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Changes in respiratory rate have been found to be one of the early signs of health deterioration in patients. In remote environments where diagnostic tools and medical attention are scarce, such as deep space exploration, the monitoring of the respiratory signal becomes crucial to timely detect life-threatening conditions. Nowadays, this signal can be measured using wearable technology; however, the use of such technology is often hampered by the low quality of the recordings, which leads more often to wrong diagnosis and conclusions. Therefore, to apply these data in diagnosis analysis, it is important to determine which parts of the signal are of sufficient quality. In this context, this study aims to evaluate the performance of a signal quality assessment framework, where two machine learning algorithms (support vector machine-SVM, and convolutional neural network-CNN) were used. The models were pre-trained using data of patients suffering from chronic obstructive pulmonary disease. The generalization capability of the models was evaluated by testing them on data from a different patient population, presenting normal and pathological breathing. The new patients underwent bariatric surgery and performed a controlled breathing protocol, displaying six different breathing patterns. Data augmentation (DA) and transfer learning (TL) were used to increase the size of the training set and to optimize the models for the new dataset. The effect of the different breathing patterns on the performance of the classifiers was also studied. The SVM did not improve when using DA, however, when using TL, the performance improved significantly (p < 0.05) compared to DA. The opposite effect was observed for CNN, where the biggest improvement was obtained using DA, while TL did not show a significant change. The models presented a low performance for shallow, slow and fast breathing patterns. These results suggest that it is possible to classify respiratory signals obtained with wearable technologies using pre-trained machine learning models. This will allow focusing on the relevant data and avoid misleading conclusions because of the noise, when designing bio-monitoring systems. ispartof: FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY vol:10 ispartof: location:Switzerland status: published

Cardiovascular diseases (CVD) are often characterized by their multifactorial complexity. This makes remote monitoring and ambulatory cardiac rehabilitation (CR) therapy challenging. Current wearable multimodal devices enable remote monitoring. Machine learning (ML) and artificial intelligence (AI) can help in tackling multifaceted datasets. However, for clinical acceptance, easy interpretability of the AI models is crucial. The goal of the present study was to investigate whether a multi-parameter sensor could be used during a standardized activity test to interpret functional capacity in the longitudinal follow-up of CR patients. A total of 129 patients were followed for 3 months during CR using 6-min walking tests (6MWT) equipped with a wearable ECG and accelerometer device. Functional capacity was assessed based on 6MWT distance (6MWD). Linear and nonlinear interpretable models were explored to predict 6MWD. The t-distributed stochastic neighboring embedding (t-SNE) technique was exploited to embed and visualize high dimensional data. The performance of support vector machine (SVM) models, combining different features and using different kernel types, to predict functional capacity was evaluated. The SVM model, using chronotropic response and effort as input features, showed a mean absolute error of 42.8 m (&plusmn, 36.8 m). The 3D-maps derived using the t-SNE technique visualized the relationship between sensor-derived biomarkers and functional capacity, which enables tracking of the evolution of patients throughout the CR program. The current study showed that wearable monitoring combined with interpretable ML can objectively track clinical progression in a CR population. These results pave the road towards ambulatory CR.

AIMS: Chronic stress is an important factor for a variety of health problems, highlighting the importance of early detection of stress-related problems. This methodological pilot study investigated whether the physiological response to and recovery from a stress task can differentiate healthy participants and persons with stress-related complaints. METHODS AND RESULTS: Healthy participants (n = 20) and participants with stress-related complaints (n = 12) participated in a laboratory stress test, which included 3 stress tasks. Three physiological signals were recorded: galvanic skin response (GSR), heart rate (HR), and skin temperature (ST). From these signals, 126 features were extracted, including static (eg, mean) and dynamic (eg, recovery time) features. Unsupervised feature selection reduced the set to 26 features. A logistic regression model was developed for 6 feature sets, analysing single-parameter and multiparameter models as well as models using recovery vs response-related features. The highest classification performance (accuracy = 78%) was obtained using the response-related feature set, including all physiological signals and using GSR-related features. A worse performance was obtained using single-signal feature sets based on HR (accuracy = 66%) and ST (accuracy = 59%). Response-related features outperformed recovery-related features (accuracy = 63%). CONCLUSION: Participants with stress-related complaints may be differentiated from healthy controls by physiological responses to stress tasks. We aimed to bring attention to new exploratory methodologies; further research is needed to validate and replicate the results on larger populations and patients on different areas along the stress continuum. ispartof: HEALTH SCIENCE REPORTS vol:1 issue:8 ispartof: location:United States status: published

