Multi Modal Mobile Microscopy For Visualization Of Biological Agents

"Biological and biomedical research is often contingent upon microscopy techniques for observation and studying of biological features and processes, and subsequent analysis. For many applications, it is necessary that the selected imaging system provide high spatial resolution and large field-of-view, in order to be able to visualize individual biological structures or agents within the sample, while capturing an area large enough, where meaningful analysis, such as particle tracking, could be performed within a single frame. Various lens-based and lens-free imaging platforms, each with their own sets of advantages and disadvantages, offer different imaging modalities suitable for different specimens and applications, but they all suffer from a main limitation: the trade-off between spatial resolution and field-of-view. This competition cannot be eliminated but could be optimized, based on the chosen imaging system specifications. This work addresses the restrictive trade-off, and introduces a mobile phone-based illumination-imaging platform that maximizes the attainable field-of-view at high resolution, and expands the use of phone screen illumination to a lens-free platform.The thesis transitions from a broad introduction to microscopy in the biological and biomedical fields into a general protocol for identification of imaging system requirements for a targeted application, modelled after a specific example for imaging of a biocomputational microfluidic device that utilizes microorganisms as exploratory problem-solving agents. The following chapters introduce the aforementioned dual-phone system, which uses a phone camera with an external lens for imaging, to achieve a spatial resolution of at least 2 [mu]m, and a large field-of-view of 3.6 × 2.7mm. For illumination, it uses the screen of another phone to project multi-modal illumination patterns, including but not limited to bright-field, dark-field, Rheinberg illumination, point illumination, fluorescence, and differential phase contrast. Put together, this illumination-imaging system forms a novel, inexpensive, compact, portable, and versatile microscope for use in low-resource environments. It could be used in research, medical, educational, and environmental settings for both qualitative and quantitative imaging of cells, microorganisms, and other micron-sized objects. The adaptability of phone screen illumination allows it to be further integrated into lens-free imaging platforms, as well as conventional microscopes"--