Integrated circuits for near-infrared biomedical signal acquisition.

Wong, Kak Yeung Alex.Thesis submitted in: November 2007.Thesis (M.Phil.)--Chinese University of Hong Kong, 2008.Includes bibliographical references (leaves 86-89).Abstracts in English and Chinese.Acknowledgement --- p.iAbstract --- p.iii摘要 --- p.vTable of contents --- p.viList of tables --- p.ixList of Figures --- p.xChapter Chapter1 --- Introduction --- p.1Chapter 1.1 --- Background --- p.1Chapter 1.2 --- Motivation --- p.1Chapter 1.3 --- Summary of Contributions and Thesis Outline --- p.4Chapter Chapter 2 --- System Design and Architecture --- p.6Chapter 2.1 --- Architectural Consideration --- p.6Chapter 2.1.1 --- Previous work --- p.6Chapter 2.1.2 --- Proposed work --- p.10Chapter A) --- Transimpedance amplifier with off-chip component --- p.10Chapter B) --- Dual-loop transimpedance amplifier --- p.12Chapter 2.2 --- Design consideration for ultra low cutoff frequency filter --- p.13Chapter 2.2.1 --- Previous work on low cutoff frequency filter --- p.14Chapter A) --- GM-C with current division and sub-threshold operation --- p.14Chapter B) --- Capacitance Multiplier --- p.15Chapter C) --- Switched-opamp switched-capacitor (SO-SC) filter --- p.16Chapter 2.2.2 --- Proposed work for the ultra low cutoff frequency filter --- p.17Current steering lowpass filter --- p.17Chapter 2.1 --- Summary --- p.18Chapter Chapter 3 --- Transimpedance Amplifier Design --- p.21Chapter 3.1 --- Transimpedance amplifiEr with off-chip component --- p.21Chapter 3.1.1 --- Transimpedance amplifier with dc photocurrent rejection --- p.21Chapter 3.1.2 --- Proposed solution - Transimpedance amplifier with sample-and-hold in feedback --- p.23Chapter A) --- Operating principle --- p.23Chapter B) --- Simulation results --- p.25Chapter 3.2 --- Dual-loop transimpedance amplifier with DC photocurrent rejection --- p.27Chapter 3.2.1 --- Evolution from basic to proposed work --- p.27Chapter 3.2.2 --- Operating principle --- p.31Chapter 3.2.3 --- Development of the analytic model --- p.32Chapter 3.2.4 --- Derivation of frequency response --- p.37Chapter 3.2.5 --- Noise derivation --- p.40Total input referred noise --- p.43Chapter 3.3 --- Implementation and experimental results --- p.45Chapter 3.3.1 --- Off-chip capacitor TIA --- p.45Measurement results --- p.46Chapter 3.3.2 --- Dual-loop TIA --- p.49Measurement results --- p.51Chapter 3.4 --- Summary and comparison --- p.62Chapter Chapter 4 --- Ultra-Low Cutoff Frequency Filter Design --- p.65Chapter 4.1 --- Current-steering lowpass filter --- p.65Chapter 4.2 --- "Implementation, experimental and measurement results" --- p.67Chapter 4.2.1 --- Measurement results for CS-LPF --- p.68Chapter 4.2.2 --- Measurement results for overall system --- p.75Chapter 4.3 --- Summary --- p.82Chapter Chapter 5 --- Conclusions and Future Work --- p.84Chapter 5.1 --- Conclusions --- p.84Chapter 5.2 --- Future work --- p.85Bibliography --- p.86Appendix A Details about operation --- p.90Appendix B Complex pole derivation --- p.93Appendix C Details about noise derivation --- p.94Appendix D Details about sub-threshold operation --- p.98Appendix E (in CD-ROM) Transfer Function DerivationAppendix F (in CD-ROM) Noise Transfer Function Derivatio

On-Chip Integrated Functional Near Infra-Red Spectroscopy (fNIRS) Photoreceiver for Portable Brain Imaging

RÉSUMÉ L'imagerie cérébrale fonctionnelle utilisant la Spectroscopie Fonctionnelle Proche-Infrarouge (SFPI) propose un outil portatif et non invasif de surveillance de l'oxygénation du sang. SFPI est une technique de haute résolution temporelle non invasive, sûr, peu intrusive en temps réel et pour l'imagerie cérébrale à long terme. Il permet de détecter des signaux hémodynamiques à la fois rapides et neuronaux ou lents. Outre les avantages importants des systèmes SFPI, ils souffrent encore de quelques inconvénients, notamment d’une faible résolution spatiale, d’un bruit de niveau modérément élevé et d’une grande sensibilité au mouvement. Afin de surmonter les limites des systèmes actuellement disponibles de SFPI non-portables, dans cette thèse, nous en avons introduit une nouvelle de faible puissance, miniaturisée sur une puce photodétecteur frontal destinée à des systèmes de SFPI portables. Elle contient du silicium photodiode à avalanche (SiAPD), un amplificateur de transimpédance (TIA), et « Quench-Reset », circuits mis en oeuvre en utilisant les technologies CMOS standards pour fonctionner dans les deux modes : linéaire et Geiger. Ainsi, elle peut être appliquée pour les deux fNIRS : en onde continue (CW- SFPI) et pour des applications de comptage de photon unique. Plusieurs SiAPDs ont été mises en oeuvre dans de nouvelles structures et formes (rectangulaires, octogonales, double APDs, imbriquées, netted, quadratiques et hexadecagonal) en utilisant différentes techniques de prévention de la dégradation de bord prématurée. Les principales caractéristiques des SiAPDs sont validées et l'impact de chaque paramètre ainsi que les simulateurs de l'appareil (TCAD, COMSOL, etc) ont été étudiés sur la base de la simulation et de mesure des résultats. Proposées SiAPDs techniques d'exposition avec un gain de grande avalanche, tension faible ventilation et une grande efficacité de détection des photons dans plus de faibles taux de comptage sombres. Trois nouveaux produits à haut gain, bande passante (GBW) et à faible bruit TIA sont introduits basés sur le concept de gain distribué, d’amplificateur logarithmique et sur le rejet automatique du bruit pour être appliqué en mode de fonctionnement linéaire. Le TIA proposé offre une faible consommation, un gain de haute transimpédance, une bande passante ajustable et un très faible bruit d'entrée et de sortie. Le nouveau circuit mixte trempe-reset (MQC) et un MQC contrôlable (CMQC) frontaux offrent une faible puissance, une haute vitesse de comptage de photons avec un commandable de temps de hold-off et temps de réinitialiser. La première intégration sur puce de SiAPDs avec TIA et Photon circuit de comptage a été démontrée et montre une amélioration de l'efficacité de la photodétection, spécialement en ce qui concerne la sensibilité, la consommation d'énergie et le rapport signal sur bruit.