Optofluidic Microscopy: Technology Development and Its Applications in Biology

The Optofluidic Microscope (OFM) is a new imaging platform based upon nanoapertures that are fabricated on planar metallic film, whilst microfluidic delivery technology is used to transport the objects-of-interest. The planar nature of OFM makes it ideal to integrate with other micro total analysis systems, such as cell sorters or cell culturing chambers. Furthermore, a variety of imaging functionalities, such as differential phase contrast, fluorescence, and Raman spectroscopy can potentially fit into a single OFM device. This thesis reports on the early technology development of Optofluidic Microscopy. I have built a variety of off-chip prototypes of OFM that all possess different functionalities. These OFM prototypes include 1D array OFM, hydraulically pumped OFM, 2D nanoaperture grid OFM, super high-resolution OFM, OFM coupled with optical tweezer actuation, fluorescent OFM, electrokinetic enabled OFM, etc. I applied the first OFM prototype in imaging Caenorhabditis elegans (C. elegans) larvae and characterizing different genotypes. Later on, the microscopy properties of OFM, such as the optical resolution and the depth of field, were thoroughly investigated both experimentally and theoretically. More recently, I successfully combined optical tweezers with a grid-based OFM prototype, which was then used in high-resolution imaging of microspheres and a few biological samples. In addition, preliminary results on fluorescence OFM imaging were also demonstrated. I trust that these functionalities, after being demonstrated off-chip, can be readily fabricated and then assembled as a complete on-chip OFM. It will eventually enable a real "microscale microscope on a chip".