Monitoring biopotential signals such as electrocardiography (ECG) and electroencephalography (EEG) provides important information about certain health-related conditions which open up a broad range of applications. The electrical and mechanical properties of electrodes used for the measurements have a great impact on the quality of the signals. Conventional wet electrodes, which contain conductive gel to hydrate the skin and lower the electrode/skin impedance, are widely used. Furthermore, the flexible gel stays in good contact with the skin during movement, hence the impedance also remains low when the subject is moving. However, the gel’s various drawbacks are also well-known. For example, before an EEG monitoring, the setup of wet electrodes is not only often time-consuming but also ought to be done by an expert. During EEG monitoring, signal degradation occurs due to the gel drying out, and skin irritation due to the glue used to fix the electrodes on the scalp are often observed. After EEG recording, removing the glue to detach the electrode is difficult and can mess up the hairstyle. To avoid these drawbacks of the wet electrodes, various types of dry electrodes have been introduced. In this thesis, dry electrodes fabricated from a flexible conductive polymer are presented. The elastic properties -especially the flexibility- of the conductive polymer ensure higher user comfort than obtained by rigid metal electrodes. The conductivity of the polymer does away with the need for any extra conductive coating layer, which often flakes off during use. Electrodes with various pin-shapes (length, width, density) are fabricated for different applications. Various additives have also been added to the polymer, and additive type and quantity are optimized to obtain low contact impedance and good mechanical properties for better comfort and skin contact. Impedance measurements on phantoms and human skin are carried out for impedance characterization. The electrodes with optimal material composition, i.e. polymer containing 43% of carbon, show only ~10 times higher electrode/skin impedance than that of wet electrodes. Applying abrasive gel or lotion with the polymer dry electrodes and producing sweat before the measurements reduce the impedance of polymer electrodes. However, the impedance does not remain low because the agents reducing the impedance (gel, lotion or sweat) disappear with time. The influences of these skin pretreatments and sweat processes on the electrode/skin impedance with time are investigated by modelling the recorded impedance with the equivalent electrical circuits. To investigate the mechanical properties of the polymer dry electrodes, compression tests are carried out for elastic modulus and compliance characterization. The elastic modulus of polymer materials increases with growing carbon content and electrodes made from polymer with a higher carbon content show to be less compliant. Also the electrode shape is influencing the mechanical properties: the electrodes with more pins, thicker pins and shorter pins are less compliant. The compliance of the pin-shaped electrodes can be predicted rather well using the elastic moduli of the polymer materials and the shapes of the electrodes. Polymer electrodes with optimal material composition are directly capable of recording strong biopotential signals such as ECG. The ECG signals recorded using polymer dry electrodes show a high similarity to those recorded by the neighboring wet electrodes when the subjects sit still and avoid movements. Pin-shaped polymer electrodes are sensitive to motion artifacts when applied on non-hairy skin. This proves that the shape of the electrode should depend on the applications. To record low amplitude signals such as EEG, polymer electrodes need to be coupled with active circuits. In this thesis, our own active circuits are fabricated, and their compatibility with commercial EEG recording systems is investigated. The EEG signals recorded by polymer dry electrodes are compared with those of their adjacent wet electrodes. Polymer dry electrodes are capable of recording good quality EEG signals however they are more sensitive to pick up power line interferences (50 Hz signals) and they show more baseline drift (low frequency signals). Both of the 50 Hz signals and the baseline drift can easily be filtered out and the baseline drift reduced while polymer electrodes are becoming stabilized. The signals containing baseline drift still have sufficient good quality for interpretation by an experienced medical staff. However, it has to be noted that the baseline drift in the raw signals might result in misinterpretation of EEG signals distributed at low frequency (< 2 Hz). Besides using the commercial EEG recording systems, the signals of polymer dry electrodes are compared with those of wet electrodes and AgCl-coated polymer electrodes using imec’s EEG recording system. Polymer electrodes show higher impedance and slightly lower signal quality than the other 2 types of electrodes, which might be improved after they are stabilized. A stabilized electrode shows fewer impedance variation and baseline drift resulting in better signals. Besides the electrical and mechanical properties of the polymer electrodes, biocompatibility and user comfort are also important criteria of good electrodes. The polymer material used in this thesis is non-cytotoxic. No skin irritation is found after applying the polymer electrodes up to a few days. In addition, no participants report any skin discomfort during and after measurements. As to the user comfort of EEG monitoring, only a few participants with a larger head-size experience local pressure from the one-size electrode fixation device. Furthermore, all participants report that the application and removal of polymer dry electrodes are much more convenient than conventional wet electrodes. To conclude, our polymer dry electrodes show high user comfort and are able to record good quality ECG and EEG signals. Therefore, combining polymer electrodes with the proper fixation devices may be seen as promising alternatives to either the commercially available devices equipped with dry electrodes or the conventional wet electrodes. nrpages: 246 status: published

