A microscale optical implant for continuous in vivo monitoring of intraocular pressure

Intraocular pressure (IOP) is a key clinical parameter in glaucoma management. However, despite the potential utility of daily measurements of IOP in the context of disease management, the necessary tools are currently lacking, and IOP is typically measured only a few times a year. Here we report on a microscale implantable sensor that could provide convenient, accurate, on-demand IOP monitoring in the home environment. When excited by broadband near-infrared (NIR) light from a tungsten bulb, the sensor’s optical cavity reflects a pressure-dependent resonance signature that can be converted to IOP. NIR light is minimally absorbed by tissue and is not perceived visually. The sensor’s nanodot-enhanced cavity allows for a 3–5 cm readout distance with an average accuracy of 0.29 mm Hg over the range of 0–40 mm Hg. Sensors were mounted onto intraocular lenses or silicone haptics and secured inside the anterior chamber in New Zealand white rabbits. Implanted sensors provided continuous in vivo tracking of short-term transient IOP elevations and provided continuous measurements of IOP for up to 4.5 months

Development of a MEMS device to continuously monitor glaucoma

The objective of this thesis was to investigate the development of a micro-electromechanical system (MEMS) which can be implanted in the eye to provide continuous monitoring of glaucoma conditions. Current glaucoma monitoring involves taking laboratory based intra ocular pressure (IOP) measurements. The measurement of intraocular fluid flow and IOP parameters related to blockage formation in the eye require to be continuously monitored in Glaucoma. Making blockage related information available to patients could indicate the conditions leading to a blockage and help to improve glaucoma treatment and reduce the risk of permanent blindness. The specific aim of this research was to develop an implantable micro device capable of responding to the blockage of fluid flow in the eye. A mathematical model of the IOP dynamics in the eye, incorporating the IOP exponential decay phenomenon, was used to study the pressure changes that will occur in the eye due to glaucoma during external measurements. The mathematical model helped to analyse the principle behind IOP measurement and was extended to internal measurements by analysing time-based changes of variables integral to the process, such as eye rigidity, size, pressure, volume etc. The mathematical simulations helped to determine the physical requirements of an implantable micro device capable of increasing the IOP temporarily for the duration of a measurement. Finite element method analyses were conducted to determine the dimensions of a MEMS pressure sensor that could respond mechanically to the pressure changes initiated inside the eye by the micro device and convert the responses to electrically measurable units. The pressure resolution required of the MEMS pressure sensor was learned from the investigations and the electrical output indicative of the extent of glaucoma in an eye was also calculated. Integrating the intraocular dynamics and the MEMS pressure sensor responses constituted a mathematical model of the implantable micro system. The micro system model was tested for normal and adverse eye operating conditions to estimate the output based on various internal IOP measurements. The output that would be obtained from the implantable micro system was compared to responses from external measurements and found to be comparable. An overview of a comprehensive MEMS monitoring system including the micro device to increase the pressure within the eye, a MEMS pressure sensor, and powering and signal conditioning electronics was provided. A description of the technologies that could be used for the fabrication and packaging of the device and the sensor was also included at the end of the thesis along with a discussion on bio-compatibility and implanting issues. Thus the feasibility of combining a micro device and a micro sensor with powering and signal conditioning electronics to create an implantable MEMS system that can make continuous measurements which can indicate the onset of or an increase in blockage of the eye of a person with glaucoma is presented in the thesis

FM Continuous Monitoring of Intraocular Pressure, an Engineering Perspective

This chapter discusses the problem of continuously monitoring intraocular pressure (IOP) from an engineering perspective. It is aimed to all public in general although we think that medical staff and engineers may benefit the most from it. Although equations are included for engineers to get a glimpse of how the system works, this chapter does not go into great detail in mathematics and physics to make it understandable to medical staff. It provides though references for engineers who wish to get a better understanding of key subjects tackled in this chapter. The chapter is organized as follows: Section 1 introduces intraocular pressure (IOP) and need for its continuous monitoring. Section 2 describes the most recent efforts to develop a continuous IOP monitoring system. Section 3 shows what medical and engineering considerations must be taken into account to effectively measure IOP. Section 4 deals with health issues due to tissue warming and how to prevent them. Section 5 explains how an implant can be fabricated using either passive electronic components or active ones. Finally, Section 6 explains how the pressure sensor and the electronic circuits can be integrated

