Tissue optical properties, absorption, scattering and fluorescence, reveal important information about health, and holds the potential for non-invasive diagnosis and therefore earlier treatment for many diseases. On the other hand, tissue structure determines its function. Studying tissue structural properties helps us better understand structure-function relationship. Optical imaging is an ideal tool to study these tissue properties. However, conventional optical imaging techniques have limitations, such as not being able to quantitatively evaluate tissue absorption and scattering properties and only providing volumetrically averaged quantities with no depth control capability. To better study tissue properties, we integrated spatial frequency domain imaging (SFDI) with conventional reflectance imaging modalities. SFDI is a non-invasive, non-contact wide-field imaging technique which utilizes structured illumination to probe tissues. SFDI imaging is able to accurately quantify tissue optical properties. By adjusting spatial frequency, the imaging depth can be tuned which allows for depth controlled imaging. Especially at high spatial frequency, SFDI reflectance image is more sensitive to tissue scattering property than absorption property. The imaging capability of SFDI allows for studying tissue properties from a whole new perspective. In our study, we developed both benchtop and handheld SFDI imaging systems to accommodate different applications. By evaluating tissue optical properties, we corrected attenuation in fluorescence imaging using an analytical model; and we quantified optical and physical properties of skin diseases. By imaging at high spatial frequency, we demonstrated that absorption in fluorescence imaging can also be reduced because of a reduced imaging depth. This correction can be performed in real-time at 19 frames/second. Furthermore, fibrous structures orientation from the superficial layer can be accurately quantified in a multi-layered sample by limiting imaging depth. Finally, we color rendered SFDI reflectance image at high spatial frequency to reveal structural changes in skin lesions.

The pharmaceutical process of dry granulation using roller-compaction (DG/RC) is effectively a non-batch based procedure orientated to deliver a continuous stream of material free of a pre-defined batch-size with reduced plant equipment/scale-up R&D resources and an enhanced work-throughput, particularly suitable for moisture sensitive formulation. The desirable accreditations of DG/RC are many; yet by the nature of a more flexible approach than (i.e. wet-granulation), it must be highly monitored and controlled to accomplish higher-throughput rates and reduced ‘static’ material testing stages. To monitor rapidly and in-line with production, pre-granulated ribbons of RC (which highly correlates to the post milled granulates), terahertz time-domain spectroscopy (TDS) is used to elucidate the key physical attributes of post-compression density and thickness uniformity, key to end-product consistency. Invariably a great number of conditions apply to DG/RC (viz: System design, material characteristics, environmental and unit configuration), although widely regarded as the key processing parameters (PP’s) are roll-pressure and roll-gap [1-4]. The target of the study is to derive a strategy to position TDS as PAT to DG/RC. Two terahertz time-domain TD methods of a conventional transmission setup and reflection (TPI) THz analysis are used on standards of glass slides for verifying the interpretational foundations of the TD methods. Achieving RI/thickness error-discrepancies +2.2 to -0.4% c.f. literature ([150]) values provides foundations to test the solid-fraction ratios of pharma tablets with regard to RI’s being surrogate values to SF/path-length (R2 = 1). Combining transmission principles to the portion of reflected EMR removes the pre-requisite for RI or path-length knowledge, giving +1.5 to +2.4% RI agreement (vs. frequency-domain attained results) thus enabling thickness estimations to be above 95% against physical micrometre judgement in all models. Augmentation of the TD methods, refined in Experimental chapter 2 ,then chiefly focuses on TPI as the principle THz-TD method (as the most ideal tool for PAT) for adopting the RI measures for ribbon uniformity analysis in Experimental chapter 4 in an off-line environment again resulting in RI and thicknesses < 5 % error of known parameters of thickness and further use of RI as a proxy porosity equivalent to gas pycnometry. Elucidated in the work are the limitations encountered with tablets and RC’s, data interpretation of industrial considerations. Experimental chapter 3 diverges from RI to differentiate thickness in-order to assess the FD transmission for non-destructive mechanical assessment. This demonstrates a clear relationship between compaction force and the surrogate value for density, following a linear trend below a certain threshold of force. The ‘threshold’ value is observed for less massive tablets, and concluded is that the mechanistic interplay and permanent (plastic) consolidation is greater in instances where compaction-force increases proportionally with target-fill weights, and thus the various behaviour of MCC to stress.

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Organic semiconductors show promise to yield a novel class of bendable electronic devices, and much research efforts have focused on the optimization of these films for device performance. It is well known that the structure of organic films has a large influence over the electronic properties. In particular, the carrier mobility is often highly anisotropic, and domain boundaries have a detrimental effect on charge transport. Therefore the domain structure and lattice orientation are of particular interest. However, little is known about the domain structure of organic films, and techniques to study these properties have only begun to emerge in recent years. In this thesis, we apply two experimental techniques, Grazing-Incidence X-ray Diffraction (GIXD) and Lateral Force Microscopy (LFM), toward studying the lattice and domain structure of tetracene films grown on the silicon(001)-monohydride surface. We describe the necessary steps toward optimizing the sensitivity of these techniques to the domain structure. Results show that the crystalline tetracene films form a layered morphology in which the a-b plane lies parallel to the substrate surface. The film lattice structure is similar to bulk tetracene, and the lattice is confined to two orthogonal orientations, forming a partially-commensurate relationship with the substrate surface lattice along the film 'a' axis. LFM images reveal two types of polycrystalline domains. The first type ("major domains") are tens of microns in size, and are classified by their lattice orientation. They are subdivided into the second type ("sub-domains"), which range from 0.1 to 5um in size, and are argued to represent regions of uniform molecular tilt direction. The GIXD data show that the single-crystal domains which comprise these two larger domain types are anisotropic in size, being up to two times longer along the film 'b' axis than along 'a'. The single-crystal domains range from 0.05 to 0.2um in size, depending on lattice orientation and film thickness. The mathematical basis for these single-crystal domain size calculations is presented. The single-crystal domain sizes are thickness-dependent, and are two orders of magnitude smaller than a typical surface island observed in atomic-force microscopy (AFM) topographs. Substrate steps can also significantly influence the film structure by inducing boundaries in the single-crystal domains and sub-domains, but not in the major domains. This detailed knowledge of the domain structure of organic thin-films may assist in our understanding of the factors which affect charge transport in thin films, and may help to direct research efforts in optimizing the film structure for device performance. / Natural Sciences and Engineering Research Council (NSERC), Canadian Foundation for Innovation (CFI), Ontario Innovation Trust (OIT).