Packaging of traditional integrated circuits (IC s) has been reliant for several decades on the techniques of metal bonding and plastic overmolding. However, such conventional packaging techniques are failing to cope with the rapidly shrinking IC dimensions and the growing variety of new microsystems (like micro-electro-mechanical systems, or MEMS) used in modern appliances including biomedical implants and smartphones. In thiscontext rises the need for this research to set a step forward in the direction of package miniaturization, improved reliability and increased functionality of state-of-the-art microsystems.This thesis deals with the technological challenges as well as with the design and performance aspects of new micropackages created using thin membranes of nanoporous alumina. The new micropackages are intended to encapsulate microsystems and MEMS in particular at wafer-level in a controlled environment. Such a micropackage can accommodate one or more microsystems in a planar microcavity of 1 to 10 µm height with lateral dimensions between 0.1 and 1.0 mm. The on-wafer microcavities are formed by etching a sacrificial layer underneath nanoporous alumina membranes of 1 to 3 µm thickness. These membranes feature a large density of cylindrical nanopores with diameters between 10 and 20 nm and height equal to the thickness of the membrane; facilitating the sacrificial layer etching process. A novel wafer-level anodization process performed at a temperature close to 30 °C is developed to produce fully perforated nanoporous alumina membranes within an Al thin film in a single fabrication step. A specially designed photoresist mask is used to define the lateral shapesof the alumina membranes with high precision, while maintaining a low-resistance path for the anodization current across the large area of a 200 mm wafer. A controlled environment inside the microcavities is achieved during a process of depositing an impermeable sealing layer on top of the nanoporous alumina membranes. The resulting micropackages typically feature dielectric (and optically transparent) caps with a thickness between 4 and 9 µm. The caps are normally anchored around the microcavities using an Al-based sealing ring of 10 to 50 µm width. Empty micropackages of different shapes and configurations as well as encapsulated RF transmission lines and other microsystems (like Ni-based MEMS) have been produced on 200 mm Si wafers. Moreover, micropackages with sufficient robustness to undergo a plastic overmolding process performed at high pressure of 30 bar and a high temperature of 175 °C have been designed, fabricated and tested.Analytical and finite element models have been developed to analyze the thermomechanical and electromagnetic characteristics of the new micropackages and the embedded microsystems. These models provide much insight into the strength, reliability and compatibility of the micropackages with different applications. Furthermore, experimental studies of the hermeticity and reliability of the new micropackages are presented. An extensive hermeticity analysis is carried out based on optical monitoring of the cap deformation under different environmental conditions. This includes short-term (less than 10 days) exposure to helium at 3 bar pressure and long-term (up to 14 months) exposure to air under atmospheric pressure. In this experiment, the significant impact of the sealing ring configuration on the package hermeticity is demonstrated. Moreover, other methods for hermeticity evaluation, including the use of an embedded microresonator or micro-Pirani gauge, are discussed. Additionally, the outcome of a comprehensiveset of reliability tests is presented; including the impact of repeatedexposure to mechanical shocks and extreme temperatures, in addition to exposure to high humidity levels (at high temperatures). Finally, the compatibility of the new micropackages with radio frequency (RF) microsystems is evaluated. Special Al-based feedthroughs that can transmit high frequency signals through the package boundaries with minimal added losses have been designed, implemented and tested. nrpages: 180 status: published

