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In elite European football, 6 to 7 hamstring muscle injuries occur per team per season, which results in an absence of 14 to 180 days (Ekstrand et al. 2017). These injuries occur typically in the last part of a training or match. This implies that the accumulation of demanding actions is an important factor for hamstring injury risk. In current practice, physical player load is measured at the field by deriving the global location of the player with GPS and RFID systems. However, these systems are not able to monitor leg movement and to distinguish demanding actions like kicking, cutting and jumping.In order to monitor these actions in the field, a novel design is being developed. The design consists of five sensor nodes with IMUs (Inertial measurement units), integrated in sports tights. IMUs can measure linear accelerations, angular velocities and magnetic fields in three directions. From these measurements, 3D kinematics of the lower limbs can be derived. An iterative design approach is used to develop the tights. Four prototypes will be developed. Each prototype is tested in a football specific setting, to identify areas of improvement from a technical point of view as well as from a user’s perspective. The final aim of this research is to develop sensor tights that can be worn unobtrusively by football players in the field. Real-time data are retrieved by the coach. This allows the coach to intervene when there is a high injury risk. Keywords: wearable sensors; injury prevention; smart clothing

In-vivo sensors yield valuable medical information by measuring directly on the living tissue of a patient. These devices can be surface or implant devices. Electrical activity in the body, from organs or muscles can be measured using surface electrodes. For short term internal devices, catheters are used. These include cardiac catheter (in blood vessels) and bladder catheters. Due to the size and shape of the catheters, silicon devices provided an excellent solution for sensors. Since many cardiac catheters are disposable, the high volume has led to lower prices of the silicon sensors. Many catheters use a single sensor, but silicon offers the opportunity to have multi sensors in a single catheter, while maintaining small size. The cardiac catheter is usually inserted for a maximum of 72 h. Some devices may be used for a short-to-medium period to monitor parameters after an operation or injury (1–4 weeks). Increasingly, sensing, and actuating, devices are being applied to longer term implants for monitoring a range of parameters for chronic conditions. Devices for longer term implantation presented additional challenges due to the harshness of the environment and the stricter regulations for biocompatibility and safety. This paper will examine the three main areas of application for in-vivo devices: surface devices and short/medium-term and long-term implants. The issues of biocompatibility and safety will be discussed.

Sweating is a normal reaction of the body to exercise. Although much of sweat is water, there are many other components. These components can be an indication of the condition of the athlete. Increase of elements and salts in the tissue will also work their way through to the sweat. Measurement directly in tissue can be an excellent indicator, but a non-invasive approach is simpler to use and safer. Concentrations in sweat can also be an indication that the athlete is in danger of collapse. This paper looks into the components in sweat and how this change with exercise. The aim is to develop a simple, wearable system able to warn the athlete of the impending danger and prevent a potential accident.

Cochlear implants (CIs) are commonly accepted therapeutic devices for clinical use and have restored hearing to more than 230,000 profoundly deaf people. CI devices consists of an external part comprising a speech processor (DSP) a microphone which together receive and convert the sound into a digital data stream using a speech processing strategy. The digital data is then transferred via an RF link to the internal part, viz. the receiver-stimulator package, which receives power and decodes the instructions for controlling the electrical stimulation via a multichannel electrode array placed inside the cochlea, giving a rich and natural perception of sound [Fig.1].

A method for determining a spring constant k for a deformable probe element (102) of a scanning probe microscope SPM (100). The probe (102) has an outer surface area consisting of a tip area (112) on a first probe side (108) and a tip-less area (113). The probe (102) also has a probe electrode (114) and a scanning probe tip (104) in the tip area (112). The method comprises: providing an actuation electrode (116) that is spatially separated from the probe (102); adjusting a potential difference V applied between the probe electrode (114) and the actuation electrode (116); deflecting the probe (102) into a contacted state of the actuation electrode (116) with only a contact portion of the tip-less probe area (113); measuring an EPI-potential difference Vpi between probe electrode (114) and actuation electrode (116), and deriving the spring constant k, based on the EPI-potential difference Vpi. Furthermore, an SPM (100) and calibration device with this method functionality are provided.

The interaction between electrical engineering and bio-medicine can be traced back centuries to the discovery that muscles work with electrical pulses. However, these early experiments did not lead to direct medical applications. The era of microelectronics has brought many new medical applications, from devices to improve the quality of life, such as hearing aids, to live saving devices for the operating theatre.

The invention relates to a infrared sensor (1) comprising a Golay cell (2) in the form of a chamber that houses a heatable gas, which chamber is delimited by a movable diaphragm (3), wherein there are conversion means (4) for converting a movement of the diaphragm into a variation of a measurable electrical parameter, wherein the diaphragm comprises a thermal absorber material (6) or is externally provided with a thermal absorber layer.

This paper presents a new low-cost, CMOS-compatible and robust wafer-level encapsulation technique developed using a stress-optimised PECVD SiC as the capping and sealing material, imparting harsh environment capability. This technique has been applied for the fabrication and encapsulation of a wide variety of surface- and thin-SOI microstructures that included microcavities, a RF switch and various accelerometers. Advantages of our technique are its versatility, smaller footprint, reduced chip thickness and process complexity, post-CMOS batch processing capability and added functionality due to the possibility of integrating additional electrodes for MEMS. Besides fabrication details, this work also discusses design aspects and demonstrates the encapsulation results. Encapsulation of structural area as large as 955 x 827 µm^2 has been successfully achieved.

Leakage at the site of an anastomosis is the main, yet unsolved reason for mortality in abdominal surgery. Every year, a large number of patients die due to anastomotic leakage after surgery. An objective aid to monitor the anastomotic site pre- and postoperatively and detect leakage at an early stage, is needed. Therefore, a miniature, wireless measurement system to detect tissue viability during and after colon surgery (continuously for 7 days) is being developed. The complete sensor chip should include an oxygen- saturation sensor (sO2) an oxygen-tension sensor (pO2) a carbon-dioxide tension sensor (pCO2)and a temperature sensor. The present work focuses on the use of the oxygen-tension and temperature sensors for animal studies. Initial in-vivo measurements were carried out on the small and large intestines of male wistar rats. The main goal was to measure the distribution of pO2 on the colon around the anastomosis and to determine the changes in pO2 during repetitive ischemia-and-reperfiision experiments on the small intestine. The paper presents the obtained measurement results.

Surgical drill system comprising a mechanical drill bit and means for imaging the vicinity of the drill bit tip, said means comprising: at least one optical fiber having a distal end and a proximal end, said distal end being located adjacent said drill bit tip, an optical processing unit, said proximal end of said at least one optical fiber being operatively connected to said processing unit, said at least one optical fiber directing light transmitted therethrough to the vicinity of said drill bit tip and collecting light reflected back from the vicinity of the drill bit tip, whereby an image in the vicinity of the drill bit tip is produced, wherein at least one optical fiber is housed within the drill bit.

