A Microfluidic Brain Interface for In Vivo Recording of Neurochemical Activity

Neurological disorders have a strong negative impact on the quality of life of affected patients, their close relatives as well as on the health economic system. Early diagnosis associated with better treatment outcomes remain difficult to reach. Similarly, misdiagnosis is frequent and can lead to the delivery of the wrong treatment to the patient. As a matter of fact, the therapeutic strategies developed to treat Alzheimer's Disease (AD) and Parkinson's Disease (PD), two major neurodegenerative diseases, are unfortunately only effective for reducing the symptoms. This illustrates the lack of complete understanding of the mechanisms underlining neurodegeneration. In this context, this thesis aims to contribute to a precise comprehension of the synaptic transmission, at the cellular level, by providing a biocompatible brain interface capable of collecting neurochemicals while establishing a tight electrical connection with the cerebral tissues. The first part of this thesis deals with the design and microfabrication of a novel neural probe which includes microelectrodes and a micro-scale droplet generator for the efficient collection of extracellular fluid. The design choices and the microfabrication approach are detailed while the behavior of the device is assessed using fluidic modeling. Experimental results regarding the neural probe's mechanical strength, electrical and fluidic functions are then presented. In particular, the electrode-tissue interface is assessed using impedance spectroscopy. The probe fluidic function and its ability to perform high frequency (6Hz) droplet segmented collection in a rapidly changing environment is experimentally demonstrated. In a second phase is reported the successful in vivo testing of the neural probe in the framework of a pilot animal trial performed on rats. A custom microfabricated analysis platform enabling to efficiently detect the content of the collected brain fluid samples is presented as well. In particular a microfabricated target plate for the distribution and handling of the segmented samples during analysis is reported. This unique approach allows to maintain the temporal history of the flow-segmented samples. Combined with Inductively Coupled (ICP) Mass Spectrometry (MS), the detection results show the presence in significant quantity of Na, Mg, K and Ca, reflecting the neurochemical state of the brain over time. Quantitative measurements are demonstrated, highlighting the power of this approach. Simultaneous cerebral tissues electrical modulation and neurochemical recording during periods of 15 min is demonstrated in a third phase. A significant neurochemical response is detected in correlation with the electrical stimulation periods (2 x 1 min). In particular, the extracellular K+ ion concentration appears to rise during these periods which is further confirmed on each of the 3 implanted subjects. It is stated that the electrical stimulation delivered to the tissues set the neurons in a permanent hyperpolarized state, forcing a strong K+ ions efflux towards the extracellular space. This work sets a basis for the development of novel approaches in the detection of malfunction in synaptic transmission. Future perspectives of this technology include new methods enabling earlier diagnosis of neurodegenerative diseases and more efficient treatments based on a closed-loop adjustment of electrical stimulation.

SOI mixed-mode design techniques and case studies

Marija Blagojevic

Since the emergence of Silicon On Insulator (SOI) technology the research activities have been concentrated on a detailed analysis of SOI devices and their use in different application fields (low-voltage, low-power circuits, high temperature electronics, digital circuits, etc.). The present thesis deals with low-voltage, low-power mixed-mode design using a SOI technology. The goal is to establish the concepts that allow one to design SOI mixed-mode circuits, and to apply these concepts to the design of fully depleted (FD) and partially depleted (PD) SOI circuits and systems. Two studies have been realized in the scope of this work: a Hall sensor based microsystem design using an experimental FD SOI technology a DRAM design using capacitor-less 1T floating-body PD SOI memory cells. At the beginning of this thesis, two major types of SOI devices are introduced, namely FD and PD devices. The most important properties of these devices are then presented and compared to those of CMOS bulk devices. A design methodology based on design retargeting from bulk to SOI technology is further proposed. This methodology is developed with the aim of being implemented for the design of FD SOI circuits. It consists in using the same device dimensions and bias currents for the bulk and the corresponding FD SOI design. The analysis performed proves that such an approach permits one to obtain better circuit performances using the FD SOI technology. The EKV model is chosen for Spice simulations. For that purpose the extraction of the EKV intrinsic parameters has been performed for the experimental 0.5 μm FD SOI technology. The EKV model card obtained from transistor measurements is implemented straightforwardly for circuit simulations. The first study presented in this thesis is an FD SOI Hall sensor front-end for energy measurement. The mixed-mode microsystem design is completely based on the proposed design methodology. The system level solutions are also included, such as the spinning-current method that serves for reduction of the offset and low frequency noise of the analog front-end, and a high resolution analog-to-digital conversion technique. The integrated microsystem is entirely functional. Furthermore, according to the existing literature, this integrated circuit is the first microsystem completely realized using FD SOI technology. The overall system error that is obtained is less than 1.5 %. During the second part of this work, a novel sensing scheme that exploits an automatic reference generation based on successive approximations has been developed for the PD SOI capacitor-less 1T DRAM. The 1T DRAM reference current is generated by an adjustable current source. The electrical calibration of the reference current is performed using a digital-to-analog converter and successive approximations algorithm. The proposed scheme is evaluated in a 2 kb test chip. The circuit integrated using PD SOI technology contains a 2 kb 1T memory array, as well as automatic reference generators and peripheral circuits. The automatic reference generator comprises current mode sense amplifier, M/3M converter, and successive approximations register. All blocks implemented in the test chip are described in detail, and PD SOI design issues are discussed. A number of experimental results demonstrate the potential of the PD SOI 1T DRAM for future embedded DRAM applications. The measured retention time under holding conditions is higher than 1s. In the continuous read mode, a few hundreds of the read cycles can be performed without a refresh operation. The test chip has a measured access time of 25 ns with a read cycle time of 70 ns.

