High-precision fluorescence photometry for real-time biomarkers detection

Les derniers évènements planétaires et plus particulièrement l'avènement sans précédent du nouveau coronavirus augmente la demande pour des appareils de test à proximité du patient. Ceux-ci fonctionnent avec une batterie et peuvent identifier rapidement des biomarqueurs cibles. Pareils systèmes permettent aux utilisateurs, disposant de connaissances limitées en la matière, de réagir rapidement, par exemple dans la détection d'un cas positif de COVID-19. La mise en œuvre de l'élaboration d'un tel instrument est un projet multidisciplinaire impliquant notamment la conception de circuits intégrés, la programmation, la conception optique et la biologie, demandant tous une maîtrise pointue des détails. De plus, l'établissement des spécifications et des exigences pour mesurer avec précision les interactions lumière-échantillon s'additionnent au besoin d'expérience dans la conception et la fabrication de tels systèmes microélectriques personnalisés et nécessitent en elles-mêmes, une connaissance approfondie de la physique et des mathématiques. Ce projet vise donc à concevoir et à mettre en œuvre un appareil sans fil pour détecter rapidement des biomarqueurs impliqués dans des maladies infectieuses telles que le COVID-19 ou des types de cancers en milieu ambulatoire. Cette détection se fait grâce à des méthodes basées sur la fluorescence. La spectrophotométrie de fluorescence permet aux médecins d'identifier la présence de matériel génétique viral ou bactérien tel que l'ADN ou l'ARN et de les caractériser. Les appareils de paillasse sont énormes et gourmand énergétiquement tandis que les spectrophotomètres à fluorescence miniatuarisés disponibles dans le commerce sont confrontés à de nombreux défis. Ces appareils miniaturisés ont été découverts en tirant parti des diodes électroluminescentes (DEL) à semi-conducteurs peu coûteuses et de la technologie des circuits intégrés. Ces avantages aident les scientifiques à réduire les erreurs possibles, la consommation d'énergie et le coût du produit final utilisé par la population. Cependant, comme leurs homologues de paillasse, ces appareils POC doivent quantifier les concentrations en micro-volume d'analytes sur une large gamme de longueurs d'onde suivant le cadre d'une économie en ressources. Le microsystème envisagé bénéficie d'une approche de haute précision pour fabriquer une puce microélectronique CMOS. Ce procédé se fait de concert avec un boîtier personnalisé imprimé en 3D pour réaliser le spectrophotomètre à la fluorescence nécessaire à la détection quantitative d'analytes en microvolume. En ce qui a trait à la conception de circuits, une nouvelle technique de mise à auto-zeroing est appliquée à l'amplificateur central, celui-ci étant linéarisé avec des techniques de recyclage et de polarisation adaptative. Cet amplificateur central est entièrement différentiel et est utilisé dans un amplificateur à verrouillage pour récupérer le signal d'intérêt éclipsé par le bruit. De plus, l'augmentation de la sensibilité de l'appareil permet des mesures quantitatives avec des concentrations en micro-volume d'analytes ayant moins d'erreurs de prédiction de concentration. Cet avantage cumulé à une faible consommation d'énergie, un faible coût, de petites dimensions et un poids léger font de notre appareil une solution POC prometteuse dans le domaine de la spectrophotométrie de fluorescence. La validation de ce projet s'est fait en concevant, fabriquant et testant un prototype discret et sans fil. Son article de référence a été publié dans IEEE LSC 2018. Quant à la caractérisation et l'interprétation du prototype d'expériences in vitro à l'aide d'une interface MATLAB personnalisée, cet article a été publié dans IEEE Sensors journal (2021). Les circuits intégrés et les photodétecteurs ont été fabriqués ont été conçus et fabriqués par Cadence en 2019. Relativement aux solutions de circuit proposées, elles ont été fabriquées avec la technologie CMOS 180 nm et publiées lors de la conférence IEEE MWSCAS 2020. Tout comme cette dernière contribution, les expériences in vitro avec le dispositif proposé incluant la puce personnalisée et le boîtier imprimé en 3D ont été réalisés et les résultats électriques et optiques ont été soumis au IEEE Journal of Solid-State Circuits (JSSC 2022).The most recent and unprecedented experience of the novel coronavirus increases the demand for battery-operated near-patient testing devices that can rapidly identify the target biomarkers. Such systems enable end-users with limited resources to quickly get feedback on various medical tests, such as detecting positive COVID-19 cases. Implementing such a device is a multidisciplinary project dealing with multiple areas of expertise, including integrated circuit design, programming, optical design, and biology, each of which needs a firm grasp of details. Alongside the need for experience in designing and manufacturing custom microelectronic systems, establishing the specifications and requirements to precisely measure the light-sample interactions requires an in-depth knowledge of physics and mathematics. This project aims to design and implement a wireless point-of-care (POC) device to rapidly detect biomarkers involved in infectious diseases such as COVID-19 or different types of cancers in an ambulatory setting using fluorescence-based methods. Fluorescence spectrophotometry allows physicians to identify and characterize viral or bacterial genetic materials such as DNAs or RNAs. The benchtop devices that are currently available are bulky and power-hungry, whereas the commercially available miniaturized fluorescence spectrophotometers are facing many challenges. Many of these difficulties have been resolved in literature thanks to inexpensive semiconductor light-emitting diodes (LEDs) and integrated circuits technology. Such advantages aid scientists in decreasing the size, power consumption, and cost of the final product for end-users. However, like the benchtop counterparts, such POC devices must quantify micro-volume concentrations of analytes across a wide wave length range under an economy of resources. The envisioned microsystem benefits from a high-precision approach to fabricating a CMOS microelectronic chip combined with a custom 3D-printed housing. This implementation results in a fluorescence spectrophotometer for qualitative and quantitative detection of micro-volume analytes. In terms of circuit design, a novel switched-biasing ping-pong auto-zeroed technique is applied to the core amplifier, linearized with recycling and adaptive biasing techniques. The fully differential core amplifier is utilized within a lock-in amplifier to retrieve the signal of interest overshadowed by noise. Increasing the device's sensitivity allows quantitative measurements down to micro-volume concentrations of analytes with less concentration prediction error. Such an advantage, along with low-power consumption, low cost, low weight, and small dimensions, make our device a promising POC solution in the fluorescence spectrophotometry area. The approach of this project was validated by designing, fabricating, and testing a discrete and wireless prototype. Its conference paper was published in IEEE LSC 2018, and the prototype characterization and interpretation of in vitro experiments using a custom MATLAB interface were published in IEEE Sensors Journal (2021). The integrated circuits and photodetectors were designed and fabricated by the Cadence circuit design toolbox (2019). The proposed circuit solutions were fabricated with 180-nm CMOS technology and published at IEEE MWSCAS 2020 conference. As the last contribution, the in vitro experiments with the proposed device, including the custom chip and 3D-printed housing, were performed, and the electrical and optical results were submitted to the IEEE Journal of Solid-State Circuits (JSSC 2022)