Tissue vitality is monitored by means of a sensor attached to the tissue. Preferably, the sensor is attached to the tissue at the end of a surgical intervention, for example after anastomosis of the colon. The sensor is attached to the tissue with a sensitive surface facing the tissue, e.g. at a point of anastomosis. The sensor is designed to measure for example (partial) carbondioxide or oxygen pressure of the tissue, or the amount of oxygenated hemoglobin in the tissue. The sensor is incorporated in a sensing device with a wireless transponder circuit to read sensor output data from a wireless transponder circuit. As a result the sensor can subsequently be used to read out information about tissue vitality, even if the sensor itself is located in an inaccessible location, such as the inside of the colon, without physically perturbing the tissue

This paper presents an on-going work to develop micromachined silicon-based strain sensor inspired from the campaniform sensillum of insects. We present simple optical setup for the characterisation of a membrane-in-recess structure as an early stage in mimicking the natural sensor. The microstructure is a 500 nm-thick SiO2/SiN circular membrane, burried 13 ?m from the surface of a 3x3 mm, 525 ?m thick Si-chip. The chip was attached to a 45x10x0.525 mm Si beam. The simple optical characterisation setup is based on imaging the reflected laser beam from the biomimetic structure. Since an optical cavity between the membrane and the Si beams beneath was formed, ideal flat-parallel Fabry-Perot interferometer equation was applied to interpret the results semi-quantitatively. We obtained 2-D interference fringe pattern having 3 orders of maxima from the middle to the edge of the circular apperture, as a result of an initial internal membrane stress. The pattern changed non-linearly as we applied flexural strain from behind the beam up to 50 ?m, most probably caused by nonlinear deflection of the membrane (i.e. the membrane did not deflect similarly as the beam beneath it). This phenomena might explain one of the strain-amplifying properties of this biomimetic strain sensing microstructure.

Planar silicon carbide (SiC) waveguides are proposed for fabrication on a silicon substrate with a oxide isolation layer. Using post deposition annealing it is possible to achieve low Polarization-Dependent Loss (PDL) within optical SiC waveguides fabricated using a low temperature deposition technique. Those waveguides have been successfully used in power splitters and cantilivers. These first devices open the way for photonic sensing in harsh environment using SiC.

This is the second part of two articles reporting investigation on a thermal-detector-type far-infrared sensor operating in the 8–14 µm wavelength region using Low-Pressure Chemical Vapor Deposition (LPCVD) deposited low-stress Si-rich nitride (SiN) membrane as its thermal absorber. The use of the SixNy membrane material as a far-infrared radiation absorber has been reported in many papers, there are still few reports addressing its fundamental optical absorption property at thiswavelength region, in relation with its thermal properties, utilized in an infrared sensing device. After dealing with optical absorptivity of suchmembrane in the first paper, this second article deals with the thermal property, aswell as the overall sensitivity issue of the sensor. In this report, similarly, a combination of analytical modelling, numerical simulation, and experimental characterisation is carried out. The issue of scaling down is also addressed. Results show that the thermal sensitivity depends on the membrane size. A 1000µm×1000µm will achieve 80 K/(Wcm−2), while membrane as small as 10µm×10µm has only 0.15–0.3 K/(Wcm−2).

Medulloblastoma, a common pediatric malignant central nervous system tumour, represent a small proportion of brain tumours in adults. Previously it has been shown that in adults, Sonic Hedgehog (SHH)-activated tumours predominate, with Wingless-type (WNT) and Group 4 being less common, but molecular risk stratification remains a challenge. We performed an integrated analysis consisting of genome-wide methylation profiling, copy number profiling, somatic nucleotide variants and correlation of clinical variables across a cohort of 191 adult medulloblastoma cases identified through the Medulloblastoma Advanced Genomics International Consortium. We identified 30 WNT, 112 SHH, 6 Group 3, and 41 Group 4 tumours. Patients with SHH tumours were significantly older at diagnosis compared to other subgroups (p < 0.0001). Five-year progression-free survival (PFS) for WNT, SHH, Group 3, and Group 4 tumours was 64.4 (48.0-86.5), 61.9% (51.6-74.2), 80.0% (95% CI 51.6-100.0), and 44.9% (95% CI 28.6-70.7), respectively (p = 0.06). None of the clinical variables (age, sex, metastatic status, extent of resection, chemotherapy, radiotherapy) were associated with subgroup-specific PFS. Survival among patients with SHH tumours was significantly worse for cases with chromosome 3p loss (HR 2.9, 95% CI 1.1-7.6; p = 0.02), chromosome 10q loss (HR 4.6, 95% CI 2.3-9.4; p < 0.0001), chromosome 17p loss (HR 2.3, 95% CI 1.1-4.8; p = 0.02), and PTCH1 mutations (HR 2.6, 95% CI 1.1-6.2; p = 0.04). The prognostic significance of 3p loss and 10q loss persisted in multivariable regression models. For Group 4 tumours, chromosome 8 loss was strongly associated with improved survival, which was validated in a non-overlapping cohort (combined cohort HR 0.2, 95% CI 0.1-0.7; p = 0.007). Unlike in pediatric medulloblastoma, whole chromosome 11 loss in Group 4 and chromosome 14q loss in SHH was not associated with improved survival, where MYCN, GLI2 and MYC amplification were rare. In sum, we report unique subgroup-specific cytogenetic features of adult medulloblastoma, which are distinct from those in younger patients, and correlate with survival disparities. Our findings suggest that clinical trials that incorporate new strategies tailored to high-risk adult medulloblastoma patients are urgently needed.

© The Author(s), under exclusive licence to Springer Nature Limited 2019, In cancer, recurrent somatic single-nucleotide variants-which are rare in most paediatric cancers-are confined largely to protein-coding genes1-3. Here we report highly recurrent hotspot mutations (r.3A>G) of U1 spliceosomal small nuclear RNAs (snRNAs) in about 50% of Sonic hedgehog (SHH) medulloblastomas. These mutations were not present across other subgroups of medulloblastoma, and we identified these hotspot mutations in U1 snRNA in only

Outbreaks of bacteria have caused many problems over the last few years and are a major public health concern. Bacteria are now affecting our lives in many ways to a more severe extent, from contaminated food in markets to polluted water. There are some devices available which detect bacteria, however, all of them can only be used in the lab condition and are very expensive. This research is aimed at the development of a biomedical sensor which is capable of monitoring bacteria, especially focusing on diagnosing colorectal anastomotic leakage (AL) in patients at an early stage by detecting the existence of E. coli in the drain fluid. The occurrence of AL in patients after colon surgery is high and is cause for concern as it can lead to severe consequences, such as morbidity or even mortality. Therefore, there is a vital need for an efficient, on-line bedside tool to monitor the bacteria in the leakage: a diagnostic on-line device that is accurate, cost-effective, and ideally operates in an easy plug-and-play fashion which is beneficial for practical application.

While molecular subgrouping has revolutionized medulloblastoma classification, the extent of heterogeneity within subgroups is unknown. Similarity network fusion (SNF) applied to genome-wide DNA methylation and gene expression data across 763 primary samples identifies very homogeneous clusters of patients, supporting the presence of medulloblastoma subtypes. After integration of somatic copy-number alterations, and clinical features specific to each cluster, we identify 12 different subtypes of medulloblastoma. Integrative analysis using SNF further delineates group 3 from group 4 medulloblastoma, which is not as readily apparent through analyses of individual data types. Two clear subtypes of infants with Sonic Hedgehog medulloblastoma with disparate outcomes and biology are identified. Medulloblastoma subtypes identified through integrative clustering have important implications for stratification of future clinical trials.

