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)

Design of PVT Tolerant Inverter Based Circuits for Low Supply Voltages

University of Minnesota Ph.D. dissertation. June 2015. Major: Electrical Engineering. Advisor: Ramesh Harjani. 1 computer file (PDF); xiv, 187 pages.Rapid advances in the field of integrated circuit design has been advantageous from the point of view of cost and miniaturization. Although technology scaling is advantageous to digital circuits in terms of increased speed and lower power, analog circuits strongly suffer from this trend. This is becoming a crucial bottle neck in the realization of a system on chip in scaled technology merging high-density digital parts, with high performance analog interfaces. This is because scaled technologies reduce the output impedance (gain) and supply voltage which limits the dynamic range (output swing). One way to mitigate the power supply restrictions is to move to current mode circuit circuit design rather than voltage mode designs. This thesis focuses on designing Process Voltage and Temperature (PVT) tolerant base band circuits at lower supply voltages and in lower technologies. Inverter amplifiers are known to have better transconductance efficiency, better noise and linearity performance. But inverters are prone to PVT variations and has poor CMRR and PSRR. To circumvent the problem, we have proposed various biasing schemes for inverter like semi constant current biasing, constant current biasing and constant gm biasing. Each biasing technique has its own advantages, like semi constant current biasing allows to select different PMOS and NMOS current. This feature allows for higher inherent inverter linearity. Similarly constant current and constant gm biasing allows for reduced PVT sensitivity. The inverter based OTA achieves a measured THD of -90.6 dB, SNR of 78.7 dB, CMRR 97dB, PSRR 61 dB wile operating from a nominal power of 0.9V and at output swing of 0.9V{pp,diff} in TSMC 40nm general purpose process. Further the measured third harmonic distortion varies approximately by 11.5dB with 120C variation in temperature and 9dB with a 18% variation in supply voltage. The linearity can be increased by increasing the loop gain and bandwidth in a negative feedback circuit or by increasing the over drive voltage in open loop architectures. However both these techniques increases the noise contribution of the circuit. There exist a trade off between noise and linearity in analog circuits. To circumvent this problem, we have introduced nonlinear cancellation techniques and noise filtering techniques. An analog-to-digital converter (ADC) driver which is capable of amplifying the continuous time signal with a gain of 8 and sample onto the input capacitor(1pF) of 1 10 bit successive approximation register (SAR) ADC is designed in TSMC 65nm general purpose process. This exploits the non linearity cancellation in current mirror and also allows for higher bandwidth operation by decoupling closed loop gain from the negative feedback loop. The noise from the out of band is filtered before sampling leading to low noise operation. The measured design operates at 100MS/s and has an OIP_3 of 40dBm at the nyquist rate, noise power spectral density of 17nV/sqrt{Hz} and inter modulation distortion of 65dB. The intermodulation distortion variation across 10 chips is 6dB and 4dB across a temperature variation of 120C. Non linearity cancellation is exploited in designing two filters, an anti alias filter and a continuously tunable channel select filter. Traditional active RC filters are based on cascade of integrators. These create multiple low impedance nodes in the circuit which results in a higher noise. We propose a real low pass filter based filter architecture rather than traditional integrator based approach. Further the entire filtering operation takes place in current domain to circumvent the power supply limitations. This also facilitates the use of tunable non linear metal oxide semiconductor capacitor (MOSCAP) as filter capacitors. We introduce techniques of self compensation to use the filter resistor and capacitor as compensation capacitor for lower power. The anti alias filter designed for 50MHz bandwidth is fabricated in IBM 65nm process achieves an IIP3 of 33dBm, while consuming 1.56mW from 1.2 V supply. The channel select filter is tunable from 34MHz to 314MHz and is fabricated in TSMC 65nm general purpose process. This filter achieves an OIP3 of 25.24 dBm at the maximum frequency while drawing 4.2mA from 1.1V supply. The measured intermodulation distortion varies by 5dB across 120C variation in temperature and 6.5dB across a 200mV variation in power supply. Further this filter presents a high impedance node at the input and a low impedance node at the output easing system integration. SAR ADCs are becoming popular at lower technologies as they are based on device switching rather than amplifying circuits. But recent SAR ADCs that have good energy efficiency have had relatively large input capacitance increasing the driver power. We present a 2X time interleaved (TI) SAR ADC which has the lowest input capacitance of 133fF in literature. The sampling capacitor is separated from the capacitive digital to analog converter (DAC) array by performing the input and DAC reference subtraction in the current domain rather than as done traditionally in charge domain. The proposed ADC is fabricated in TSMC's 65nm general purpose process and occupies an area of 0.0338 mm^2. The measured ADC spurious free dynamic range (SFDR) is 57dB and the measured effective number of bits (ENOB) at nyquist rate is 7.55 bit while using 1.55mW power from 1 V supply. A sub 1V reference circuit is proposed, that exploits the complementary to absolute temperature (CTAT) and proportional to absolute temperature (PTAT) voltages in the beta multiplier circuit to attain a stable voltage with temperature and power supply. A one-time calibration is integrated in the architecture to get a good performance over process. Chopper stabilization is employed to reduce the flicker noise of the reference circuit. The prototype was simulated in TSMC 65nm process and we obtain the nominal output of 236mW, while consuming 0.7mW from power supply. Simulations show a temperature coefficient of 18 ppmC from -40 to 100C and with a power supply ranging from 0.8 to 2V

