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)

Miniaturized wireless cell spectrophotometer platform in visible and near-IR range

In this paper, a new miniaturized wireless cell spectrophotometer is presented. This system can scan a sample, detect incoming light power and transmit corresponding data to a base station for further analysis in the range of 340 nm to 850 nm. In vitro measurement results with VERO E6 cells tagged with DAPI and Alexa Fluor488 are presented to demonstrate its performance. The proposed system uses two small Lithium-ion batteries that provide a 7.4 V supply voltage. The system's low power consumption (88 mW), its minimal use of hardware resources, and its total weight of 17 g incorporated into a small wireless platform make the proposed device suitable for real-time implementation in most common low-power cell spectrophotometer applications

A Low-Power Sigma-Delta Modulator for Healthcare and Medical Diagnostic Applications

This paper presents a switched-capacitor Sigma-Delta modulator designed in 90-nm CMOS technology, operating at 1.2-V supply voltage. The modulator targets healthcare and medical diagnostic applications where the readout of small-bandwidth signals is required. The design of the proposed A/D converter was optimized to achieve the minimum power consumption and area. A remarkable performance improvement is obtained through the integration of a low-noise amplifier with modified Miller compensation and rail-to-rail output stage. The manuscript also presents a set of design equations, from the small-signal analysis of the amplifier, for an easy design of the modulator in different technology nodes. The Sigma-Delta converter achieves a measured 96-dB dynamic range, over a 250-Hz signal bandwidth, with an oversampling ratio of 500. The power consumption is 30 μW, with a silicon area of 0.39 mm²

The Boston University Photonics Center annual report 2009-2010

This repository item contains an annual report that summarizes activities of the Boston University Photonics Center for the period from July 2009 through June 2010. The report provides quantitative and descriptive information regarding photonics programs in education, interdisciplinary research, business innovation, and technology development. The Boston University Photonics Center (BUPC) is an interdisciplinary hub for education, research, scholarship, innovation, and technology development associated with practical uses of light.This report summarizes activities of the Boston University Photonics Center (BUPC) during the period July 2009 through June 2010. These activities span the Center’s complementary missions in education, research, technology development, and commercialization. In education, twenty-three BUPC graduate students received Ph.D. diplomas. BUPC faculty taught thirty-one photonics courses. Five graduate students were funded through the Photonics Fellowship Program. BUPC supported a Research Experiences for Undergraduates (REU) site in Photonics, which hosted summer interns in a ten-week program. Each REU student presented their research results to a panel of faculty and graduate students. Professors Goldberg and Swan continued their work with K-12 student outreach programs. Professor Goldberg’s Boston Urban Fellows Project started its sixth year. Professor Swan’s collaborative Four Schools for Women in Engineering program entered its third year. For more on our education programs, turn to the Education section on page 67. In research, BUPC faculty published journal papers spanning the field of photonics. Twelve patents were awarded to faculty this year for new innovations in the field. A number of awards for outstanding achievement in education and research were presented to BUPC faculty members. These honors include NSF CAREER Awards for Professors Altug, Dal Negro and Reinhard. New external grant funding for the 2009-2010 fiscal year totaled $21.1M, including$4.0M through a Cooperative Agreement with the U.S. Army Research Laboratory (ARL). For more information on our research activities, turn to the Research section on page 24. In technology development, the Department of Defense (DoD) continued to support the COBRA prototype systems. These photonics-technologies were pioneered by BUPC faculty and staff and have been deployed for field test and use at the United States Army Medical Research Institute for Infectious Diseases. New technology development projects for nuclear weapon detection, biodosimetry and terahertz imaging were launched and previously developed technologies for bacterial and viral sensing advanced toward commercial transition. For more information on our technology development pipeline and projects, turn to the Technology Development section on page 54. In commercialization, the business incubator continues to operate at capacity. Its tenants include more than a dozen technology companies with core business interests primarily in photonics and life sciences. It houses several companies founded by current and former BU faculty and students and provides students with an opportunity to assist, observe, and learn from start-up companies. For more information about business incubator activities, turn to the Business Incubation chapter in the Facilities and Equipment section on page 84. In early 2010, the BUPC unveiled a five-year strategic plan as part of the University’s comprehensive review of centers and institutes. The BUPC strategic plan will enhance the Center’s position as an international leader in photonics research. For more information about the strategic plan, turn to the BUPC Strategic Plan section on page 8

