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A fully implantable intracochlear drug delivery device : development and characterization

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

Fabrication methods and performance of low-permeability microfluidic components for a miniaturized wearable drug delivery system

In this paper, we describe low-permeability components of a microfluidic drug delivery system fabricated with versatile micromilling and lamination techniques. The fabrication process uses laminate sheets which are machined using XY milling tables commonly used in the printed-circuit industry. This adaptable platform for polymer microfluidics readily accommodates integration with silicon-based sensors, printed-circuit, and surface-mount technologies. We have used these methods to build components used in a wearable liquid-drug delivery system for in vivo studies. The design, fabrication, and performance of membrane-based fluidic capacitors and manual screw valves provide detailed examples of the capability and limitations of the fabrication method. We demonstrate fluidic capacitances ranging from 0.015 to 0.15 muL/kPa, screw valves with on/off flow ratios greater than 38000, and a 45times reduction in the aqueous fluid loss rate to the ambient due to permeation through a silicone diaphragm layer.National Institute of Deafness and other Communication Disorders (U.S.) (NIDCD) (Grant 5 R01 DC 006848-02

Mastoid Cavity Dimensions and Shape: Method of Measurement and Virtual Fitting of Implantable Devices

Temporal bone implants can be used to electrically stimulate the auditory nerve, to amplify sound, to deliver drugs to the inner ear and potentially for other future applications. The implants require storage space and access to the middle or inner ears. The most acceptable space is the cavity created by a canal wall up mastoidectomy. Detailed knowledge of the available space for implantation and pathways to access the middle and inner ears is necessary for the design of implants and successful implantation. Based on temporal bone CT scans a method for three-dimensional reconstruction of a virtual canal wall up mastoidectomy space is described. Using Amira® software the area to be removed during such surgery is marked on axial CT slices, and a three-dimensional model of that space is created. The average volume of 31 reconstructed models is 12.6 cm3 with standard deviation of 3.69 cm3, ranging from 7.97 to 23.25 cm3. Critical distances were measured directly from the model and their averages were calculated: height 3.69 cm, depth 2.43 cm, length above the external auditory canal (EAC) 4.45 cm and length posterior to EAC 3.16 cm. These linear measurements did not correlate well with volume measurements. The shape of the models was variable to a significant extent making the prediction of successful implantation for a given design based on linear and volumetric measurement unreliable. Hence, to assure successful implantation, preoperative assessment should include a virtual fitting of an implant into the intended storage space. The above-mentioned three-dimensional models were exported from Amira to a Solidworks application where virtual fitting was performed. Our results are compared to other temporal bone implant virtual fitting studies. Virtual fitting has been suggested for other human applications