An Integrated Platform for Differential Electrochemical and ISFET Sensing

A fully-integrated differential biosensing platform on CMOS is presented for miniaturized enzyme-based electrochemical sensing. It enables sensor background current elimination and consists of a differential sensor array and a differential readout IC (DiRIC). The sensor array includes a four-electrode sensor for amperometric electrochemical sensing, as well as a differential ISFET-based pH sensor to calibrate the biosensors. The ISFET is biased in weak inversion and co-designed with DiRIC to enable pH measurements from 1 to 14 with resolution of 0.1 pH. DiRIC enables differential current measurement in the range of ¿¿100 ¿¿A with more than 120dB dynamic range

Chemical Bionics - a novel design approach using ion sensitive field effect transistors

In the late 1980s Carver Mead introduced Neuromorphic engineering in which various aspects of the neural systems of the body were modelled using VLSI1 circuits. As a result most bio-inspired systems to date concentrate on modelling the electrical behaviour of neural systems such as the eyes, ears and brain. The reality is however that biological systems rely on chemical as well as electrical principles in order to function. This thesis introduces chemical bionics in which the chemically-dependent physiology of specific cells in the body is implemented for the development of novel bio-inspired therapeutic devices. The glucose dependent pancreatic beta cell is shown to be one such cell, that is designed and fabricated to form the first silicon metabolic cell. By replicating the bursting behaviour of biological beta cells, which respond to changes in blood glucose, a bio-inspired prosthetic for glucose homeostasis of Type I diabetes is demonstrated. To compliment this, research to further develop the Ion Sensitive Field Effect Transistor (ISFET) on unmodified CMOS is also presented for use as a monolithic sensor for chemical bionic systems. Problems arising by using the native passivation of CMOS as a sensing surface are described and methods of compensation are presented. A model for the operation of the device in weak inversion is also proposed for exploitation of its physical primitives to make novel monolithic solutions. Functional implementations in various technologies is also detailed to allow future implementations chemical bionic circuits. Finally the ISFET integrate and fire neuron, which is the first of its kind, is presented to be used as a chemical based building block for many existing neuromorphic circuits. As an example of this a chemical imager is described for spatio-temporal monitoring of chemical species and an acid base discriminator for monitoring changes in concentration around a fixed threshold is also proposed

Chemical Current-Conveyor: a new approach in biochemical computation

Biochemical sensors that are low cost, small in size and compatible with integrated circuit technology play an essential part in the drive towards personalised healthcare and the research described in this thesis is concerned with this area of medical instrumentation. A new biochemical measurement system able to sense key properties of biochemical fluids is presented. This new integrated circuit biochemical sensor, called the Chemical Current-Conveyor, uses the ion sensitive field effect transistor as the input sensor combined with the current-conveyor, an analog building-block, to produce a range of measurement systems. The concept of the Chemical Current-Conveyor is presented together with the design and subsequent fabrication of a demonstrator integrated circuit built on conventional 0.35μm CMOS silicon technology. The silicon area of the Chemical Current-Conveyor is (92μm x 172μm) for the N-channel version and (99μm x 165μm) for the P-channel version. Power consumption for the N-channel version is 30μW and 43μW for the P-channel version with a full load of 1MΩ. The maximum sensitivity achieved for pH measurement was 46mV per pH. The potential of the Chemical Current Conveyor as a versatile biochemical integrated circuit, able to produce output information in an appropriate form for direct clinical use has been confirmed by applications including measurement of (i) pH, (ii) buffer index ( ), (iii) urea, (iv) creatinine and (v) urea:creatinine ratio. In all five cases the device has been demonstrated successfully, confirming the validity of the original aim of this research project, namely to produce a versatile and flexible analog circuit for many biochemical measurement applications. Finally, the thesis closes with discussion of another potential application area for the Chemical Current Conveyor and the main contributions can be summarised by the design and development of the first: ISFET based current-conveyor biochemical sensor, called 'Chemical Current Conveyor, CCCII+' has been designed and developed. It is a general purpose biochemical analog building-block for several biochemical measurements. Real-time buffer capacity measurement system, based on the CCCII+, which exploits the imbedded analog computation capability of the CCCII+. Real-time enzyme based CCCII+ namely, Creatinine-CCCII+ and Urea-CCCII+ for real-time monitoring system of renal system. The system can provide outputs of 3 important parameters of the renal system, namely (i) urea concentration, (ii) creatinine concentration, and (ii) urea to creatinine ratio