----------ABSTRACT Optical brain imaging using functional near infra-red spectroscopy (fNIRS) offers a direct and noninvasive tool for monitoring of blood oxygenation. fNIRS is a noninvasive, safe, minimally intrusive, and high temporal-resolution technique for real-time and long-term brain imaging. It allows detecting both fast-neuronal and slow-hemodynamic signals. Besides the significant advantages of fNIRS systems, they still suffer from few drawbacks including low spatial- resolution, moderately high-level noise and high-sensitivity to movement. In order to overcome the limitations of currently available non-portable fNIRS systems, we have introduced a new low-power, miniaturized on-chip photodetector front-end intended for portable fNIRS systems. It includes silicon avalanche photodiode (SiAPD), Transimpedance amplifier (TIA), and Quench- Reset circuitry implemented using standard CMOS technologies to operate in both linear and Geiger modes. So it can be applied for both continuous-wave fNIRS (CW-fNIRS) and also single-photon counting applications. Several SiAPDs have been implemented in novel structures and shapes (Rectangular, Octagonal, Dual, Nested, Netted, Quadratic and Hexadecagonal) using different premature edge breakdown prevention techniques. The main characteristics of the SiAPDs are validated and the impact of each parameter and the device simulators (TCAD, COMSOL, etc.) have been studied based on the simulation and measurement results. Proposed techniques exhibit SiAPDs with high avalanche-gain (up to 119), low breakdown-voltage (around 12V) and high photon-detection efficiency (up to 72% in NIR region) in additional to a low dark- count rate (down to 30Hz at 1V excess bias voltage). Three new high gain-bandwidth product (GBW) and low-noise TIAs are introduced and implemented based on distributed-gain concept, logarithmic-amplification and automatic noise-rejection and have been applied in linear-mode of operation. The implemented TIAs offer a power-consumption around 0.4 mW, transimpedance gain of 169 dBΩ, and input-output current/voltage noises in fA/pV range accompanied with ability to tune the gain, bandwidth and power-consumption in a wide range. The implemented mixed quench-reset circuit (MQC) and controllable MQC (CMQC) front-ends offer a quenchtime of 10ns, a maximum power-consumption of 0.4 mW, with a controllable hold-off and resettimes. The on-chip integration of SiAPDs with TIA and photon-counting circuitries has been demonstrated showing improvement of the photodetection-efficiency, specially regarding to the sensitivity, power-consumption and signal-to-noise ratio (SNR) characteristics

Sources of inaccuracy in photoplethysmography for continuous cardiovascular monitoring

Photoplethysmography (PPG) is a low-cost, noninvasive optical technique that uses change in light transmission with changes in blood volume within tissue to provide information for cardiovascular health and fitness. As remote health and wearable medical devices become more prevalent, PPG devices are being developed as part of wearable systems to monitor parameters such as heart rate (HR) that do not require complex analysis of the PPG waveform. However, complex analyses of the PPG waveform yield valuable clinical information, such as: blood pressure, respiratory information, sympathetic nervous system activity, and heart rate variability. Systems aiming to derive such complex parameters do not always account for realistic sources of noise, as testing is performed within controlled parameter spaces. A wearable monitoring tool to be used beyond fitness and heart rate must account for noise sources originating from individual patient variations (e.g., skin tone, obesity, age, and gender), physiology (e.g., respiration, venous pulsation, body site of measurement, and body temperature), and external perturbations of the device itself (e.g., motion artifact, ambient light, and applied pressure to the skin). Here, we present a comprehensive review of the literature that aims to summarize these noise sources for future PPG device development for use in health monitoring

Retainer-Free Optopalatographic Device Design and Evaluation as a Feedback Tool in Post-Stroke Speech and Swallowing Therapy

Stroke is one of the leading causes of long-term motor disability, including oro-facial impairments which affect speech and swallowing. Over the last decades, rehabilitation programs have evolved from utilizing mainly compensatory measures to focusing on recovering lost function. In the continuing effort to improve recovery, the concept of biofeedback has increasingly been leveraged to enhance self-efficacy, motivation and engagement during training. Although both speech and swallowing disturbances resulting from oro-facial impairments are frequent sequelae of stroke, efforts to develop sensing technologies that provide comprehensive and quantitative feedback on articulator kinematics and kinetics, especially those of the tongue, and specifically during post-stroke speech and swallowing therapy have been sparse. To that end, such a sensing device needs to accurately capture intraoral tongue motion and contact with the hard palate, which can then be translated into an appropriate form of feedback, without affecting tongue motion itself and while still being light-weight and portable. This dissertation proposes the use of an intraoral sensing principle known as optopalatography to provide such feedback while also exploring the design of optopalatographic devices itself for use in dysphagia and dysarthria therapy. Additionally, it presents an