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Abstract

Visualization of organs and cells in the interior of living beings is a challenging task due to the light absorption and multiple light scattering occurring in biological tissue that prevents the di-rect transmission of images. A standard visualization approach is based on the use of endo-scopes which is accomplished through apertures in the body. Since their invention, the light transmission capability of optical fibers has enabled fiber optic based endoscopy with devices based on bundles of optical fibers that can directly relay images. Due to their small diameter, fiber optic endoscopes are standard in minimally invasive applications either with a white light illumination or as a fluorescent imaging device. The principle behind fluorescent endoscopy consists on the scanning of light intensity over a fluorescent sample, which is achieved by se-quential illumination of each one of the fiber bundles or by mechanical scanning of a single-mode double-cladding fiber. Collecting the fluorescent signal through the light guiding medium, an image can be reconstructed. The main drawback of fiber bundle endoscopes is the pixelated limited resolution given by the presence of thousands of cores that conform the bundle. In the double cladding fiber endoscopes, there is a limit to the miniaturization of the endoscope due to the requirement of mechanical elements at the tip of the fiber to scan the illumination over the sample. In this thesis, methods for focusing and digital scanning of optical light pulses through multimode optical fibers without any distal mechanical element are developed. Such techniques are based on spatial light modulation. Spatial phase modulation allows the control of light propagation in scrambling media, as in a multimode fiber, enabling the generation of intensity light foci or arbitrary intensity profiles. The high intensity of the transmitted pulses permits multi-photon imaging through multimode optical fibers, resulting in imaging probes of higher resolution than in the case of fiber bundles. We demonstrate in a working prototype that this approach provides all the advantages of multi-photon microscopy at the tip of an ultra-thin probe, such as a reduced photo bleaching of the sample, optical sectioning and enhanced image contrast. The developed methods can also be employed for material processing that requires high in-tensity light pulses. In specific, we demonstrate additive manufacturing, also known as 3D printing, at the tip of an ultra-thin needle. The working principle is based on two-photon polymerization, which is accomplished by scanning intense light pulses on a photosensitive material that hardens when exposed to light. All other additive manufacturing methods require very large nozzles or components in close proximity to the structure that they build, up to now. With an ultra-thin 3D printing probe we enable micro-fabrication through very small apertures, in places of difficult access or in the interior of living beings. We call it, endofabrication.

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