Designing Liquid Crystal for Optoacoustic Detection

This research impacts the development of a cost-saving, on-chip device that can replace a wide range of costly, bulky sensors for commercial and defense applications. In particular, the goals of this work were to design and test a sensor that uses the optical properties of liquid crystal (LC) to detect acoustic waves. This began with developing a method to fine-tune the optical features of the liquid crystal. Statistical analysis of select experimental variables, or factors, lead to ideal settings of those variables when creating the sensor. A two-factor and three-factor experiment were separately conducted and analyzed as a preliminary demonstration of this system. The identification of dominant and ideal factor levels, including their interactions, enabled a statistically enhanced molecular design method of LC for use in many types of sensor applications. Detecting acoustic waves using the optical properties of a material, or optoacoustic detection, was chosen as the application to test the designed LC. Research continued with analytically calculating the interaction between the soundwaves and the optical and mechanical properties of the LC. Systematic comparisons between a commercially available acoustic sensor system and this theoretical LC optoacoustic detector are provided. Development concluded with a test which demonstrated that ordered, chiral nematic phase of LC can inherently improve an existing acoustic sensing device. Recommendations for further development are discussed

High-resolution 3D printing enabled, minimally invasive fibre optic sensing and imaging probes

Minimally invasive surgical procedures have become more favourable to their traditional surgical counterparts due to their reduced risks, faster recovery times and decreased trauma. Despite this, there are still some limitations involved with these procedures, such as the spatial confinement of operating through small incisions and the intrinsic lack of visual or tactile feedback. Specialised tools and imaging equipment are required to overcome these issues. Providing better feedback to surgeons is a key area of research to enhance the outcomes and safety profiles of minimally invasive procedures. This thesis is centred on the development of new microfabrication methods to create novel fibre optic imaging and sensing probes that could ultimately be used for improving the guidance of minimally invasive surgeries. Several themes emerged in this process. The first theme involved the use and optimisation of high-resolution 3D injection of polymers as sacrificial layers onto which parylene-C was deposited. One outcome from this theme was a series of miniaturised parylene-C based membranes to create fibre optic pressure sensors for physiological pressure measurements and for ultrasound reception. The pressure sensor sensitivity was found to vary from 0.02 to 0.14 radians/mmHg, as the thickness of parylene was decreased from 2 to 0.5 μm. The ultrasound receivers were characterised and exhibited a noise equivalent pressure (NEP) value of ~100 Pa (an order of magnitude improvement compared to similarly sized piezoelectric hydrophones). A second theme employed high-resolution 3D printing to create microstructures of polydimethylsiloxane (PDMS) and subsequently formed nanocomposites, to create microscale acoustic hologram structures. This theme included the development of innovative manufacturing processes such as printing directly onto optical fibres, micro moulding and precise deposition which enabled the creation of such devices. These microstructures were investigated for reducing the divergence of photoacoustically-generated ultrasound beams. Taken together, the developments in this thesis pave the way for 3D microfabricated polymer-based fibre optic sensors that could find broad clinical utility in minimally invasive procedures

Diseño y desarrollo de un sistema optoacústico de múltiples longitudes de onda basado en fuentes de diodos láseres de alta potencia: generación de señales optoacústicas con nanopartículas para aplicaciones biomédicas

