Microfabricated Implantable Parylene-Based Wireless Passive Intraocular Pressure Sensors

This paper presents an implantable parylene-based wireless pressure sensor for biomedical pressure sensing applications specifically designed for continuous intraocular pressure (IOP) monitoring in glaucoma patients. It has an electrical LC tank resonant circuit formed by an integrated capacitor and an inductor coil to facilitate passive wireless sensing using an external interrogating coil connected to a readout unit. Two surface-micromachined sensor designs incorporating variable capacitor and variable capacitor/inductor resonant circuits have been implemented to realize the pressure-sensitive components. The sensor is monolithically microfabricated by exploiting parylene as a biocompatible structural material in a suitable form factor for minimally invasive intraocular implantation. Pressure responses of the microsensor have been characterized to demonstrate its high pressure sensitivity (> 7000 ppm/mmHg) in both sensor designs, which confirms the feasibility of pressure sensing with smaller than 1 mmHg of resolution for practical biomedical applications. A six-month animal study verifies the in vivo bioefficacy and biostability of the implant in the intraocular environment with no surgical or postoperative complications. Preliminary ex vivo experimental results verify the IOP sensing feasibility of such device. This sensor will ultimately be implanted at the pars plana or on the iris of the eye to fulfill continuous, convenient, direct, and faithful IOP monitoring

Wireless Intraocular Pressure Sensing Using Microfabricated Minimally Invasive Flexible-Coiled LC Sensor Implant

This paper presents an implant-based wireless pressure sensing paradigm for long-range continuous intraocular pressure (IOP) monitoring of glaucoma patients. An implantable parylene-based pressure sensor has been developed, featuring an electrical LC-tank resonant circuit for passive wireless sensing without power consumption on the implanted site. The sensor is microfabricated with the use of parylene C (poly-chlorop- xylylene) to create a flexible coil substrate that can be folded for smaller physical form factor so as to achieve minimally invasive implantation, while stretched back without damage for enhanced inductive sensor–reader coil coupling so as to achieve strong sensing signal. A data-processed external readout method has also been developed to support pressure measurements. By incorporating the LC sensor and the readout method, wireless pressure sensing with 1-mmHg resolution in longer than 2-cm distance is successfully demonstrated. Other than extensive on-bench characterization, device testing through six-month chronic in vivo and acute ex vivo animal studies has verified the feasibility and efficacy of the sensor implant in the surgical aspect, including robust fixation and long-term biocompatibility in the intraocular environment. With meeting specifications of practical wireless pressure sensing and further reader development, this sensing methodology is promising for continuous, convenient, direct, and faithful IOP monitoring

Implantable parylene-based wireless intraocular pressure sensor

This paper presents a novel implantable, wireless, passive pressure sensor for ophthalmic applications. Two sensor designs incorporating surface-micromachined variable capacitor and variable capacitor/inductor are implemented to realize the pressure sensitive components. The sensor is monolithically microfabricated using parylene as a biocompatible structural material in a suitable form factor for increased ease of intraocular implantation. Pressure responses of the microsensor are characterized on-chip to demonstrate its high pressure sensitivity (> 7000 ppm/mmHg) with mmHg level resolution. An in vivo animal study verifies the biostability of the sensor implant in the intraocular environment after more than 150 days. This sensor will ultimately be implanted at the pars plana or iris of the eye to fulfill continuous intraocular pressure (IOP) monitoring in glaucoma patients

Q-enhanced fold-and-bond MEMS inductors

This work presents a novel coil fabrication technology to enhance quality factor (Q factor) of microfabricated inductors for implanted medical wireless sensing and data/power transfer applications. Using parylene as a flexible thin-film device substrate, a post-microfabrication substrate folding-and-bonding method is developed to effectively increase the metal thickness of the surface-micromachined inductors, resulting in their lower self-resistance so their higher quality factor. One-fold-and-bond coils are successfully demonstrated as an example to verify the feasibility of the fabrication technology with measurement results in good agreements with device simulation. Depending on target specifications, multiple substrate folding-and-bonding can be extensively implemented to facilitate further improved electrical characteristics of the coils from single fabrication batch. Such Q-enhanced inductors can be broadly utilized with great potentials in flexible integrated wireless devices/systems for intraocular prostheses and other biomedical implants

Generalized Parity-Time Symmetry Condition for Enhanced Sensor Telemetry

Wireless sensors based on micro-machined tunable resonators are important in a variety of applications, ranging from medical diagnosis to industrial and environmental monitoring.The sensitivity of these devices is, however, often limited by their low quality (Q) factor.Here, we introduce the concept of isospectral party time reciprocal scaling (PTX) symmetry and show that it can be used to build a new family of radiofrequency wireless microsensors exhibiting ultrasensitive responses and ultrahigh resolution, which are well beyond the limitations of conventional passive sensors. We show theoretically, and demonstrate experimentally using microelectromechanical based wireless pressure sensors, that PTXsymmetric electronic systems share the same eigenfrequencies as their parity time (PT)-symmetric counterparts, but crucially have different circuit profiles and eigenmodes. This simplifies the electronic circuit design and enables further enhancements to the extrinsic Q factor of the sensors

