Doctor of Philosophy (Ph.D.)
Degree Granting Department
Christopher L. Passaglia, Ph.D.
Wilfrido Moreno, Ph.D.
Paris Wiley, Ph.D.
Jing Wang, Ph.D.
Radouil Tzekov, Ph.D.
Animal Models, Biomedical Devices, Control Systems, Glaucoma, Intraocular Pressure, Wireless Power
Animal models of ocular hypertension are important for glaucoma research but come with experimental costs. Available methods of intraocular pressure (IOP) elevation are not always successful, the amplitude and time course of IOP changes are unpredictable and irreversible, and IOP measurement by tonometry is laborious. This dissertation focuses on the development and implementation of two novel systems for monitoring and controlling IOP without these limitations. The first device consists of a cannula implanted in the anterior chamber of the eye, a pressure sensor that continually measures IOP, and a bidirectional pump driven by control circuitry that can infuse or withdraw fluid to hold IOP at user-desired levels. A portable version was developed for tethered use on rats. The system was fully characterized and deemed ready for cage- or bench-side applications. The results lay the foundation for an implantable version that would give glaucoma researchers unparalleled knowledge and control of IOP in rats and potentially larger animals.
Moreover, a novel mathematical technique was developed to efficiently analyze IOP records obtained using the pressure controlling device. The algorithm successfully yields the value of several parameters that influence ocular physiology and are commonly linked to glaucoma development. This unique methodology uses information regarding the amount of volume necessary to maintain IOP at different levels to quantify the outflow facility of perfused eyes. The use of this technology largely simplifies the investigator’s experimental set-up and cuts procedural times in half.
The second device is an implantable pressure sensor for continuously monitoring IOP. The miniature system is equipped with pressure and temperature transducers, on-board amplifiers and a powerful microcontroller that ensure data quality. The sensor is able to obtain measurements with twice the accuracy and precision of any other IOP sensor used to date, avoid electronic drifts commonly seen in commercial sensing devices, and can potentially be used in a variety of animal models. The sensor was characterized and tested in alert rats for weeks on end. Data obtained with this device showed the presence of previously reported circadian rhythms, with IOP significantly increasing during nocturnal cycles. This technology provides researchers with an unprecedented tool to analyze IOP dynamics over time. The characterization of the amplitude, period and phase of the IOP profiles of normal and glaucomatous eyes may help establish a definitive correlation between ocular hypertension and glaucoma progression.
While implantable systems provide investigators with essential physiological data, their implementation can be difficult. Challenges such as reduced operational lifetimes and limited data acquisition capabilities are commonly faced by most bio-devices. These limitations are frequently linked to small battery capacities, however the implementation of bigger batteries is not usually viable due to size requirements. Energy harvesting technologies have surfaced in recent years in an attempt to replace battery applications; however, most technologies provide low power densities and cannot deliver continuous telemetric operation. An innovative wireless powering system was developed to overcome these limitations. The technology uses radio frequency (RF) energy transfer to continuously harvest high energy levels. Taking advantage of the controlled environment under which most research animals are housed, RF transmitters are placed around the cage to form strong, omnidirectional electric fields. An especial antenna was designed to be worn by the animal and collect large energy levels, irrespective of animal movements and positioning. The system was tested on the implantable IOP sensor for weeks, providing robust performances and allowing the sensor to collect data continuously with high precision. The device consistently generated power densities much greater than those required by the sensor. The surplus of energy could be used to operate multiple sensors simultaneously, greatly increasing the investigator’s leverage. The technology is easily adaptable to other bio-sensors and has the potential to revolutionize the biomedical field.
Scholar Commons Citation
Bello, Simon Antonio, "Intraocular Pressure Sensing and Control for Glaucoma Research" (2016). Graduate Theses and Dissertations.
Available for download on Wednesday, November 15, 2017