Real-Time In Vivo Intraocular Pressure Monitoring using an Optomechanical Implant and an Artificial Neural Network

Optimized glaucoma therapy requires frequent monitoring and timely lowering of elevated intraocular pressure (IOP). A recently developed microscale IOP-monitoring implant, when illuminated with broadband light, reflects a pressure-dependent optical spectrum that is captured and converted to measure IOP. However, its accuracy is limited by background noise and the difficulty of modeling non-linear shifts of the spectra with respect to pressure changes. Using an end-to-end calibration system to train an artificial neural network (ANN) for signal demodulation we improved the speed and accuracy of pressure measurements obtained with an optically probed IOP-monitoring implant and make it suitable for real-time in vivo IOP monitoring. The ANN converts captured optical spectra into corresponding IOP levels. We achieved an IOP-measurement accuracy of ±0.1 mmHg at a measurement rate of 100 Hz, which represents a ten-fold improvement from previously reported values. This technique allowed real-time tracking of artificially induced sub-1 s transient IOP elevations and minor fluctuations induced by the respiratory motion of the rabbits during in vivo monitoring. All in vivo sensor readings paralleled those obtained concurrently using a commercial tonometer and showed consistency within ±2 mmHg. Real-time processing is highly useful for IOP monitoring in clinical settings and home environments and improves the overall practicality of the optical IOP-monitoring approach

Recent Advances on Implantable Wireless Sensor Networks

Implantable electronic devices are undergoing a miniaturization age, becoming more efficient and yet more powerful as well. Biomedical sensors are used to monitor a multitude of physiological parameters, such as glucose levels, blood pressure and neural activity. A group of sensors working together in the human body is the main component of a body area network, which is a wireless sensor network applied to the human body. In this chapter, applications of wireless biomedical sensors are presented, along with state-of-the-art communication and powering mechanisms of these devices. Furthermore, recent integration methods that allow the sensors to become smaller and more suitable for implantation are summarized. For individual sensors to become a body area network (BAN), they must form a network and work together. Issues that must be addressed when developing these networks are detailed and, finally, mobility methods for implanted sensors are presented

Real-Time In Vivo Intraocular Pressure Monitoring using an Optomechanical Implant and an Artificial Neural Network

Optimized glaucoma therapy requires frequent monitoring and timely lowering of elevated intraocular pressure (IOP). A recently developed microscale IOP-monitoring implant, when illuminated with broadband light, reflects a pressure-dependent optical spectrum that is captured and converted to measure IOP. However, its accuracy is limited by background noise and the difficulty of modeling non-linear shifts of the spectra with respect to pressure changes. Using an end-to-end calibration system to train an artificial neural network (ANN) for signal demodulation we improved the speed and accuracy of pressure measurements obtained with an optically probed IOP-monitoring implant and make it suitable for real-time in vivo IOP monitoring. The ANN converts captured optical spectra into corresponding IOP levels. We achieved an IOP-measurement accuracy of ±0.1 mmHg at a measurement rate of 100 Hz, which represents a ten-fold improvement from previously reported values. This technique allowed real-time tracking of artificially induced sub-1 s transient IOP elevations and minor fluctuations induced by the respiratory motion of the rabbits during in vivo monitoring. All in vivo sensor readings paralleled those obtained concurrently using a commercial tonometer and showed consistency within ±2 mmHg. Real-time processing is highly useful for IOP monitoring in clinical settings and home environments and improves the overall practicality of the optical IOP-monitoring approach

Wireless Transceivers for Implantable Microsystems.