BACKGROUND: Patients with incomplete surgical resection of medulloblastoma are controversially regarded as having a marker of high-risk disease, which leads to patients undergoing aggressive surgical resections, so-called second-look surgeries, and intensified chemoradiotherapy. All previous studies assessing the clinical importance of extent of resection have not accounted for molecular subgroup. We analysed the prognostic value of extent of resection in a subgroup-specific manner. METHODS: We retrospectively identified patients who had a histological diagnosis of medulloblastoma and complete data about extent of resection and survival from centres participating in the Medulloblastoma Advanced Genomics International Consortium. We collected from resections done between April, 1997, and February, 2013, at 35 international institutions. We established medulloblastoma subgroup affiliation by gene expression profiling on frozen or formalin-fixed paraffin-embedded tissues. We classified extent of resection on the basis of postoperative imaging as gross total resection (no residual tumour), near-total resection (30 Gy vs no craniospinal irradiation). The primary analysis outcome was the effect of extent of resection by molecular subgroup and the effects of other clinical variables on overall and progression-free survival. FINDINGS: We included 787 patients with medulloblastoma (86 with WNT tumours, 242 with SHH tumours, 163 with group 3 tumours, and 296 with group 4 tumours) in our multivariable Cox models of progression-free and overall survival. We found that the prognostic benefit of increased extent of resection for patients with medulloblastoma is attenuated after molecular subgroup affiliation is taken into account. We identified a progression-free survival benefit for gross total resection over sub-total resection (hazard ratio [HR] 1·45, 95% CI 1·07-1·96, p=0·16) but no overall survival benefit (HR 1·23, 0·87-1·72, p=0·24). We saw no progression-free survival or overall survival benefit for gross total resection compared with near-total resection (HR 1·05, 0·71-1·53, p=0·8158 for progression-free survival and HR 1·14, 0·75-1·72, p=0·55 for overall survival). No significant survival benefit existed for greater extent of resection for patients with WNT, SHH, or group 3 tumours (HR 1·03, 0·67-1·58, p=0·89 for sub-total resection vs gross total resection). For patients with group 4 tumours, gross total resection conferred a benefit to progression-free survival compared with sub-total resection (HR 1·97, 1·22-3·17, p=0·0056), especially for those with metastatic disease (HR 2·22, 1·00-4·93, p=0·050). However, gross total resection had no effect on overall survival compared with sub-total resection in patients with group 4 tumours (HR 1·67, 0·93-2·99, p=0·084). INTERPRETATION: The prognostic benefit of increased extent of resection for patients with medulloblastoma is attenuated after molecular subgroup affiliation is taken into account. Although maximum safe surgical resection should remain the standard of care, surgical removal of small residual portions of medulloblastoma is not recommended when the likelihood of neurological morbidity is high because there is no definitive benefit to gross total resection compared with near-total resection. FUNDING: Canadian Cancer Society Research Institute, Terry Fox Research Institute, Canadian Institutes of Health Research, National Institutes of Health, Pediatric Brain Tumor Foundation, and the Garron Family Chair in Childhood Cancer Research.

Neural stimulation is an established treatment methodology for an increasing number of diseases. Electrical Stimulation injects a stimulation signal through electrodes that are implanted in the target area of the central or peripheral nervous system in order to evoke a specific neuronal response that suppresses or treats pathological activity. This thesis discusses the design of neural stimulators: the device that is responsible for generating the stimulation signal in a safe, efficient and controlled manner. The design of such a device requires a highly multidisciplinary approach which involves disciplines such as neuroscience, electrophysiology, electrochemistry and electrical engineering. The first part of this thesis focuses on the processes associated with the neuronal recruitment. After describing the stimulation processes in detail at various levels, the discussion zooms in on the processes at the electrode-tissue interface and in particular the electrochemical behavior. Many neural stimulators include coupling capacitors between the stimulator and the electrodes to reduce the risk of potentially harmful electrochemical reactions. However, it is shown that coupling capacitors also have negative implications that need to be considered, such as a shift in the equilibrium potential of the electrode-tissue interface. Also, the reversibility of charge transfer processes at the electrode-tissue interface is analyzed. Most studies rely on monitoring the electrode-tissue interface potential to determine the maximum reversible charge injection limits. By measuring the reversible charge in a more direct way, it was found that under specific conditions the irreversible charge transfer processes already play a role for stimulation intensities that are well below the established charge injection limits. The extensive description of the stimulation process is furthermore used to introduce a fundamentally different stimulation paradigm. Instead of using a constant current or voltage to stimulate the electrodes, a high frequency, switched-mode stimulation signal is applied. The advantage of such a stimulation pattern is that it can be generated in a power efficient way by the neurostimulator circuit using switched-mode operation that is common in energy efficient amplifiers (class-D operation) or power management circuits. The efficacy of the proposed stimulation pattern is verified both using modeling as well as using in vitro measurements by analyzing the response of patch-clamped Purkinje cells. The second part of the thesis focuses on the electrical design of neural stimulators. The first system is designed to be used in a specific neuroscientific experiment and features arbitrary waveform stimulation. The user has full flexibility over the choice of stimulation waveform, while the stimulator circuit guarantees safety by ensuring charge balanced operation. The stimulator circuit is realized and included in a system implementation that is suitable for the specific in vivo experimental setup. The stimulation pulse (which uses a burst pattern) is synchronized with auditory stimulation in an attempt to recondition the neural pathways in a mouse that suffers from tinnitus. The second design implements the high-frequency switched-mode stimulation pattern that was introduced in the first part of the thesis. The system features an unfiltered forward buck-boost converter at its core to directly stimulate the target tissue. It is possible to operate the system with multiple independent channels that connect to an arbitrary electrode configuration, making the system well suited for current steering techniques. Furthermore, comprehensive control was implemented using a dual clock configuration that allows both autonomic tonic stimulation, as well as single shot stimulation. Each channel can be configured individually with tailored stimulation parameters and multiple channels can operate in a synchronized fashion. The system is power efficient, especially when compared with state-of-the-art constant current stimulators with an adaptive power supply that operate in multichannel mode. Efficiency improvements up to 200% compared with state of the art constant current stimulators are demonstrated. Furthermore, the number of external components required is reduced to a single inductor.

This thesis investigates a novel deformable mirror that works on the basis of the electrostatic deformation of a liquid surface. The liquid mirror allows large surface displacements, a large number of actuators, and the modification of its properties, while at the same time the mirror design is simple and may be realized without sophisticated technology. The mirror is capable of dynamic wavefront correction, fine imaging, and spatial light modulation. The mirror is demonstrated to be a low-cost versatile tool for Adaptive Optics that can be implemented for less than 100 Euro.