Durante los últimos años, el rápido avance de las tecnologías ópticas para la obtención de imágenes biomédicas hace posible revelar importantes informaciones biológicas a partir de la interacción entre la luz y el tejido. El interés emergente en nuevas técnicas de obtención de imágenes biomédicas está motivado por la necesidad de detectar células malignas y otras enfermedades durante las etapas precoces de evolución. La limitada profundidad de penetración de la energía óptica en medios biológicos se debe principalmente al alto nivel de dispersión óptica. Además, la difusión de la luz en los tejidos biológicos limita la resolución espacial de las imágenes adquiridas. La técnica optoacústica sobresale estos problemas combinando el alto contraste de la imagen óptica con la alta resolución espacial de los sistemas de ultrasonido en los tejidos profundos. Asimismo, la baja dispersión de las ondas ultrasónicas producidas en los tejidos biológicos facilita la adquisición de imágenes de alta resolución. Dos importantes aspectos a considerar demás en las aplicaciones optoacústicas para una imagen funcional son el uso de agentes de contraste óptico para mejorar la absorción de energía óptica en aquellas áreas donde la dispersión es dominante y la cantidad de energía óptica suministrada por las fuentes láseres para penetrar en profundidad. La necesidad de fuentes láseres compactas y de bajo coste con las características requeridas por las aplicaciones optoacústicas ha impulsado los estudios presentados en esta tesis, proponiendo el uso de diodos láseres de alta potencia en lugar de los clásicos láseres de estado sólido. Generalmente, los láseres de estado sólido como el Nd:YAG y los osciladores ópticos paramétricos se utilizan para la generación de señales optoacústicas, pero su uso en el ambiente clínico está limitado por sus altos costes, bajas frecuencias de repetición y tamaños voluminosos. Por otro lado, los diodos láseres de alta potencia emergen como una potencial alternativa, debido a sus relativamente bajos costes, altas frecuencias de repetición requeridas para una rápida adquisición de imágenes y tamaños compactos. Sin embargo, la potencia de los diodos láseres de alta potencia es todavía relativamente baja en comparación con los láseres de estado sólido y por esta razón se necesita combinarlos para conseguir la cantidad de potencia óptica requerida para las aplicaciones optoacústicas. Un sistema optoacústico basado en diodos láseres de alta potencia ha sido implementado y mejorado a lo largo de los estudios presentados en esta tesis. Se han realizado experimentos optoacústicos a diferentes longitudes de onda utilizando varios tipos de absorbentes colocados en cubeta de cuarzo u hospedados dentro de un “phantom” que simula la dispersión óptica de un tejido blando. Soluciones de nanotubos de carbono, óxido de grafeno y nanoparticulas de oro se han utilizado como absorbentes a lo largo de los experimentos. Los primeros experimentos realizados en espacio libre para enfocar la luz en los absorbentes se han mejorado mediante el uso de fibras ópticas en una segunda etapa. Por último, se han propuesto barras de diodos láseres comercialmente disponibles para sustituir los diodos láseres de alta potencia con el objetivo de aumentar la potencia óptica para futuras implementaciones en los sistemas optoacústicos. Las simulaciones ópticas han demostrado la posibilidad de enfocar el haz emitido por barras de diodos láseres de diferentes longitudes de onda en fibras ópticas por medio de microlentes cilíndricas. En una segunda etapa, las barras de diodos láseres han sido ensambladas en un único sistema para simular un sistema de múltiples longitudes de onda. Los haces han sido combinados por medio de espejos dicroicos y enfocados en una fibra óptica multimodo. Este trabajo de investigación ha abierto nuevas líneas de investigación en el desarrollo de fuentes láser de alta potencia para la endoscopia optoacústica y la tomografía en aplicaciones biomédicas.Over last few years, the rapid growth of optical technologies for biomedical imaging makes possible to reveal important biological information of tissues from light-tissue interaction. The emerging interest on new biomedical imaging techniques is motivated by the necessity to detect malignant cells and other diseases at early growth stages. The limited penetration depth of optical energy in biological media is primarily due to the high level of optical scattering. In addition, the diffusion of light in biological tissues limits the spatial resolution of the images acquired. The optoacoustic technique overcomes these issues combining the high contrast of optical imaging with the high spatial resolution of ultrasound systems in deep tissues. As well, the low scattering of the ultrasound waves produced in the biological tissues facilitates the acquisition of high-resolution images. Two more important aspects to be considered in optoacoustic applications for a functional imaging are the use of optical contrast agents to increase the absorption of optical energy in those areas where the scattering is dominant, and the amount of optical energy delivered by laser sources to penetrate in depth. The necessity of compact and cost-effective laser sources with the characteristics required by optoacoustic applications has encouraged the studies presented in this thesis, proposing the use of high-power diode lasers instead of the classical solid state lasers. Generally, solid-state lasers like Nd:YAG and optical parametric oscillators are used for the generation of optoacoustic signals, but their use in clinical environment is limited by their high costs, low repetition rates and bulky sizes. On the other hand, high-power diode lasers emerge as a potential alternative, due to their relatively low costs, high repetition rates required for fast image acquisition and compact sizes. However, the power of high-power diode lasers is still relatively low compared to solid-state lasers and for this reason they need to be combined in arrays to reach the amount of the optical power required for optoacoustic applications. An optoacoustic setup based on small arrays of high-power diode lasers has been implemented and improved along the studies presented in this thesis. Optoacoustic experiments have been performed at different wavelengths using several kinds of absorbers hosted in a quartz cuvette or embedded within a phantom that simulates the optical scattering of a soft tissue. Solutions of carbon nanotubes, graphene oxide and gold nanorods have been used as absorbers in the experiments. The first experiments done in free space to focus the light in the absorbers have been improved by using optical fibers in a second stage. Lastly, some commercially available diode laser bars have been proposed to replace the high-power diode lasers with the aim to increase the optical power for future implementations in the optoacoustic systems. Optical simulations have demonstrated the possibility to focus the beam of diode laser bars operating at different wavelengths into optical fibers by means of cylindrical microlenses. In a second step, the diode laser bars have been assembled together to simulate a multi-wavelength system. The beams have been combined by dichroic mirrors and focused in a multi-mode optical fiber. This research work has opened up new lines of investigation in the development of high-power laser sources for optoacoustic endoscopy and tomography in biomedical applications.Programa Oficial de Doctorado en Ingeniería Eléctrica, Electrónica y AutomáticaPresidente: Alexander A. Oraevsky.- Secretario: José Antonio García Souto.- Vocal: Ana Pilar González Marco

