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

A Three – tier bio-implantable sensor monitoring and communications platform

One major hindrance to the advent of novel bio-implantable sensor technologies is the need for a reliable power source and data communications platform capable of continuously, remotely, and wirelessly monitoring deeply implantable biomedical devices. This research proposes the feasibility and potential of combining well established, ‘human-friendly' inductive and ultrasonic technologies to produce a proof-of-concept, generic, multi-tier power transfer and data communication platform suitable for low-power, periodically-activated implantable analogue bio-sensors. In the inductive sub-system presented, 5 W of power is transferred across a 10 mm gap between a single pair of 39 mm (primary) and 33 mm (secondary) circular printed spiral coils (PSCs). These are printed using an 8000 dpi resolution photoplotter and fabricated on PCB by wet-etching, to the maximum permissible density. Our ultrasonic sub-system, consisting of a single pair of Pz21 (transmitter) and Pz26 (receiver) piezoelectric PZT ceramic discs driven by low-frequency, radial/planar excitation (-31 mode), without acoustic matching layers, is also reported here for the first time. The discs are characterised by propagation tank test and directly driven by the inductively coupled power to deliver 29 μW to a receiver (implant) employing a low voltage start-up IC positioned 70 mm deep within a homogeneous liquid phantom. No batteries are used. The deep implant is thus intermittently powered every 800 ms to charge a capacitor which enables its microcontroller, operating with a 500 kHz clock, to transmit a single nibble (4 bits) of digitized sensed data over a period of ~18 ms from deep within the phantom, to the outside world. A power transfer efficiency of 83% using our prototype CMOS logic-gate IC driver is reported for the inductively coupled part of the system. Overall prototype system power consumption is 2.3 W with a total power transfer efficiency of 1% achieved across the tiers

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

Portable Bio-Devices: Design of Electrochemical Instruments from Miniaturized to Implantable Devices

The integration of biosensors and electronic technologies allows the development of biomedical systems able to diagnose and monitoring pathologies by detecting specific biomarkers. The chapter presents the main modules involved in the development of such devices, generically represented in Fig. 1, and focuses its attention on the essential components of these systems to address questions such as: how is the device powered? How does it communicate the measured data? What kind of sensors could be used?, and What kinds of electronics are used

Fully Integrated Biochip Platforms for Advanced Healthcare

Recent advances in microelectronics and biosensors are enabling developments of innovative biochips for advanced healthcare by providing fully integrated platforms for continuous monitoring of a large set of human disease biomarkers. Continuous monitoring of several human metabolites can be addressed by using fully integrated and minimally invasive devices located in the sub-cutis, typically in the peritoneal region. This extends the techniques of continuous monitoring of glucose currently being pursued with diabetic patients. However, several issues have to be considered in order to succeed in developing fully integrated and minimally invasive implantable devices. These innovative devices require a high-degree of integration, minimal invasive surgery, long-term biocompatibility, security and privacy in data transmission, high reliability, high reproducibility, high specificity, low detection limit and high sensitivity. Recent advances in the field have already proposed possible solutions for several of these issues. The aim of the present paper is to present a broad spectrum of recent results and to propose future directions of development in order to obtain fully implantable systems for the continuous monitoring of the human metabolism in advanced healthcare applications

Design of Wireless Power Transfer and Data Telemetry System for Biomedical Applications

With the advancement of biomedical instrumentation technologies sensor based remote healthcare monitoring system is gaining more attention day by day. In this system wearable and implantable sensors are placed outside or inside of the human body. Certain sensors are needed to be placed inside the human body to acquire the information on the vital physiological phenomena such as glucose, lactate, pH, oxygen, etc. These implantable sensors have associated circuits for sensor signal processing and data transmission. Powering the circuit is always a crucial design issue. Batteries cannot be used in implantable sensors which can come in contact with the blood resulting in serious health risks. An alternate approach is to supply power wirelessly for tether-less and battery- less operation of the circuits.Inductive power transfer is the most common method of wireless power transfer to the implantable sensors. For good inductive coupling, the inductors should have high inductance and high quality factor. But the physical dimensions of the implanted inductors cannot be large due to a number of biomedical constraints. Therefore, there is a need for small sized and high inductance, high quality factor inductors for implantable sensor applications. In this work, design of a multi-spiral solenoidal printed circuit board (PCB) inductor for biomedical application is presented. The targeted frequency for power transfer is 13.56 MHz which is within the license-free industrial, scientific and medical (ISM) band. A figure of merit based optimization technique has been utilized to optimize the PCB inductors. Similar principal is applied to design on-chip inductor which could be a potential solution for further miniaturization of the implantable system. For layered human tissue the optimum frequency of power transfer is 1 GHz for smaller coil size. For this reason, design and optimization of multi-spiral solenoidal integrated inductors for 1 GHz frequency is proposed. Finally, it is demonstrated that the proposed inductors exhibit a better overall performance in comparison with the conventional inductors for biomedical applications

