Application of neural prostheses in today's medicine successfully helps patients to increase their activities of daily life and participate in social activities again. These implantable microsystems provide an interface to the nervous system, giving cellular resolution to physiological processes unattainable today with non-invasive methods. The latest developments in genetic engineering, nanotechnologies and materials science have paved the way for these complex systems to interface the human nervous system. The ideal system for neural signal recording would be a fully implantable device which is capable of amplifying the neural signals and transmitting them to the outside world while sustaining a long-term and accurate performance, therefore different sciences from neurosciences, biology, electrical engineering and computer science have to interact and discuss the synergies to develop a practical system which can be used in daily medicine practice. This work investigates the main building blocks necessary to improve the quality of acquired signal from the micro-electronics and MEMS perspectives. While all of these components will be ultimately embedded in a fully implantable recording probe, each of them addresses and deals with a specific obstacle in the neural signal recording path. Specifically we present a low-voltage low-noise low-power CMOS amplifier particularly designed for neural recording applications. This is done by surveying a number of designs and evaluating each design against the requirements for a neural recording system such as power dissipation and noise, and then choosing the most suitable topology for design and implementation of a fully implantable system. In addition a surface modification method is investigated to improve the sacrificial properties and biocompatibility of probe in order to extend the implant life and enhance the signal quality.

Application of neural prostheses in today's medicine successfully helps patients to increase their activities of daily life and participate in social activities again. These implantable microsystems provide an interface to the nervous system, giving cellular resolution to physiological processes unattainable today with non-invasive methods. The latest developments in genetic engineering, nanotechnologies and materials science have paved the way for these complex systems to interface the human nervous system. The ideal system for neural signal recording would be a fully implantable device which is capable of amplifying the neural signals and transmitting them to the outside world while sustaining a long-term and accurate performance, therefore different sciences from neurosciences, biology, electrical engineering and computer science have to interact and discuss the synergies to develop a practical system which can be used in daily medicine practice. This work investigates the main building blocks necessary to improve the quality of acquired signal from the micro-electronics and MEMS perspectives. While all of these components will be ultimately embedded in a fully implantable recording probe, each of them addresses and deals with a specific obstacle in the neural signal recording path. Specifically we present a low-voltage low-noise low-power CMOS amplifier particularly designed for neural recording applications. This is done by surveying a number of designs and evaluating each design against the requirements for a neural recording system such as power dissipation and noise, and then choosing the most suitable topology for design and implementation of a fully implantable system. In addition a surface modification method is investigated to improve the sacrificial properties and biocompatibility of probe in order to extend the implant life and enhance the signal quality.

Application of neural prostheses in today's medicine successfully helps patients to increase their activities of daily life and participate in social activities again. These implantable microsystems provide an interface to the nervous system, giving cellular resolution to physiological processes unattainable today with non-invasive methods. The latest developments in genetic engineering, nanotechnologies and materials science have paved the way for these complex systems to interface the human nervous system. The ideal system for neural signal recording would be a fully implantable device which is capable of amplifying the neural signals and transmitting them to the outside world while sustaining a long-term and accurate performance, therefore different sciences from neurosciences, biology, electrical engineering and computer science have to interact and discuss the synergies to develop a practical system which can be used in daily medicine practice. This work investigates the main building blocks necessary to improve the quality of acquired signal from the micro-electronics and MEMS perspectives. While all of these components will be ultimately embedded in a fully implantable recording probe, each of them addresses and deals with a specific obstacle in the neural signal recording path. Specifically we present a low-voltage low-noise low-power CMOS amplifier particularly designed for neural recording applications. This is done by surveying a number of designs and evaluating each design against the requirements for a neural recording system such as power dissipation and noise, and then choosing the most suitable topology for design and implementation of a fully implantable system. In addition a surface modification method is investigated to improve the sacrificial properties and biocompatibility of probe in order to extend the implant life and enhance the signal quality. / Applied Science, Faculty of / Electrical and Computer Engineering, Department of / Graduate

Reliable chronic neural recording from focal deep brain structures is impeded by insertion injury and foreign body response, the magnitude of which is correlated with the mechanical mismatch between the electrode and tissue. Thin and flexible neural electrodes cause less glial scarring and record longer than stiff electrodes. However, the insertion of flexible microelectrodes in the brain has been a challenge. A novel insertion method is proposed, and demonstrated, for precise targeting deep brain structures using flexible micro-wire electrodes. A novel electrode guiding system is designed based on the principles governing the buckling strength of electrodes. The proposed guide significantly increases the critical buckling force of the microelectrode. The electrode insertion mechanism involves spinning of the electrode during insertion. The spinning electrode is slowly inserted in the brain through the electrode guide. The electrode guide does not penetrate into cortex. The electrode is inserted in the brain without stiffening it by coating with foreign material or by attaching a rigid support and hence the method is less invasive. Based on two new mechanisms, namely spinning and guided insertion, it is possible to insert ultra-thin micro-wire flexible electrodes in rodent brains without buckling. I have demonstrated successful insertion of 25 µm platinum micro-wire electrodes about 10 mm deep in rat brain. A novel micro-motion compensated ultra-thin flexible platinum microelectrode has been presented for chronic single unit recording. Since manual insertion of the proposed microelectrode is not possible, I have developed a microelectrode insertion device based on the proposed method. A low power low noise 16 channel programmable neural amplifier ASIC has been designed and used to record the neural spikes. The ability to record neural activity during insertion is a unique feature of the developed inserter. In vivo implantation process of the microelectrode has been demonstrated. Microelectrodes were inserted in the Botzinger complex of rat and long term respiratory related neural activity was recorded from live rats. The developed microelectrode has also been used to study brain activity during seizures. In-vivo experimental results show that the proposed method and the prototype insertion system can be used to implant flexible microelectrode in deep brain structures of rodent for brain studies.