MEMS enabled miniaturisation of photoacoustic imaging and sensing systems

This work presents multiple advances toward miniaturised photoacoustic imaging systems. Miniaturising the system is done in two steps. Firstly, by using novel custom arrays of piezoelectric miniaturised ultrasound transducers. The arrays were fabricated using a cost-efficient multi-user process. The achievable upper frequency limits were restricted by the design limitations of the multi-user process. The designs comprised of a single frequency and two frequency staggered arrays. They were characterised using laser Doppler velocimetry, pitch and catch technique as well as photoacoustic excitation. Additionally, the arrays were compared to commercial bulk ultrasound transducers. The custom-made PMUT arrays perform well compared to commercial transducer, despite their significantly smaller (two orders of magnitude) detection area. Secondly, an optical resolution photoacoustic microscope consisting consisting of MEMS based excitation - using a fast-scanning micro-mirror for Q-switching - and detection schemes is built and used to image synthetic targets and phantoms. Furthermore, a simulation model of the system is developed to evaluate influences of the miniaturised elements on the photoacoustic signal generation and received spectra and signal strength. Finally, a novel photoacoustic excitation scheme based on CW - laser excitation and a MEMS based fast-scanning micro-mirror is presented and its performance relative to pulsed excitation photoacoustic imaging is evaluated. Here, the photoacoustic excitation is not due to fast pulsed laser excitation, but caused by scanning a focused CW - beam over a sample.This work presents multiple advances toward miniaturised photoacoustic imaging systems. Miniaturising the system is done in two steps. Firstly, by using novel custom arrays of piezoelectric miniaturised ultrasound transducers. The arrays were fabricated using a cost-efficient multi-user process. The achievable upper frequency limits were restricted by the design limitations of the multi-user process. The designs comprised of a single frequency and two frequency staggered arrays. They were characterised using laser Doppler velocimetry, pitch and catch technique as well as photoacoustic excitation. Additionally, the arrays were compared to commercial bulk ultrasound transducers. The custom-made PMUT arrays perform well compared to commercial transducer, despite their significantly smaller (two orders of magnitude) detection area. Secondly, an optical resolution photoacoustic microscope consisting consisting of MEMS based excitation - using a fast-scanning micro-mirror for Q-switching - and detection schemes is built and used to image synthetic targets and phantoms. Furthermore, a simulation model of the system is developed to evaluate influences of the miniaturised elements on the photoacoustic signal generation and received spectra and signal strength. Finally, a novel photoacoustic excitation scheme based on CW - laser excitation and a MEMS based fast-scanning micro-mirror is presented and its performance relative to pulsed excitation photoacoustic imaging is evaluated. Here, the photoacoustic excitation is not due to fast pulsed laser excitation, but caused by scanning a focused CW - beam over a sample

Multimodal photoacoustic remote sensing (PARS) microscopy combined with swept-source optical coherence tomography (SS-OCT) for in-vivo, non-contact, functional and structural ophthalmic imaging applications