alternative means of holding the device in place inside the oral cavity with a newly developed palatal adhesive instead of relying on dental retainers, which previously limited device usage to a single person. The evaluation was performed on the task of automatically classifying different functional tongue exercises from one another with application in dysphagia therapy, whereas a phoneme recognition task was conducted with application in dysarthria therapy. Results on the palatal adhesive suggest that it is indeed a valid alternative to dental retainers when device residence time inside the oral cavity is limited to several tens of minutes per session, which is the case for dysphagia and dysarthria therapy. Functional tongue exercises were classified with approximately 61 % accuracy across subjects, whereas for the phoneme recognition task, tense vowels had the highest recognition rate, followed by lax vowels and consonants. In summary, retainer-free optopalatography has the potential to become a viable method for providing real-time feedback on tongue movements inside the oral cavity, but still requires further improvements as outlined in the remarks on future development.:1 Introduction 1.1 Motivation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 1.2 Problem statement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 1.3 Goals and contributions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 1.4 Scope and limitations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 2 Basics of post-stroke speech and swallowing therapy 2.1 Dysarthria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 2.2 Dysphagia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 2.3 Treatment rationale and potential of biofeedback . . . . . . . . . . . . . . . . . 13 2.4 Summary and conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 3 Tongue motion sensing 3.1 Contact-based methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 3.1.1 Electropalatography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 3.1.2 Manometry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20 3.1.3 Capacitive . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 3.2 Non-contact based methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23 3.2.1 Electromagnetic articulography . . . . . . . . . . . . . . . . . . . . . . . 23 3.2.2 Permanent magnetic articulography . . . . . . . . . . . . . . . . . . . . 24 3.2.3 Optopalatography (related work) . . . . . . . . . . . . . . . . . . . . . . 25 3.3 Electro-optical stomatography . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26 3.4 Extraoral sensing techniques . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27 3.5 Summary, comparison and conclusion . . . . . . . . . . . . . . . . . . . . . . . 29 4 Fundamentals of optopalatography 4.1 Important radiometric quantities . . . . . . . . . . . . . . . . . . . . . . . . . . 32 4.1.1 Solid angle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32 4.1.2 Radiant flux and radiant intensity . . . . . . . . . . . . . . . . . . . . . 33 4.1.3 Irradiance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33 4.1.4 Radiance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33 4.2 Sensing principle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34 4.2.1 Analytical models . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35 4.2.2 Monte Carlo ray tracing methods . . . . . . . . . . . . . . . . . . . . . . 37 4.2.3 Data-driven models . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38 4.2.4 Model comparison . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39 4.3 A priori device design consideration . . . . . . . . . . . . . . . . . . . . . . . . 41 4.3.1 Optoelectronic components . . . . . . . . . . . . . . . . . . . . . . . . . 41 4.3.2 Additional electrical components and requirements . . . . . . . . . . . . 43 4.3.3 Intraoral sensor layout . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44 5 Intraoral device anchorage 5.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45 5.1.1 Mucoadhesion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46 5.1.2 Considerations for the palatal adhesive . . . . . . . . . . . . . . . . . . . 48 5.2 Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48 5.2.1 Polymer selection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48 5.2.2 Fabrication method . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49 5.2.3 Formulations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50 5.2.4 PEO tablets . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50 5.2.5 Connection to the intraoral sensor’s encapsulation . . . . . . . . . . . . 50 5.2.6 Formulation evaluation . . . . . . . . . . . . . . . . . . . . . . . . . . . 51 5.3 Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54 5.3.1 Initial formulation evaluation . . . . . . . . . . . . . . . . . . . . . . . . 54 5.3.2 Final OPG adhesive formulation . . . . . . . . . . . . . . . . . . . . . . 56 5.4 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57 6 Initial device design with application in dysphagia therapy 6.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58 6.2 Optode and optical sensor selection . . . . . . . . . . . . . . . . . . . . . . . . . 60 6.2.1 Optode and optical sensor evaluation procedure . . . . . . . . . . . . . . 61 6.2.2 Selected optical sensor characterization . . . . . . . . . . . . . . . . . . 62 6.2.3 Mapping from counts to millimeter . . . . . . . . . . . . . . . . . . . . . 62 6.2.4 Results and discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62 6.3 Device design and hardware implementation . . . . . . . . . . . . . . . . . . . . 64 6.3.1 Block diagram . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64 6.3.2 Optode placement and circuit board dimensions . . . . . . . . . . . . . 64 6.3.3 Firmware description and measurement cycle . . . . . . . . . . . . . . . 