Development of a wireless platform to generate nitric oxide for implanted biomedical devices

The perturbation of homeostatic mechanisms caused by interactions between any indwelling biomedical device and the biological medium into which it is implanted initiates a dynamic wound healing response from the host which can be rigorous and ongoing. The typical result of this response is a severe degradation in the performance and safety of the device, often to the extent of precluding their clinical use. Nitric oxide (NO) is an endogenously produced biomolecule capable of mediating many of the cellular processes leveraged against implanted devices. The in vivo performance of indwelling devices prepared with NO release coatings has recently been evaluated with very encouraging results. This work developed a platform capable of both generating programmable fluxes of NO and directly evaluating the performance of indwelling probes under different profiles of NO generation. This platform can be used to improve the efficacy of NO release materials in mitigating the host response.

DESIGN AND APPLICATION OF WIRELESS PASSIVE MAGNETOELASTIC RESONANCE AND MAGNETOHARMONIC FORCE SENSORS

The objective of the work described in this dissertation is the development of new wireless passive force monitoring platforms for applications in the medical field, specifically monitoring lower limb prosthetics. The developed sensors consist of stress sensitive, magnetically soft amorphous metallic glass materials. The first technology is based on magnetoelastic resonance. Specifically, when exposed to an AC excitation field along with a constant DC bias field, the magnetoelastic material mechanically vibrates, and may reaches resonance if the field frequency matches the mechanical resonant frequency of the material. The presented work illustrates that an applied loading pins portions of the strip, effectively decreasing the strip length, which results in an increase in the frequency of the resonance. The developed technology is deployed in a prototype lower limb prosthetic sleeve for monitoring forces experienced by the distal end of the residuum. This work also reports on the development of a magnetoharmonic force sensor comprised of the same material. According to the Villari effect, an applied loading to the material results in a change in the permeability of the magnetic sensor which is visualized as an increase in the higher-order harmonic fields of the material. Specifically, by applying a constant low frequency AC field and sweeping the applied DC biasing field, the higher-order harmonic components of the magnetic response can be visualized. This sensor technology was also instrumented onto a lower limb prosthetic for proof of deployment; however, the magnetoharmonic sensor illustrated complications with sensor positioning and a necessity to tailor the interface mechanics between the sensing material and the surface being monitored. The novelty of these two technologies is in their wireless passive nature which allows for long term monitoring over the life time of a given device. Additionally, the developed technologies are low cost. Recommendations for future works include improving the system for real-time monitoring, useful for data collection outside of a clinical setting.

Wireless and passive pressure sensor system based on the magnetic higher-order harmonic field

The goal of this work is to develop a magnetic-based passive and wireless pressure sensor for use in biomedical applications. Structurally, the pressure sensor, referred to as the magneto-harmonic pressure sensor, is composed of two magnetic elements: a magnetically-soft material acts as a sensing element, and a magnetically hard material acts as a biasing element. Both elements are embedded within a rigid sensor body and sealed with an elastomer pressure membrane. Upon excitation of an externally applied AC magnetic field, the sensing element is capable of producing higher-order magnetic signature that is able to be remotely detected with an external receiving coil. When exposed to environment with changing ambient pressure, the elastomer pressure membrane of pressure sensor is deflected depending on the surrounding pressure. The deflection of elastomer membrane changes the separation distance between the sensing and biasing elements. As a result, the higher-order harmonic signal emitted by the magnetically-soft sensing element is shifted, allowing detection of pressure change by determining the extent of the harmonic shifting. The passive and wireless nature of the sensor is enabled with an external excitation and receiving system consisting of an excitation coil and a receiving coil. These unique characteristics made the sensor suitable to be used for continuous and long-term pressure monitoring, particularly useful for biomedical applications which often require frequent surveillance. In this work, abdominal aortic aneurysm is selected as the disease model for evaluation the performance of pressure sensor and system. Animal model, with subcutaneous sensor implantation in mice, was conducted to demonstrate the efficacy and feasibility of pressure sensor in biological environment.

A BACKING DEVICE BASED ON AN EMBEDDED STIFFENER AND RETRACTABLE INSERTION TOOL FOR THIN-FILM COCHLEAR ARRAYS

Intracochlear trauma from surgical insertion of bulky electrode arrays and inadequate pitch perception are areas of concern with current hand-assembled commercial cochlear implants. Parylene thin-film arrays with higher electrode densities and lower profiles are a potential solution, but lack rigidity and hence depend on manually fabricated permanently attached polyethylene terephthalate (PET) tubing based bulky backing devices. As a solution, we investigated a new backing device with two sub-systems. The first sub-system is a thin poly(lactic acid) (PLA) stiffener that will be embedded in the parylene array. The second sub-system is an attaching and detaching mechanism, utilizing a poly(N-vinylpyrrolidone)-block-poly(d,l-lactide) (PVP-b-PDLLA) copolymer-based biodegradable and water soluble adhesive, that will help to retract the PET insertion tool after implantation. As a proof-of-concept of sub-system one, a microfabrication process for patterning PLA stiffeners embedded in parylene has been developed. Conventional hotembossing, mechanical micromachining, and standard cleanroom processes were integrated for patterning fully released and discrete stiffeners coated with parylene. The released embedded stiffeners were thermoformed to demonstrate that imparting perimodiolar shapes to stiffener-embedded arrays will be possible. The developed process when integrated with the array fabrication process will allow fabrication of stiffener-embedded arrays in a single process. As a proof-of-concept of sub-system two, the feasibility of the attaching and detaching mechanism was demonstrated by adhering 1x and 1.5x scale PET tube-based insertion tools and PLA stiffeners embedded in parylene using the copolymer adhesive. The attached devices survived qualitative adhesion tests, thermoforming, and flexing. The viability of the detaching mechanism was tested by aging the assemblies in-vitro in phosphate buffer solution. The average detachment times, 2.6 minutes and 10 minutes for 1x and 1.5x scale devices respectively, were found to be clinically relevant with respect to the reported array insertion times during surgical implantation. Eventually, the stiffener-embedded arrays would not need to be permanently attached to current insertion tools which are left behind after implantation and congest the cochlear scala tympani chamber. Finally, a simulation-based approach for accelerated failure analysis of PLA stiffeners and characterization of PVP-b-PDLLA copolymer adhesive has been explored. The residual functional life of embedded PLA stiffeners exposed to body-fluid and thereby subjected to degradation and erosion has been estimated by simulating PLA stiffeners with different parylene coating failure types and different PLA types for a given parylene coating failure type. For characterizing the PVP-b-PDLLA copolymer adhesive, several formulations of the copolymer adhesive were simulated and compared based on the insertion tool detachment times that were predicted from the dissolution, degradation, and erosion behavior of the simulated adhesive formulations. Results indicate that the simulation-based approaches could be used to reduce the total number of time consuming and expensive in-vitro tests that must be conducted.