Browsing by Subject "Physics, Optics"

This dissertation describes three computational sensors. The first sensor is a scanning multi-spectral aperture-coded microscope containing a coded aperture spectrometer that is vertically scanned through a microscope intermediate image plane. The spectrometer aperture-code spatially encodes the object spectral data and nonnegative

least squares inversion combined with a series of reconfigured two-dimensional (2D spatial-spectral) scanned measurements enables three-dimensional (3D) (x, y, λ) object estimation. The second sensor is a coded aperture snapshot spectral imager that employs a compressive optical architecture to record a spectrally filtered projection

of a 3D object data cube onto a 2D detector array. Two nonlinear and adapted TV-minimization schemes are presented for 3D (x,y,λ) object estimation from a 2D compressed snapshot. Both sensors are interfaced to laboratory-grade microscopes and

applied to fluorescence microscopy. The third sensor is a millimeter-wave holographic imaging system that is used to study the impact of 2D compressive measurement on 3D (x,y,z) data estimation. Holography is a natural compressive encoder since a 3D

parabolic slice of the object band volume is recorded onto a 2D planar surface. An adapted nonlinear TV-minimization algorithm is used for 3D tomographic estimation from a 2D and a sparse 2D hologram composite. This strategy aims to reduce scan time costs associated with millimeter-wave image acquisition using a single pixel receiver.

Optical interrogation techniques are particularly well-suited for imaging tissue morphology, biological dynamics, and disease pathogenesis by providing noninvasive access to subcellular-resolution diagnostic information. State-of-the-art spectral domain optical coherence tomography (SDOCT) systems provide real-time optical biopsies of in vivo tissue, and have demonstrated clinical potential, particularly for applications in ophthalmology.

Recent advances in microscopy and endoscopy have led to improved resolution and compact optical designs, beyond those of conventional imaging systems. Application of encoded and multiplexed illumination and detection schemes may allow for the development of optical tools that surpass classical imaging limitations. Furthermore, complementary technologies can be combined to create multimodal optical imaging tools with advantages over current-generation systems.

In this dissertation, the development of coherence-gated and resolution-multiplexed technologies, aimed towards applications in human vitreoretinal imaging is described. Technology development in coherence-gated systems included increasing the imaging range of SDOCT by removing the complex conjugate artifact, improving acquisition speed using a scanning spectrometer design and a two-dimensional detector array, and hardware and algorithmic implementations that facilitated imaging of Doppler flow.

Structured illumination microscopy techniques were applied for resolution enhancement, and a spectrally encoded ophthalmic imaging system was developed for en face confocal fundus imaging through a single-mode fiber. These devices were resolution-multiplexed extensions of existing ophthalmic imaging devices, such as scanning laser ophthalmoscopes (SLO), which demonstrated improved resolution and more compact optical designs as compared to their conventional counterparts.

Finally, several multimodal ophthalmic diagnostic tools were developed that combined the advantages of OCT with existing imaging devices. These included a combined SLO-OCT system and a vitreoretinal surgical microscope combined with OCT. These devices allowed for concurrent ophthalmic imaging using complementary modalities for improved visualization and clinical utility.

Developmental biology is a field in which explorations are made to answer how an organism transforms from a single cell to a complex system made up of trillions of highly organized and highly specified cells. This field, however, is not just for discovery, it is crucial for unlocking factors that lead to diseases, defects, or malformations. The one key ingredient that contributes to the success of studies in developmental biology is the technology that is available for use. Optical coherence tomography (OCT) is one such technology. OCT fills a niche between the high resolution of confocal microscopy and deep imaging penetration of ultrasound. Developmental studies of the chicken embryo heart are of great interest. Studies in mature hearts, zebrafish animal models, and to a more limited degree chicken embryos, indicate a relationship between blood flow and development. It is believed that at the earliest stages, when the heart is still a tube, the purpose of blood flow is not for convective transport of oxygen, nutrients and waster, bur rather to induce shear-related gene expressions to induce further development. Yet, to this date, the simple question of "what makes blood flow?" has not been answered. This is mainly due limited availability to adequate imaging and blood flow measurement tools. Earlier work has demonstrated the potential of OCT for use in studying chicken embryo heart development, however quantitative measurement techniques still needed to be developed. In this dissertation I present technological developments I have made towards building an OCT system to study chick embryo heart development. I will describe: 1) a swept-source OCT with extended imaging depth; 2) a spectral domain OCT system for non-invasive small animal imaging; 3) Doppler flow imaging and techniques for quantitative blood flow measurement in living chicken embryos; and 4) application of the OCT system that was developed in the Specific Aims 2-5 to test hypotheses generated by a finite element model which treats the embryonic chick heart tube as a modified peristaltic pump.

Spectral Domain Optical Coherence Tomography (SDOCT) is a high-speed, high resolution imaging modality capable of structural and functional resolution of tissue microstructure. SDOCT fills a niche between histology and ultrasound imaging, providing non-contact, non-invasive backscattering amplitude and phase from a sample. Due to the translucent nature of the tissue, ophthalmic imaging is an ideal space for SDOCT imaging.