Broadband nonlinear modulation of incoherent light using a transparent optoelectronic neuron array

Nonlinear optical processing of ambient natural light is highly desired in computational imaging and sensing applications. A strong optical nonlinear response that can work under weak broadband incoherent light is essential for this purpose. Here we introduce an optoelectronic nonlinear filter array that can address this emerging need. By merging 2D transparent phototransistors (TPTs) with liquid crystal (LC) modulators, we create an optoelectronic neuron array that allows self-amplitude modulation of spatially incoherent light, achieving a large nonlinear contrast over a broad spectrum at orders-of-magnitude lower intensity than what is achievable in most optical nonlinear materials. For a proof-of-concept demonstration, we fabricated a 10,000-pixel array of optoelectronic neurons, each serving as a nonlinear filter, and experimentally demonstrated an intelligent imaging system that uses the nonlinear response to instantly reduce input glares while retaining the weaker-intensity objects within the field of view of a cellphone camera. This intelligent glare-reduction capability is important for various imaging applications, including autonomous driving, machine vision, and security cameras. Beyond imaging and sensing, this optoelectronic neuron array, with its rapid nonlinear modulation for processing incoherent broadband light, might also find applications in optical computing, where nonlinear activation functions that can work under ambient light conditions are highly sought.Comment: 20 Pages, 5 Figure

Hybrid Micro-Electro-Mechanical Tunable Filter

While advantages such as good thermal stability and processing-chemical compatibilities exist for common monolithic-integrated micro-electro-mechanically tunable filters (MEM-TF) and MEM-tunable vertical cavity surface emitting lasers (MT-VCSEL), they often require full processing to determine device characteristics. Alternatively, the MEM actuators and the optical parts may be fabricated separately, then subsequently bonded. This hybrid approach potentially increases design flexibility. Since hybrid techniques allow integration of heterogeneous material systems, best of breed compound optoelectronic devices may be customized to enable materials groups to be optimized for tasks they are best suited. Thus, as a first step toward a hybrid (AlxGa1-xAs-polySi) MT-VCSEL, this dissertation reports the design, fabrication, and demonstration of an electrostatically actuated hybrid MEM-TF. A 250x250-µm2, 4.92-µm-thick, Al0.4Ga0.6As-GaAs distributed Bragg reflector was successfully flip-bonded to a polySi piston electrostatic actuator using SU-8 photoresist as bonding adhesive. The device demonstrated 53nm (936.5 - 989.5nm) of resonant wavelength tuning over the actuation voltage range of 0 to 10 V