Packaging has evoluted for years with the sole purpose of protecting the electronics from the environment and providing a suitable operating environment. Integration became a necessity and technologies as System-in-Package emerged and enabled the integration of components built with different technologies within a single package. All this evolution lead to technologies as Wireless Sensor Networks (WSNs), networks composed of nodes which at the time contain sensors to monitor environmental variables like temperature, humidity, pressure, location, etc. in different locations at the same time. The nodes communicate the obtained data to a main location or share it with nearby nodes. WSNs are the perfect example of a technology that requires a SiP approach since it is composed by an antenna and a radio chip to provide communication skills, one or more sensors to provide sensing skills, a microcontroler to provide processing capabilities and a battery to provide electrical energy to the system. New technologies create new needs. In the areas of logistics and asset management those new needs will be created by the technology proposed in the PLEISTER (Packaged Label Electronics Including Sensing Talkative Enhanced Radio). This thesis is the product of working on low-temperature and low-cost packaging solutions for the PLEISTER project. In the vision of the PLEISTER project, a group of Wireless Sensor Network nodes can form a self-contained network capable of monitoring itself; that is to say, if a node joins/leaves the network, this will be noticed automatically and reported to other nodes. Furthermore, the network can sense and monitor status information as location, temperature, humidity, among others. In addition, the methods proposed and developed within the frame of the PLEISTER project are extended for their application on packaging solutions for microfluidics. Accelerated testing is used to test the compatibility of the different materials used within determined packaging solution and accelerate the possible failures. Failure analysis techniques are used to locate and analyse the failures. What concerns the Wireless Sensor Network nodes, the packaging solutions are developed from two points of view, the practical approach and the research approach. The practical approach uses technologies already tested and available in the market to propose a packaging solution while the research approach investigates the use of new methods to propose a packaging solution for WSN nodes. Two topics are developed during the research approach: the use of Electrically Conductive Adhesives (ECAs), as a replacement for ultrasonic welding and soldering, to electrically and mechanically attach the Li-ion batteries to the electronics, and the use of inkjet printing technology to print interconnection lines directly on top of the battery and therefore replace the substrate material by the battery. What concerns the ECAs, the contact resistance of glued bonds is higher than the contact resistance of welded bonds. When welding, the oxide layer of the material is completely removed and when gluing, the oxide layer is not totally removed due to the instant contact of the surface with oxygen prior to gluing and after removing the oxide. When low-temperatures are desired during the fabrication process and welding is not possible, gluing is a good option. If used for long time, the contacts corrode due to the presence of humidity and the composition of the joined materials (aluminum and silver) causing an increase in the contact resistance; however, biased tests prove that the increased contact resistance may not be a problem, depending on the currents required by the application. Furthermore, inkjet printing of reliable interconnection lines directly on Li-ion batteries is possible. The packaging foil from the Li-ion battery presented in this work is hydrophobic and therefore a plasma treatment is desired to improve the wettability of the surface. Silver inks present good electrical performance, the resistivity and microstructure is not affected by different ageing processes and there is no indication of silver migration; however, the adhesion can be improved and optimized according to the ink-substrate combination to be used. The application requires inks that cure at less than 155 °C; the lines must be printed before forming the battery. UV curable or room temperature curable inks are desired; in this case, the lines can be printed after forming the battery. In the second part, packaging solutions for microfluidic applications are developed. A packaging concept to integrate electronics and nano/microfluidic chips in one device is developed. For this, the use of PCB material as substrate and mechanical support for the chips is suggested. The use of TMMF dry film resist to create channels on top of the PCB material and chips is proposed. The inlaying of the chips in the PCB material is experimentally researched as well as the lamination of the microfluidic channels. Furthermore, inkjet printing is used to print electrical interconnection lines from the pads on the chip to the tracks on the PCB. Inlaying the chips in the PCB is the most critical part of the process, the chip and the PCB have to be at the same level and the space between the chip and the PCB must be controlled to ensure that the profile of the surface on which the channels and interconnection lines are fabricated, is as flat as possible. The printed lines should be printed before laminating the channels since the ink cures at 125 °C. UV inks and room temperature curing inks are desired. Laminating TMMF channels is possible, however the baking temperatures during the fabrication process need to be ramped slowly to avoid cracks in the TMMF laminated over the chips. Furthermore, since the channels are wide (more than 500 µm), the sealing of the channels has to be performed at room temperature; this causes a weak seal and thus the devices should be used carefully. The integration methods developed and researched in this thesis can be expanded to a broad range of applications.

This dissertation aims to advance the current state of cantilevers with integrated metal thermal and deflection sensing elements. Metallic sensing elements enable the use of alternative substrate materials (such as polymers), that tend to exhibit higher compliance properties and are more robust (less brittle) compared to Si or Si3N4 cantilevers. To this end, the research consists of exploring the properties of thin films with thicknesses of 100 nm or less and studying a number of applications in thermal sensing, micro-heating, and deflection sensing. In order to achieve these goals three fabrication processes for microcantilevers were developed. The minimum detectable temperature change of a cantilever with the 10 nm gold thermal sensing element was measured at 0.4 K, corresponding to 17 ppm changes in probe resistance. Finite element analysis simulations indicate a strong correlation between thermal probe sensitivity and probe tip curvature, suggesting that the sensitivity of the thermal probe can be improved by increasing the probe tip curvature, though at the expense of the spatial resolution provided by sharper tips. Simulations also indicated that new designs such as a bow-tie metallization design could yield an additional 5- to 7-fold increase in sensitivity. The gauge factor of the thin film is enhanced to 3.24 for a 10 nm gold sensor and 4.1 for the 5 nm gold sensor doubling that of bulk gold. The sensors on silicon cantilevers exhibited large dynamic range of tens of microns and were used to measure: the mechanical properties of materials, the melting points of materials, topographical imaging, and high throughput measurements. Moving nano-heater were used to direct chemical vapor deposition reactions (nano-CVD) demonstrating a tip-based nanofabrication (TBN) method. The silicon cantilevers with embedded thin film heaters were used for localized nano-CVD to grow copper (Cu) and copper oxide (CuO) from gases. Polyimide cantilevers with thin metallic sensing elements were coated with colorimetric sensing material and used for explosive detection enhancing the sensitivity by 30x compared to what was previously found when the colorimetric sensing material was used alone. Metal thin films on cantilevers with thicknesses

This thesis studies the effects of scaling on the characterisation and readout of micro-electro mechanical systems (MEMS) to nano-electro mechanical systems (NEMS). In particular it focuses on cantilever, which is a basic device building block and an important transducer in many sensing applications. This thesis presents an overview of major scaling effects and discusses their scaling factors. It includes scaling analysis on physical property aspects such as quality factor, Young’s modulus, thermal noise and elastic non-linearity. It also includes scaling analysis on practical aspects such as sensitivity, mass-stiffness decoupling and surface contamination. Furthermore, it studies the scaling of different cantilever detection techniques, in particular the laser deflection, hard contact, field emission and piezoresistive sensing techniques. Down-scaling a cantilever sensor is an intuitive way of increasing its sensitivity and responsiveness. However the advantages gained must be weighed against other effects which also became significant due to the scaling. For this reason, this thesis provides the necessary information, analysis and methods that help assessing the advantages and disadvantages of scaling.

