An Extended CMOS ISFET Model Incorporating the Physical Design Geometry and the Effects on Performance and Offset Variation

This paper presents an extended model for the CMOS-based ion-sensitive field-effect transistor, incorporating design parameters associated with the physical geometry of the device. This can, for the first time, provide a good match between calculated and measured characteristics by taking into account the effects of nonidealities such as threshold voltage variation and sensor noise. The model is evaluated through a number of devices with varying design parameters (chemical sensing area and MOSFET dimensions) fabricated in a commercially available 0.35-µm CMOS technology. Threshold voltage, subthreshold slope, chemical sensitivity, drift, and noise were measured and compared with the simulated results. The first- and second-order effects are analyzed in detail, and it is shown that the sensors' performance was in agreement with the proposed model

Field-effect based chemical and biological sensing : theory and implementation

Electrochemical sensors share many properties of an ideal (bio)chemical sensor. They can be easily miniaturized with high parallel sensing capabilities,with rugged structure and at low cost. The response obtained from thetarget analyte is directly in electrical form allowing convenient data post-processing and simple interfacing to standard electrical components. With field-effect transistor (FET) based sensors, the transducing principle relies on direct detection of interfacial charge allowing detection of various ions and charged macromolecules. This thesis investigates FET based sensors for biological and chemical sensing. First, an ion-sensitive floating gate FET (ISFGFET) structure is studied and modeled. The proposed model reveals novel abilities of the structure not found in conventional ion-sensitive FETs (ISFETs). With IS-FGFET, we can simultaneously optimize the transistor operating point and modulate the charging of the surface and the ionic screening layer via the field effect. This control is predicted to allow reduced electric double layer screening as well as the possibility to enhance charged molecule attachment to the sensing surface. The model can predict sensor characteristic curves in pH sensing in absolute terms and allows any potential to be computed in the sensor including the electrical part and the electrolyte solution. Furthermore, a compact ISFGFET variant is merged into electric circuit simulator, which allows it to be simulated as a standard electrical component with electrical simulations tools of high computational efficiency, and allows simple modifications such as addition of parasitic elements, temperature effects, or even temporal drifts. Next, another transistor based configuration, the extended-gate ISFET is studied. The simplicity of the proposed configuration allows a universal potentiometric approach where a wide variety of chemical and biological sensors can be constructed. The design philosophy for this sensing structure is to use the shelf electric components and standard electric manufacturing processes. Such an extended-gate structure is beneficial since the dry electronics can be completely separated from the wet sensing environment. The extended-gate allows simple functionalization towards chemical and biological sensing. A proof-of-concept of this structure was verified through organo modified gold platforms with ion-selective membranes. A comparison with standard open-circuit potentiometry reveals that the sensing elements in a disposable sensing platform arrays provide comparable performance to traditional electrodes. Finally, a universal battery operated hand-held electrical readout device is designed for multiplexed detection of the disposable sensors with wireless smartphone data plotting, control, and storage. Organic polymers play an important role in the interfacial properties of sensors studied in this thesis. The polymer coating is attractive in chemical sensing because of its redox sensitivity, bio-immobilization capability, ion-to-electron transducing capability, and applicability, for example via a simple low-cost drop-casting. This structure simplifies the design of the sensor substantially and the coating increases the amount of possible target applications.Siirretty Doriast

Design Optimization of Transistors Used for Neural Recording

Neurons cultured directly over open-gate field-effect transistors result in a hybrid device, the neuron-FET. Neuron-FET amplifier circuits reported in the literature employ the neuron-FET transducer as a current-mode device in conjunction with a transimpedance amplifier. In this configuration, the transducer does not provide any signal gain, and characterization of the transducer out of the amplification circuit is required. Furthermore, the circuit requires a complex biasing scheme that must be retuned to compensate for drift. Here we present an alternative strategy based on the design approach to optimize a single-stage common-source amplifier design. The design approach facilitates in circuit characterization of the neuron-FET and provides insight into approaches to improving the transistor process design for application as a neuron-FET transducer. Simulation data for a test case demonstrates optimization of the transistor design and significant increase in gain over a current mode implementation

General Approach to Model the Surface Charge Induced by Multiple Surface Chemical Reactions in Potentiometric FET Sensors

We propose a general methodology to calculate the individual sensitivity and the cross-sensitivities of potentiometric sensor devices (e.g., ion sensitive FETs (ISFETs), CHEMFETs) with an arbitrary number of non-interacting receptors binding to ionic species or analytes in the electrolyte. The surface charge generated at the (bare or functionalized) interface with the electrolyte is described by the Poisson equation coupled to a linear system of equations for each type of receptor, where the unknowns are the fractions of sites binding with a given ion/analyte. Our general model encompasses in a unique framework a few simple special cases so far separately reported in the literature and provides for them closed-form expressions of the average site occupation probability. Detailed procedural description of the usage and benefits of the model is shown for specific cases with concurring surface chemical reactions

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

Ion-Sensitive Field-Effect Transistor for Biological Sensing

In recent years there has been great progress in applying FET-type biosensors for highly sensitive biological detection. Among them, the ISFET (ion-sensitive field-effect transistor) is one of the most intriguing approaches in electrical biosensing technology. Here, we review some of the main advances in this field over the past few years, explore its application prospects, and discuss the main issues, approaches, and challenges, with the aim of stimulating a broader interest in developing ISFET-based biosensors and extending their applications for reliable and sensitive analysis of various biomolecules such as DNA, proteins, enzymes, and cells

Ion camera development for real–time acquisition of localised pH responses using the CMOS based 64×64–pixel ISFET sensor array technology

