Brian A. Murphy

Development of a Microfluidics-Based Intracochlear Drug Delivery Device

Background: Direct delivery of drugs and other agents into the inner ear will be important for many emerging therapies, including the treatment of degenerative disorders and guiding regeneration. Methods: We have taken a microfluidics/MEMS (MicroElectroMechanical Systems) technology approach to develop a fully implantable reciprocating inner-ear drug-delivery system capable of timed and sequenced delivery of agents directly into perilymph of the cochlea. Iterations of the device were tested in guinea pigs to determine the flow characteristics required for safe and effective delivery. For these tests, we used the glutamate receptor blocker DNQX, which alters auditory nerve responses but not cochlear distortion product otoacoustic emissions. Results: We have demonstrated safe and effective delivery of agents into the scala tympani. Equilibration of the drug in the basal turn occurs rapidly (within tens of minutes) and is dependent on reciprocating flow parameters. Conclusion: We have described a prototype system for the direct delivery of drugs to the inner ear that has the potential to be a fully implantable means for safe and effective treatment of hearing loss and other diseases.

Osteomark: A surgical navigation system for oral and maxillofacial surgery

The purpose of this project was to test a surgical navigation tool designed to help execute a surgical treatment plan. It consists of an electromagnetically tracked pencil that is used to mark bone intraoperatively. The device was tested on a precision block, an ex vivo pig mandible and during performance of six endoscopic vertical ramus osteotomies on pig cadavers. The difference between actual pencil position and that displayed by the computer was measured three times each at ten 2mm holes on the block (n=30 observations) and on the ex vivo mandible (n=11 measurements). Errors between planned and actual osteotomy locations for the cadaver procedures were measured. The mean distance between known and displayed locations was 1.55 ± 0.72 mm on the precision block and 2.10 ± 0.88 mm on the pig mandible. The error measured marking the same point on the block multiple (n=5) times was 0.58 ± 0.37 mm. The mean error on the simulated osteotomies was 2.35 ± 1.35 mm. Osteomark was simple to use and permitted localisation of holes and osteotomies with acceptable accuracy. In the future, the device and algorithms will be revised to further decrease error and the system will be tested on live animals.

Electro-Optical Nanotraps for Neutral Atoms

We propose a new class of nanoscale electro-optical traps for neutral atoms. A prototype is the toroidal trap created by a suspended, charged carbon nanotube decorated with a silver nanosphere dimer. An illuminating laser field, blue detuned from an atomic resonance frequency, is strongly focused by plasmons induced in the dimer and generates both a repulsive potential barrier near the nanostructure surface and a large viscous damping force that facilitates trap loading. Atoms with velocities of several meters per second may be loaded directly into the trap via spontaneous emission of just two photons.

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.

Assessment of the OsteoMark-Navigation System for Oral and Maxillofacial Surgery.

PURPOSE To assess the accuracy of a novel navigation system for maxillofacial surgery using human cadavers and a live minipig model. MATERIALS AND METHODS We tested an electromagnetic tracking system (OsteoMark-Navigation) that uses simple sensors to determine the position and orientation of a hand-held pencil-like marking device. The device can translate 3-dimensional computed tomographic data intraoperatively to allow the surgeon to localize and draw a proposed osteotomy or the resection margins of a tumor on bone. The accuracy of the OsteoMark-Navigation system in locating and marking osteotomies and screw positions in human cadaver heads was assessed. In group 1 (n = 3, 6 sides), OsteoMark-Navigation marked osteotomies and screw positions were compared to virtual treatment plans. In group 2 (n = 3, 6 sides), marked osteotomies and screw positions for distraction osteogenesis devices were compared with those performed using fabricated guide stents. Three metrics were used to document the precision and accuracy. In group 3 (n = 1), the system was tested in a standard operating room environment. RESULTS For group 1, the mean error between the points was 0.7 mm (horizontal) and 1.7 mm (vertical). Compared with the posterior and inferior mandibular border, the mean error was 1.2 and 1.7 mm, respectively. For group 2, the mean discrepancy between the points marked using the OsteoMark-Navigation system and the surgical guides was 1.9 mm (range 0 to 4.1). The system maintained accuracy on a live minipig in a standard operating room environment. CONCLUSION Based on this research OsteoMark-Navigation is a potentially powerful tool for clinical use in maxillofacial surgery. It has accuracy and precision comparable to that of existing clinical applications.