66 6.3.4 Encapsulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67 6.3.5 Fully assembled OPG device . . . . . . . . . . . . . . . . . . . . . . . . 67 6.4 Evaluation on the gesture recognition task . . . . . . . . . . . . . . . . . . . . . 69 6.4.1 Exercise selection, setup and recording . . . . . . . . . . . . . . . . . . . 69 6.4.2 Data corpus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70 6.4.3 Sequence pre-processing . . . . . . . . . . . . . . . . . . . . . . . . . . . 70 6.4.4 Choice of classifier . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71 6.4.5 Training and evaluation . . . . . . . . . . . . . . . . . . . . . . . . . . . 72 6.4.6 Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73 6.5 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74 7 Improved device design with application in dysarthria therapy 7.1 Device design . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79 7.1.1 Design considerations . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80 7.1.2 General system overview . . . . . . . . . . . . . . . . . . . . . . . . . . . 81 7.1.3 Intraoral sensor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81 7.1.4 Receiver and controller . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82 7.1.5 Multiplexer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85 7.2 Hardware implementation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87 7.2.1 Optode placement and circuit board layout . . . . . . . . . . . . . . . . 87 7.2.2 Encapsulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89 7.3 Device characterization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90 7.3.1 Photodiode transient response . . . . . . . . . . . . . . . . . . . . . . . 91 7.3.2 Current source and rise time . . . . . . . . . . . . . . . . . . . . . . . . 91 7.3.3 Multiplexer switching speed . . . . . . . . . . . . . . . . . . . . . . . . . 92 7.3.4 Measurement cycle and firmware implementation . . . . . . . . . . . . . 93 7.3.5 In vitro measurement accuracy . . . . . . . . . . . . . . . . . . . . . . . 95 7.3.6 Optode measurement stability . . . . . . . . . . . . . . . . . . . . . . . 96 7.4 Evaluation on the phoneme recognition task . . . . . . . . . . . . . . . . . . . . 98 7.4.1 Corpus selection and recording setup . . . . . . . . . . . . . . . . . . . . 98 7.4.2 Annotation and sensor data post-processing . . . . . . . . . . . . . . . . 98 7.4.3 Mapping from counts to millimeter . . . . . . . . . . . . . . . . . . . . . 99 7.4.4 Classifier and feature selection . . . . . . . . . . . . . . . . . . . . . . . 100 7.4.5 Evaluation paradigms . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103 7.5 Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105 7.5.1 Tongue distance curve prediction . . . . . . . . . . . . . . . . . . . . . . 105 7.5.2 Tongue contact patterns and contours . . . . . . . . . . . . . . . . . . . 105 7.5.3 Phoneme recognition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 106 7.6 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 108 8 Conclusion and future work 115 9 Appendix 9.1 Analytical light transport models . . . . . . . . . . . . . . . . . . . . . . . . . . 119 9.2 Meshed Monte Carlo method . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120 9.3 Laser safety . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122 9.4 Current source modulation voltage . . . . . . . . . . . . . . . . . . . . . . . . . 123 9.5 Transimpedance amplifier’s frequency responses . . . . . . . . . . . . . . . . . . 123 9.6 Initial OPG device’s PCB layout and circuit diagrams . . . . . . . . . . . . . . 127 9.7 Improved OPG device’s PCB layout and circuit diagrams . . . . . . . . . . . . 129 9.8 Test station layout drawing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 138 Bibliography 152Der Schlaganfall ist eine der häufigsten Ursachen für motorische Langzeitbehinderungen, einschließlich solcher im Mund- und Gesichtsbereich, deren Folgen u.a. Sprech- und Schluckprobleme beinhalten, welche sich in den beiden Symptomen Dysarthrie und Dysphagie äußern. In den letzten Jahrzehnten haben sich Rehabilitationsprogramme für die Behandlung von motorisch ausgeprägten Schlaganfallsymptomatiken substantiell weiterentwickelt. So liegt nicht mehr die reine Kompensation von verlorengegangener motorischer Funktionalität im Vordergrund, sondern deren aktive Wiederherstellung. Dabei hat u.a. die Verwendung von sogenanntem Biofeedback vermehrt Einzug in die Therapie erhalten, um Motivation, Engagement und Selbstwahrnehmung von ansonsten unbewussten Bewegungsabläufen seitens der Patienten zu fördern. Obwohl jedoch Sprech- und Schluckstörungen eine der häufigsten Folgen eines Schlaganfalls darstellen, wird diese Tatsache nicht von der aktuellen Entwicklung neuer Geräte und Messmethoden für quantitatives und umfassendes Biofeedback reflektiert, insbesondere nicht für die explizite Erfassung intraoraler Zungenkinematik und -kinetik und für den Anwendungsfall in der Schlaganfalltherapie. Ein möglicher Grund dafür liegt in den sehr strikten Anforderungen an ein solche Messmethode: Sie muss neben Portabilität idealerweise sowohl den Kontakt zwischen der Zunge und dem Gaumen, als auch die dreidimensionale Bewegung der Zunge in der Mundhöhle erfassen, ohne dabei die Artikulation selbst zu beeinflussen. Um diesen Anforderungen gerecht zu werden, wird in dieser Dissertation das Messprinzip der Optopalatographie untersucht, mit dem Schwerpunkt auf der Anwendung in der Dysarthrie- und Dysphagietherapie. Dies beinhaltet auch die Entwicklung eines entsprechenden Gerätes sowie dessen Befestigungsmethode in der Mundhöhle über ein dediziertes Mundschleimhautadhäsiv. Letzteres umgeht das bisherige Problem der notwendigen Anpassung eines solchen intraoralen Gerätes an einen einzelnen Nutzer. Für die Anwendung in der Dysphagietherapie erfolgte die Evaluation anhand einer automatischen Erkennung von Mobilisationsübungen