Continuous-time low-pass filters for integrated wideband radio receivers

This thesis concentrates on the design and implementation of analog baseband continuous-time low-pass filters for integrated wideband radio receivers. A total of five experimental analog baseband low-pass filter circuits were designed and implemented as a part of five single-chip radio receivers in this work. After the motivation for the research work presented in this thesis has been introduced, an overview of analog baseband filters in radio receivers is given first. In addition, a review of the three receiver architectures and the three wireless applications that are adopted in the experimental work of this thesis is presented. The relationship between the integrator non-idealities and integrator Q-factor, as well as the effect of the integrator Q-factor on the filter frequency response, are thoroughly studied on the basis of a literature review. The theoretical study that is provided is essential for the gm-C filter synthesis with non-ideal lossy integrators that is presented after the introduction of different techniques to realize integrator-based continuous-time low-pass filters. The filter design approach proposed for gm-C filters is original work and one of the main points in this thesis, in addition to the experimental IC implementations. Two evolution versions of fourth-order 10-MHz opamp-RC low-pass filters designed and implemented for two multicarrier WCDMA base-station receivers in a 0.25-µm SiGe BiCMOS technology are presented, along with the experimental results of both the low-pass filters and the corresponding radio receivers. The circuit techniques that were used in the three gm-C filter implementations of this work are described and a common-mode induced even-order distortion in a pseudo-differential filter is analyzed. Two evolution versions of fifth-order 240-MHz gm-C low-pass filters that were designed and implemented for two single-chip WiMedia UWB direct-conversion receivers in a standard 0.13-µm and 65-nm CMOS technology, respectively, are presented, along with the experimental results of both the low-pass filters and the second receiver version. The second UWB filter design was also embedded with an ADC into the baseband of a 60-GHz 65-nm CMOS radio receiver. In addition, a third-order 1-GHz gm-C low-pass filter was designed, rather as a test structure, for the same receiver. The experimental results of the receiver and the third gm-C filter implementation are presented

Advances in Solid State Circuit Technologies

This book brings together contributions from experts in the fields to describe the current status of important topics in solid-state circuit technologies. It consists of 20 chapters which are grouped under the following categories: general information, circuits and devices, materials, and characterization techniques. These chapters have been written by renowned experts in the respective fields making this book valuable to the integrated circuits and materials science communities. It is intended for a diverse readership including electrical engineers and material scientists in the industry and academic institutions. Readers will be able to familiarize themselves with the latest technologies in the various fields

Low Power High Efficiency Integrated Class-D Amplifier Circuits for Mobile Devices