This thesis presents the development and test of an integrated ion camera chip for monitoring highly localised ion fluxes of electrochemical processes using an ion sensitive sensor array. Ionic concentration fluctuations are shown to travel across the sensor array as a result of citric acid injection and the BZ-reaction. The imaging capability of non-equilibrium chemical activities is also demonstrated monitoring self-assembling micrometre sized polyoxometalate tubular and membranous architectures. The sufficient spatial resolution for the visualisation of the 10-60 µm wide growing trajectories is provided by the dense sensor array containing 64×64 pixels. In the case of citric acid injection and the BZ-reaction the ion camera chip is shown to be able to resolve pH differences with resolution as low as the area of one pixel. As a result of the transient and volatile ionic fluxes high time resolution is required, thus the signal capturing can be performed in real.time at the maximum sampling rate of 40 µs per pixel, 10.2 ms per array. The extracted sensor data are reconstructed into ionic images and thus the ionic activities can be displayed as individual figures as well as continuous video recordings. This chip is the first prototype in the envisioned establishment of a fully automated CMOS based ion camera system which would be able to image the invisible activity of ions using a single microchip. In addition the capability of detecting ultra-low level pH oscillations in the extracellular space is demonstrated using cells of the slime mould organism. The detected pH oscillations with extent of ~0.022 pH furthermore raise the potential for observing fluctuations of ion currents in cell based tissue environments. The intrinsic noise of the sensor devices are measured to observe noise effect on the detected low level signals. It is experimentally shown that the used ion sensitive circuits, similarly to CMOS, also demonstrate 1/f noise. In addition the reference bias and pH sensitivity of the measured noise is confirmed. Corresponding to the measurement results the noise contribution is approximated with a 28.2 µV peak-to-peak level and related to the 450 µV �+/- 70 µV peak-to-peak oscillations amplitudes of the slime mould. Thus a maximum intrinsic noise contribution of 6.2 �+/- 1.2 % is calculated. A H+ flickering hypothesis is also presented that correlates the pH fluctuations on the surface of the device with the intrinsic 1/f noise. The ion camera chip was fabricated in an unmodified 4-metal 0.35 µm CMOS process and the ionic imaging technology was based on a 64�×64-pixel ion sensitive field effect transistor (ISFET) array. The high-speed and synchronous operation of the 4096 ISFET sensors occupying 715.8×715.8 µm space provided a spatial resolution as low as one pixel. Each pixel contained 4 transistors with 10.2×10.2 µm layout dimensions and the pixels were separated by a 1 µm separation gap. The ion sensitive silicon nitride based passivation layer was in contact with the floating gates of the ISFET sensors. It allowed the capacitive measurements of localised changes in the ionic concentrations, e.g. pH, pNa, on the surface of the chip. The device showed an average ionic sensitivity of 20 mV/pH and 9 mV/pNa. The packaging and encapsulation was carried out using PGA-100 chip carriers and two-component epoxies. Custom designed printed circuit boards (PCBs) were used to provide interface between the ISFET array chip and the data acquisition system. The data acquisition and extraction part of the developed software system was based on LabVIEW, the data processing was carried out on Matlab platform

Spatial and temporal measurements using polyoxometalate, enzymatic and biofilm layers on a CMOS 0.35 μm 64 X 64-pixel I.S.F.E.T. array sensor

This thesis presents the achievements and scientific work conducted using a previously designed and fabricated 64 x 64-pixel ion camera with the use of a 0.35 μm CMOS technology. We used an array of Ion Sensitive Field Effect Transistors (ISFETs) to monitor and measure chemical and biochemical reactions in real time. The area of our observation was a 4.2 x 4.3 mm silicon chip while the actual ISFET array covered an area of 715.8 x 715.8 μm consisting of 4096 ISFET pixels in total with a 1 μm separation space among them. The ion sensitive layer, the locus where all reactions took place was a silicon nitride layer, the final top layer of the austriamicrosystems 0.35 μm CMOS technology used. Our final measurements presented an average sensitivity of 30 mV/pH. With the addition of extra layers we were able to monitor a 65 mV voltage difference during our experiments with glucose and hexokinase, whereas a difference of 85 mV was detected for a similar glucose reaction mentioned in literature, and a 55 mV voltage difference while performing photosynthesis experiments with a biofilm made from cyanobacteria, whereas a voltage difference of 33.7 mV was detected as presented in literature for a similar cyanobacterial species using voltamemtric methods for detection. To monitor our experiments PXIe-6358 measurement cards were used and measurements were controlled by LabVIEW software. The chip was packaged and encapsulated using a PGA-100 chip carrier and a two-component commercial epoxy. Printed circuit board (PCB) has also been previously designed to provide interface between the chip and the measurement cards

Detection principles of biological and chemical FET sensors

The seminal importance of detecting ions and molecules for point-of-care tests has driven the search for more sensitive, specific, and robust sensors. Electronic detection holds promise for future miniaturized in-situ applications and can be integrated into existing electronic manufacturing processes and technology. The resulting small devices will be inherently well suited for multiplexed and parallel detection. In this review, different field-effect transistor (FET) structures and detection principles are discussed, including label-free and indirect detection mechanisms. The fundamental detection principle governing every potentiometric sensor is introduced, and different state-of-the-art FET sensor structures are reviewed. This is followed by an analysis of electrolyte interfaces and their influence on sensor operation. Finally, the fundamentals of different detection mechanisms are reviewed and some detection schemes are discussed. In the conclusion, current commercial efforts are briefly considered