About 50 million people worldwide suffer from epilepsy and one third of them have seizures that are refractory to medication. In the past few decades, deep brain stimulation (DBS) has been explored by researchers and physicians as a promising way to control and treat epileptic seizures. To make the DBS therapy more efficient and effective, the feedback loop for titrating therapy is required. It means the implantable DBS devices should be smart enough to sense the brain signals and then adjust the stimulation parameters adaptively. This research proposes a signal-sensing channel configurable to various neural applications, which is a vital part for a future closed-loop epileptic seizure stimulation system. This doctoral study has two main contributions, 1) a micropower low-noise neural front-end circuit, and 2) a low-power configurable neural recording system for both neural action-potential (AP) and fast-ripple (FR) signals. The neural front end consists of a preamplifier followed by a bandpass filter (BPF). This design focuses on improving the noise-power efficiency of the preamplifier and the power/pole merit of the BPF at ultra-low power consumption. In measurement, the preamplifier exhibits 39.6-dB DC gain, 0.8 Hz to 5.2 kHz of bandwidth (BW), 5.86-μVrms input-referred noise in AP mode, while showing 39.4-dB DC gain, 0.36 Hz to 1.3 kHz of BW, 3.07-μVrms noise in FR mode. The preamplifier achieves noise efficiency factor (NEF) of 2.93 and 3.09 for AP and FR modes, respectively. The preamplifier power consumption is 2.4 μW from 2.8 V for both modes. The 6th-order follow-the-leader feedback elliptic BPF passes FR signals and provides -110 dB/decade attenuation to out-of-band interferers. It consumes 2.1 μW from 2.8 V (or 0.35 μW/pole) and is one of the most power-efficient high-order active filters reported to date. The complete front-end circuit achieves a mid-band gain of 38.5 dB, a BW from 250 to 486 Hz, and a total input-referred noise of 2.48 μVrms while consuming 4.5 μW from the 2.8 V power supply. The front-end NEF achieved is 7.6. The power efficiency of the complete front-end is 0.75 μW/pole. The chip is implemented in a standard 0.6-μm CMOS process with a die area of 0.45 mm^2. The neural recording system incorporates the front-end circuit and a sigma-delta analog-to-digital converter (ADC). The ADC has scalable BW and power consumption for digitizing both AP and FR signals captured by the front end. Various design techniques are applied to the improvement of power and area efficiency for the ADC. At 77-dB dynamic range (DR), the ADC has a peak SNR and SNDR of 75.9 dB and 67 dB, respectively, while consuming 2.75-mW power in AP mode. It achieves 78-dB DR, 76.2-dB peak SNR, 73.2-dB peak SNDR, and 588-μW power consumption in FR mode. Both analog and digital power supply voltages are 2.8 V. The chip is fabricated in a standard 0.6-μm CMOS process. The die size is 11.25 mm^2. The proposed circuits can be extended to a multi-channel system, with the ADC shared by all channels, as the sensing part of a future closed-loop DBS system for the treatment of intractable epilepsy.

La bioélectronique est un domaine transdisciplinaire qui oeuvre, entre autres, àl’interconnexion entre des systèmes biologiques présentant une activité électrique et le mondede l’électronique. Cette communication avec le vivant implique l’observation de l’activitéélectrique des cellules considérées et nécessite donc une chaine d’acquisition électronique.L’utilisation de Multi/Micro Electrodes Array débouche sur des systèmes devantacquérir un grand nombre de canaux en parallèle, dès lors la consommation etl’encombrement des circuits d’acquisition ont un impact significatif sur la viabilité dusystème destiné à être implanté.Cette thèse propose deux réflexions à propos de ces circuits d’acquisition. Une ces desréflexions a trait aux circuits d’amplification, à leur impédance d’entrée et à leurconsommation ; l’autre concerne un détecteur de potentiels d’action analogique, samodélisation et son optimisation.Ces travaux théoriques ayant abouti à des résultats concrets, un ASIC a été conçu,fabriqué, testé et caractérisé au cours de cette thèse. Cet ASIC à huit canaux comporte doncdes amplificateurs et des détecteurs de potentiels d’action analogiques et constitue le principalapport de ce travail de thèse. / Bioelectronics is a transdisciplinary field which develops interconnection devicesbetween biological systems presenting electrical activity and the world of electronics. Thiscommunication with living tissues implies to observe the electrical activity of the cells andtherefore requires an electronic acquisition chain.The use of Multi / Micro Electrode Array leads to systems that acquire a large numberof parallel channels, thus consumption and congestion of acquisition circuits have asignificant impact on the viability of the system to be implanted.This thesis proposes two reflections about these acquisition circuits. One of thesereflections relates to amplifier circuits, their input impedance and consumption; the otherconcerns an analogue action potentials detector, its modeling and optimization.These theoretical work leading to concrete results, an ASIC was designed,manufactured, tested and characterized in this thesis. This eight-channel ASIC thereforeincludes amplifiers and analogue action potentials detector and is the main contribution of thisthesis.