der Zunge, welche routinemäßig in der funktionalen Dysphagietherapie durchgeführt werden. Für die Anwendung in der Dysarthrietherapie wurde eine Lauterkennung durchgeführt. Die Resultate bezüglich der Verwendung des Mundschleimhautadhäsives suggerieren, dass dieses tatsächlich eine valide Alternative zu den bisher verwendeten Techniken zur Befestigung intraoraler Geräte in der Mundhöhle darstellt. Zungenmobilisationsübungen wurden über Probanden hinweg mit einer Rate von 61 % erkannt, wogegen in der Lauterkennung Langvokale die höchste Erkennungsrate erzielten, gefolgt von Kurzvokalen und Konsonanten. Zusammenfassend lässt sich konstatieren, dass das Prinzip der Optopalatographie eine ernstzunehmende Option für die intraorale Erfassung von Zungenbewegungen darstellt, wobei weitere Entwicklungsschritte notwendig sind, welche im Ausblick zusammengefasst sind.:1 Introduction 1.1 Motivation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 1.2 Problem statement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 1.3 Goals and contributions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 1.4 Scope and limitations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 2 Basics of post-stroke speech and swallowing therapy 2.1 Dysarthria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 2.2 Dysphagia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 2.3 Treatment rationale and potential of biofeedback . . . . . . . . . . . . . . . . . 13 2.4 Summary and conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 3 Tongue motion sensing 3.1 Contact-based methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 3.1.1 Electropalatography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 3.1.2 Manometry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20 3.1.3 Capacitive . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 3.2 Non-contact based methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23 3.2.1 Electromagnetic articulography . . . . . . . . . . . . . . . . . . . . . . . 23 3.2.2 Permanent magnetic articulography . . . . . . . . . . . . . . . . . . . . 24 3.2.3 Optopalatography (related work) . . . . . . . . . . . . . . . . . . . . . . 25 3.3 Electro-optical stomatography . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26 3.4 Extraoral sensing techniques . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27 3.5 Summary, comparison and conclusion . . . . . . . . . . . . . . . . . . . . . . . 29 4 Fundamentals of optopalatography 4.1 Important radiometric quantities . . . . . . . . . . . . . . . . . . . . . . . . . . 32 4.1.1 Solid angle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32 4.1.2 Radiant flux and radiant intensity . . . . . . . . . . . . . . . . . . . . . 33 4.1.3 Irradiance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33 4.1.4 Radiance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33 4.2 Sensing principle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34 4.2.1 Analytical models . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35 4.2.2 Monte Carlo ray tracing methods . . . . . . . . . . . . . . . . . . . . . . 37 4.2.3 Data-driven models . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38 4.2.4 Model comparison . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39 4.3 A priori device design consideration . . . . . . . . . . . . . . . . . . . . . . . . 41 4.3.1 Optoelectronic components . . . . . . . . . . . . . . . . . . . . . . . . . 41 4.3.2 Additional electrical components and requirements . . . . . . . . . . . . 43 4.3.3 Intraoral sensor layout . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44 5 Intraoral device anchorage 5.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45 5.1.1 Mucoadhesion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46 5.1.2 Considerations for the palatal adhesive . . . . . . . . . . . . . . . . . . . 48 5.2 Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48 5.2.1 Polymer selection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48 5.2.2 Fabrication method . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49 5.2.3 Formulations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50 5.2.4 PEO tablets . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50 5.2.5 Connection to the intraoral sensor’s encapsulation . . . . . . . . . . . . 50 5.2.6 Formulation evaluation . . . . . . . . . . . . . . . . . . . . . . . . . . . 51 5.3 Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54 5.3.1 Initial formulation evaluation . . . . . . . . . . . . . . . . . . . . . . . . 54 5.3.2 Final OPG adhesive formulation . . . . . . . . . . . . . . . . . . . . . . 56 5.4 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57 6 Initial device design with application in dysphagia therapy 6.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58 6.2 Optode and optical sensor selection . . . . . . . . . . . . . . . . . . . . . . . . . 60 6.2.1 Optode and optical sensor evaluation procedure . . . . . . . . . . . . . . 61 6.2.2 Selected optical sensor characterization . . . . . . . . . . . . . . . . . . 62 6.2.3 Mapping from counts to millimeter . . . . . . . . . . . . . . . . . . . . . 62 6.2.4 Results and discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62 6.3 Device design and hardware implementation . . . . . . . . . . . . . . . . . . . . 64 6.3.1 Block diagram . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64 6.3.2 Optode placement and circuit board dimensions . . . . . . . . . . . . . 64 6.3.3 Firmware description and measurement cycle . . . . . . . . . . . . . . . 66 6.3.4 Encapsulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67 6.3.5 Fully assembled OPG device . . . . . . . . . . . . . . . . . . . . . . . . 67 6.4 Evaluation on the gesture recognition task . . . . . . . . . . . . . . . . . . . . . 69 6.4.1 Exercise selection, setup and recording . . . . . . . . . . . . . . . . . . . 