coherence of the echo. By suppressing clutter, a sufficient improvement in the visualization of the endocardial border could minimize the need for contrast agents and potentially reduce the level of expertise necessary to interpret images. Though promising in preliminary studies, SLSC has a high computational demand that limited previous studies to offline image reconstruction. The goal of this research was to implement spatial coherence imaging in real-time, and to assess its performance in echocardiography.
First, the existing spatial coherence estimation methodology was investigated, and three computationally efficient modifications were proposed: a reduced kernel, a downsampled receive aperture, and the use of an ensemble correlation coefficient. The proposed methods were implemented in simulation and in vivo studies. Reducing the kernel to a single sample improved computational throughput and improved axial resolution. Downsampling the receive aperture was found to have negligible effect on estimator variance, and improved computational throughput by an order of magnitude for a downsample factor of 4. The ensemble correlation estimator was found to have lower variance than the currently used average correlation estimator. Combining the three methods, the throughput was improved 105-fold in simulation with a downsample factor of 4 and 20-fold in vivo with a downsample factor of 2.
Spatial coherence estimation techniques were also expanded to 2D matrix array transducers. SLSC images generated with a 2D array yielded superior contrast-to-noise ratio (CNR) and texture signal-to-noise ratio (SNR) measurements over SLSC images made on a corresponding 1D array and over B-mode imaging. SLSC images generated with square subapertures were found to be superior to SLSC images generated with subapertures of equal surface area that spanned the whole array in one dimension. Subaperture beamforming was found to have little effect on SLSC imaging performance for subapertures up to 8x8 elements in size on a 64x64 element transducer. Additionally, the use of 8x8, 4x4, and 2x2 element subapertures provided an 8, 4, and 2 times improvement in channel SNR along with a 2640-, 328-, and 25-fold reduction in computation time, respectively.
The improved spatial coherence estimation methodology was implemented using a GPU-based software beamformer to develop a real-time SLSC imaging system suitable for echocardiography. The system went through several iterations, with the final form consisting of a stand-alone CUDA C++ library for GPU-based beamforming, and a second CUDA C++ library to interface a research ultrasound scanner with the first. The resulting system was capable of live spatial coherence imaging at more than 30 frames per second, a rate sufficient for echocardiography.
The system was then used in a clinical study to image 15 stress echocardiography patients with poor image quality. A fundamental and harmonic imaging study was conducted. The latter study, which had greater clinical significance, was an assessment of the visibility of 17 LV segments using conventional tissue harmonic imaging (THI) and harmonic spatial coherence imaging (HSCI). A cardiologist rated the visibility of each of 17 LV segments as 0=invisible, 1=poorly visualized, or 2=well visualized, where scores of 0 and 1 indicated a need for contrast agent. There was a clear superiority of HSCI over THI in a comparison of overall segment scores (p < 0.0001 by symmetry test unadjusted for clustering). When comparing the number of segments with clinically acceptable image quality per patient, HSCI again showed superiority over THI (p < 0.0001 by McNemar test adjusted for clustering). In one patient, HSCI improved visualization sufficiently to eliminate the need for contrast agents altogther. These results indicate that spatial coherence imaging may provide sufficient improvements in LV wall visualization in certain patients to proceed without contrast agents.
The research in spatial coherence estimation techniques also proved fruitful in other areas of ultrasound imaging, such as ultrasound molecular imaging (USMI). USMI is accomplished by detecting microbubble (MB) contrast agents that have bound to specific biomarkers, and can be used for the early detection of cancer. However, USMI in humans is challenging because of the signal degradation caused by the presence of heterogenous subcutaneous tissue. In a phantom and in vivo study, USMI performance was assessed using conventional contrast-enhanced ultrasound (CEUS) imaging and SLSC-CEUS. In a USMI-mimicking phantom, SLSC-CEUS was found to be more robust than DAS to additive thermal noise, with a 9 dB and 15 dB SNR improvement without and with -6 dB thermal noise, respectively. USMI performance was also measured in vivo using VEGFR2-targeted MBs in mice with subcutaneous human hepatocellular carcinoma tumors. SLSC-CEUS improved the SNR in each of 10 tumors by an average of 65%, corresponding to 4.3 dB SNR. These results indicate that the SLSC beamformer is well-suited for USMI applications because of its high sensitivity and robust properties.
These studies are a demonstration of the feasibility of real-time spatial coherence imaging using current technology, and an exposition of its utility in medical ultrasound imaging.
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