Developing ultrasensitive and CMOS compatible ISFETs in the BEOL of industrial UTBB FDSOI transistors

Le marché des capteurs a récemment connu une croissance spectaculaire alimentée par l'application remarquable de capteurs dans l'électronique de consommation, l'industrie de l'automatisation, les appareils portables, le secteur automobile et l'internet des objets de plus en plus adopté. La technologie avancée des complementary metal oxide semiconductor (CMOS), les technologies de nano et de micro-fabrication et les plateformes de synthèse de matériaux innovantes sont également des moteurs du développement incroyable de l'industrie des capteurs. Ces progrès ont permis la réalisation de capteurs dotés de nombreuses caractéristiques telles que la précision accrue, les dimensions miniaturisées, l’intégrabilité, la production de masse, le coût très réduit et le temps de réponse rapide. Les ion-sensitive field-effect transistors (ISFETs) sont des capteurs à l'état solide (bio) chimiques, destinés à la détection des ions H+ (pH), Na+ et K+. Malgré cela, la commercialisation des ISFETs est encore à ses balbutiements, après près de cinq décennies de recherche et développement. Cela est dû principalement à la sensibilité limitée, à la controverse sur l'utilisation de l'électrode de référence pour le fonctionnement des ISFETs et à des problèmes de stabilité. Dans cette thèse, les ISFETs ultrasensibles et compatibles CMOS sont intégrés dans le BEOL des transistors UTBB FDSOI standard. Un circuit diviseur capacitif est utilisé pour polariser la grille d’avant afin d'assurer des performances stables du capteur. En exploitant la fonction d’amplification intrinsèque fournie par les transistors UTBB FDSOI, nous avons présenté des ISFET ultra sensibles. L'amplification découle du fort couplage électrostatique entre la grille avant et la grille arrière du FDSOI et des capacités asymétriques des deux grilles. Un changement de tension au niveau de la grille avant apparaît sur la grille arrière sous la forme d'un décalage amplifié de la tension. L'amplification, représentée par le facteur de couplage (γ), est égale au rapport de la capacité de l'oxyde de grille et de la capacité de le buried oxide (BOX). Par conséquent, en fonctionnalisant la détection du pH sur la grille avant pour les dispositifs FDSOI, la modification du potentiel de surface sur la grille avant est détectée par la grille arrière et amplifiée du facteur de couplage (γ), donnant lieu à un capteur chimique à l'état solide à sensibilité ultra-élevée. L'intégration de la fonctionnalité de détection a été réalisée en back end of line (BEOL), ce qui offre les avantages d'une fiabilité et d'une durée de vie accrues du capteur, d'une compatibilité avec le processus CMOS standard et d'une possibilité d'intégration d'un circuit diviseur capacitif. Le fonctionnement des MOSFETs, sans une polarisation appropriée de la grille avant, les rend vulnérables aux effets de grilles flottantes indésirables. Le circuit diviseur capacitif résout ce problème en polarisant la grille avant tout enmaintenant la fonctionnalité de détection sur la même grille par un couplage capacitif au métal commun du BEOL. Par conséquent, le potentiel au niveau du métal BEOL est une somme pondérée du potentiel de surface au niveau de la grille de détection et de la polarisation appliquée au niveau de la grille de contrôle. Le capteur proposé est modélisé et simulé à l'aide de TCAD-Sentaurus. Un modèle mathématique complet a été développé. Il fournit la réponse du capteur en fonction du pH de la solution (entrée du capteur) et des paramètres de conception du circuit diviseur capacitif et du transistor UTBB FDSOI. Dans ce cas, des résultats cohérents ont été obtenus des travaux de modélisation et de simulation, avec une sensibilité attendue de 780 mV / pH correspondant à un film de détection ayant une réponse de Nernst. La modélisation et la simulation du capteur proposé ont également été validées par une fabrication et une caractérisation du capteur de pH à grille étendue avec validation de son concept. Ces capteurs ont été développés par un traitement séparé du composant de détection de pH, qui est connecté électriquement au transistor uniquement lors de la caractérisation du capteur. Ceci permet une réalisation plus rapide et plus simple du capteur sans avoir besoin de masques et de motifs par lithographie. Les capteurs à grille étendue ont présenté une sensibilité de 475 mV/pH, ce qui est supérieur aux ISFET de faible puissance de l'état de l’art. Enfin, l’intégration de la fonctionnalité de détection directement dans le BEOL des dispositifs FDSOI UTBB a été poursuivie. Une sensibilité expérimentale de 730 mV/pH a été obtenue, ce qui confirme le modèle mathématique et la réponse simulée. Cette valeur est 12 fois supérieure à la limite de Nernst et supérieure aux capteurs de l'état de l’art. Les capteurs sont également évalués pour la stabilité, la résolution, l'hystérésis et la dérive dans lesquels d'excellentes performances sont démontrées. Une nouvelle architecture de détection du pH est également démontrée avec succès, dans laquelle la détection est fonctionnalisée au niveau de la diode de protection de la grille plutôt que de la grille