Cleaning validation of pharmaceutical manufacturing equipment is required by legislation. Generally, wet chemical techniques are employed using swabbing and/or rinse sampling methods. These are generally either selective and time consuming, or less selective and give results in a shorter period. The infrared reflection absorption spectroscopy (IRRAS) technique explored here attempts to deliver accurate, selective surface contamination information in real time to complement current methods and reduce down-time. The IRRAS instrument used in this research is a Fourier transform infrared (FTIR) spectrometer coupled by an IR fibre-optic cable to a grazing-angle sampling head with a fixed incidence angle of 80°. The introduced flexibility permits collection of in situ spectra from contaminated surfaces. Calibration models are developed using the multivariate, linear partial least squares (PLS) statistical method. The research focuses on sodium dodecyl sulfate (SDS), a model cleaning agent, on metal (aluminium and stainless steel) and dielectric (glass, EPDM and silicone) surfaces. The effects of surface finish are investigated for SDS on stainless steel. Calibrations for SDS and paracetamol in the presence of each other on glass surfaces are examined, as well as a common industrial cleaner (P3 cosa® PUR80) on polished stainless steel. For the calibration sets in this thesis, RMSECV values were < 0.41 µg cm⁻², corresponding to conservative surface residues detection limits of better than ~0.86 µg cm⁻². However, RMSECV values depend on the calibration loading range, and the detection limits were typically ~0.2 µg cm⁻² for loading ranges 0-2.5 µg cm⁻². These are below visual detection limits, generally taken to be 1-4 µg cm⁻², depending on the analyte and substrate. This shows that IRRAS is a viable method for the real-time detection and quantification of surface contamination by surfactants and active pharmaceutical ingredients on metals and dielectrics.

Cleaning validation of pharmaceutical manufacturing equipment is required by legislation. Generally, wet chemical techniques are employed using swabbing and/or rinse sampling methods. These are generally either selective and time consuming, or less selective and give results in a shorter period. The infrared reflection absorption spectroscopy (IRRAS) technique explored here attempts to deliver accurate, selective surface contamination information in real time to complement current methods and reduce down-time. The IRRAS instrument used in this research is a Fourier transform infrared (FTIR) spectrometer coupled by an IR fibre-optic cable to a grazing-angle sampling head with a fixed incidence angle of 80°. The introduced flexibility permits collection of in situ spectra from contaminated surfaces. Calibration models are developed using the multivariate, linear partial least squares (PLS) statistical method. The research focuses on sodium dodecyl sulfate (SDS), a model cleaning agent, on metal (aluminium and stainless steel) and dielectric (glass, EPDM and silicone) surfaces. The effects of surface finish are investigated for SDS on stainless steel. Calibrations for SDS and paracetamol in the presence of each other on glass surfaces are examined, as well as a common industrial cleaner (P3 cosa® PUR80) on polished stainless steel. For the calibration sets in this thesis, RMSECV values were < 0.41 µg cm⁻², corresponding to conservative surface residues detection limits of better than ~0.86 µg cm⁻². However, RMSECV values depend on the calibration loading range, and the detection limits were typically ~0.2 µg cm⁻² for loading ranges 0-2.5 µg cm⁻². These are below visual detection limits, generally taken to be 1-4 µg cm⁻², depending on the analyte and substrate. This shows that IRRAS is a viable method for the real-time detection and quantification of surface contamination by surfactants and active pharmaceutical ingredients on metals and dielectrics.

