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

3D-Printed Hermetic Alumina Housings

Ceramics are repeatedly investigated as packaging materials because of their gas tightness, e.g., as hermetic implantable housing. Recent advances also make it possible to print the established aluminum oxide in a Fused Filament Fabrication process, creating new possibilities for manufacturing personalized devices with complex shapes. This study was able to achieve integration of channels with a diameter of 500 m (pre-sintered) with a nozzle size of 250 m (layer thickness 100 m) and even closed hemispheres were printed without support structures. During sintering, the weightbearing feedstock shrinks by 16.7%, resulting in a relative material density of 96.6%. The well-known challenges of the technology such as surface roughness (Ra = 15–20 m) and integrated cavities remain. However, it could be shown that the hollow structures in bulk do not represent a mechanical weak point and that the material can be gas-tight (<1012 mbar s1). For verification, a volume-free helium leak test device was developed and validated. Finally, platinum coatings with high adhesion examined the functionalization of the ceramic. All the prerequisites for hermetic housings with integrated metal structures are given, with a new level of complexity of ceramic shapes available

Beyond Tissue replacement: The Emerging role of smart implants in healthcare

Smart implants are increasingly used to treat various diseases, track patient status, and restore tissue and organ function. These devices support internal organs, actively stimulate nerves, and monitor essential functions. With continuous monitoring or stimulation, patient observation quality and subsequent treatment can be improved. Additionally, using biodegradable and entirely excreted implant materials eliminates the need for surgical removal, providing a patient-friendly solution. In this review, we classify smart implants and discuss the latest prototypes, materials, and technologies employed in their creation. Our focus lies in exploring medical devices beyond replacing an organ or tissue and incorporating new functionality through sensors and electronic circuits. We also examine the advantages, opportunities, and challenges of creating implantable devices that preserve all critical functions. By presenting an in-depth overview of the current state-of-the-art smart implants, we shed light on persistent issues and limitations while discussing potential avenues for future advancements in materials used for these devices

Brain–Machine Interfaces: The Role of the Neurosurgeon

The neurotechnology field is set to expand rapidly in the coming years as technological innovations in hardware and software are translated to the clinical setting. Given our unique access to patients with neurological disorders, expertise with which to guide appropriate treatments and technical skills to implant brain-machine interfaces (BMIs), neurosurgeons have a key role to play in the progress of this field. We outline the current state and key challenges in this rapidly advancing field including implant technology, implant recipients, implantation methodology, implant function, ethical, regulatory and economic considerations. Our key message is to encourage the neurosurgical community to proactively engage in collaborating with other healthcare professionals, engineers, scientists, ethicists and regulators in tackling these issues. By doing so, we will equip ourselves with the skills and expertise to drive the field forward and avoid being mere technicians in an industry driven by those around us

Wireless body sensor networks for health-monitoring applications

This is an author-created, un-copyedited version of an article accepted for publication in Physiological Measurement. The publisher is not responsible for any errors or omissions in this version of the manuscript or any version derived from it. The Version of Record is available online at http://dx.doi.org/10.1088/0967-3334/29/11/R01

Long-Term Neural Recordings Using MEMS Based Movable Microelectrodes in the Brain

One of the critical requirements of the emerging class of neural prosthetic devices is to maintain good quality neural recordings over long time periods. We report here a novel MEMS (Micro Electro Mechanical Systems) based technology that can move microelectrodes in the event of deterioration in neural signal to sample a new set of neurons. Microscale electro-thermal actuators are used to controllably move microelectrodes post-implantation in steps of approximately 9 μm. In this study, a total of 12 movable microelectrode chips were individually implanted in adult rats. Two of the twelve movable microelectrode chips were not moved over a period of 3 weeks and were treated as control experiments. During the first 3 weeks of implantation, moving the microelectrodes led to an improvement in the average signal to noise ratio (SNR) from 14.61 ± 5.21 dB before movement to 18.13 ± 4.99 dB after movement across all microelectrodes and all days. However, the average root-mean-square values of noise amplitudes were similar at 2.98 ± 1.22 μV and 3.01 ± 1.16 μV before and after microelectrode movement. Beyond 3 weeks, the primary observed failure mode was biological rejection of the PMMA (dental cement) based skull mount resulting in the device loosening and eventually falling from the skull. Additionally, the average SNR for functioning devices beyond 3 weeks was 11.88 ± 2.02 dB before microelectrode movement and was significantly different (p < 0.01) from the average SNR of 13.34 ± 0.919 dB after movement. The results of this study demonstrate that MEMS based technologies can move microelectrodes in rodent brains in long-term experiments resulting in improvements in signal quality. Further improvements in packaging and surgical techniques will potentially enable movable microelectrodes to record cortical neuronal activity in chronic experiments