Research in the field of Micro/nanofluidics has been extensively carried out for the last few years. With the available technological advancements today many complex systems can be fabricated in a more efficient and simpler way. Conventional methods in a laboratory consumes a lot of time, chemicals and in turn generates a lot of waste unlike the Lab-on-a-chip (LOC) devices where all the processes are carried out on a small chip with small drops of chemicals, negligible wastes and in minimum time. Most of all this is very efficient and inexpensive. Most of the work in this project was concentrated on developing and optimizing the technologies for the fabrication of micro and nanofluidic devices. Conventional soft-lithography was used initially to fabricate the microfluidic devices using PDMS. Realizing the limitations in working with PDMS the choice was made to replace PDMS with TMMF S2030 dry film photoresist (DFR) which turned out to be fruitful. Working with DFR is inexpensive, more accurate and easier compared to working with PDMS in microfluidics. Dry film photoresist (DFR) is a new type of photoresists, which is gaining importance in semiconductor industry. These are generally negative tone photoresists in the form of a thin foil protected by PET (Polyethylene terephthalate) on both sides. They are differentiated into permanent and non-permanent resists. The minimum known thickness of the available dry films is 15 µm and the maximum reaching to few hundreds of microns. They can potentially replace soft lithographic materials, since they are easier to process. Dry film photoresists have a big role to play in microfluidics, which is yet to be completely explored. Manipulating a single cell has been an interesting topic for the researchers in the field of microfluidics for a long time. Our design fulfils the idea of trapping, cell viability, manipulation, sensing and detection. The devices were equipped with different channels for different applications like, providing nutrients to the cell, to hold the cell with suction and to collect the reaction by-products, sense and detect them. Di-electrophoresis is a well known technique for manipulating neutral particles/cells in fluids and it is widely used in micro fluidic systems for forcing particles to desired trajectories. Since the particle has to be moved in the horizontal plane, the width and the introduction point of the particle are more critical variables. Presorter electrodes were introduced more upstream in the entrance channel which will bring far-off particles to the trapping range and also a minimum distance between presorter and trapping electrodes should be regarded. One more important goal is to keep the cell in the reservoir once it is there. This can be achieved by a simple electrode pair blocking the outlet of the hole. The particle is repelled from the resulting field. The same repelling force will prevent other particles to enter the hole. The geometry of electrodes was designed so that it is only necessary to modify the applied voltage according to the entrance speed. Experiments for trapping polystyrene beads followed by E.coli bacteria were successfully carried out with the help of a dedicated holder and an Olympus inverted microscope. Research stops nowhere. Following the path from microfluidic devices for single cell analysis, we have concentrated on developing nanofluidic devices for DNA analysis. Lot of research has been carried out in nanofluidics for DNA, protein and nucleic acid analysis studies. Existing devices have electrodes placed at the ends of microchannels and a potential is applied to move the particles into the nanochannels. The devices we aimed at have electrodes embedded within the nanochannels along with electrodes at the junctions of micro and nanochannels. The main idea in designing and fabricating these devices with embedded electrodes is to study the behavior of the biomolecules in a localized electrical field. Devices were fabricated by a conventional anodic bonding process and a completely new single silicon wafer process. To our knowledge this is the first time that nanofluidic devices (200 nm deep channels and integrated electrodes) were fabricated on a single silicon wafer. The nanochannels in this case were defined by sacrificial etching. Electrodes were patterned on the top side of the nanochannels. Microchannels were etched from the back side of the silicon wafer connecting to the nanochannels through a membrane of silicon nitride. Initial experiments were carried out with rhodamine + ethanol solution to prove the opening of nanochannels without any leakage followed by trapping carboxylate modified fluorescent polystyrene beads to confirm the working of embedded electrodes. Further experiments were carried out with DNA molecules tagged with a fluorescent dye. DNA molecules were injected into the microchannel and once the channels were filled completely, electrodes in the microchannels were switched on to drag the DNA molecule towards the entrance of the nanochannel. Then the EOF voltage over the nanochannel was switched on to drag the DNA through the nanochannel. A single DNA molecule was successfully tracked over the length of the nanochannel. Time and the distance travelled by the molecule were calculated. Using microfluidic devices further experiments on sensing and detection can be carried out with single cells. Behavior of different lengths of DNA within the electrical double layer in a localized electric field can be studied with the help of the fabricated nanofluidic devices. Experiments were also carried out to define the best etch mask to etch completely through a glass wafer. Amorphous silicon turned out to be the best etch mask material to etch the glass in 40% HF. Even though slight pin holes were observed by using PECVD amorphous silicon, we recommend that thick layers sputtered in batches will resolve this problem and a clear surface can be achieved. It is recommended that LPCVD amorphous silicon would be the best etch mask if it can be sputtered at lower temperatures. Along with amorphous silicon, Molybdenum can also be a good etch mask if more research has been done on improving the adhesion of ‘Mo’ to glass substrates.

HEALTHCARE in the 21st century is changing rapidly. In advanced countries, in particular, healthcare is moving from a public to a more personalized nature. However, the costs of healthcare worldwide are increasing every year. Better use of technology can and should be used to get control of these costs. At the same time, implants have clearly benefitted from the astounding technology-miniaturization trends of late, boasting smaller sizes, lower power consumption and increased performance of the transistor devices. However, such advances do not come for free. Adverse effects in current implant designs are being witnessed, such as increasing power consumption, absence of design for reliability and highly application-specific nature. Operating under the assumption that implants will constitute an important means towards improved, personal healthcare and, in view of the aforementioned design phenomena, we believe that a new paradigm in implant design is required. This dissertation establishes the concept of Smart implantable Medical Systems (SiMS). SiMS is a systematic approach – a framework – for providing biomedical researchers and, hopefully, industry with a toolbox of ready-to-use, highly reliable implant sub-systems and models in order to construct optimal implants for various medical applications. The SiMS framework has to guarantee essential attributes, such as high dependability, modular design, ultra-low power consumption and miniature size. Having defined the SiMS framework, this dissertation is, then, concerned with exploring the optimal microarchitectural details of a crucial SiMS component: the SiMS processor. Contrary to the current state of the art, this processor aspires to be a new universal, low-power and low-cost processor and capable of efficiently serving a wide range of diverse implant applications.

The massive integration of micromechanical structures on ICs to allow microsystems to sense and control the environment is expected to be one of the most important technological breakthroughs of the future. At present, cheap and small MEMS sensors are emerging in countless applications. Automotive and telecommunication industry have fueled the biggest R&D effort so far in this area. Prominent results, among others, are the accelerometer guarding the safety systems in vehicles, the miniature microphone in cellphones and inkjet printing heads. Although miniaturization is the main driver of MEMS development in industry – reducing cost by decreasing material consumption and allowing batch fabrication, MEMS offer an important collateral benefit with respect to traditional systems: an increase of applicability and reliability. This development very much concerns existing microelectronic building blocks that by efficient integration with each other can grow to more functional, intelligent systems on the same chip. One such block is the crystal oscillator for frequency reference used in clocks, radios, computers and cellphones etc. to provide a stable clock signal for digital integrated circuits, and to stabilize frequencies for radio transmitters and receivers. Regarding the vast demand of timing devices for time-keeping and frequency reference applications, the research of MEMS based oscillators has a lot of attention. It is expected that these oscillators – built with a MEMS resonator – will offer smaller form factor, improved reliability, and lower solution cost than the common crystal oscillator with its IC incompatible quartz resonator. Efforts over recent years have shown that MEMS resonators are capable of high quality factor Q, exhibit low temperature drift and pair excellent phase noise performance to low power consumption. As MEMS based oscillators need vacuum conditions for proper and reliable operation of the mechanical resonator, the packaging process of these devices must provide direct caps to the resonators that make a hermetic sealing. The life-time testing of these sealings pose a big challenge to in-situ pressure detection methods in resonator samples during fabrication. We have realized a sensitive pressure sensing operation of the resonator itself by reading out the damping forces exerted by the residual gas in an out-of-plane, low frequency resonance mode. No additional structures or signals other than the common resonance parameters, Q and !0, required! The behavior of the damping forces in the resonator agrees well to a new model that we particularly developed for designing resonators as pressure sensors in the mbar range. Thanks to free molecular flow in the cavity of typical resonators these forces can be formulated analytically with just one parameter dependent on numerical evaluation. Because of the direct physical significance of this and other parameters in the derived formulas, the model provides valuable clues for the optimization of sensor design. It saves time-consuming trial-and-error loops of design and fabrication that would be needed alternatively. The methods and results of this thesis demonstrate that out-of-plane, low frequency resonance mode operation of resonator samples establishes sensitive detection of cavity pressure offering cheap and easy life-time testing in industry. Our designoriented model for the governing forces between residual gas and resonator structure holds for a multitude of different geometries within a margin of error of 12%, making model-based design of MEMS resonant pressure sensors to a reality.