Bragg scattering of optical waves in thick gratings at extreme angles, where the scattered wave propagates parallel (extremely asymmetric scattering - EAS) or nearly parallel (grazing angle scattering - GAS) to the grating boundaries, is associated with many unique and practically important resonant phenomena. It has been demonstrated that one of the main physical mechanisms for these resonant phenomena is the diffractional divergence of the scattered wave inside and outside the grating region. This thesis fills the gaps in the theoretical and experimental understanding of Bragg scattering in gratings at extreme angles by investigating EAS and GAS in structures where diffractional divergence of waves is significantly affected by anisotropy and/or non-uniformities of the dielectric permittivity. Unusually high sensitivity of wave scattering in thick periodic gratings to small step-like variations of mean structural parameters at the grating boundaries is predicted and described for the case when the scattered wave (the +1 diffracted order) propagates almost parallel to the front grating boundary (the geometry of GAS). A unusual pattern of strong multiple resonances for bulk electromagnetic waves is predicted and analysed numerically in thick periodic holographic gratings in a guiding slab with mean permittivity that is greater than that of the surrounding media. It is demonstrated that these resonances are related to resonant generation of a new type of eigenmodes in a thick slab with a periodic grating. These eigenmodes are generically related to the grating -- they do exist not if the grating amplitude is zero. A new type of resonant coupling of bulk radiation into the conventional guided modes of a slab with a thick holographic grating is predicted and explained theoretically. It occurs in the presence of strong frequency detunings of the Bragg condition by means of interaction of the strongly non-eigen +1 diffracted order with the slab-grating boundaries. Therefore, it is only in the presence of step-like variations of the mean permittivity at the grating boundaries that this type of resonant coupling can occur. A new method for the analysis of EAS and GAS in anisotropic gratings is developed. This method is based on the consideration of the diffractional divergence of the scattered wave and the two-wave approximation in anisotropic gratings. Special efforts are focused on the analysis of EAS and GAS of extraordinary waves in uniaxial gratings. In particular, it is demonstrated that increasing curvature of the normal surface in the direction of propagation of the scattered wave results in increase of its diffraction divergence and the resonant amplitude. A theoretical model is developed for comparison of the theoretical predictions with data obtained from experimental observations of EAS in a holographic grating written in a photorefractive medium. The developed model is applied for the interpretation of experimental observations of EAS in BaTiO3 photorefractive crystals. Good agreement with the theoretical predictions is demonstrated.

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This thesis fills in the gaps in the existing theory of wave phenomena in thick diffraction gratings at extreme angles of scattering, i.e. when the scattered wave propagates parallel or almost parallel to the grating boundaries. A consistent theory of a new type of Bragg scattering of bulk and guided optical modes in thick uniform and non-uniform, dissipative and non-dissipative, slanted periodic gratings has been developed. This type of scattering is called extremely asymmetrical scattering (EAS). One of the main distinctive features of EAS is the strong resonant increase of the scattered wave amplitude compared to the amplitude of the incident wave. Several unique combinations of strong resonances shaping a complex multi-resonant pattern of EAS in different types of gratings have been predicted and investigated theoretically and numerically. This includes the prediction of a new resonant wave effect in non-uniform gratings with varying phase – double-resonant EAS, the discovery of several sharp and strong resonances with respect to scattering angle in gratings with the scattered wave propagating almost parallel to the grating boundaries (grazing-angle scattering (GAS)) for the case of second-order scattering, and the prediction of a new type of eigenmode in gratings with second-order scattering (especially in gratings with large amplitude). In addition, several other important practical problems that may be crucial for the experimental observation and application of EAS and GAS have been solved. These are the determination of the tolerance of EAS to small grating imperfections, e.g., fluctuations of the grating amplitude, prediction of unusually high sensitivity of second-order EAS to small variations of mean structural parameters, determination of the effect of weak dissipation on EAS, etc. Physical reasons for the predicted resonances and effects are explained. In particular, the crucial role of the diffractional divergence for EAS and GAS has been revealed, especially for non-uniform gratings. Methods of analysis involve the approximate and rigorous approaches. The approximate method is based on understanding the role of the diffractional divergence in the geometry of EAS and the two-wave approximation (valid for any types of waves). The rigorous approach is based on the rigorous coupled-wave analysis (RCWA) and, in particular, the known enhanced T-matrix algorithm (by Moharam, et al.) that is numerically stable for narrow and wide gratings with arbitrary amplitude (valid only for bulk electromagnetic waves).