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The purpose of this work is the development of MEMS-based resonant sensors for liquid-phase biochemical sensing applications. Specifically, the sensors developed here are aimed at embedded or point-of-sampling applications: (1) when there is not enough time to send a sample to a lab for analysis, (2) in resource-poor settings, (3) when collecting analyte and shipping it to a lab would damage the sample, or (4) for in-situ monitoring. To this end, a bulk micromachined resonant cantilever sensor and a surface micromachined sensor based on the spring-softening effect are investigated as transducer elements. The developed cantilever resonators are operated in an in-plane vibration mode to reduce fluid damping and mass loading by the surrounding fluid. The surface of the resonator is either coated with a chemically sensitive polymer film for chemical sensing or with a layer of protein or antibody for biosensor testing. Chemical tests for sensing volatile organic compounds using polymer-coated in-plane resonators in the liquid-phase give estimated limits of detection below 100 ppb. In addition, biosensor tests for the detection of anti-IgG yield estimated limits of detection around 100 ng/ml. In an attempt to further improve sensor reliability and to further lower the limits of detection, a second sensing concept has been investigated. The presented sensing scheme is capacitive with a resonator acting as an analog-to-digital converter. The resonator and the sensing capacitors are coupled via the spring softening effect. Through this mechanism a change in capacitance causes a shift in resonant frequency. Extensive device modeling has been performed and a process has been developed allowing for fabrication and on-chip packaging of these sensor structures. Initial mechanical characterization data show that the resonators do in fact vibrate.

Cette thèse présente la conception de MEMS à base de matériaux organiques et cela, en vue de réaliser des capteurs biochimiques. Dans ces travaux les matériaux organiques ont été proposés en tant qu’alternative au silicium afin, d’une part, de réduire le coût des capteurs biochimiques par le développement de procédés de structuration simples et peu couteux et, d’autre part, car les polymères peuvent être synthétisés de telle sorte à leur conférer des propriétés spécifiques et contrôlables pour une application visée. Dans ces travaux à fort caractère technologique, des méthodes adaptées à la structuration de ce type de matériau ont été développées. Une de ces méthodes consiste à déposer le matériau organique au travers d’un micropochoir fait en SU-8. Cette méthode permet de déposer et de structurer le matériau en une seule étape, d’une part, et d’autre part de mettre en forme des polymères photo et thermosensibles. Une méthode de report inspirée du «  wafer-bonding en SU-8 » a été adaptée pour la fabrication collective de puces de microleviers organiques. Ensuite, un actionnement électromagnétique a été intégré aux structures afin d’améliorer les performances de ces dernières utilisées en tant que résonateur.Et enfin, un concept original de biocapteur de masse basé sur des microleviers monocouches a été développé. Dans ce cas, la couche sensible faite d’un polymère à empreinte moléculaire assure à la fois, la reconnaissance biologique et la transduction de l’effet mécanique du microlevier. / This thesis presents the design of MEMS-based on organic materials to achieve biochemical sensors. In this work, organic materials have been proposed as an alternative to silicon to reduce the cost of biochemical sensors by developing simple and inexpensive processes, and because polymers can be synthesized to give them specific and controllable properties. In this technological work, suitable methods to pattern this type of materials have been developed. One of these methods combines deposition and patterning in one step thanks to spray-coating through polymer microstencils. Then, to obtain collective production of organic chips free-standing microcantilevers from a free structure, wafer-bonding approach based on bonding of two SU-8 layers has been introduced. On the other hand, an electromagnetic actuator has been integrated into the structures to improve the performances of theses structures used as resonators.And finally, an original concept of mass biosensor based on monolayer microcantilevers has been developed. In this case, the sensitive layer made ​​of molecularly imprinted polymer allows the biological detection and the transduction of the mechanical effect.