avant des dispositifs UTBB FDSOI. La commutation de courant abrupte, aussi basse que 9 mV/decade, pourrait potentiellement augmenter la sensibilité de polarisation fixée à 6,6 decade/pH. Nous avons démontré expérimentalement une sensibilité de 1,25 decade/pH supérieure à la sensibilité reportée à l’état de l’art.Abstract: The sensor market has recently seen a dramatic growth fueled by the remarkable application of sensors in the consumer electronics, automation industry, wearable devices, the automotive sector, and in the increasingly adopted internet of things (IoT). The advanced complementary metal oxide semiconductor (CMOS) technology, the nano and micro fabrication technologies, and the innovative material synthesis platforms are also driving forces for the incredible development of the sensor industry. These technological advancements have enabled realization of sensors with characteristic features of increased accuracy, miniaturized dimension, integrability, volume production, highly reduced cost, and fast response time. Ion-sensitive field-effect transistors (ISFETs) are solid state (bio)chemical sensors, for pH (H+), Na+, K+ ion detection, that are equipped with the promise of the highly aspired features of CMOS devices. Despite this, the commercialization of ISFETs is still at the stage of infancy after nearly five decades of research and development. This is due mainly to the limited sensitivity, the controversy over the use of the reference electrode for ISFET operation, and because of stability issues. In this thesis, ultrasensitive and CMOS compatible ISFETs are integrated in the back end of line (BEOL) of standard UTBB FDSOI transistors. A capacitive divider circuit is employed for biasing the front gate for stable performance of the sensor. Exploiting the intrinsic amplification feature provided by UTBB FDSOI transistors, we demonstrated ultrahigh sensitive ISFETs. The amplification arises from the strong electrostatic coupling between the front gate and the back gate of the FDSOI, and the asymmetric capacitances of the two gates. A change in voltage at the front gate appears at the back gate as an amplified shift in voltage. The amplification, referred to as the coupling factor (γ), is equal to the ratio of the gate oxide capacitance and the buried oxide (BOX) capacitance. Therefore, functionalizing the pH sensing at the front gate of FDSOI devices, the change in surface potential at the front gate is detected at the back gate amplified by the coupling factor (γ), giving rise to an ultrahigh-sensitive solid state chemical sensor. Integration of the sensing functionality was made in the BEOL which gives the benefits of increased reliability and life time of the sensor, compatibility with the standard CMOS process, and possibility for embedding a capacitive divider circuit. Operation of the MOSFETs without a proper front gate bias makes them vulnerable for undesired floating body effects. The capacitive divider circuit addresses these issues by biasing the front gate simultaneously with the sensing functionality at the same gate through capacitive coupling to a common BEOL metal. Therefore, the potential at the BEOL metal would be a weighted sum of the surface potential at the sensing gate and the applied bias at the control gate. The proposed sensor is modeled and simulated using TCAD-Sentaurus. A complete mathematical model is developed which provides the output of the sensor as a function of the solution pH (input to the sensor), and the design parameters of the capacitive divider circuit and the UTBB FDSOI transistor. In that case, consistent results have been obtained from the modeling and simulation works, with an expected sensitivity of 780 mV/pH corresponding to a sensing film having Nernst response. The modeling and simulation of the proposed sensor was further validated by a proof of concept extended gate pH sensor fabrication and characterization. These sensors were developed by a separated processing of just the pH sensing component, which is electrically connected to the transistor only during characterization of the sensor. This provides faster and simpler realization of the sensor without the need for masks and patterning by lithography. The extended gate sensors showed 475 mV/pH sensitivity which is superior to state of the art low power ISFETs. Finally, integration of the sensing functionality directly in the BEOL of the UTBB FDSOI devices was pursued. An experimental sensitivity of 730 mV/pH is obtained which is consistent with the mathematical model and the simulated response. This is more than 12-times higher than the Nernst limit, and superior to state of the art sensors. Sensors are also evaluated for stability, resolution, hysteresis, and drift in which excellent performances are demonstrated. A novel pH sensing architecture is also successfully demonstrated in which the detection is functionalized at the gate protection diode rather than the front gate of UTBB FDSOI devices. The abrupt current switching, as low as 9 mV/decade, has the potential to increase the fixed bias sensitivity to 6.6 decade/pH. We experimentally demonstrated a sensitivity of 1.25 decade/pH which is superior to the state of the art sensitivity