Skeletal and Soft Tissue Response to Automated, Continuous, Curvilinear Distraction Osteogenesis

PURPOSE To document the bone formation and soft tissue changes in response to automated, continuous, curvilinear distraction osteogenesis (DO) at rates greater than 1 mm/day in a minipig model. MATERIALS AND METHODS Two groups of Yucatan minipigs underwent automated, continuous, curvilinear DO of the right mandible: group A, 1.5 mm/day (n = 5); and group B, 3.0 mm/day (n = 5). Each minipig underwent 12 mm of distraction followed by 24 days of fixation. The distracted and contralateral mandibles were harvested at the end of fixation. The percentage of surface area (PSA) of the regenerate occupied by bone, fibrous tissue, cartilage, and hematoma was determined using computerized histomorphometric analysis. The control groups consisted of DO wounds distracted discontinuously at 1 mm/day and the nonoperated contralateral mandible. The ipsilateral and contralateral digastric muscles were harvested and stained for proliferating cell nuclear antigen (PCNA), myogenic differentiation-1 (MyoD), and paired Box 7 protein (PAX7). RESULTS All 10 minipigs completed the distraction and fixation period. The PSA occupied by bone was similar for groups A (PSA 64.36% ± 5.87%) and B (PSA 63.83% ± 3.37%) and the control group (1 mm/day; PSA 64.89% ± 0.56%) but was less than that on the nonoperated side (PSA 84.67% ± 0.86%). The PSA occupied by cartilage and hematoma in all groups was minimal (<1.1%). The digastric muscles had no abnormal tissue or inflammation, and PAX7, MyoD, and PCNA expression had returned to the baseline levels. CONCLUSIONS The results of the present study indicate that bone formation in response to automated, continuous, and curvilinear DO at a rate of 1.5 and 3.0 mm/day is nearly identical to that with discontinuous DO at 1 mm/day. In addition, no deleterious effects were found on the digastric muscles.

Bilateral Continuous Automated Distraction Osteogenesis: Proof of Principle.

AbstractThe purpose of this study was to demonstrate that automated, continuous, curvilinear distraction osteogenesis (DO) in a minipig model is effective when performed bilaterally, at rates up to 3 mm/day, to achieve clinically relevant lengthening.A Yucatan minipig in the mixed dentition phase underwent bilaterally, at a continuous DO at a rate of 2 mm/day at the center of rotation; 1.0 and 3.0 mm/day at the superior and inferior regions, respectively. The distraction period was 13 days with no latency period. Vector and rate of distraction were remotely monitored without radiographs, using the device sensor. After fixation and euthanasia, the mandible and digastric muscles were harvested. The ex vivo appearance, stability, and radiodensity of the regenerate were evaluated using a semiquantitative scale. Percent surface area (PSA) occupied by bone, fibrous tissue, cartilage, and hematoma were calculated using histomorphometrics. The effects of DO on the digastric muscles and mandibular condyles were assessed via microscopy, and degenerative changes were quantified.The animal was distracted to 21 mm and 24 mm on the right and left sides, respectively. Clinical appearance, stability, and radiodensity were scored as “3” bilaterally indicating osseous union. The total PSA occupied by bone (right = 75.53 ± 2.19%; left PSA = 73.11 ± 2.18%) approached that of an unoperated mandible (84.67 ± 0.86%). Digastric muscles and condyles showed negligible degenerative or abnormal histologic changes.This proof of principle study is the first report of osseous healing with no ill-effect on associated soft tissue and the mandibular condyle using bilateral, automated, continuous, and curvilinear DO at rates up to 3 mm/day. The model approximates potential human application of continuous automated distraction with a semiburied device.