The main topic of this thesis is the performance improvement of microresonators as mass-sensitive biochemical sensors in a liquid environment. Resonant microstructures fabricated on silicon substrates with CMOS-compatible micromachining techniques are mainly investigated. Two particular approaches have been chosen to improve the resolution of resonant chemical/biochemical sensors. The first approach is based on designing a microresonator with high Q-factor in air and in liquid, thus, improving its frequency resolution. The second approach is based on minimizing the frequency drift of microresonators by compensating for temperature-induced frequency variations. A disk-shape resonant microstructure vibrating in a rotational in-plane mode has been designed, fabricated and extensively characterized both in air and in water. The designed resonators have typical resonance frequencies between 300 and 1,000kHz and feature on-chip electrothermal excitation elements and a piezoresistive Wheatstone-bridge for vibration detection. By shearing the surrounding fluid instead of compressing it, damping is reduced and quality factors up to 5800 in air and 94 in water have been achieved. Short-term frequency stabilities obtained from Allan-variance measurements with 1-sec gate time are as low as 1.1 10-8 in air and 2.3 10-6 in water. The performance of the designed resonator as a biological sensor in liquid environment has been demonstrated experimentally using the specific binding of anti-beta-galactosidase antibody to beta-galactosidase enzyme covalently immobilized on the resonator surface. An analytical model of the disk resonator, represented by a simple harmonic oscillator, has been derived and compared with experimental results. The resonance frequency and the Q-factor of the disk resonator are determined from analytical expressions for the rotational spring constant, rotational moment of inertia, and energy loss by viscous damping. The developed analytical models show a good agreement with FEM simulation and experimental results and facilitate the geometrical optimization of the disk-type resonators. Finally, a new strategy to compensate for temperature-induced frequency drifts of resonant microstructures has been developed based on a controlled stiffness modulation by an electronic feedback loop. The developed method is experimentally verified by compensating for temperature-induced frequency fluctuations of a microresonator. In principle, the proposed method is applicable to all resonant microstructures featuring excitation and detection elements.

In der vorliegenden Arbeit wurde eine neue Klasse von implantierbaren biochemischen Sensoren bezüglich ihrer Sensitivität im physiologisch relevanten pH- (pH 7,4) sowie Glukose-Konzentrationsbereich (2 - 20 mM) entwickelt und untersucht. Die Glukose-sensitiven Hydrogele basieren auf der Bindung von 5-fach-Zuckern an Boronsäuregruppen, die in einem Acrylamid-basierten Hydrogel mit N,N′-Methylenbisacrylamid (BIS) als Vernetzter (AAm/APB/BIS, 80/20/0,75 mol%) verankert sind. Weiterhin konnten pH-sensitive Hydrogele auf Basis von 2-(Dimethylamino)ethyl Methacrylate (DMAEMA), Hydroxypropyl-methacrylat (HPMA) sowie Tetraethyleneglycol dimethacrylate (TEGDMA) als Vernetzter in unterschiedlichen Zusammensetzungen und Geometrien untersucht werden. Die verwendeten Hydrogele wurden hinsichtlich der Diffusionsprozesse sowie ihrer Quellkinetik charakterisiert, um deren Sensitivität, Selektivität, Reproduzierbarkeit und Ansprechzeit gegenüber den physiologischen Parametern (pH, pCO2, Glukose) zu verbessern. Die aufgebauten pCO2-Sensoren zeigten vielversprechende Ansprechzeiten von wenigen Minuten. Die Glukose und pH-Sensoren wiesen im physiologischen Medium (PBS) deutlich höhere Ansprechzeiten von mehreren Stunden auf. Die Kombination von piezoresistiven Drucksensoren mit Stimuli-sensitiven Hydrogelen bietet nicht nur eine große Vielfalt bezüglich der zu detektierenden Analyten, sondern ermöglicht auch miniaturisierte und implantierbare Sensoren für die kontinuierliche Erfassung von physiologischen Parametern. So war die Verkapselung zum Schutz und zugleich zur Gewährleistung der Biokompatibilität und ohne Beeinträchtigung der Funktionalität und Flexibilität der elektronischen Bauteile das Ziel. Dazu wurden die Sensoren mit dem Polymer Parylene C eingehaust, dass zusätzlich eine Polyethylenglykolschicht enthielt. Hierfür wurden Blockcopolymere mittels Ringöffnungspolymerisation synthetisiert, die Polyaminosäuren als Linkermoleküle und PEG zur gezielten Funktionalisierung enthalten. Nach kovalenter Anbindung an die inerte Parylene C-Oberfläche zeigten sich deutlich veränderte Oberflächeneigenschaften und eine verbesserte Zellkompatibilität und Hämokompatibilität. Zudem wurde der sogenannte Tarnkappeneffekt von PEG-Ketten, die sich in der Schicht