Wafer-Level Parylene Packaging With Integrated RF Electronics for Wireless Retinal Prostheses

This paper presents an embedded chip integration technology that incorporates silicon housings and flexible Parylene-based microelectromechanical systems (MEMS) devices. Accelerated-lifetime soak testing is performed in saline at elevated temperatures to study the packaging performance of Parylene C thin films. Experimental results show that the silicon chip under test is well protected by Parylene, and the lifetime of Parylenecoated metal at body temperature (37°C) is more than 60 years, indicating that Parylene C is an excellent structural and packaging material for biomedical applications. To demonstrate the proposed packaging technology, a flexible MEMS radio-frequency (RF) coil has been integrated with an RF identification (RFID) circuit die. The coil has an inductance of 16 μH with two layers of metal completely encapsulated in Parylene C, which is microfabricated using a Parylene–metal–Parylene thin-film technology. The chip is a commercially available read-only RFID chip with a typical operating frequency of 125 kHz. The functionality of the embedded chip has been tested using an RFID reader module in both air and saline, demonstrating successful power and data transmission through the MEMS coil

Wearable smart sensor systems integrated on soft contact lenses for wireless ocular diagnostics

Wearable contact lenses which can monitor physiological parameters have attracted substantial interests due to the capability of direct detection of biomarkers contained in body fluids. However, previously reported contact lens sensors can only monitor a single analyte at a time. Furthermore, such ocular contact lenses generally obstruct the field of vision of the subject. Here, we developed a multifunctional contact lens sensor that alleviates some of these limitations since it was developed on an actual ocular contact lens. It was also designed to monitor glucose within tears, as well as intraocular pressure using the resistance and capacitance of the electronic device. Furthermore, in-vivo and in-vitro tests using a live rabbit and bovine eyeball demonstrated its reliable operation. Our developed contact lens sensor can measure the glucose level in tear fluid and intraocular pressure simultaneously but yet independently based on different electrical responses.ope

Implantable Flexible-Coiled Wireless Intraocular Pressure Sensor

This work presents an implantable wireless passive pressure sensor for long-range continuous intraocular pressure (IOP) monitoring of glaucoma patients. The sensor is microfabricated with use of parylene C (poly-chloro-p-xylylene) to create a flexible coil substrate that can be folded during implantation for suture-less minimally invasive surgery, while stretched back without damage for enhanced inductive sensor-reader coil coupling and the corresponding sensing signal. Extensive device characterizations including on-bench testing and in vivo and ex vivo animal studies verify the device feasibility in both engineering (1 mmHg pressure sensing accuracy and 2 cm sensing distance) and surgical (robust fixation to the iris and long-term biocompatibility in the intraocular environment) aspects, all meeting specifications for future practical implementation of such IOP sensing technology

Doctor of Philosophy

dissertationImplantable devices have the potential to solve current challenges in both physiological monitoring and drug delivery by introducing in situ measurement and treatment. In this dissertation, two types of implantable devices will be discussed. First, implantable devices for monitoring intraocular pressure (IOP) will be addressed. Second, implantable devices made of both nonbiodegradable and biodegradable materials for bridging a peripheral nerve gap by in situ drug delivery will be discussed. Elevated IOP serves as a major factor that leads to glaucoma, a permanent vision loss disease, and a real-time monitoring implantable IOP sensor with polydimethylsiloxane membrane that was developed. This IOP sensor can be either implanted in the lens capsular bag after cataract surgery or sandwiched between the sclera and the conjunctiva; the latter being more favorable due to easy signal retrieval. For this approach, batch testing data showed a sensitivity of 0.67 mm/mmHg with the range of the device closely matching that expected for glaucoma patients. Another medical challenge addressed in this dissertation is that peripheral nerve gaps longer than 10mm require special bridging techniques to repair. Autologous nerve grafts are the gold standard to repair peripheral nerve gaps; however, it possesses donor site deficit. Hence, a drug delivery device consisting of a nerve conduit for guided axon growth is proposed, fabricated and verified in this dissertation. Both nonbiodegradable materials and biodegradable materials were used to make the device that can deliver vascular growth factor, nerve growth factor (NGF), bovine serum albumin and polysaccharide. Furthermore, a bioactivity test verified that the NGF released from the device was still bioactive in promoting axonal outgrowth on chick dorsal root ganglia explants. Two 3-week pilot animal studies in mice and rats also showed that the device is biocompatible with no noticeable inflammatory response. For the release kinetics, the device using diffusion through holes instead of a filter membrane had better consistency in release kinetics. Two mathematical models were also developed to identify the optimal design of the nerve conduit and the model was verified by an in vitro release study. Thus, the model will be used to help determine future nerve conduit designs