One in eight women in America will develop breast cancer at some point in their lives. Breast cancer is the second deadliest form of cancer for women in the United States. When a suspicious region of the breast is detected, the tissue is diagnosed by removing a sample, preparing an H&E section, and performing histopathology. This procedure is expensive, invasive, and can take days to return a diagnosis. An alternative to excision biopsies is to instead perform an optical biopsy. This work details endomicroscopes intended to perform optical biopsies in breast tissue. The work address two issues limiting current optical biopsy systems: insufficient resolution and inability to reject out of focus light. To improve the resolution of current endomicroscopes, ultra-slim objectives are developed using optical plastics and zero alignment fabrication techniques. These objectives can outperform current alternative endomicroscope objectives in terms of performance across the field of view and chromatic aberration correction, while remaining as narrow as a biopsy needle. Next, an endomicroscope which utilizes structured illumination to perform optical section is designed, tested, and evaluated on ex vivo breast biopsies. The new endomicroscope provides high contrast images by reducing out of focus background light. Finally, an achromatic, ultra-slim objective and the structured illumination endomicroscope are integrated to form an optical biopsy system with improved lateral resolution and axial response. This integrated system is a step forward for in vivo microscopy and cancer diagnoses.

The use of optical fibre as a mechanism for the delivery of the trapping laser beam to the sample chamber significantly reduces both the size and the build costs of “Optical Tweezers”. Furthermore, the use of fibre facilitates the decoupling of the optical trapping beam from the microscope optics, which provides further scope for the development of a portable optical trapping system, and the potential for uncomplicated integration with other advanced microscopy systems such as an atomic force microscope (AFM) for example. For use with an AFM, the optical fibre must be inserted at an angle of 10° with respect to the sample chamber floor. However, previous literature suggests that 3D optical trapping with a single fibre inserted at an angle ≤20° is not feasible. This thesis presents the design, development, build and test of a single beam optical fibre based gradient force optical tweezers system and its associated software. An investigation is conducted to ascertain why optical trapping, using single fibre systems, cannot be achieved at sub 20° insertion angles, the result of which formed the basis of a hypothesis that explains this limitation. This finding led to the development of tapered optical fibre tips that are cable of 3D optical trapping at an insertion angle of ≤10°. The optimised optical fibre tapers are presented and their ability to trap both organic and inanimate material in 3D at an insertion angle of 10° is demonstrated. The near-horizontal insertion angle introduced a maximum trapping range (MTR). The MTR of the tips is determined empirically, evaluated against simulated data, and found to be tuneable through taper optimisation. Optical trap characterisation has been undertaken in terms of the optical trapping forces acting on the trapping subjects. Finally, the fibre tapering devices ability to reproduce identical tapers, or not, using the same device parameters, was investigated and the results in terms of geometric profile and optical performance are presented.

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