69 6.4.2 Data corpus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70 6.4.3 Sequence pre-processing . . . . . . . . . . . . . . . . . . . . . . . . . . . 70 6.4.4 Choice of classifier . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71 6.4.5 Training and evaluation . . . . . . . . . . . . . . . . . . . . . . . . . . . 72 6.4.6 Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73 6.5 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74 7 Improved device design with application in dysarthria therapy 7.1 Device design . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79 7.1.1 Design considerations . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80 7.1.2 General system overview . . . . . . . . . . . . . . . . . . . . . . . . . . . 81 7.1.3 Intraoral sensor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81 7.1.4 Receiver and controller . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82 7.1.5 Multiplexer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85 7.2 Hardware implementation . . . . . . . . . . . . . . . . . . . . .

Photonic Technology for Precision Metrology

Photonics has had a decisive influence on recent scientific and technological achievements. It includes aspects of photon generation and photon–matter interaction. Although it finds many applications in the whole optical range of the wavelengths, most solutions operate in the visible and infrared range. Since the invention of the laser, a source of highly coherent optical radiation, optical measurements have become the perfect tool for highly precise and accurate measurements. Such measurements have the additional advantages of requiring no contact and a fast rate suitable for in-process metrology. However, their extreme precision is ultimately limited by, e.g., the noise of both lasers and photodetectors. The Special Issue of the Applied Science is devoted to the cutting-edge uses of optical sources, detectors, and optoelectronics systems in numerous fields of science and technology (e.g., industry, environment, healthcare, telecommunication, security, and space). The aim is to provide detail on state-of-the-art photonic technology for precision metrology and identify future developmental directions. This issue focuses on metrology principles and measurement instrumentation in optical technology to solve challenging engineering problems

A low-voltage CMOS-compatible time-domain photodetector, device & front end electronics

During the last decades, the usage of silicon photodetectors, both as stand-alone sensor or integrated in arrays, grew tremendously. They are now found in almost any application and any market range, from leisure products to high-end scientific apparatuses, including, among others, industrial, automotive, and medical equipment. The impressive growth in photodetector applications is closely linked to the development of CMOS technology, which now offers inexpensive and efficient analog and digi-tal signal processing capabilities. Detectors are often integrated with their respective front end and application-specific digital circuit on the same silicon die, forming complete systems on chip. In some cases the detector itself is not on the same chip but often part of the same package. However, this trend of co-integration of analog front end and digital circuits complicates the design of the analog part. The ever-decreasing supply voltage and the smaller transistors in advanced processes (which are driven by the development of digital cir-cuits) negatively impact the performance of the analog structures and complicates their design. For photodetector systems, the effect most importantly translates into a degradation of dynamic range and signal-to-noise ratio. One way to circumvent the problem of low supply voltages is to shift the operation from voltage domain to time domain. By doing so, the signal is no longer constrained by the supply rails and analog amplification is avoided. The signal takes the form of a time-based modulation, such as pulse-width modulation or pulse-frequency modulation. Another advantage is that the output signal of a time-domain photodetection system is directly interfaceable with digital circuits. In this work, a new type of CMOS-compatible photodetector displaying intrinsic light-to-time conversion is proposed. Its physical structure consists of a MOS gate interleaved with a PN junction. The MOS structure is acting as a photogate. The depletion region shrinks when photogenerated carriers fill the potential well. At some point, the anode of the PN structure is de-isolated from the rest of the detector and triggers a positive-feedback effect that leads to a very steep current increase through the PN-junction. This translates into a signal of very high amplitude and independent from light-intensity, which can be almost directly interfaced with digital circuits. This simplifies the front end circuit compared to photodiode-based systems. The physical behavior of the device is analyzed with the help of TCAD simulations and simple behavioral and shot-noise models are proposed. The device has been co-integrated with its driver and front end circuit in a standard CMOS process and its characteristics have been measured with a custom-made measurement system. The effect of bias parameters on the performance of the sensor are also analyzed. The limitations of the device are discussed, the most important ones being dark current and linearity. Techno-logical solutions, such as the implementation of the detector on Silicon-on-Insulator technology, are proposed to overcome the limitations. Finally, some application demonstrators have been realized. Other applications that could benefit from the detector are suggested, such as digital applications taking advantage of the latching behavior of the device, and a Photoplethysmography (PPG) system that uses a PLL-based control loop to minimize the emitting LED-current