In this thesis, we present the first-ever fully integrated mm3 low-power biomedical transceiver with 1 meter of range that is powered by a mm2 thin-film battery. The transceiver is targeted for biomedical implants where size and energy constraints dictated by application make design challenging. Despite all the previous work in RFID tags, form factor of such radios is incompatible with mm3 biomedical implants. The proposed transceiver bridges this gap by providing a compact low-power solution that can run off small thin-film batteries and can be stacked with other system components in a 3D fashion. On the sensor-to-external side, we proposed a novel FSK architecture based on dual-resonator LC oscillators to mitigate unwanted overlap of two FSK tones’ phase noise spectrum. Due to inherent complexity of such systems, fourth order dual-resonator oscillators can exhibit instable operation. We mathematically modeled the instability and derive design conditions for stable oscillations. Through simulation and measurements, validity of derived models was confirmed. Together with other low-power system blocks, the transmitter was successfully implanted in live mouse and in-vivo measurements were performed to confirm successful transmission of vital signals through organic tissue. The integrated transmitter achieved a bit-error-rate of 10-6 at 10cm with 4.7nJ/bit energy consumption. On the external-to-sensor link, we proposed a new protocol to lower receiver peak power, which is highly limited due to small size of mm3 microsystem battery. In the proposed protocol, sending same data multiple times drastically relaxes jitter requirement on the sensor side at the cost of increased power consumption on the external side without increasing peak power radiated by the external unit. The receiver also uses a dual-coil LNA to improve range by 22% with only 11% area overhead. An asynchronous controller manages protocol timing and limits total monitoring current to 43nA. The fabricated receiver consumes 1.6nJ/bit at 40kbps while positioned 1m away from a 2W source.PhDElectrical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/102458/1/ghaed_1.pd

Next generation RFID telemetry design for biomedical implants.

The design and development of a Radio Frequency Identification (RFID) based pressure-sensing system to increase the range of current Intra-Ocular Pressure (IOP) sensing systems is described in this dissertation. A large number of current systems use near-field inductive coupling for the transfer of energy and data, which limits the operational range to only a few centimeters and does not allow for continuous monitoring of pressure. Increasing the powering range of the telemetry system will offer the possibility of continuous monitoring since the reader can be attached to a waist belt or put on a night stand when sleeping. The system developed as part of this research operates at Ultra-High Frequencies (UHF) and makes use of the electromagnetic far field to transfer energy and data, which increases the potential range of operation and allows for the use of smaller antennas. The system uses a novel electrically small antenna (ESA) to receive the incident RF signal. A four stage Schottky circuit rectifies and multiplies the received RF signal and provides DC power to a Colpitts oscillator. The oscillator is connected to a pressure sensor and provides an output signal frequency that is proportional to the change in pressure. The system was fabricated using a mature, inexpensive process. The performance of the system compares well with current state of the art, but uses a smaller antenna and a less expensive fabrication process. The system was able to operate over the desired range of 1 m using a half-wave dipole antenna. It was possible to power the system over a range of at least 6.4 cm when the electrically small antenna was used as the receiving antenna

Design of a Customized multipurpose nano-enabled implantable system for in-vivo theranostics

The first part of this paper reviews the current development and key issues on implantable multi-sensor devices for in vivo theranostics. Afterwards, the authors propose an innovative biomedical multisensory system for in vivo biomarker monitoring that could be suitable for customized theranostics applications. At this point, findings suggest that cross-cutting Key Enabling Technologies (KETs) could improve the overall performance of the system given that the convergence of technologies in nanotechnology, biotechnology, micro&nanoelectronics and advanced materials permit the development of new medical devices of small dimensions, using biocompatible materials, and embedding reliable and targeted biosensors, high speed data communication, and even energy autonomy. Therefore, this article deals with new research and market challenges of implantable sensor devices, from the point of view of the pervasive system, and time-to-market. The remote clinical monitoring approach introduced in this paper could be based on an array of biosensors to extract information from the patient. A key contribution of the authors is that the general architecture introduced in this paper would require minor modifications for the final customized bio-implantable medical device