In this paper, we report on the strain and pressure testing of highly flexible skins embedded with Bragg grating sensors recorded in either silica or polymer optical fibre. The photonic skins, with a size of 10cm x 10cm and thickness of 1mm, were fabricated by embedding the polymer fibre or silica fibre containing Bragg gratings in Sylgard 184 from Dow Corning. Pressure sensing was studied using a cylindrical metal post placed on an array of points across the skin. The polymer fibre grating exhibits approximately 10 times the pressure sensitivity of the silica fibre and responds to the post even when it is placed a few centimetres away from the sensing fibre. Although the intrinsic strain sensitivities of gratings in the two fibre types are very similar, when embedded in the skin the polymer grating displayed a strain sensitivity approximately 45 times greater than the silica device, which also suffered from considerable hysteresis. The polymer grating displayed a near linear response over wavelength shifts of 9nm for 1% strain. The difference in behaviour we attribute to the much greater Young's modulus of the silica fibre (70 GPa) compared to the polymer fibre (3 GPa).

Polymer photonic crystal fibres combine two relatively recent developments in fibre technology. On the one hand, polymer optical fibre has very different physical and chemical properties to silica. In particular, polymer fibre has a much smaller Young's modulus than silica, can survive higher strains, is amenable to organic chemical processing and, depending on the constituent polymer, may absorb water. All of these features can be utilised to extend the range of applications of optical fibre sensors. On the other hand, the photonic crystal - or microstructured - geometry also offers advantages: flexibility in the fibre design including control of the dispersion properties of core and cladding modes, the possibility of introducing minute quantities of analyte directly into the electric field of the guided light and enhanced pressure sensitivity. When brought together these two technologies provide interesting possibilities for fibre sensors, particularly when combined with fibre Bragg or long period gratings. This paper discusses the features of polymer photonic crystal fibre relevant to sensing and provides examples of the applications demonstrated to date.

The fields of health care and environment control have an increasing demand for sensors able to detect low concentrations of specific molecules in gaseous or liquid samples. The recent introduction of microfabricated devices in these fields gave rise to sensors with attractive properties. A cutting edge technology is based on guided acoustic waves, which are perturbed by events occurring at the nanometer scale. A first part of the thesis investigates the Love mode waveguide, a versatile structure in which a thin film is guiding the acoustic wave generated in a piezoelectric substrate. A systematic analysis of its sensitivity was obtained using a transmission line model generalized to discriminate the rigid or viscous nature of the probed layers. We developed a novel integrated combination of the Love mode device with a Surface Plasmon Resonance optical sensor to quantify the thickness and the composition of soft layers. The electromagnetic interferences in the recorded signal were modeled to determine the phase velocity in the sensing area and to provide new mechanisms for an enhanced sensitivity. The experimental aspects of this work deal with the fabrication, the important issue of the packaging and the sensitivity calibration of the Love mode biosensor. A second part of the thesis investigates nanocrystalline diamond under the form of a thin film membrane suspended to a rigid silicon frame. The high mechanical and chemical resistance of nanocrystalline diamond, close to single-crystal diamond, open ways to membrane based acoustic sensors such as Flexural Plate Wave and thin Film Bulk Acoustic Resonators (FBAR). A novel dynamic characterization of the thin film is reported and the properties of composite FBAR devices including a diamond thin film membrane and a piezoelectric aluminum nitride layer are assessed using the perturbation theory. This study is applied to evaluate the high sensing potential of the first prototype of an actual diamond-based composite FBAR. (FSA 3)--UCL, 2006

