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Lensfree Holographic On-Chip Imaging and Three-Dimensional Tracking

Abstract

Despite the rapid progress in optical imaging, most of the advanced microscopy modalities still require complex and costly set-ups that unfortunately limit their use beyond well-equipped laboratories. To provide affordable and easy-to-use microscopes for resource-limited settings, I developed a holographic on-chip imaging technology that utilizes cost-effective and compact optoelectronic components to enable the digital reconstruction of microscopic amplitude and phase images for biological cells with sub-micron resolution over a field-of-view of >24 mm^2. Without the need for any lenses, bulky optical components or coherent sources such as lasers, this partially-coherent computational imaging modality can automatically analyze thousands of cells in parallel for their cell type, concentration, structure, and dynamics. As being compact, light-weight, cost-effective, high-throughput, and highly-sensitive, this lensfree imaging technology is especially suitable for field diagnostics applications involving global health problems such as HIV, malaria, infectious diarrhea, or male infertility.

Based on this lensfree imaging technology, I also devised a dual-angle dual-color holographic scheme to achieve sub-micron accuracy and sub-12-minisecond resolution for three-dimensional tracking of >1,500 human sperms in a field-of-view of >17 mm^2 and a depth-of-field of >0.5 mm. The high accuracy and high throughput of this lensfree imaging platform enabled the first observation of human sperms' tight (1-6um wide), fast (3-20 r/sec), and rare (4- 5%) helical trajectories, which surprisingly are dominated by right-handed ones (~90%) and can be significantly suppressed by seminal plasma. Such a high-throughput 3D tracking platform can also be a valuable tool for observing the statistical swimming patterns of various microorganisms, leading to new insights in their 3D dynamics.

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