The potential of light in diagnosis and therapy has been long recognised. With the advent of scientific progress in our understanding of light propagation and interaction with tissue and parallel major technological advances in how optical energy can be generated, detected and processed, this potential is being realised. Linking with this trend, this thesis is devoted to the investigation and development of new instrumentation and numerical tools for biophotonics. This work is presented with an emphasis on its application to osseous tissue, although its possible usages are much broader. The introductory chapter gives gives a short historical perspective on the usage of light for diagnosis and therapy, and presents an overview of goals of this thesis, motivating the work and pointing out the main scientific contributions. It also describes the organisation of the book in chapters. Chapter 2 provides the reader with the basic background knowledge that is needed to understand this thesis. It also tries to stress the existing links between the different topics discussed in the book. In particular, some concepts on bone biology are presented, followed by a description of the physics of light propagation in tissue and the basics of the Monte Carlo method used to compute it. Then, the fundamentals of Optical Coherence Tomography are presented, together with basic elements of Planar Waveguide Technology. Chapter 3 contains a description of a novel code for Monte Carlo simulation for arbitrarily complex geometries. This code was required due to the intricate architecture of bone, which was not tractable using available tools. Specifically, it is shown that using a hierarchical space partitioning scheme and simple shape elements, such as triangles, the intersection test between photon and geometry has a very small computational cost. This code has been used in later chapters to simulate light transport in reality based models of trabecular bone. Chapter 4 summarises the research done on light propagation in bone and the effect of bone histology on the average optical properties that can be measured using techniques based on the diffusion approximation. It starts by describing a numerical study where light propagation through models of trabecular bone recovered from micro computed tomography is calculated using the Monte Carlo code described in chapter 3. The simulated time-resolved curves are then fitted using a model based on the diffusion approximation, recovering homogenised parameters. Since it is possible to change the properties postulated in the model for the calcified matrix of bone and marrow separately, we can isolate the role of micro structure easily. The results of this study show that the architecture of bone, together with the properties of the individual phases determine the homogenised properties of tissue. More precisely, the volume fractions are the most important factor, while other morphological parameters such as trabecular connectivity or thickness have a statistically significant, but minor, role as predictors. Using numerical methods, we have also evaluated the value of the average optical properties as predictors of clinically relevant histological and morphological parameters. We have observed that although the optical properties are a direct function of the individual properties of the phases plus the structure, lack of knowledge about the individual constituents obscures the recovery of values such as bone volume fraction or scattering coefficient of the matrix in a general case. However, if multiple wavelengths are combined, this indetermination could be overcome. This investigation was combined with experimental work on the same samples that were used for the numerical study. Making use of ultrafast time-resolved equipment it was possible to reproduce the transmittance signals simulated, and the homogenised optical transport parameters of bone were then calculated using the same type of curve fitting approach. A statistical analysis was done on the relation between these average values and the histological and morphological properties of bone as calculated from micro computed tomography data. It was found that the optical coefficients are statistically significant predictors of the apparent mineral density of bone even at a single wavelength, but the determination is somewhat low. If the mineral density of the calcified matrix is included as a predictor, then the regression for the bone volume fraction gets a much higher determination, underlining the interwoven nature of the relation between optical and histomorphological properties. Work at multiple wavelengths has shown us that a regression with only a synthetic parameter computed from the spectral behaviour of the scattering coefficient has a strong predictive value for the bone mineral density, confirming our observation in the numerical part that spectral measurements can offer a full characterisation of bone. Chapter 5 describes a silicon photonics implementation of a thermo-optic rapid scanning delay line for Optical Coherence Tomography, a crucial component in the implementation of this imaging technology. The proposed device has obvious advantages in terms of cost, reliability and system size and complexity. All these factors are very important for the widespread adoption of OCT in surgical guidance applications, which are the ones that are expected to be most commonly involved in the study of bone tissue. In particular, in this chapter we describe in detail the fabrication of the device, present a thorough analysis of its thermal and optical performance and show experimental performance results. We have demonstrated that this approach is valid and meets the performance requirements demanded by most surgical guidance applications. The ability to produce this crucial element on a general purpose photonic platform, opens the door to full OCT systems on a chip. Chapter 6 discusses the concept of implantable solid state optode systems. We illustrate this idea by presenting preliminary work done on two exemplary applications. The first one is related to monitoring bone growth around a special type of skeletal implant —the spinal cage— and the second one concerns itself with the monitoring and delivery of Photodynamic Therapy for Glioblastoma Multiforme. The first application was explored using a numerical and an in vitro evaluation of the forward problem to estimate light distribution around the implant and compute the expected signal intensities, while the second one had a stronger focus on implementation, with a telemetric single optode implant being constructed and demonstrated. Some conclusions on the results reported throughout the thesis are drawn in the last chapter. There, the relevance of the individual chapters is presented in the context of the thesis. The author’s opinions on the possible future evolution of the topics discussed in this book are also put forward.

There was an explosive growth in the bioprocess industry market during the last decade. The tight control of these processes is often very critical in order to optimize the process efficiency or even achieve the right product. Capillary electrophoresis (CE) system is a good option for process monitoring and controlling, since it has already been proved to be a powerful analytical tool used in laboratory situations. However the extremely high separation voltage required by CE operation is preventing the system miniaturization and integration, and thus hindering its way to in-line application. Therefore, in this work, two low-voltage separation methods are proposed and investigated with the aim of substituting the conventional microfluidic CE. In the first DEP method, the curved parts of a serpentine channel are effectively used for dielectrophoretic separation. The second method moving field CE is basically an evolution version of the traditional CE, in which the required separation voltage is significantly reduced by decreasing the span of the electrodes in the channel. For the DEP method, the curves are the essential parts where the dielectrophoretic separation takes place. A DC-biased AC electric field allows small particle separation in a curve as the dielectrophoresis is decoupled from the electroosmosis. The separation sensitivity was found to have a second order dependence on the ratio of AC to DC amplitudes and a linear dependence on the particle size. The separation resolution is limited by the Brownian motion and is voltage dependent. Since the curves are bended in the opposite directions, the separation will be wiped out in the next curve. Therefore, focusing must be conducted to bring all the particles to the same entering point for the next curve. In terms of focusing, the top-and-bottom electrode structure performs superior to the planar array for negative DEP because stronger electric field gradients are generated and particles are forced away from walls where nonuniform flow and nonspecific particle adhesion can occur. Because the hydrodynamic flow profile in a curve also decreases monotonously from the channel center to the outer sidewall, the same device can be used for both hydrodynamic and electrokinetic DEP separation. The hydrodynamic DEP,bearing a higher flow gradient, is expected to produce a larger separation than the electrokinetic DEP. The DEP device was fabricated by bonding of two processed substrates with an SU-8 layer sandwiched in between. The retention time of 2 µm and 4 µm PS particles in a channel segment containing 4 curves was measured in the case of hydrodynamic DEP. The 4 µm particles turn out to take an average 10% longer retention time than the 2 µm particles, which proves the concept. It was revealed that applying a DC voltage over a fraction of the channel will evoke flow distortion in moving field CE operation, and will in turn cause plug dispersion and peak broadening. For a given voltage, the smaller fraction it is applied on, the larger flow distortion will be caused in the EOF region. By extracting and analyzing the equivalent circuits of the fluid system, the flow distortion was found to be the consequence of a backward flow. The method we proposed is to generate, by coupling an electroosmotic pump (EOP), a forward flow and compensate the backward flow in the EOF segment. Specific pump structures were designed to relieve the driving voltage to the same level as the separation voltage. They are an array of slender channels and a broad thin channel. In order to minimize the flow loss, the channel arrays are proposed to be used in the injection channels as well to increase the flow resistance. The moving field CE prototype device was fabricated by laminating two layers of dry film resist on a processed glass substrate. The first layer is used to define the channel structure and the second acts as the lid of the channel. The flow distortion compensation was observed when the EOP driving voltage was increased to a certain level. The required EOP driving voltages with respect to different separation voltages were measured, which exhibit a linear relationship as expected. To detect cells at extremely low concentrations, we additionally proposed a biomass concentration detection method in which an electrokinetic technology is used for rapidly increasing the concentration of the cells while measuring the concentration. Due to the dielectric contrast between the viable cell and the surrounding medium, the cells could be trapped and accumulated by positive dielectrophoresis. Based on the simplified homogeneous sphere model, the frequency dependence of the induced dipole strength of the yeast cell was studied by computer methods. The threshold DEP forces required to dominate over the Brownian motion for cell trapping were investigated. To achieve accurate and sensitive detection, a contactless 4-electrode conductivity detector was suggested to be used. Readout circuits and measurement setups were verified by using ideal resistors to mimic the environment of a liquid suspension. This method is recommended to be further investigated by using viable yeast cells in future research.

