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Roger D. Kamm. Swan, Erin Eileen Leary, 1976- Massachusetts Institute of Technology. Dept. of Mechanical Engineering. Massachusetts Institute of Technology. Department of Mechanical Engineering 2010-05-25T21:11:16Z 2010-05-25T21:11:16Z 2009 2009 http://hdl.handle.net/1721.1/55258 612432705 Thesis (Sc. D.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 2009. Cataloged from PDF version of thesis. Includes bibliographical references. In a collaborative effort with the Massachusetts Eye and Ear Infirmary, Draper Laboratory is developing an implantable microfluidic drug delivery system for long-term treatment of inner ear disorders and prevention of sensorineural hearing loss. This versatile device is envisioned to deliver multiple therapies and control the sequence and rate of drug dosing. Such a system could have an immediate application in the treatment of ototoxic and inflammatory conditions affecting the inner ear, including autoimmune inner ear disease and cisplatin-induced ototoxicity. Current efforts include ongoing refinement of the design, miniaturization of components, and testing in an in vivo guinea pig model. This thesis focuses on the interactions between the device and inner ear, including the investigation of drug transport due to convective diffusion in the cochlea during drug delivery. A lumped-parameter model was implemented in an electrical circuit simulator after converting mechanical variables to their electrical analogues. A flow module described the output of the microfluidic system and used storage and loss elements to represent cochlear anatomy contributing to the flow profile. In the other portion of the model, a transport module solved for the drug concentration profile within the cochlea resulting from diffusion and convection. The model was validated using a bench-top fluorescent flow study and was compared to in vivo animal drug delivery studies. Additionally, mechanical and biological interactions related to protein and tissue biofouling were investigated. (cont.) The protein composition of the endogenous fluid of the inner ear was analyzed using a mass-spectrometry approach, and in vitro flow experiments were implemented to quantify biofouling in the device due to protein build-up and determine the impact of biofouling on microfluidic device performance. The effects of tissue build-up on the implanted system were studied through the use of histology preparation of the cochlea after long-term implantation. Further work included the fabrication and testing of microfluidic components, diaphragm-based capacitive elements and manual valves, for integration into the device. Through this research, both the impact of this device on the animal and the result of implantation on the device were more fully characterized. by Erin E. Leary Swan. Sc.D. 166 p. eng Massachusetts Institute of Technology M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission. http://dspace.mit.edu/handle/1721.1/7582 Mechanical Engineering. A fully implantable intracochlear drug delivery device : development and characterization Thesis application/pdf Publication unknown unknown <Publication xmlns="https://www.openaire.eu/cerif-profile/1.1/" id="1baf4317-82bc-4d3a-807f-ae6771e2d84d"> <Type xmlns="https://www.openaire.eu/cerif-profile/vocab/COAR_Publication_Types">http://purl.org/coar/resource_type/c_1843</Type> <Language>eng</Language> <Title>A fully implantable intracochlear drug delivery device : development and characterization</Title> <PublishedIn> <Publication> </Publication> </PublishedIn> <PublicationDate>2009</PublicationDate> <Authors> <Author> <DisplayName>Swan, Erin Eileen Leary, 1976-</DisplayName> <Affiliation> <OrgUnit> </OrgUnit> </Affiliation> </Author> </Authors> <Editors> </Editors> <Publishers> <Publisher> <DisplayName>Massachusetts Institute of Technology</DisplayName> <OrgUnit /> </Publisher> </Publishers> <License>http://dspace.mit.edu/handle/1721.1/7582</License> <Keyword>Mechanical Engineering.</Keyword> <Abstract>In a collaborative effort with the Massachusetts Eye and Ear Infirmary, Draper Laboratory is developing an implantable microfluidic drug delivery system for long-term treatment of inner ear disorders and prevention of sensorineural hearing loss. This versatile device is envisioned to deliver multiple therapies and control the sequence and rate of drug dosing. Such a system could have an immediate application in the treatment of ototoxic and inflammatory conditions affecting the inner ear, including autoimmune inner ear disease and cisplatin-induced ototoxicity. Current efforts include ongoing refinement of the design, miniaturization of components, and testing in an in vivo guinea pig model. This thesis focuses on the interactions between the device and inner ear, including the investigation of drug transport due to convective diffusion in the cochlea during drug delivery. A lumped-parameter model was implemented in an electrical circuit simulator after converting mechanical variables to their electrical analogues. A flow module described the output of the microfluidic system and used storage and loss elements to represent cochlear anatomy contributing to the flow profile. In the other portion of the model, a transport module solved for the drug concentration profile within the cochlea resulting from diffusion and convection. The model was validated using a bench-top fluorescent flow study and was compared to in vivo animal drug delivery studies. Additionally, mechanical and biological interactions related to protein and tissue biofouling were investigated.</Abstract> <Abstract>(cont.) The protein composition of the endogenous fluid of the inner ear was analyzed using a mass-spectrometry approach, and in vitro flow experiments were implemented to quantify biofouling in the device due to protein build-up and determine the impact of biofouling on microfluidic device performance. The effects of tissue build-up on the implanted system were studied through the use of histology preparation of the cochlea after long-term implantation. Further work included the fabrication and testing of microfluidic components, diaphragm-based capacitive elements and manual valves, for integration into the device. Through this research, both the impact of this device on the animal and the result of implantation on the device were more fully characterized.</Abstract> <Access xmlns="http://purl.org/coar/access_right" > </Access> </Publication>