Efficient and precise assembly of very-large quantities of sub-millimeter-sized devices onto pre-processed substrates is presently a key frontier for microelectronics, in its aspiration to large-scale mass production of devices with new functionalities and applications (e.g. thin dies embedded into flexible substrates, 3D microsystem integration). In this perspective, on the one hand established pick&place assembly techniques may be unsuitable, due to a trade-off between throughput and placement accuracy and to difficulties in predictably handling very-small devices. On the other hand, self-assembly processes are massively parallel, may run unsupervised and allow contactless manipulation of objects. The convergence between robotic assembly and self-assembly, epitomized by capillarity-enhanced flip-chip assembly, can therefore enable an ideal technology meeting short-to-medium-term electronic packaging and assembly needs. The objective of this thesis is bridging the gap between academic proofs-of- concept of capillary self-assembly and its industrial application. Our work solves several issues relevant to capillary self-assembly of thin dies onto preprocessed substrates. Very-different phenomena and aspects of both scientific and technological interest coexist in such a broad context. They were tackled both experimentally and theoretically. After a critical review of the state-of-the-art in microsystem integration, a complete quasi-static study of lateral capillary meniscus forces is presented. Our experimental setup enables also a novel method to measure the contact angle of liquids. Recessed binding sites are introduced to obtain perfectly-conformal fluid dip-coating of patterned surfaces, which enables the effective and robust coding of geometrical information into binding sites to direct the assembly of parts. A general procedure to establish solder-mediated electro-mechanical interconnections between parts and substrate is validated. Smart surface chemistries are invoked to solve the issue of mutual adhesion between parts during the capillary self-assembly process. Two chemical kinetic-inspired analytic models of fluidic self-assembly are presented and criticized to introduce a novel agent-based model of the process. The latter approach allows realistic simulations by taking into account spatial factors and collision dynamics. Concluding speculations propose envisioned solutions to residual open issues and further perspectives for this field of rapidly-growing importance.

In traditional electrical sensing applications, multiplexing and interconnecting the different sensing elements is a major challenge. Recently, many optical alternatives have been investigated including optical fiber sensors of which the sensing elements consist of fiber Bragg gratings. Different sensing points can be integrated in one optical fiber solving the interconnection problem and avoiding any electromagnetical interference (EMI). Many new sensing applications also require flexible or stretchable sensing foils which can be attached to or wrapped around irregularly shaped objects such as robot fingers and car bumpers or which can even be applied in biomedical applications where a sensor is fixed on a human body. The use of these optical sensors however always implies the use of a light-source, detectors and electronic circuitry to be coupled and integrated with these sensors. The coupling of these fibers with these light sources and detectors is a critical packaging problem and as it is well-known the costs for packaging, especially with optoelectronic components and fiber alignment issues are huge. The end goal of this embedded sensor is to create a flexible optical sensor integrated with (opto)electronic modules and control circuitry. To obtain this flexibility, one can embed the optical sensors and the driving optoelectronics in a stretchable polymer host material. In this article different embedding techniques for optical fiber sensors are described and characterized. Initial tests based on standard manufacturing processes such as molding and laser structuring are reported as well as a more advanced embedding technique based on soft lithography processing.