Design and Development of Smart Brain-Machine-Brain Interface (SBMIBI) for Deep Brain Stimulation and Other Biomedical Applications

Machine collaboration with the biological body/brain by sending electrical information back and forth is one of the leading research areas in neuro-engineering during the twenty-first century. Hence, Brain-Machine-Brain Interface (BMBI) is a powerful tool for achieving such machine-brain/body collaboration. BMBI generally is a smart device (usually invasive) that can record, store, and analyze neural activities, and generate corresponding responses in the form of electrical pulses to stimulate specific brain regions. The Smart Brain-Machine-Brain-Interface (SBMBI) is a step forward with compared to the traditional BMBI by including smart functions, such as in-electrode local computing capabilities, and availability of cloud connectivity in the system to take the advantage of powerful cloud computation in decision making. In this dissertation work, we designed and developed an innovative form of Smart Brain-Machine-Brain Interface (SBMBI) and studied its feasibility in different biomedical applications. With respect to power management, the SBMBI is a semi-passive platform. The communication module is fully passive—powered by RF harvested energy; whereas, the signal processing core is battery-assisted. The efficiency of the implemented RF energy harvester was measured to be 0.005%. One of potential applications of SBMBI is to configure a Smart Deep-Brain-Stimulator (SDBS) based on the general SBMBI platform. The SDBS consists of brain-implantable smart electrodes and a wireless-connected external controller. The SDBS electrodes operate as completely autonomous electronic implants that are capable of sensing and recording neural activities in real time, performing local processing, and generating arbitrary waveforms for neuro-stimulation. A bidirectional, secure, fully-passive wireless communication backbone was designed and integrated into this smart electrode to maintain contact between the smart electrodes and the controller. The standard EPC-Global protocol has been modified and adopted as the communication protocol in this design. The proposed SDBS, by using a SBMBI platform, was demonstrated and tested through a hardware prototype. Additionally the SBMBI was employed to develop a low-power wireless ECG data acquisition device. This device captures cardiac pulses through a non-invasive magnetic resonance electrode, processes the signal and sends it to the backend computer through the SBMBI interface. Analysis was performed to verify the integrity of received ECG data

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

Learning-Based Hardware Design for Data Acquisition Systems

This multidisciplinary research work aims to investigate the optimized information extraction from signals or data volumes and to develop tailored hardware implementations that trade-off the complexity of data acquisition with that of data processing, conceptually allowing radically new device designs. The mathematical results in classical Compressive Sampling (CS) support the paradigm of Analog-to-Information Conversion (AIC) as a replacement for conventional ADC technologies. The AICs simultaneously perform data acquisition and compression, seeking to directly sample signals for achieving specific tasks as opposed to acquiring a full signal only at the Nyquist rate to throw most of it away via compression. Our contention is that in order for CS to live up its name, both theory and practice must leverage concepts from learning. This work demonstrates our contention in hardware prototypes, with key trade-offs, for two different fields of application as edge and big-data computing. In the framework of edge-data computing, such as wearable and implantable ecosystems, the power budget is defined by the battery capacity, which generally limits the device performance and usability. This is more evident in very challenging field, such as medical monitoring, where high performance requirements are necessary for the device to process the information with high accuracy. Furthermore, in applications like implantable medical monitoring, the system performances have to merge the small area as well as the low-power requirements, in order to facilitate the implant bio-compatibility, avoiding the rejection from the human body. Based on our new mathematical foundations, we built different prototypes to get a neural signal acquisition chip that not only rigorously trades off its area, energy consumption, and the quality of its signal output, but also significantly outperforms the state-of-the-art in all aspects. In the framework of big-data and high-performance computation, such as in high-end servers application, the RF circuits meant to transmit data from chip-to-chip or chip-to-memory are defined by low power requirements, since the heat generated by the integrated circuits is partially distributed by the chip package. Hence, the overall system power budget is defined by its affordable cooling capacity. For this reason, application specific architectures and innovative techniques are used for low-power implementation. In this work, we have developed a single-ended multi-lane receiver for high speed I/O link in servers application. The receiver operates at 7 Gbps by learning inter-symbol interference and electromagnetic coupling noise in chip-to-chip communication systems. A learning-based approach allows a versatile receiver circuit which not only copes with large channel attenuation but also implements novel crosstalk reduction techniques, to allow single-ended multiple lines transmission, without sacrificing its overall bandwidth for a given area within the interconnect's data-path