Electronic Devices for the Combination of Electrically Controlled Drug Release, Electrostimulation, and Optogenetic Stimulation for Nerve Tissue Regeneration

[ES] La capacidad de las células madre para proliferar formando distintas células especializadas les otorga la potencialidad de servir de base para terapias efectivas para patologías cuyo tratamiento era inimaginable hasta hace apenas dos décadas. Sin embargo, esta capacidad se encuentra mediada por estímulos fisiológicos, químicos, y eléctricos, específicos y complejos, que dificultan su traslación a la rutina clínica. Por ello, las células madre representan un campo de estudio en el que se invierten amplios esfuerzos por parte de la comunidad científica. En el ámbito de la regeneración nerviosa, para modular su desarrollo y diferenciación el tratamiento farmacológico, la electroestimulación, y la estimulación optogenética son técnicas que están consiguiendo prometedores resultados. Es por ello por lo que en la presente tesis se ha desarrollado un conjunto de sistemas electrónicos para permitir la aplicación combinada de estas técnicas in vitro, con perspectiva a su aplicación in vivo. Hemos diseñado una novedosa tecnología para la liberación eléctricamente controlada de fármacos. Esta tecnología está basada en nanopartículas de sílice mesoporosa y puertas moleculares de bipiridina-heparina. Las puertas moleculares son electroquímicamente reactivas, y encierran los fármacos en el interior de las nanopartículas, liberándolos ante un estímulo eléctrico. Hemos caracterizado esta tecnología, y la hemos validado mediante la liberación controlada de rodamina en cultivos celulares de HeLa. Para la combinación de liberación controlada de fármacos y electroestimulación hemos desarrollado dispositivos que permiten aplicar los estímulos eléctricos de forma configurable desde una interfaz gráfica de usuario. Además, hemos diseñado un módulo de expansión que permite multiplexar las señales eléctricas a diferentes cultivos celulares. Además, hemos diseñado un dispositivo de estimulación optogenética. Este tipo de estimulación consiste en la modificación genética de las células para que sean sensibles a la radiación lumínica de determinada longitud de onda. En el ámbito de la regeneración de tejido mediante células precursoras neurales, es de interés poder inducir ondas de calcio, favoreciendo su diferenciación en neuronas y la formación de circuitos sinápticos. El dispositivo diseñado permite obtener imágenes en tiempo real mediante microscopía confocal de las respuestas transitorias de las células al ser irradiadas. El dispositivo se ha validado irradiando neuronas modificadas con luz pulsada de 100 ms. También hemos diseñado un dispositivo electrónico complementario de medida de irradiancia con el doble fin de permitir la calibración del equipo de irradiancia y medir la irradiancia en tiempo real durante los experimentos in vitro. Los resultados del uso de los bioactuadores en procesos complejos y dinámicos, como la regeneración de tejido nervioso, son limitados en lazo abierto. Uno de los principales aspectos analizados es el desarrollo de biosensores que permitiesen la cuantización de ciertas biomoléculas para ajustar la estimulación suministrada en tiempo real. Por ejemplo, la segregación de serotonina es una respuesta identificada en la elongación de células precursoras neurales, pero hay otras biomoléculas de interés para la implementación de un control en lazo cerrado. Entre las tecnologías en el estado del arte, los biosensores basados en transistores de efecto de campo (FET) funcionalizados con aptámeros son realmente prometedores para esta aplicación. Sin embargo, esta tecnología no permitía la medición simultánea de más de una biomolécula objetivo en un volumen reducido debido a las interferencias entre los distintos FETs, cuyos terminales se encuentran inmersos en la solución. Por ello, hemos desarrollado instrumentación electrónica capaz de medir simultáneamente varios de estos biosensores, y la hemos validado mediante la medición simultánea de pH y la detección preliminar de serotonina y glutamato.[CA] La capacitat de les cèl·lules mare per a proliferar formant diferents cèl·lules especialitzades els atorga la potencialitat de servir de base per a teràpies efectives per a patologies el tractament de les quals era inimaginable fins fa a penes dues dècades. No obstant això, aquesta capacitat es troba mediada per estímuls fisiològics, químics, i elèctrics, específics i complexos, que dificulten la seua translació a la rutina clínica. Per això, les cèl·lules mare representen un camp d'estudi en el qual s'inverteixen amplis esforços per part de la comunitat científica. En l'àmbit de la regeneració nerviosa, per a modular el seu desenvolupament i diferenciació el tractament farmacològic, l'electroestimulació, i l'estimulació optogenética són tècniques que estan aconseguint prometedors resultats. És per això que en la present tesi s'ha desenvolupat un conjunt de sistemes electrònics per a permetre l'aplicació combinada d'aquestes tècniques in vitro, amb perspectiva a la seua aplicació in vivo. Hem dissenyat una nova tecnologia per a l'alliberament elèctricament controlat de fàrmacs. Aquesta tecnologia està basada en nanopartícules de sílice mesoporosa i portes moleculars de bipiridina-heparina. Les portes moleculars són electroquímicament reactives, i tanquen els fàrmacs a l'interior de les nanopartícules, alliberant-los davant un estímul elèctric. Hem caracteritzat aquesta tecnologia, i l'hem validada mitjançant l'alliberament controlat de rodamina en cultius cel·lulars de HeLa. Per a la combinació d'alliberament controlat de fàrmacs i electroestimulació hem desenvolupat dispositius que permeten aplicar els estímuls elèctrics de manera configurable des d'una interfície gràfica d'usuari. A més, hem dissenyat un mòdul d'expansió que permet multiplexar els senyals elèctrics