Блок прецизійного вимірювання температури головного мозку у зоні оптичного опромінення

Тема магістерської дисертації: “Блок прецизійного вимірювання температури головного мозку у зоні оптичного опромінення”. Обсяг дисертації становить 63 сторінку, міститься 17 таблиць, 15 рисунків. Загалом опрацьовано 38 джерело. Актуальність: Робота є частиною проекту між двома науковими закладами Korea Institute of Science and Technology(KIST) та Korean advanced Institute of Science and Technology(KAIST), що включає в себе створення приладу з наступними функціями: ● запис електрофізіологічного сигналу головного мозку; ● реалізація оптичного опромінення ділянки головного мозку; ● вимірювання температури опромінюваної ділянки головного мозку за допомогою масиву фотодіодів. Завдання даної роботи є створення інтегральної мікросхеми для вимірювання струму та перетворення його в цифровий сигнал для вимірювання температури . Метою МД є розробка інтегральної мікросхеми для вимірювання струму датчиків температури. Завдання: • Розробка електрично-принципової схеми • Підтвердження виконання функції • Розташування та створення топології • Після топологічна симуляція • Виготовлення прототипу інтегральної мікросхеми • Створення програмного забезпечення для керування чіпом. • Лабораторні випробування створеного протопипу системи. Об’єкт дослідження: методи і засоби контролю температури ділянки мозку під час терапії оптичним опроміненням. Предмет дослідження: засоби перетворення температури у електричний сигнал, підсилення, фільтрації, перетворення у цифрову форму і технічна реалізація блоку вимірювання температури. Методи дослідження – використання пакетів прикладних програм для створення принципово електричної схеми, проведення симуляції роботи системи, створення топології системи. Основні результати: сформовано технічні вимоги до прототипу, розроблено принципову електричну схему, розроблено топологію інтегральної мікросхеми, розроблено топологію друкованої плати блоку, виготовлено прототип інтегральної мікросхеми, створено програмний продукт для роботи з розробленим прототипом, проведені випробування прототипу в лабораторії.Theme of the thesis: “Integrated circuit for brain temperature measurement in the area of optical stimulation” The amount of work is 63 pages long, contains 15 illustrations, 17 tables. In total, 38 sources were processed. Relevance: The work is part of a project between two research institutes, the Korea Institute of Science and Technology (KIST) and the Korean Advanced Institute of Science and Technology (KAIST), which includes the development of a device with the following functions: ● recording of a brain electrophysiological signal; ● implementation of optical irradiation of the brain; ● measuring the temperature of the irradiated area of the brain using an array of photodiodes. The purpose of this work is a development of an integrated circuit for detection of temperature sensors current. Tasks: • Schematic design • System level confirmation • Placement and layout • Post-layout simulation • Manufacturing of the system prototype. • Creating software to control the chip. • Laboratory tests of the created system prototype. Subject of research: means of temperature conversion into electrical signal, amplification, filtration, digital conversion and technical implementation of temperature measurement unit. Research methods: the use of application software packages to create a schematic of electrical circuit, simulation of the system, creating a system topology. Main results: technical requirements to the prototype are formed, the electric scheme is designed, the topology of the integrated circuit is developed, the topology of the printed circuit board of the block is designed, the prototype of the chip is manufactured; the software product to control the developed prototype is created.Тема магистерской диссертации: "Блок прецизионного измерения температуры головного мозга в зоне оптического излучения". Объем диссертации составляет 61 страницу, содержится 17 таблиц, 15 рисунков. В общем обработано 38 источник. Актуальность: Работа является частью проекта между двумя научными учреждениями Korea Institute of Science and Technology (KIST) и Korean advanced Institute of Science and Technology (KAIST), включающегов себя создание прибора со следующими функциями: ● запись электрофизиологического сигнала головного мозга ● реализация оптического излучения участки головного мозга ● измерения температуры облучаемого участка головного мозга с помощью массива фотодиодов. Задача данной работы является создание интегральной микросхемы для измерения тока и преобразования его в цифровой сигнал для измерения температуры. Целью МД является разработка интегральной микросхемы для измерения тока датчиков температуры. Задачи: • Разработка электрически принципиальной схемы • Подтверждение выполнения функции • Расположение и создания топологии • После топологическая симуляция •Изготовление прототипа чипа • Создание программного обеспечения для управления чипом. • Лабораторные испытания созданного протопип системы. Объект исследования: методы и средства контроля температуры участки мозга во время терапии оптическим облучением. Предмет исследования: средства преобразования температуры в электрический сигнал, усиления, фильтрации, преобразования в цифровую форму и техническая реализация блока измерения температуры. Методы исследования - использование пакетов прикладных программ для создания принципиально электрической схемы, проведения симуляции работы системы, создания топологии системы. Основные результаты: сформирована технические требования к прототипу, разработана принципиальная электрическая схема, разработаны топологию интегральной микросхемы, разработаны топологию печатной платы блока, изготовлено прототип чипа, создан программный продукт для работы с разработанным прототипом, проведены испытания прототипа в лаборатории