EPFL2005

A modular software package for the analysis of power networks and electrical drives

Alain Sapin, Jean-Jacques Simond

This paper deals with a software package for the numerical analysis in transient and steady-state modes of power electrical networks or variable speed drives with arbitrary topologies. The package is composed of a series of units, each representing a specific cell in the network : voltage supply, electrical machine, mechanical system, transmission line, circuit-breaker, phase shifting transformer, static converter with control and command organ, regulator, etc. SIMSEN is highly flexible and efficient. It is implanted on microcomputer or on workstation. The network or the variable speed drive to be simulated is assembled using a graphic input interface by adequatly choosing and linking the building units, so as to fulfill a desired topology. An existing system may be easily extended or modified. A simple procedure can be used in order to define a new unit or to modify an existing one. The initial conditions of operation can be partly or entirely specified by the user. A transient mode of operation may include several successive perturbations. The simulation results are displayed through an efficient graphic interface. An original feature of SIMSEN is its ability to analyse electrical networks involving semi-conductors (diodes rectifiers, thyristor or GTO current converters, voltage inverters, etc.). Thus, systems having a complex structure can be simulated. Practical examples of applications to such systems constitute the main part of this paper : constant or variable speed groups involving induction and synchronous machines, HVDC networks, reactive power static converter SVC. These examples show how SIMSEN can be used for an optimized design of complex networks.

1995

Epitaxial Piezoelectric MEMS on Silicon

Don Isarakorn

Integration of new functional materials into silicon microsystems is a key factor to enable technology for a wide range of innovative MEMS devices. Piezoelectric materials are of primary interest for integrating sensing and actuation functions in MEMS due to their high forces and high energy densities. The use of PZT thin films in MEMS applications offers the possibility of increasing the sensitivity or actuation capabilities of the devices compared to alternatives such as AlN and ZnO. In general, PZT thin films exhibit smaller piezoelectric coefficients and polarizations than PZT bulk materials due to grain size, composition, crystallographic orientation, non-defined stoichiometry and mechanical boundary conditions. Moreover, PZT thin films are typically grown onto amorphous surfaces resulting in polycrystalline structures, which often lead to degraded performance due to fatigue and aging characteristics. Since epitaxial PZT films exhibit properties, including piezoelectric coefficients, polarizations, and dielectric constants, generally superior to polycrystalline films, it is of high interest to consider their application in MEMS devices, however, there are some real challenges to be solved. Once these issues are overcome, epitaxial PZT thin films could offer interesting potentials in the realization of high performance piezoelectric MEMS. In this thesis, several aspects related to the development of epitaxial piezoelectric MEMS on silicon are investigated, which cover the following topics: the deposition and integration of high quality epitaxial PZT thin films on silicon wafers; the establishment of microfabrication techniques with associated process flows; and the FEM supported design, and characterization of epitaxial piezoelectric MEMS. A short overview is first given on the current state-of-the-art of piezoelectric MEMS. The integration of epitaxial oxide films on silicon wafers and their properties is then briefly described. The epitaxial oxide thin film heterostructures are based on a piezoelectric Pb(Zr0.2Ti0.8)O3 layer grown on 2'' silicon wafers through two oxide layers: SrTiO3 used as buffer and metallic SrRuO3 used as bottom electrode. The optimized microfabrication process for these oxide layers with specific attention in maintaining the piezoelectric properties of the epitaxial PZT films is presented. The polarization was measured to optimize their processing with at the end no degradation of the piezoelectric properties throughout the process. The epitaxial PZT thin films exhibit a large piezoelectric coefficient d31 of 130-140 pm V-1, allowing the realization of MEMS devices with enhanced actuation/detection properties, such as large amplitude actuation with lower driving voltage, high sensitivity, and high efficiency in energy conversion. The superior properties of the epitaxial PZT thin film and the effectiveness of the optimized microfabrication techniques have been demonstrated by two examples of epitaxial PZT MEMS devices. First, different epitaxial PZT cantilevers with and without a Si proof mass have been developed for vibration energy harvesting applications. A high power density of up to 14 µW g-2 was obtained with high current generation and usable voltage, while maintaining lower optimal resistive load. The second application is based on an epitaxial PZT membrane to produce a resonating device. The study of basic characteristics of such device has shown excellent results as it shows a strong harmonic oscillation response with a high quality factor at atmospheric pressure. The finite element model of the epitaxial PZT membrane has then been developed for localized-mass sensing application to determine the resonant frequency, and the effect of the position of the mass and of the resonant mode on the mass sensitivity. The mass sensitivity is of the order 10-12 g Hz-1, which is in excellent agreement with the simulated value. The minimum detectable mass of ∼5 ng can be achieved. These results indicate that the integration of epitaxial thin films on silicon is a promising technology, which improves the performances of piezoelectric MEMS devices. Finally, the concept of charge integration technique for static measurement in piezoelectric sensors is proposed. This technique improves the detection sensitivity of piezoelectric sensors in low frequency measurements, which makes them suitable for chemical and biological detection in a liquid environment.