Circuito condicionador de ultrabaixo consumo para sensor ISFET

Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro Tecnológico, Programa de Pós-Graduação em Engenharia Elétrica, Florianópolis, 2015Este trabalho apresentou o projeto, simulação e medição de dois circuitos condicionadores, empregando componentes discretos, para ISFET (Transistor de Efeito de Campo Sensível a Íons). O primeiro circuito condicionador desenvolvido foi o seguidor de fonte-e-dreno, em que a operação do ISFET em modo CVCC (Tensão Constante e Corrente Constante) permitiu a leitura do pH no terminal de fonte do ISFET com uma linearidade igual a1, obtida pelo coeficiente de determinação R2. Os resultados experimentais indicaram uma faixa de variação de 1,404 V aplicando um potencial de referência de -0,290 V a 0,136 V e uma responsividade igual a 3,3 V/V. O segundo circuito condicionador apresentado, denominado neste trabalho por pHCO, foi desenvolvido como alternativa ao condicionamento do sinal do elemento sensor via medição da frequência de pulsos na saída do circuito. Neste caso, a informação do pH está representada digitalmente e codificada no domínio do tempo. Isto eliminou o uso de ADCs no projeto,reduzindo o consumo elétrico geral e minimizando a instrumentação do circuito condicionador. Ademais, a representação digital efetuada diretamente pelo circuito condicionador proporciona uma maior integridade da informação, melhor interfaceamento com blocos digitais além de permitir que a informação seja processada remotamente por um dispositivo microcontrolador. Os resultados experimentais obtidos com este circuito indicaram uma faixa de variação igual a 9 kHz, um coeficiente de determinação R2 igual a 0,993 e uma responsividade igual a 9 kHz/pH. Complementarmente, uma versão integrada do circuito condicionador pHCO foi projetada em tecnologia IBM 0,18 mm, utilizando sete níveis de metal e modelo de transistor BSIM3v3. Os resultados de simulação mostraram que o circuito condicionador integrado consome apenas 114 mW de potência elétrica e é competitivo com demais trabalhos de relevância da área. A motivação deste trabalho e do projeto do circuito condicionador integrado está relacionada na medição da glicemia para diagnóstico e tratamento da diabetes melito via redes corporais sem fio (WBANs).Abstract: This work presented the design, the simulation and the measurementof two conditioning circuits for the sensor ISFET (Ion Sensitive Field EffectTransistor). The first conditioning circuit designed was based in the so-calledsource-drain follower configuration. The experimental results indicated a coefficientof determination R2 equal to 1 measured in a span equal to 1.404 V.The voltage range applied to the reference potential was varied from -0.290V to 0.136 V and the sensitivity obtained was equal to 3.3 V/V.The second conditioning circuit, called in this work by pHCO, convertsthe pH input in a digital output representation whose information isencoded in the frequency domain. This approach has enabled the minimizationof the analog front-end instrumentation providing reduction of the overallpower consumption. Furthermore, the digital output representation providesbetter information integrity rather than interfacing with digital blocks. Theexperimental results obtained with this circuit showed a span equal to 9 kHz,a coefficient of determination R2 equal to 0.993 and a sensitivity equal to 9kHz/pH.In addition, an integrated version of the pHCO conditioning circuitwas designed in the IBM 0.18 mm technology, using seven metal layers andthe BSIM3v3 transistor model. The simulation results showed that the circuituses only 114 mW of electric power and is competitive with other relevantworks in the area. The motivation of this work and the design of the integratedconditioning circuit is related to the treatment of diabetes mellitus via wirelessbody area networks (WBANs)