LASER Tech Briefs, September 1993

This edition of LASER Tech briefs contains a feature on photonics. The other topics include: Electronic Components and Circuits. Electronic Systems, Physical Sciences, Materials, Computer Programs, Mechanics, Machinery, Fabrication Technology, Mathematics and Information Sciences, Life Sciences and books and reports

Road Traffic Rules Violators' Monitoring System

This purpose of this system is to catch vehicle, which breaks the red traffic signal by sending the unique characters (e.g. vehicle's registration number) to the database and keep the record for future action. The main objective of this project is to transmit alphanumeric characters through RF medium and display the characters on the LCD matrix at the receiver. The system is using digital RF transmitter and receiver integrated with 16F84A PIC micro controller for the ASCII code conversion, data encoding and decoding task. Thus, the next objective is to develop the programming code for the 16F84A to perform all these tasks. In the project, the assembly language is used to develop the programming code. The VMS operates only when the traffic signal is red. In this project, a switch is used to trigger the transmitter in the vehicle at that particular time. The switch is only working under certain state condition (RED light is ON). In the future and practical used, the switch can be replaced with a Hall sensor. The hall sensor detects the magnetic flux introduced by the electromagnet, which is installed under the road surface. The first section of the report will tell about the introduction of background of the project, the concept ofRTRVMS, problem statement, objectives and scopes of study. The second section of the report is literature review of the components used in the system. The third section will be the methodology and project work including the project development. The forth section! is the project Findings and discussion throughout this semester and also the problem facing. This simple system can be one of the solutions to control the road traffic violent in the future

High performance photodetectors for multimode optical data links

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2006.Includes bibliographical references (p. 233-240).The majority of photodetectors presented in the literature, or available commercially, have dimensions on the order of 50 Ym or smaller, suitable for glass multimode or single mode fibre applications. The recent successful commercialisation of very large core diameter plastic optical fibre in systems based around 650 nm emitters, as well as the recent emergence of new polymer materials enabling relatively low loss at the more standard 780 nm and 850 nm wavelengths, has exposed the need for integrated photodetectors with dimensions well above 100 /m and capable of bitrates from 250 Mb/s for low-cost consumer applications to multiple Gb/s for high performance short reach interconnects. This size-performance regime has been largely ignored until now. This work examines interdigitated detector structures in multiple material systems by measurement and simulation. An optoelectronic frequency response measurement system was designed and implemented for this work, allowing measurement up to 8 GHz using 850 nm or 1550 nm sources. The full expression for frequency response of diffusion current under different illumination scenarios was derived, a topic normally omitted in the discussion of photodetectors, and applied to the analysis of device measurements.(cont.) Silicon detectors of various geometries were fabricated, with measured bandwidths at 5 V reverse bias up to 2 GHz for 200 ym diameter devices and 4 GHz for 50 and 100 ym diameter devices. The latter is the highest bandwidth reported for a silicon detector fabricated in a CMOS-compatible process and biased at a practically accessible voltage. Device performance was confirmed by simulation, and a novel structure is proposed featuring a buried junction on SOI determined by simulation to have twice as high a responsivity-bandwidth product as the best reported devices fabricated on high resistivity SOI. The silicon device structure was modified for epitaxial germanium wafers, and devices were fabricated. The germanium devices were simulated to determine the appropriate technology scaling direction and maximum device dimensions for desired performance specifications.by Wojciech Piotr Giziewicz.Ph.D

Monolithic integration of 1.55 micron photodetectors with GaAs electronics for high speed optical communications