Ophthalmic imaging has long played an important role in the understanding, diagnosis, and treatment of a wide variety of ocular disorders. Currently, available clinical ophthalmic imaging instruments are primarily optical-based, including slit-lamp microscopy, fundus photography, confocal microscopy, scanning laser ophthalmoscopy, and optical coherence tomography (OCT). The development of these imaging instruments has greatly extended our ability to evaluate the ocular environment. Studies have shown that at least 40% of blinding disorders in the United States are either preventable or treatable with timely diagnosis and intervention. OCT is a state-of-the-art imaging technique extensively used in preclinical and clinical applications for imaging both anterior and posterior parts of the eye. OCT has become a standard of care for the assessment and treatment of most ocular conditions. The technology enables non-contact, high-speed, cross-sectional imaging over a large field of view with submicron resolutions. In eye imaging applications, functional extensions of OCT such as spectroscopic OCT and Doppler OCT have been applied to provide a better understanding of tissue activity. Spectroscopic OCT is usually achieved through OCT systems in the visible spectral range, and it enables the amount of light absorption inside the ocular environment to be measured. This indirect optical absorption measurement is used to estimate the amount of ocular oxygen saturation (SO2) which is a well-known biomarker in prevalent eye diseases including diabetic retinopathy, glaucoma, and retinal vein occlusions. Despite all the advancements in functional spectroscopic OCT methods, they still rely primarily on measuring the backscattered photons to quantify the absorption of chromophores inside the tissue. Therefore, they are sensitive to local geometrical parameters, such as retinal thickness, vessel diameters, and retinal pigmentation, and may result in biased estimations. Of the various optical imaging modalities, photoacoustic imaging (PAI) offers unique imaging contrast of optical absorption because PAI can image any target that absorbs light energy. This unique imaging ability makes PAI a favorable candidate for various functional and molecular imaging applications as well as for measuring chromophore concentration. Over the past decade, photoacoustic ophthalmoscopy has been applied for visualizing hemoglobin and melanin content in ocular tissue, quantifying ocular SO2, and measuring the metabolic rate of oxygen consumption (MRO2). Despite all these advantages offered by PAI devices, a major limitation arises from their need to be in contact with the ocular tissues. This physical contact may increase the risk of infection and cause patient discomfort. Furthermore, this contact-based imaging approach applies pressure to the eye and introduces barriers to oxygen diffusion. Thus, it has a crucial influence on the physiological and pathophysiological balance of ocular vasculature function, and it is not capable of studying dynamic processes under normal conditions. To overcome these limitations and to benefit from the numerous advantages offered by photoacoustic ophthalmoscopy, non-contact detection of photoacoustic signals has been a long-lasting goal in the field of ocular imaging. In 2017 Haji Reza et al. developed photoacoustic remote sensing (PARS) for non-contact, non-interferometric detection of photoacoustic signals. PARS is the non-contact, all-optical version of optical-resolution photoacoustic microscopy (OR-PAM), where the acoustically coupled ultrasound transducer is replaced with a co-focused probe beam. This all-optical detection scheme allows the system to measure the photoacoustic pressure waves at the subsurface origin where the pressure is at a maximum. In a very short time, PARS technology has proven its potential for various biomedical applications, including label-free histological imaging, SO2 mapping, and angiogenesis imaging. PARS is an ideal companion for OCT in ophthalmic applications, where the depth-resolved, detailed scattering information of OCT is well complemented by rich absorption information of PARS. This combined multimodal imaging technology has the potential to provide chromophore selective absorption contrast in concert with depth-resolved scattering contrast in the ocular environment. The main goals of this PhD project are to: • Develop a photoacoustic remote sensing microscopy system for in-vivo, non-contact ophthalmic imaging. This is the first time a non-contact photoacoustic imaging has been used for in-vivo imaging of the eye. • Develop a robust and temporally stable multiwavelength light source for functional photoacoustic imaging applications. • Develop a multimodal PARS-OCT imaging system that can image in-vivo and record, simultaneously, functional, and structural information in the anterior segment of a rodent eye. This is the first time a multiwavelength non-contact photoacoustic system is used for in-vivo measurement of oxygen saturation in the ocular environment. • Develop and modify the multimodal PARS-OCT imaging system for non-contact, in-vivo, functional, and structural imaging of the posterior part of the rodent eye

Cascaded plasmon resonances for enhanced nonlinear optical response

The continued development of integrated photonic devices requires low-power, small volume all-optical modulators. The weak nonlinear optical response of conventional optical materials requires the use of high intensities and large interaction volumes in order to achieve significant light modulation, hindering the miniaturization of all-optical switches and the development of lightweight transmission optics with nonlinear optical response. These challenges may be addressed using plasmonic nanostructures due to their unique ability to confine and enhance electric fields in sub-wavelength volumes. The ultrafast nonlinear response of free electrons in such plasmonic structures and the fast thermal nonlinear optical response of metal nanoparticles, as well as the plasmon enhanced nonlinear Kerr-type response of the host material surrounding the nanostructures could allow ultrafast all-optical modulation with low modulation energy. In this thesis, we investigate the linear and nonlinear optical response of engineered effective media containing coupled metallic nanoparticles. The fundamental interactions in systems containing coupled nanoparticles with size, shape, and composition dissimilarity, are evaluated analytically and numerically, and it is demonstrated that under certain conditions the achieved field enhancement factors can exceed the single-particle result by orders of magnitude in a process called cascaded plasmon resonance. It is demonstrated that these conditions can be met in systems containing coupled nanospheres, and in systems containing non-spherical metal nanoparticles that are compatible with common top-down nanofabrication methods such as electron beam lithography and nano-imprint lithography. We show that metamaterials based on such cascaded plasmon resonance structures can produce enhanced nonlinear optical refraction and absorption compared to that of conventional plasmonic nanostructures. Finally, it is demonstrated that the thermal nonlinear optical response of metal nanoparticles can be enhanced in carefully engineered heterogeneous nanoparticle clusters, potentially enabling strong and fast thermal nonlinear optical response in system that can be produced in bulk through chemical synthesis

NASA patent abstracts bibliography: A continuing bibliography. Section 1: Abstracts (supplement 17)

Abstracts are cited for 150 patents and applications for patents introduced into the NASA scientific and technical information system during the period January 1980 through June 1980. Each entry consists of a citation, an abstract, and in most cases, a key illustration selected from the patent or application for patent