Structural imaging of the retina has provided new insights into ophthalmic disease. The phase component of SDOCT images remains largely underexplored, though. While Doppler SDOCT has been explored in a research setting, it remains to catch on in the clinic. Other, functional exploitations of the phase are possible and necessary to expand the utility of SDOCT. Spectral Domain Phase Microscopy (SDPM) is an extension of SDOCT that is capable of resolving sub-wavelength displacements within a focal volume. Application of sub-wavelength displacement measurement ophthalmic imaging could provide a new method for imaging of optophysiology.

This body of work encompasses both hardware and software design and development for implementation of SDOCT. Structural imaging was proven in both the lab and the clinic. Coarse phase changes associated with Doppler flow frequency shifts were recorded and a study was conducted to validate Doppler measurement. Fine phase changes were explored through SDPM applications. Preliminary optophysiology data was acquired to study the potential of sub-wavelength measurements in the retina. To remove the complexity associated with in-vivo human retinal imaging, a first principles approach using isolated nerve samples was applied using standard SDPM and a depth-encoded technique for measuring conduction velocity.

Results from amplitude as well as both coarse and fine phase processing are presented. In-vivo optophysiology using SDPM is a promising avenue for exploration, and projects furthering or extending this body of work are discussed.

The refractive index sensitivity of plasmonic nanoparticles is utilized in the development of real-time, label-free biodetection. Analyte molecules that bind to receptor-conjugated nanoparticles cause an increase in local refractive index that in turn induces an energy shift in the optical resonance of the particle. Biomolecular binding is quantified by quantitatively measuring these resonance shifts. This work describes the application and optimization of a biomolecular detection system based on gold nanorods as an optical transducer.

A microspectroscopy system was developed to collect scattering spectra of single nanoparticles, and measure shifts of the spectra as a function of biomolecular binding. The measurement uncertainty of LSPR peak shifts of the system was demonstrated to be 0.3 nm. An analytical model was also developed that provides the optimal gold nanorod geometry for detection with specified receptor-analyte pair. The model was applied to the model biotin-streptavidin system, which resulted in sensing system with a detection limit of 130 pM - an improvement by four orders of magnitude over any other single-particle biodetection previously presented in the literature.

Alternative optical detection schemes were also investigated that could facilitate mulitplexed biosensing. A theoretical model was built to investigate the efficacy of using a multi-channel detector analogous to a conventional RGB camera. The results of the model indicated that even in the best case, the detection capabilities of such a system did not provide advantages over the microspectroscopic approach.

We presented a novel hyperspectral detection scheme we term Dual-Order Spectral Imaging (DOSI) which is capable of simultaneously measuring spectra of up to 160 individual regions within a microscope's field of view. This technique was applied to measuring shifts of individual nanoparticles and was found to have a peak measurement uncertainty of 1.29 nm, at a measurement rate of 2-5 Hz.

Quantum chemical computations provide convenient and effective ways for molecular design using computers. In this dissertation, the molecular designs of optimal nonlinear optical (NLO) materials were investigated through three aspects. First, an inverse molecular design method was developed using a linear combination of atomic potential approach based on a Hückel-like tight-binding framework, and the optimizations of NLO properties were shown to be both efficient and effective. Second, for molecules with large first-hyperpolarizabilities, a new donor-carbon-nanotube paradigm was proposed and analyzed. Third, frequency-dependent first-hyperpolarizabilities were predicted and interpreted based on experimental linear absorption spectra and Thomas-Kuhn sum rules. Finally, molecular interferometers were designed to control charge-transfer using vibrational excitation. In particular, an ab initio vibronic pathway analysis was developed to describe inelastic electron tunneling, and the mechanism of vibronic pathway interferences was explored.

This research presents the development of a phase-based lithographic system for three-dimensional micropatterning and manipulation. The system uses a spatial light modulator (SLM) to display specially designed phase holograms. The use of holograms with the SLM provides a novel approach to photolithography that offers the unique ability to operate in both serial and single-shot modes. In addition to the lithographic applications, the optical system also possesses the capability to optically trap microparticles. New advances include the ability to rapidly modify pattern templates for both serial and single-shot lithography, individually control three-dimensional structural properties, and manipulate Janus particles with five degrees of freedom.

A number of separate research investigations were required to develop the optical system and patterning method. The processes for designing a custom optical system, integrating a computer aided design/computer aided manufacturing (CAD/CAM) platform, and constructing series of phase holograms are presented. The resulting instrument was used primarily for the photonic excitation of both photopolymers and proteins and, in addition, for the manipulation of Janus particles. Defining research focused on the automated fabrication of complex three-dimensional microscale structures based on the virtual designs provided by a custom CAD/CAM interface. Parametric studies were conducted to access the patterning transfer rate and resolution of the system.

The research presented here documents the creation of an optical system that is capable of the accurate reproduction of pre-designed microstructures and optical paths, applicable to many current and future research applications, and useable by anyone interested in researching on the microscale.