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Lensfree Optical Tomography for High-Throughput 3D Imaging on a Chip


Light microscopes provide us with the key to observe objects that are orders of magnitude smaller than what the unaided eye can see. Therefore, microscopy has been the cornerstone of science and medicine for centuries. Recently, optical microscopy has seen a growing interest in developing three-dimensional (3D) imaging techniques that enable sectional imaging of biological specimen. These imaging techniques, however, are generally quite complex, bulky and expensive in addition to having a limited field-of-view due to the need for lens-based optical magnification.

In this thesis, I demonstrate lensfree optical tomography (LOT) as a new 3D imaging modality that offers high-throughput imaging in a compact and simple architecture. This technique is fundamentally based on lensfree on-chip microscopy, where computation is used to replace bulky components of traditional imaging devices to reduce size, cost and complexity while at the same time significantly enlarging the imaging field-of-view. In LOT, in-line holograms of objects at different illumination angles are recorded using a digital sensor-array, which enables computing pixel super-resolved tomographic images of the specimen. LOT offers <350nm lateral resolution and ~2 μm axial resolution over large imaging volumes of e.g., 15-100 mm3, and can be assembled in lightweight and compact architectures. The imaging performance of LOT is quantified using spherical microparticles as well as using biological specimen such as C. elegans worms and H. Nana eggs.

To demonstrate that LOT could be useful for imaging applications in resource-limited settings, I also devised a field-portable, USB-powered compact and lightweight tomographic microscope that only weighs ~110 grams. This portable device can fit in a volume of 96 mm x 89 mm x 40 mm. In addition, to demonstrate the integration of LOT in microfluidic platforms and lab-on-a-chip systems, I also introduce an optofluidic tomography platform. In this system, the sample is delivered to the tomographic imager through a microfluidic chamber, which is mounted on the sensor chip. Tomographic data acquisition is performed while the objects are electrokinetically driven through the chamber.

Probing a large volume at micrometer-scale 3D spatial resolution, LOT could provide a powerful imaging tool for high-throughput imaging applications in e.g., cell and developmental biology, as well as for future lab-on-chip platforms.

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