Thesis (Ph.D.)--Massachusetts Institute of Technology, Dept. of Materials Science and Engineering, 1998.Includes bibliographical references (p. 178-194).Integrated optoelectronics has shown exciting promise for high speed optical communication systems. For better system performance and lower cost, monolithic optoelectronic integrated circuits (OEICs) are highly desirable. A novel optoelectronic integration technology for high performance OEICs was proposed and partially developed and termed Aligned Pillar Bonding (APB) process. The work began with applying GaAs-based Epitaxy-on-Electronics (EoE) technology to integrate matched pairs of 1.55 micron InGaAs photodetectors with high speed GaAs electronics, which requires the direct growth of InGaAs on lattice-mismatched GaAs substrates using molecular beam epitaxy (MBE). A customized OEIC chip was designed and fabricated. Lattice-mismatched MBE growth was studied and InGaAs photodetectors on GaAs were produced using the relaxed buffer growth. However, the device performance and uniformity deteriorated significantly from those on lattice-matched InP substrates, and thus unsuitable for high speed OEICs. Aligned pillar bonding (APB) process was hence proposed. APB integrates lattice mismatched materials using aligned, selective area wafer bonding at reduced temperature. The photonic device structures are grown on their lattice matched substrates under optimal growth condition. These structures are patterned into pillars, aligned and bonded into the designated wells on the electronic chips. Subsequent substrate removal and device fabrication results in high density OEICs. 1.55 micron InGaAs photodetectors on GaAs were demonstrated using reduced temperature Pd-assisted wafer bonding, resulting in superior device performance. While the conventional dry etching techniques are impractical to pattern the desired deep pillars, electron cyclotron resonance (ECR) enhanced reactive ion etching (RIE) of InP using chlorine/helium chemistry has been developed, resulting in fast, deep, smooth, and highly anisotropic etching at room temperature. The etching characteristics have been calibrated for both InP and GaAs. Fast etching of InGaP, InAlAs, AlAs, and GaP has also been demonstrated. The etched pillars were subsequently bonded onto a OEIC chip, and initial study of small area pillar to well bonding was performed. APB allows independent optimization of both photonics and electronics for OEIC integration, inherits the wealth of the existing electronics industry, maintains good planarization and high density, permits low parasitics and high performance, and is naturally compatible with large scale manufacturing.by Hao Wang.Ph.D

DESIGN OF SMART SENSORS FOR DETECTION OF PHYSICAL QUANTITIES

Microsystems and integrated smart sensors represent a flourishing business thanks to the manifold benefits of these devices with respect to their respective macroscopic counterparts. Miniaturization to micrometric scale is a turning point to obtain high sensitive and reliable devices with enhanced spatial and temporal resolution. Power consumption compatible with battery operated systems, and reduced cost per device are also pivotal for their success. All these characteristics make investigation on this filed very active nowadays. This thesis work is focused on two main themes: (i) design and development of a single chip smart flow-meter; (ii) design and development of readout interfaces for capacitive micro-electro-mechanical-systems (MEMS) based on capacitance to pulse width modulation conversion. High sensitivity integrated smart sensors for detecting very small flow rates of both gases and liquids aiming to fulfil emerging demands for this kind of devices in the industrial to environmental and medical applications. On the other hand, the prototyping of such sensor is a multidisciplinary activity involving the study of thermal and fluid dynamic phenomenon that have to be considered to obtain a correct design. Design, assisted by finite elements CAD tools, and fabrication of the sensing structures using features of a standard CMOS process is discussed in the first chapter. The packaging of fluidic sensors issue is also illustrated as it has a great importance on the overall sensor performances. The package is charged to allow optimal interaction between fluids and the sensors and protecting the latter from the external environment. As miniaturized structures allows a great spatial resolution, it is extremely challenging to fabricate low cost packages for multiple flow rate measurements on the same chip. As a final point, a compact anemometer prototype, usable for wireless sensor network nodes, is described. The design of the full custom circuitry for signal extraction and conditioning is coped in the second chapter, where insights into the design methods are given for analog basic building blocks such as amplifiers, transconductors, filters, multipliers, current drivers. A big effort has been put to find reusable design guidelines and trade-offs applicable to different design cases. This kind of rational design enabled the implementation of complex and flexible functionalities making the interface circuits able to interact both with on chip sensors and external sensors. In the third chapter, the chip floor-plan designed in the STMicroelectronics BCD6s process of the entire smart flow sensor formed by the sensing structures and the readout electronics is presented. Some preliminary tests are also covered here. Finally design and implementation of very low power interfaces for typical MEMS capacitive sensors (accelerometers, gyroscopes, pressure sensors, angular displacement and chemical species sensors) is discussed. Very original circuital topologies, based on chopper modulation technique, will be illustrated. A prototype, designed within a joint research activity is presented. Measured performances spurred the investigation of new techniques to enhance precision and accuracy capabilities of the interface. A brief introduction to the design of active pixel sensors interface for hybrid CMOS imagers is sketched in the appendix as a preliminary study done during an internship in the CNM-IMB institute of Barcelona