EUROSENSORS XVII : book of abstracts

Fundação Calouste Gulbenkien (FCG).Fundação para a Ciência e a Tecnologia (FCT)

The Boston University Photonics Center annual report 2011-2012

This repository item contains an annual report that summarizes activities of the Boston University Photonics Center in the 2011-2012 academic year. The report provides quantitative and descriptive information regarding photonics programs in education, interdisciplinary research, business innovation, and technology development. The Boston University Photonics Center (BUPC) is an interdisciplinary hub for education, research, scholarship, innovation, and technology development associated with practical uses of light.This report summarizes activities of the Boston University Photonics Center during the period July 2011 through June 2012. These activities span the Center’s complementary missions in education, research, technology development, and commercialization. In 2010, the Photonics Center unveiled a five-year strategic plan as part of the University’s comprehensive review of centers and institutes. The Photonics Center continues to show progress on the Photonics Center strategic plan and is growing the Center’s position as an international leader in photonics research. For more information about the strategic plan, read the Photonics Center Strategic Plan section on page 11. In research, Photonics Center faculty published more than 100 journal papers spanning the field of photonics. A number of awards for outstanding achievement in education and research were presented to Photonics Center faculty members, including a Presidential Early Career Award for Scientists and Engineers (PECASE) for Professor Altug, the Boston University Peter Paul Professorship for Professor Han, and a Dean’s Catalyst Award for Professor Joshi. New external grant funding for the 2011-2012 fiscal year totaled $15.8M. For more information on our research activities, read the Research section on page 26. In technology development, the close of FY11 marked the end of the Photonics Center’s decade-long collaboration pipeline technology development with the Army Research Laboratory (ARL). The successful outcomes of that unique partnership include a compelling series of photonics technology prototypes aimed at force protection. Our direct collaboration with Army end users has enabled transformative advanced in sniper detection of bioterror agents, and nuclear threat detection. In the past year, the Photonics Center has expanded the scope of its unique photonic technology development program to include applications in the commercial healthcare sector. For more information on our technology development program and on specific projects, read the Technology Development section on page 52. In education, 17 Photonics Center graduate students received Ph.D. diplomas. Photonics Center faculty taught 29 photonics courses. The Center supported a Research Experiences for Teachers (RET) site in Biophotonic Sensors and Systems for 10 middle school and high school teachers. The Photonics Center sponsored the Herbert J. Berman “Future of Light” Prize at the University’s Science and Engineering Day. Professor Goldberg’s Boston Urban Fellows Project started its seventh year. For more on our education programs, read the Education section on page 64. In commercialization, the Business Innovation Center continues to operate at capacity. Its tenants include 11 technology companies with a majority having core business interests primarily in photonics and life sciences. It houses several companies founded by current and former BU faculty and students and provides students with an opportunity to assist, observe, and learn from start-up companies. For more information about Business Innovation Center activities, read the Business Innovation Center chapter in the Facilities and Equipment section on page 78

Data Acquisition Applications

Data acquisition systems have numerous applications. This book has a total of 13 chapters and is divided into three sections: Industrial applications, Medical applications and Scientific experiments. The chapters are written by experts from around the world, while the targeted audience for this book includes professionals who are designers or researchers in the field of data acquisition systems. Faculty members and graduate students could also benefit from the book

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