Remote Powering and Communication of Implantable Biosensors Through Inductive Link

Nowadays there is an increasing interest in the field of implantable biosensors. The possibility of real-time monitoring of the human body from inside paves the way to a large number of applications and offers wide opportunities for the future. Within this scenario, the i-IronIC project aims to develop an implantable, low cost, health-care device for real-time monitoring of human metabolites. The contribution of this research work to the i-IronIC project consists of the design and realization of a complete platform to provide power, data communication and remote control to the implantable biosensor. High wearability of the transmitting unit, low invasivity of the implanted electronics, integration of the power management module within the sensor, and a reliable communication protocol with portable devices are the key points of this platform. The power is transmitted to the implanted sensor by exploiting an inductive link. Simulations have been performed to check the effects of several variables on the link performance. These simulations have finally confirmed the possibility to operate in the low megahertz range, where tissue absorption is minimum, even if a miniaturized receiving inductor is used. A wearable patch has been designed to transmit power through the body tissues by driving an external inductor. The same inductive link is used to achieve bidirectional data communication with the implanted device. The patch, named IronIC, is powered by lithium-ion polymer batteries and can be remotely controlled by means of a dedicated Android application running on smartphones and tablets. Long-range communication between the patch and portable devices is performed by means of Bluetooth protocol. Different typologies of receiving inductors have been designed to minimize the size of the implantable device and reduce the discomfort of the patience. Multi-layer, printed spiral inductors and microfabricated spiral inductors have been designed, fabricated and tested. Both the approaches involve a sensibly smaller size, as compared to classic “pancake” inductors used for remote powering. Furthermore, the second solution enables the realization of the receiving inductor directly on the silicon substrate hosting the sensor, thus involving a further miniaturization of the implanted device. An integrated power module has been designed and fabricated in 0.18 μm CMOS technology to perform power management and data communication with the external patch. The circuit, to be merged with the sensor readout circuit, consists of an half-wave voltage rectifier, a low-dropout regulator, an amplitude demodulator and a load modulator. The module receives the power from the implanted inductor and provides a stable voltage to the sensor readout circuit. Finally, the amplitude demodulator and the load modulator enable short-range communication with the patch

Doctor of Philosophy

dissertationSince the late 1950s, scientists have been working toward realizing implantable devices that would directly monitor or even control the human body's internal activities. Sophisticated microsystems are used to improve our understanding of internal biological processes in animals and humans. The diversity of biomedical research dictates that microsystems must be developed and customized specifically for each new application. For advanced long-term experiments, a custom designed system-on-chip (SoC) is usually necessary to meet desired specifications. Custom SoCs, however, are often prohibitively expensive, preventing many new ideas from being explored. In this work, we have identified a set of sensors that are frequently used in biomedical research and developed a single-chip integrated microsystem that offers the most commonly used sensor interfaces, high computational power, and which requires minimum external components to operate. Included peripherals can also drive chemical reactions by setting the appropriate voltages or currents across electrodes. The SoC is highly modular and well suited for prototyping in and ex vivo experimental devices. The system runs from a primary or secondary battery that can be recharged via two inductively coupled coils. The SoC includes a 16-bit microprocessor with 32 kB of on chip SRAM. The digital core consumes 350 μW at 10 MHz and is capable of running at frequencies up to 200 MHz. The integrated microsystem has been fabricated in a 65 nm CMOS technology and the silicon has been fully tested. Integrated peripherals include two sigma-delta analog-to-digital converters, two 10-bit digital-to-analog converters, and a sleep mode timer. The system also includes a wireless ultra-wideband (UWB) transmitter. The fullydigital transmitter implementation occupies 68 x 68 μm2 of silicon area, consumes 0.72 μW static power, and achieves an energy efficiency of 19 pJ/pulse at 200 MHz pulse repetition frequency. An investigation of the suitability of the UWB technology for neural recording systems is also presented. Experimental data capturing the UWB signal transmission through an animal head are presented and a statistical model for large-scale signal fading is developed

A Study of Multi-Layer Spiral Inductors for Remote Powering of Implantable Sensors

An approach based on multi-layer spiral inductors to remotely power implantable sensors is investigated. As compared to single-layer inductors having the same area, multi-layer printed inductors enable a higher efficiency (up to 35% higher) and voltage gain (almost one order of magnitude higher). A system conceived to be embedded into a skin patch is designed to verify the performance. The system is able to transmit up to 15 mW over a distance of 6 mm and up to 1.17 mW where a 17 mm beef sirloin is placed between the inductors. Furthermore, the system performs downlink communication (up to 100 kbps) and uplink communication based on the backscattering technique (up to 66.6 kbps). Long-range communication is achieved by means of a bluetooth module