Mechanical resonators are widely applied in time-keeping and frequency reference applications. Mechanical resonators are preferred over electrical resonators because of their high Q. In the $4.1 billion (2008) timing market, quartz crystals are still ubiquitous in electronic equipment. Quartz crystals show excellent performance in terms of stability (shortterm and long-term), power handling, and temperature drift. MEMS resonators are investigated as a potential alternative to the bulky quartz crystals, which cannot be integrated with IC technology. MEMS offer advantages in terms of size, cost price, and system integration. Efforts over recent years have shown that MEMS resonators are able to meet the high performance standards set by quartz. Critical success factors are high Q-factor, low temperature drift, low phase noise, and low power. This PhD thesis addresses the feasibility of scaling MEMS resonators/oscillators to frequencies above 10 MHz. The main deliverable is a 52 MHz MEMS-based oscillator. The MEMS resonators at NXP are processed on 8-inch silicon-on-insulator (SOI) wafers, with a SOI layer thickness of 1.5 µm and a buried oxide layer thickness of 1 µm. The strategic choice for thin SOI substrates has been made for two reasons. First, MEMS processing in thin silicon layers can be done with standard CMOS processing tools. The silicon dioxide layer serves as a sacrificial layer. Second, identical substrates are used for the Advanced Bipolar CMOS DMOS (ABCD) IC-processes. This class of processes can handle high voltages (ABCD2 up to 120V). The high voltage capability is suitable for the transduction of the mechanical resonator. Both MEMS and IC are processed on a similar substrate, since the strategic aim is to integrate the MEMS structure with the IC-process in the long run. Frequency scaling is investigated for both the capacitive and the piezoresistive MEMS resonator. MEMS resonators have been successfully tested from 13 MHz to over 400 MHz. This is achieved by decreasing the size of the resonator with a factor 32. We show that the thin SOI layer and the decreasing size of the resonator increase the effective impedance of the capacitive resonator at higher frequencies. For the piezoresistive resonator, we show that this readout principle is insensitive to geometrical scaling and layer thickness. Therefore, the piezoresistive readout is preferred at high frequencies. The effective impedance can be kept low, at the expense of higher power consumption. Frequency accuracy can be improved by decreasing the initial frequency spread and the temperature drift of the MEMS resonator. The main source of initial frequency spread is geometrical offset, due to the non-perfect pattern transfer from mask layout to SOI. A FEM tool has been developed in Comsol Multiphysics to obtain compensated layouts. The resonance frequency of these designs is first-order compensated for geometric offset. The FEM tool is used to obtain compensated resonators of various designs. We show empirically that the compensation by design is effective on a 52 MHz square plate design. For the compensated design, frequency spread measurements over a complete wafer show that there are other systematic sources of frequency spread. The resonance frequency of the silicon MEMS resonator drifts about –30 ppm/K. This is due to the Young’s modulus of silicon that depends on temperature. We have investigated two compensation methods. The first is passive compensation by coating the silicon resonator with a silicon dioxide skin. The Young’s modulus of silicon dioxide has a positive temperature drift. Measurements on globally oxidized structures show that the right oxide thickness reduces the linear temperature drift of the resonator to zero. A second method uses an oven-control principle. The temperature of the resonator is fixed, independent of the ambient temperature. A demo of this principle has been designed with a piezoresistive resonator in which the dc readout current through the resonator is used to control the temperature of the resonator. With both concepts, more than a factor 10 reduction in temperature drift is achieved. To demonstrate the feasibility of high-frequency oscillators, a MEMS-based 56 MHz oscillator has been designed for which a piezoresistive dogbone resonator is used. The amplifier has been designed in the ABCD2 IC-process. The MEMS oscillator consumes 6.1 mW and exhibits a phase noise of –102 dBc/Hz at 1 kHz offset from the carrier and a floor of –113 dBc/Hz. This demonstrates feasibility of the piezoresistive MEMS oscillator for lowpower, low-noise applications. Summarizing, this PhD thesis work as part of the MEMSXO project at NXP demonstrates a MEMS oscillator concept based on the piezoresistive resonator in thin SOI. It shows that by compensated designs for geometric offset and oven-control to reduce temperature drift, a frequency accuracy can be achieved that can compete with the performance of crystal oscillators. In a benchmark with MEMS competitors the concept shows the lowest phase noise, making it the most suited concept for wireless applications.

New emerging sensing applications demand novel sensors in micro-/nano-scale to enable integration and embedding into higher level structures or systems. Downsizing the structure will usually decrease the sensitivity of the sensors, since the sensitivity is a function of geometrical parameters, e.g. mass in the case of inertial sensing, and absorbing surface area in the case of an infrared sensor. To maintain a detectable readout signal for the processing electronics, new transducing mechanisms have to be devised for micro- and nano-scale sensors. Nature, especially from insects of the animal kingdom, can provide an inspiration source for the development of such novel miniaturised sensors. This thesis describes the design, analysis through simulation, fabrication, and characterisation of several examples of novel sensors inspired from natural physical sensors found in insects. The thesis serves two purposes, first, to elucidate the working mechanisms of several natural biological sensors by a combination of synthesis and analysis, and second, to implement similar working mechanisms in artificial engineering material and structure for novel sensors development. After reviewing physical sensors found in nature, and existing bio-inspired sensor developments, three cases of novel bioinspired sensors development are given. The first case is the development of a biomimetic strain sensor, inspired from the Campaniform sensillum found in insects. The second case presented is the development of a biomimetic gyroscope, inspired from the haltere found in the fly. The last case presented is the feasibility study on the development of biomimetic far infrared sensor, inspired from the biological infrared sensor found in the beetle, Melanophila acuminate. The field of applications of new transduction mechanisms inspired from biological sensors to novel ultraminiaturised sensors is very wide. Ultraminiaturised strain sensors that can be integrated into mechanical structures could provide smart structures for buildings, cars, airplanes, and robots. Novel ultraminiaturised gyroscopes could find their application in hand-held devices for personal navigation, as well as for man-machine interface. Novel ultraminiaturised infrared sensor which can be fabricated using standard CMOS technology could find its application in civilian night vision application, such as pedestrian detection in cars, and civilian security night surveillance camera.

The wavefront measurement is an important part both in adaptive optics and in optical shop testing. A number of wavefront sensors based on interferometric or on Hartmann principle is known; this thesis investigates particular technologies that can help to increase the accuracy and/or speed of existing wavefront sensors either by optimising the wavefront reconstruction algorithm or by optimising the hardware. The topics discussed are interferogram analysis, optimising of the Hartmann mask geometry, and design of a 2D heterodyne phase detector.

This thesis presents various aspects regarding the development of an ultrasound sensor systems for use in laparoscopic intervention. The accuracy achieved after using compensation technique for air flow disturbances or temperature variations remains in a convenient range of 200µm. Considering this high accuracy, the flexibility and the ergonomics achieved for this system, the final device may be adapted very easily and used also in other microsurgery applications.