nach außen ausrichten, festgestellt. Damit wurde Adsorption von Proteinen (Fibronektin, Fibrinogen), die in Entzündungsreaktionen, der Zelladhäsion sowie der Blutgerinnung maßgebend sind, deutlich verringert. / In this work a new class of implantable biochemical sensors with a high sensitivity at physiological pH (pH 7,4) and glucose (2 – 20 mM) ranges were developed and tested. The glucose sensitive hydrogel was made of acrylamide and N,N′-methylene-bis(acrylamide) as a crosslinker (AAm/APB/BIS, 80/20/0,75 mol%). The swelling mechanism was based on the reversible interaction of sugar molecules and the boronic acid groups in the hydrogel. Also a pH sensitive hydrogel made of 2-(dimethylamino) ethyl methacrylate (DMAEMA), hydroxypropyl-methacrylat (HPMA) and the crosslinker tetraethylene glycol dimethacrylate (TEGDMA) with different molar ratios and geometries was characterized. The swelling kinetics as well as the diffusion processes of different hydrogels were studied to advance sensitivity, selectivity, reproducibility and response time with respect to physiological parameters (pH, pCO2, glucose). pCO2 sensors showed promising short response times of about 4 min whereas glucose and pH sensors displayed longer response times of several hours in phosphate-buffered saline solution. The combination of piezoresistive pressure sensors and stimuli-sensitive hydrogels enables a great diversity of detecting analytes as well as miniaturized and implantable sensors for continuous measuring of physiological parameters. However, to implant the sensors an encapsulation strategy is needed that secures the electronics as well as ensures the biocompatibility without loss of functionality and flexibility. For this, the devices were coated with the polymer parylene C and an additional layer of blockcopolymers composed of polyaminoacid (PAA) and polyethyleneglycol (PEG) blocks synthesized via ring-opening polymerization. The functionalization units are carried out by the PEG blocks whereas the PAA blocks perform as linker molecules onto the activated parylene C surface. After covalent coupling of blockcopolymers to the inert polymer the surface characteristics changed and hence the cell and blood compatibility was improved. Furthermore the stealth effect of the outwards PEG chains was utilized to reduce the adsorption of proteins like fibronectin or fibrinogen. These proteins play a major role in inflammatory processes, cell adhesion and blood coagulation. The results gave proof that the encapsulation leads to decisively reduced physiological reactions.

In der vorliegenden Arbeit wurde eine neue Klasse von implantierbaren biochemischen Sensoren bezüglich ihrer Sensitivität im physiologisch relevanten pH- (pH 7,4) sowie Glukose-Konzentrationsbereich (2 - 20 mM) entwickelt und untersucht. Die Glukose-sensitiven Hydrogele basieren auf der Bindung von 5-fach-Zuckern an Boronsäuregruppen, die in einem Acrylamid-basierten Hydrogel mit N,N′-Methylenbisacrylamid (BIS) als Vernetzter (AAm/APB/BIS, 80/20/0,75 mol%) verankert sind. Weiterhin konnten pH-sensitive Hydrogele auf Basis von 2-(Dimethylamino)ethyl Methacrylate (DMAEMA), Hydroxypropyl-methacrylat (HPMA) sowie Tetraethyleneglycol dimethacrylate (TEGDMA) als Vernetzter in unterschiedlichen Zusammensetzungen und Geometrien untersucht werden. Die verwendeten Hydrogele wurden hinsichtlich der Diffusionsprozesse sowie ihrer Quellkinetik charakterisiert, um deren Sensitivität, Selektivität, Reproduzierbarkeit und Ansprechzeit gegenüber den physiologischen Parametern (pH, pCO2, Glukose) zu verbessern. Die aufgebauten pCO2-Sensoren zeigten vielversprechende Ansprechzeiten von wenigen Minuten. Die Glukose und pH-Sensoren wiesen im physiologischen Medium (PBS) deutlich höhere Ansprechzeiten von mehreren Stunden auf. Die Kombination von piezoresistiven Drucksensoren mit Stimuli-sensitiven Hydrogelen bietet nicht nur eine große Vielfalt bezüglich der zu detektierenden Analyten, sondern ermöglicht auch miniaturisierte und implantierbare Sensoren für die kontinuierliche Erfassung von physiologischen Parametern. So war die Verkapselung zum Schutz und zugleich zur Gewährleistung der Biokompatibilität und ohne Beeinträchtigung der Funktionalität und Flexibilität der elektronischen Bauteile das Ziel. Dazu wurden die Sensoren mit dem Polymer Parylene C eingehaust, dass zusätzlich eine Polyethylenglykolschicht enthielt. Hierfür wurden Blockcopolymere mittels Ringöffnungspolymerisation synthetisiert, die Polyaminosäuren als Linkermoleküle und PEG zur gezielten Funktionalisierung enthalten. Nach kovalenter Anbindung an die inerte Parylene C-Oberfläche zeigten sich deutlich veränderte Oberflächeneigenschaften und eine verbesserte Zellkompatibilität und Hämokompatibilität. Zudem wurde der sogenannte Tarnkappeneffekt von PEG-Ketten, die sich in der Schicht nach