Fischell Department of Bioengineering
Permanent URI for this communityhttp://hdl.handle.net/1903/6626
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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.Item UTILIZATION OF PNEUMATIC ARTIFICIAL MUSCLES TO STUDY EFFECTS OF LOAD HISTORY ON THE INTERVERTEBRAL DISC(2015) Russell, Joseph; Hsieh, Adam H; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Degenerative disc disease is commonly linked with low back pain, a major musculoskeletal disorder contributing to an annual socioeconomic impact of over $100 billion. The intervertebral disc (IVD) plays a critical role in spinal load bearing and many of the mechanisms of its degeneration are still unknown. This study focused on eliciting gene expression changes of the Nucleus Pulposus (NP), the inner region of the IVD critical to load support using an in vivo rat model. First, pneumatic artificial muscles (PAMs) were calibrated and integrated into a small loading device as an actuation mechanism. Next, various load histories were then applied on IVDs and gene expression was determined by qRT-PCR. Results show that discs with increased intradiscal pressure led increased expression of genes common to the NP. This study contributes to the better understanding of how load history alters IVD health and validates a device for future long term studies.Item Thermoplastic microfluidic technologies for portable and disposable bioanalytical and diagnostic platforms(2015) Rahmanian, Omid David; DeVoe, Don L; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Portable and cost-effective medical diagnostic technologies that require minimal external infrastructure for their operation are highly desirable for on-field military operations, defense against acts of bioterrorism, and infectious disease screening in resource-limited environments. Miniaturized Total Analysis Systems (µTAS) have the potential to fulfill this un-met need via low-cost, portable, and disposable point-of-care (POC) diagnostic devices. Inherent advantages of µTAS systems can be utilized to transform diagnostic technologies that currently require significant investment in centralized laboratories and highly trained personnel into automated, integrated, and miniaturized platforms. This dissertation addresses the development of microfabrication techniques and resulting component technologies that are realized in low-cost thermoplastic substrates. A thermoplastic microfabrication technique termed orogenic microfabrication, based on a non-reversible solvent-assisted swelling mechanism, is developed to provide unique capabilities for microscale and nanoscale patterning in rigid thermoplastics with minimal infrastructure. Orogenic microfabrication is compatible with multiple masking techniques including photolithography, chemical surface modification, contact and noncontact spotting, and inkjet deposition techniques, with each masking method offering unique influence on resulting orogenic structures that can be applied to microfluidic and µTAS systems. Direct ink masking is further explored as a low-cost rapid prototyping tool for fabrication of simple microfluidic devices where channel formation and bonding are combined into a single step, resulting in fully enclosed microfluidic channels within 30 minutes. Chemical surface passivation by UV-ozone treatment is utilized in combination with orogenic swelling and thermocompression bonding to develop single-use burst valves with tunable burst pressures. In addition to assisting in on-chip fluid manipulation, the normally closed burst valves enable on-chip reagent packaging and hermetic sealing of bioactive material in lyophilized format, and can be used for delivery of stored reagents for a range of disposable point-of-care assays. On-chip integrated micropumps are also developed, using simple fabrication process compatible with conventional thermoplastic fabrication techniques such as direct micromilling or injection molding. Direct displacement of liquid reagents using screw-assisted pumping can be operated either automatically or manually, with on-demand delivery of liquid reagents in a wide range of flow rates typically used in microfluidic applications. Collectively, the technologies developed in this dissertation may be applied to the future development of simple, disposable, and portable diagnostic devices that have the potential to be operated without off-chip instrumentation. On-chip storage of buffers and reagents in either dry or liquid format, and on-demand delivery of liquid reagents is packaged in a miniaturized, portable, and automated platform that can be operated in resource-constrained settings by practitioners with minimal expertise.Item CMOS SINGLE-PHOTON AVALANCHE DIODES AND MICROMACHINED OPTICAL FILTERS FOR INTEGRATED FLUORESCENCE SENSING(2012) Dandin, Marc Peralte; Abshire, Pamela A; Smela, Elisabeth; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)This dissertation presents a body of work that addresses the two most pressing challenges in the field of integrated fluorescence sensing, namely, the design of integrated optical sensors and the fabrication of high-rejection micro-scale optical filters. Two novel enabling technologies were introduced. They are: the perimeter-gated single-photon avalanche diode (PGSPAD), for on-chip photon counting, and the benzotriazole (BTA)-doped thin-film polymer filter, for on-chip ultraviolet light rejection. Experimental results revealed that the PGSPAD front-end, fabricated in a 0.5 μm standard mixed-signal CMOS process, had the capability of counting photons in the MHz regime. In addition, it was found that a perimeter gate, a structural feature used to suppress edge breakdown in the diode, also maximized the signal-to-noise-ratio in the high-count rate regime whereas it maximized sensitivity at low count rates. On the other hand, BTA-doped filters were demonstrated utilizing three commonly used polymers as hosts. The filters were patternable, utilizing the same procedures traditionally used to pattern the undoped polymer hosts, a key advantage for integration into microsystems. Filter performance was analyzed using a set of metrics developed for optoelectronic characterization of integrated fluorescence sensors; high rejection levels (nearing -40 dB) of UV light were observed in films of only 5 μm in thickness. Ultimately, BTA-doped filters were integrated into a portable sensor, and their use was demonstrated in two types of bioassays.