The consumer’s demand for state-of-the-art multimedia devices such as smart phones and tablet computers has forced manufacturers to provide more system features to compete for a larger portion of the market share. The added features increase the power consumption and heat dissipation of integrated circuits, depleting the battery charge faster. Therefore, low-power high-efficiency circuits, such as the class-D audio amplifier, are needed to reduce heat dissipation and extend battery life in mobile devices. This dissertation focuses on new design techniques to create high performance class-D audio amplifiers that have low power consumption and occupy less space. The first part of this dissertation introduces the research motivation and fundamentals of audio amplification. The loudspeaker’s operation and main audio performance metrics are examined to explain the limitations in the amplification process. Moreover, the operating principle and design procedure of the main class-D amplifier architectures are reviewed to provide the performance tradeoffs involved. The second part of this dissertation presents two new circuit designs to improve the audio performance, power consumption, and efficiency of standard class-D audio amplifiers. The first work proposes a feed-forward power-supply noise cancellation technique for single-ended class-D amplifier architectures to improve the power-supply rejection ratio across the entire audio frequency range. The design methodology, implementation, and tradeoffs of the proposed technique are clearly delineated to demonstrate its simplicity and effectiveness. The second work introduces a new class-D output stage design for piezoelectric speakers. The proposed design uses stacked-cascode thick-oxide CMOS transistors at the output stage that makes possible to handle high voltages in a low voltage standard CMOS technology. The design tradeoffs in efficiency, linearity, and electromagnetic interference are discussed. Finally, the open problems in audio amplification for mobile devices are discussed to delineate the possible future work to improve the performance of class-D amplifiers. For all the presented works, proof-of-concept prototypes are fabricated, and the measured results are used to verify the correct operation of the proposed solutions

Development and Analysis of Non-Delay-Line Constant-Fraction Discriminator Timing Circuits, Including a Fully-Monolithic CMOS Implementation

A constant-fraction discriminator (CFD) is a time pick-off circuit providing time derivation that is insensitive to input-signal amplitude and, in some cases, input-signal rise time. CFD time pick-off circuits are useful in Positron Emission Tomography (PET) systems where Bismuth Germanate (BGO)/photomultiplier scintillation detectors detect coincident, 511-keV annihilation gamma rays. Time walk and noise-induced timing jitter in time pick-off circuits are discussed along with optimal and sub-optimal timing filters designed to minimize timing jitter. Additionally, the effects of scintillation-detector statistics on timing performance are discussed, and Monte Carlo analysis is developed to provide estimated timing and energy spectra for selected detector and time pick-off circuit configurations. The traditional delay-line CFD is then described with a discussion of deterministic (non statistical) performance and statistical Monte Carlo timing performance. A new class of non-delay-line CFD circuits utilizing lowpass- and/or allpass-filter delay-line approximations is then presented. The timing performance of these non-delay-line CFD circuits is shown to be comparable to traditional delay-line CFD circuits. Following the development and analysis of non-delay-line CFD circuits, a fully-monolithic, non-delay-line CFD circuit is presented which was fabricated in a standard digital, 2-μ, double-meta], double-poly, n-well CMOS process. The CMOS circuits developed include a low time walk comparator having a time walk of approximately 175 ps for input signals with amplitudes between 10-mV to 2000-mV and a rise time (10 - 90%) of 10 ns. Additionally, a fifth-order, continuous-time filter having a bandwidth of over 100 MHz was developed to provide CFD signal shaping without a delay line. The measured timing resolution (3.26 ns FWITh1, 6.50 ns FWTM) of the fully-monolithic, CMOS CFD is comparable to measured resolution (3.30 ns FWHM, 6.40 ns FWTM) of a commercial, discrete, bipolar CFD containing an external delay line. Each CFD was tested with a PET EGO/photomultiplier scintillation detector and a preamplifier having a 10-ns (10 - 90%) rise-time. The development of a fully-monolithic, CMOS CFD circuit, believed to be the first such reported development, is significant for PET and other systems that employ many front-end CFD time pick-off circuits