außen ausrichten, festgestellt. Damit wurde Adsorption von Proteinen (Fibronektin, Fibrinogen), die in Entzündungsreaktionen, der Zelladhäsion sowie der Blutgerinnung maßgebend sind, deutlich verringert. / In this work a new class of implantable biochemical sensors with a high sensitivity at physiological pH (pH 7,4) and glucose (2 – 20 mM) ranges were developed and tested. The glucose sensitive hydrogel was made of acrylamide and N,N′-methylene-bis(acrylamide) as a crosslinker (AAm/APB/BIS, 80/20/0,75 mol%). The swelling mechanism was based on the reversible interaction of sugar molecules and the boronic acid groups in the hydrogel. Also a pH sensitive hydrogel made of 2-(dimethylamino) ethyl methacrylate (DMAEMA), hydroxypropyl-methacrylat (HPMA) and the crosslinker tetraethylene glycol dimethacrylate (TEGDMA) with different molar ratios and geometries was characterized. The swelling kinetics as well as the diffusion processes of different hydrogels were studied to advance sensitivity, selectivity, reproducibility and response time with respect to physiological parameters (pH, pCO2, glucose). pCO2 sensors showed promising short response times of about 4 min whereas glucose and pH sensors displayed longer response times of several hours in phosphate-buffered saline solution. The combination of piezoresistive pressure sensors and stimuli-sensitive hydrogels enables a great diversity of detecting analytes as well as miniaturized and implantable sensors for continuous measuring of physiological parameters. However, to implant the sensors an encapsulation strategy is needed that secures the electronics as well as ensures the biocompatibility without loss of functionality and flexibility. For this, the devices were coated with the polymer parylene C and an additional layer of blockcopolymers composed of polyaminoacid (PAA) and polyethyleneglycol (PEG) blocks synthesized via ring-opening polymerization. The functionalization units are carried out by the PEG blocks whereas the PAA blocks perform as linker molecules onto the activated parylene C surface. After covalent coupling of blockcopolymers to the inert polymer the surface characteristics changed and hence the cell and blood compatibility was improved. Furthermore the stealth effect of the outwards PEG chains was utilized to reduce the adsorption of proteins like fibronectin or fibrinogen. These proteins play a major role in inflammatory processes, cell adhesion and blood coagulation. The results gave proof that the encapsulation leads to decisively reduced physiological reactions.

The absence of appropriate media to cultivate photons efficiently at the micro or nano scale has hindered taking the full advantage of processing information with light. The proposal of such a medium for light, known as photonic crystals (PCs)--multi-dimensional artificially periodic dielectric media--brings the possibility of a revolution in communications and sensing much closer. In such media, one can manipulate light at a scale on the order of the wavelength or even shorter. Applications of PCs other than in communication include bio-sensing because of the peculiar properties of PCs such as the capability of enhance field-matter interaction and control over the group velocity. As a result, PC waveguide (PCW) structures are of interest and it is expected that PC sensors offer the feasibility of multi-analyte and compact sensing schemes as well as the ability of the detection of small absolute analyte quantities (nanoliters) and low-concentration samples (picomoles), which may be advantages over conventional approaches such as fiber optic and slab waveguide sensors. Depending on the nature of the analyte, either dispersive or absorptive sensing schemes may be implemented. Light propagation is controlled fully only with 3D PCs. One of the problems arising due to reducing the dimension to 2D is that PCs become strongly polarization sensitive. In many cases, one wants to implement polarization insensitive devices such that the PC provides a full band gap for all polarizations. To address this problem, a novel type of PC called annular PC is proposed and analyzed. The capability of tuning the TE and TM polarizations independently within the same structure provides great flexibility to produce polarization-independent or polarization-dependent devices as desired. PCW bends are expected to be the essential building blocks of photonic integrated circuits. Sharp corners having small radii of curvature can be obtained. To enhance the low-loss and narrow-band transmission through these bends, PC heterostructures waveguide concept is introduced. We show that in PCWs formed by joining different types of PCs in a single structure, light can flow around extremely sharp bends in ways that are not possible using conventional PCWs based on a single type of PC.