a diferents cultius cel·lulars. A més, hem dissenyat un dispositiu d'estimulació optogenètica. Aquest tipus d'estimulació consisteix en la modificació genètica de les cèl·lules perquè siguen sensibles a la radiació lumínica de determinada longitud d'ona. En l'àmbit de la regeneració de teixit mitjançant cèl·lules precursores neurals, és d'interés poder induir ones de calci, afavorint la seua diferenciació en neurones i la formació de circuits sinàptics. El dispositiu dissenyat permet obtindré imatges en temps real mitjançant microscòpia confocal de les respostes transitòries de les cèl·lules en ser irradiades. El dispositiu s'ha validat irradiant neurones modificades amb llum polsada de 100 ms. També hem dissenyat un dispositiu electrònic complementari de mesura d'irradiància amb el doble fi de permetre el calibratge de l'equip d'irradiància i mesurar la irradiància en temps real durant els experiments in vitro. Els resultats de l'ús dels bioactuadors en processos complexos i dinàmics, com la regeneració de teixit nerviós, són limitats en llaç obert. Un dels principals aspectes analitzats és el desenvolupament de biosensors que permeteren la quantització de certes biomolècules per a ajustar l'estimulació subministrada en temps real. Per exemple, la segregació de serotonina és una resposta identificada amb l'elongació de les cèl·lules precursores neurals, però hi ha altres biomolècules d'interés per a la implementació d'un control en llaç tancat. Entre les tecnologies en l'estat de l'art, els biosensors basats en transistors d'efecte de camp (FET) funcionalitzats amb aptàmers són realment prometedors per a aquesta aplicació. No obstant això, aquesta tecnologia no permetia el mesurament simultani de més d'una biomolècula objectiu en un volum reduït a causa de les interferències entre els diferents FETs, els terminals dels quals es troben immersos en la solució. Per això, hem desenvolupat instrumentació electrònica capaç de mesurar simultàniament diversos d'aquests biosensors i els hem validat amb mesurament simultani del pH i la detecció preliminar de serotonina i glutamat.[EN] The stem cells' ability to proliferate to form different specialized cells gives them the potential to serve as the basis for effective therapies for pathologies whose treatment was unimaginable until just two decades ago. However, this capacity is mediated by specific and complex physiological, chemical, and electrical stimuli that complicate their translation to clinical routine. For this reason, stem cells represent a field of study in which the scientific community is investing a great deal of effort. In the field of nerve regeneration, to modulate their development and differentiation, pharmacological treatment, electrostimulation, and optogenetic stimulation are techniques that are achieving promising results. For this reason, we have developed a set of electronic systems to allow the combined application of these techniques in vitro, with a view to their application in vivo. We have designed a novel technology for the electrically controlled release of drugs. This technology is based on mesoporous silica nanoparticles and bipyridine-heparin molecular gates. The molecular gates are electrochemically reactive and entrap the drugs inside the nanoparticles, releasing them upon electrical stimulus. We have characterized this technology and validated it by controlled release of rhodamine in HeLa cell cultures. For combining electrostimulation and controlled drug release we have developed devices that allow applying the different electrical stimuli in a configurable way from a graphical user interface. In addition, we have designed an expansion module that allows multiplexing electrical signals to different cell cultures. In addition, we have designed an optogenetic stimulation device. This type of stimulation consists of genetically modifying cells to make them sensitive to light radiation of a specific wavelength. In tissue regeneration using neural precursor cells, it is interesting to be able to induce calcium waves, favoring the cell differentiation into neurons and the formation of synaptic circuits. The designed device enable the obtention of real-time images through confocal microscopy of the transient responses of cells upon irradiation. The device has been validated by irradiating modified neurons with 100 ms pulsed light stimulation. We have also designed a complementary electronic irradiance measurement device to allow calibration of the irradiator equipment and measuring irradiance in real time during in vitro experiments. The results of using bioactuators in complex and dynamic processes, such as nerve tissue regeneration, are limited in an open loop. One of the main aspects analyzed is the development of biosensors that would allow quantifying of specific biomolecules to adjust the stimulation provided in real time. For instance, serotonin secretion is an identified response of neural precursor cells elongation, among other biomolecules of interest for the implementation of a closed-loop control. Among the state-of-the-art technologies, biosensors based on field effect transistors (FETs) functionalized with aptamers are promising for this application. However, this technology did not allow the simultaneous measurement of more than one target biomolecule in a small volume due to interferences between the different FETs, whose terminals are immersed in the solution. This is why we have developed electronic instrumentation capable of simultaneously measuring several of these biosensors, and we have validated it with the simultaneous pH measurement and the preliminary detection of serotonin and glutamate.Monreal Trigo, J. (2023). Electronic Devices for the Combination of Electrically Controlled Drug Release, Electrostimulation, and Optogenetic Stimulation for Nerve Tissue Regeneration [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/19384