Ultra-thin and flexible CMOS technology: ISFET-based microsystem for biomedical applications

A new paradigm of silicon technology is the ultra-thin chip (UTC) technology and the emerging applications. Very thin integrated circuits (ICs) with through-silicon vias (TSVs) will allow the stacking and interconnection of multiple dies in a compact format allowing a migration towards three-dimensional ICs (3D-ICs). Also, extremely thin and therefore mechanically bendable silicon chips in conjunction with the emerging thin-film and organic semiconductor technologies will enhance the performance and functionality of large-area flexible electronic systems. However, UTC technology requires special attention related to the circuit design, fabrication, dicing and handling of ultra-thin chips as they have different physical properties compared to their bulky counterparts. Also, transistors and other active devices on UTCs experiencing variable bending stresses will suffer from the piezoresistive effect of silicon substrate which results in a shift of their operating point and therefore, an additional aspect should be considered during circuit design. This thesis tries to address some of these challenges related to UTC technology by focusing initially on modelling of transistors on mechanically bendable Si-UTCs. The developed behavioural models are a combination of mathematical equations and extracted parameters from BSIM4 and BSIM6 modified by a set of equations describing the bending-induced stresses on silicon. The transistor models are written in Verilog-A and compiled in Cadence Virtuoso environment where they were simulated at different bending conditions. To complement this, the verification of these models through experimental results is also presented. Two chips were designed using a 180 nm CMOS technology. The first chip includes nMOS and pMOS transistors with fixed channel width and two different channel lengths and two different channel orientations (0° and 90°) with respect to the wafer crystal orientation. The second chip includes inverter logic gates with different transistor sizes and orientations, as in the previous chip. Both chips were thinned down to ∼20m using dicing-before-grinding (DBG) prior to electrical characterisation at different bending conditions. Furthermore, this thesis presents the first reported fully integrated CMOS-based ISFET microsystem on UTC technology. The design of the integrated CMOS-based ISFET chip with 512 integrated on-chip ISFET sensors along with their read-out and digitisation scheme is presented. The integrated circuits (ICs) are thinned down to ∼30m and the bulky, as well as thinned ICs, are electrically and electrochemically characterised. Also, the thesis presents the first reported mechanically bendable CMOS-based ISFET device demonstrating that mechanical deformation of the die can result in drift compensation through the exploitation of the piezoresistive nature of silicon. Finally, this thesis presents the studies towards the development of on-chip reference electrodes and biodegradable and ultra-thin biosensors for the detection of neurotransmitters such as dopamine and serotonin