Modal wavefront correctors are active optical components for the compensation of aberrated optical wavefronts in a smooth and continuous way. They are traditionally represented by membrane and continuous faceplate deformable mirrors. This thesis is dedicated to the investigation and development of modal wavefront correctors based on nematic liquid crystals. The thesis introduces a new method for evaluating the average static correction performance of a wavefront corrector applied to compensation of random phase aberrations. Statistics of the random wavefronts are described by Kolmogorov's theory. The method allows a comparison of the static correction performances of different types of deformable mirrors and different actuator structures. A range of modal liquid crystal (LC) devices is considered, including adaptive spherical and cylindrical LC lenses and three different types of multi-element wavefront correctors. The research is focused on electro-optics of the devices, consideration of potentially useful control modes, development of algorithms of optimization and control, and alternative technologies for modal addressing of LCs. A control algorithm and software have been developed for a system for practical calibration of modal LC lenses. Feasibility of control using several degrees of freedom per actuator is demonstrated for both adaptive LC lenses and multi-element modal wavefront correctors. Two new approaches to forming of the modal-type phase profiles in LC layers are considered. The first one is based on spreading of the electric field in a thick dielectric substrate and the second one is based on a passive resistive network formed in a semiconductor silicon substrate. These approaches are illustrated with practically implemented devices. Comparison of the new technologies to a previously studied one is presented.

This thesis deals with the dry etching of deep anisotropic microstructures in monocrystalline silicon by high-density plasmas. High aspect ratio trenches are necessary in the fabrication of sensitive inertial devices such as accellerometers and gyroscopes. The etching of silicon in fluorine-based plasmas is isotropic. To obtain anisotropy the addition of sidewall passivation is necessary. This is achieved with both oxygen passivation at low temperatures and fluorocarbon passivation at room temperature. A quantitative approach was pursued to explain the etching mechanism. The etch results were analysed using the measured plasma species fluxes and the surface composition. Moreover, the transport of the plasma species in narrow anisotropic structures is a fundamental factor determining the etch rate and the profile evolution. The experimental methods such as the etching equipment, plasma diagnostics, surface analysis and sample preparation are described in chapter 2. Three etching processes were investigated: the cryogenic etching process with oxygen passivation at low temperatures, the Bosch process with fluorocarbon passivation at room temperature and the novel triple pulse process that was developed in our laboratory. The polymer deposition mechanism and the characteristic role of the ions are also explained. The cryogenic etching process is discussed in chapter 3. Fluorine radicals, oxygen radicals and ion bombardment are responsible for the three main sub-processes, that is, etching, sidewall passivation and depassivation of the trench bottom, respectively. Etching experiments with an extremely low ion-to-radical flux ratio were used to reveal the etching mechanism. Crystal orientation dependent etching leading to Si(111) crystal facets is observed in a surface kinetics controlled regime. By varying the plasma conditions it is possible to adjust the etching mechanism from fluorine-limited to ion-limited. Controlled etching is obtained because the etching is tuned from aspect ratio dependent in the fluorine-limited domain to aspect ratio independent in the ion-limited domain. The transport of radicals in high aspect ratio trenches is an important limiting factor and was investigated with special structures. The etch results are described by an analytic model that is based on the surface site balance of fluorine and oxygen radicals. The results are further explained with a Monte Carlo simulation model. The Bosch process is clarified in chapter 4. The anisotropy of the etched structures is controlled by balancing the etching and passivation pulse. However, the maximal obtainable aspect ratio is limited by convergence of the trench sidewalls due to excessive passivation. The maximal obtainable aspect ratio increases if the ion-to-radical flux ratio increases. The transport of ions is an important limiting factor in the depassivation of the bottom of the trench. Divergence of the ion beam leads to a reduction of the ion flux, so that the fluorocarbon passivation is insufficiently removed near the base of the sidewalls. The average ion angle was measured and correlated to the maximal obtainable aspect ratio. The Bosch process was improved at the depassivation side with the triple pulse process and at the passivation side with preferential sidewall deposition. The triple pulse process that is described in chapter 5 has the aim to improve the depassivation in deep trenches. The three main sub-processes are decoupled using a separate depassivation pulse directly after the etching and passivation pulses. The fluorocarbon passivation is efficiently removed with low-pressure, high-density, oxygen-based plasmas. The investigated plasma chemistries include O2, CO2 and SO2. The triple pulse process leads to better profile control with a straight trench bottom. However, the maximal obtainable aspect ratio is comparable to the Bosch process because a larger etch depth and a small lateral etch cancel out. The polymer deposition mechanism is treated in chapter 6 with the aim to understand the fluorocarbon passivation in deep trenches. The deposition on plane surfaces and on special structures was investigated to distinguish between the radical-induced and ion-enhanced components. A simple analytical model, which explains the main deposition characteristics, was developed. Preferential sidewall deposition is obtained for higher ion fluxes and higher bias voltages where sputtering plays an important role. In this case no fluorocarbon passivation has to be removed from the bottom of the trench. The trench profile was optimised in the Bosch process by tuning the bias voltage during etching and passivation independently. It resulted in perfectly anisotropic trenches but the maximal obtainable aspect ratio was still limited by a small lateral etch. The characteristic role of the ions in the etching mechanism is explained in chapter 7. Ion-induced etching of both SiC in a SF6-O2 plasma and Si in a Cl2 plasma were investigated. The impact of the ions on the profile evolution can be examined more explicitly because spontaneous chemical reactions are absent for these plasma-material systems. The etching mechanism varies from fluorine-limited to ion-limited depending on the radical-to-ion flux ratio. Microtrenches are observed for an ion-limited etching mechanism. Fluorine-limited SiC etching is aspect ratio dependent in contrast to ion-limited SiC etching, which is aspect ratio independent. The etching of high aspect ratio SiC structures is limited by the positive sidewall taper. This is presumably caused by insufficient removal of the thin fluorocarbon layer on the surface. Si etching in a Cl2 plasma is always aspect ratio independent in contrast to SiC etching because of the low reaction probability. The conclusions and recommendations of this thesis are given in chapter 8.

This thesis addresses the design, implementation and performance of an integrated Hartmann-Shack wavefront sensor suitable for real-time operation and compatible with a standard technology. A wavefront sensor can be used for the detection of distortions in the profile of a light beam or of an optical component.With such a sensor, one can, for instance, estimate the distortions of a human-eye lens or the distortions present in a light beam after this has propagated through a turbulent atmosphere. Moreover, the wavefront sensor can be coupled to a deformable mirror such that this combination can compensatedistortions in a laser beam. This kind of adaptive system finds more and more applications in astronomy, industry andrecently in medicine. We propose the implementation of a Hartmann wavefront sensor that uses a matrix of integrated position-sensitive detectors which are compatible with standard Complementary Metal-Oxide-Semiconductor technology (CMOS). A wavefront is sampled into a number of light spots, whose displacements are proportional to local tilts of the wavefront. The idea is to have one position-sensitive detector per sampled spot, such that direct information about the spot-centroid position is available. This scheme renders faster operation than when a conventional imager is used because it circumvents the image-processing step. The developed wavefront sensor proved to meet all the initially proposed prerequisites: it is capable of real-time operation, compact, simple and compatible with a standard technology. In terms of performance, each particular application has its own requirements and the developed sensor, which should be used with light sources in the visible spectrum, shall perform well for applications involving enough light (> 0.5-mW beams) and there where lower-order wavefront aberrations are expected (< 30 Zernike terms). The sensor can be modified in a variety of ways to attend to particular applications.