CMOS ASIC Design of Multi-frequency Multi-constellation GNSS Front-ends

With the emergence of the new global navigation satellite systems (GNSSs) such as Galileo, COMPASS and GLONASS, the US Global Positioning System (GPS) has new competitors. This multiplicity of constellations will offer new services and a much better satellite coverage. Public regulated service (PRS) is one of these new services that Galileo, the first global positioning service under civilian control, will offers. The PRS is a proprietary encrypted navigation designed to be more reliable and robust against jamming and provides premium quality in terms of position and timing and continuity of service, but it requires the use of FEs with extended capabilities. The project that this thesis starts from, aims to develop a dual frequency (E1 and E6) PRS receiver with a focus on a solution for professional applications that combines affordability and robustness. To limit the production cost, the choice of a monolithic design in a multi-purpose 0.18 µm complementary metal-oxide-semiconductor (CMOS) technology have been selected, and to reduce the susceptibility to interference, the targeted receiver is composed of two independent FEs. The first ASIC described here is such FEs bundle. Each FE is composed of a radio frequency (RF) chain that includes a low-noise amplifier (LNA), a quadrature mixer, a frequency synthesizer (FS), two intermediate frequency (IF) filters, two variable-gain amplifiers (VGAs) and two 6-bit flash analog-to-digital converters (ADCs). Each have an IF bandwidth of 50 MHz to accommodate the wide-band PRS signals. The FE achieves a 30 dB of dynamic gain control at each channel. The complete receivers occupies a die area of 11.5 mm2 while consuming 115 mW from a supply of a 1.8 V. The second ASIC that targets civilian applications, is a reconfigurable single-channel FE that permits to exploit the interoperability among GNSSs. The FE can operate in two modes: a ¿narrow-band mode¿, dedicated to Beidou-B1 with an IF bandwidth of 8 MHz, and a ¿wide-band mode¿ with an IF bandwidth of 23 MHz, which can accommodate simultaneous reception of Beidou-B1/GPS-L1/Galileo-E1. These two modes consumes respectively 22.85 mA and 28.45 mA from a 1.8 V supply. Developed with the best linearity in mind, the FE shows very good linearity with an input-referred 1 dB compression point (IP1dB) of better than -27.6 dBm. The FE gain is stepwise flexible from 39 dB and to a maximum of 58 dB. The complete FE occupies a die area of only 2.6 mm2 in a 0.18 µm CMOS. To also accommodate the wide-band PRS signals in the IF section of the FE, a highly selective wide-tuning-range 4th-order Gm-C elliptic low-pass filter is used. It features an innovative continuous tuning circuit that adjusts the bias current of the Gm cell¿s input stage to control the cutoff frequency. With this circuit, the power consumption is proportional to the cutoff frequency thus the power efficiency is achieved while keeping the linearity near constant. Thanks to a Gm switching technique, which permit to keep the signal path switchless, the filter shows an extended tuning of the cutoff frequency that covers continuously a range from 7.4 MHz to 27.4 MHz. Moreover the abrupt roll-off of up to 66 dB/octave, can mitigate out-of-band interference. The filter consumes 2.1 mA and 7.5 mA at its lowest and highest cutoff frequencies respectively, and its active area occupies, 0.23 mm2. It achieves a high input-referred third-order intercept point (IIP3) of up to -1.3 dBVRMS

ダイナミック・アナログ回路を用いる高精度AD変換器の設計技術に関する研究

東京都市大学2018年度（平成30年

Design of low power, low noise instrumentation amplifiers for MEMS sensor interfacing

La presente tesi di dottorato tratta del progetto di amplificatori da strumentazione in tecnologia CMOS atti ad interfacciare sensori MEMS resistivi. Il progetto di un amplificatore da strumentazione integrato in tecnologia CMOS a basso offset e basso rumore, utilizzato per la lettura di sensori di flusso di tipo MEMS, viene ampliamente discusso. Per raggiungere l'elevata risoluzione richiesta, nell'ordine dei microvolt, sono state utilizzate tecniche dinamiche, come ad esempio la modulazione chopper e il matching dinamico delle porte di ingresso. La stretta banda di frequenze richiesta dall'applicazione viene ottenuta introducendo nell'amplificatore stesso un filtraggio passa-basso del secondo ordine. Sono inoltre stati forniti dei criteri per la progettazione ottima di filtri a bassa frequenza. Infine, viene presentato il progetto di un amplificatore da strumentazione per sensori magnetici integrati, sviluppato presso NXP Semiconductors (NL), durante una internship di 8 mesi, svolta all'interno del Programma di Dottorato