Fischell Department of Bioengineering
Permanent URI for this communityhttp://hdl.handle.net/1903/6626
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Item Development of Fluorescent Imaging Methods and Systems to Determine Photodynamic Potential and Inform Cancer Treatment Efficacy(2022) Gaitan, Brandon; Huang, Huang-Chiao; Chen, Yu; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Photodynamic therapy (PDT) is a treatment modality that has gained rapid popularity in both research and clinical settings over the past 20 years. PDT involves harmless red/near-infrared light excitation of non-toxic photosensitizers to generate reactive molecular species (RMS) that can induce tissue damage and/or cell death. In addition, the fluorescence signal generated from the photosensitizer can also be used for optical imaging. These effects have been harnessed for image-guided treatment of cancer and other diseases. As PDT gains popularity, it is crucial to understand and monitor different factors that could impact overall treatment efficacy. These factors include, but are not limited to, the RMS yield of photosensitizers, the distribution of photosensitizers in tissue, and the PDT activation depth in tissues. Our work focused on developing methodologies and devices to characterize and improve PDT treatment. In collaboration with the FDA, we developed a cell-free assay to rapidly and more quantitatively determine the potential phototoxicity of fluorescent probes through the measurement of singlet oxygen. We also developed a method to compare the maximal PDT activation depth of FDA-approved photosensitizers (BPD and PpIX) in the brain. We found that BPD can be activated 50% deeper into brain tissues compared to PpIX at the same radiant exposure. Next, we tested the ability of a 3D imaging system, Fluorescence Laminar Optical Tomography (FLOT), to image the distribution of photosensitizers in the rodent brain. We demonstrated that FLOT could accurately map the photosensitizer distribution up to 0.5 mm in tissues. Lastly, we developed an autofluorescent-based endoscopic imaging system to measure the metabolic impact of PDT on cancer and normal tissues, finding that PDT leads to significant changes in tissue metabolism immediately after treatment. In summary, we have developed a series of systems that can aid in PDT treatment optimization in three major ways:1) rapidly quantifying the singlet oxygen production of photosensitizers, 2) more accurately measuring a photosensitizers localization and activatable depth, and 3) developing the ability to measure a tissues response to PDT in real-time.Item TOWARD PHANTOM DEVELOPMENT FOR MEDICAL IMAGING USING DIRECT LASER WRITING(2020) Lamont, Andrew Carl; Sochol, Ryan D.; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)An important tool for the performance analysis and standardization of medical imaging technologies is the phantom, which offers specifically defined properties that mimic the structural and optical characteristics of a tissue of interest. The development of phantoms for high-resolution (i.e., micro-scale) three-dimensional (3D) imaging modalities can be challenging, however, as few manufacturing techniques can capture the architectural complexity of biological tissues at such scales. Direct Laser Writing (DLW) is an evolving additive manufacturing technique with nano-scale precision that can fabricate micro and nanostructures with unparalleled geometric complexity. This dissertation outlines the unique microfluidic-based DLW strategies that have been developed for novel micro-scale phantom production. First, I will outline the development and characterization of an in situ DLW strategy used to adhere printed components to the surfaces of a microchannel. I will then explain how we have leveraged this strategy for a proof-of-concept retinal cone outer segment phantom that is laden with light-scattering Titanium (IV) Dioxide nanoparticles. This phantom has valuable implications for the performance analysis of the emerging ophthalmological modality, adaptive optics-optical coherence tomography (AO-OCT). Next, I will describe the development and characterization of a microfluidic-based multi-material DLW strategy to fabricate single components from multiple materials with minimal registration error between the materials. Ultimately, we intend to use this method to develop multi-material platforms and phantoms, including high-aspect-ratio multi-material retinal cone phantoms for AO-OCT. Finally, to demonstrate the applicability of this method for applications beyond AO-OCT, I present a preliminary phantom production strategy for the light microscopy-based modality, whole slide imaging (WSI). Specifically, we assess the DLW and light microscopy performance of dyed photoresists and offer a preliminary multi-material demonstration, which are pivotal first steps toward the creation of a first-generation multi-material WSI phantom. This work provides valuable insights and strategies that leverage microfluidic-based DLW techniques to fabricate novel micro-scale phantoms. It is anticipated that these strategies will have a lasting impact, not only on the production of phantoms for medical imaging modalities, but also for the fabrication of advanced microfluidic and multi-material microstructures for fields such as meta-materials, micro-optics, lab-on-a-chip, and organ-on-a-chip.