Nanoscale BioFETs for ultrasensitive pH and biomolecular detection

In the last decade, nanoscale field-effect transistor biosensors have proven to be powerful, ultra-sensitive, label-free electrical detectors of relevant molecules ranging from solution pH to proteins to nucleic acids. Such sensors are highly amenable to scale-up and mass production and are easily integrated with necessary external electronics for point-of-care diagnostic devices, or lab-on-a-chip systems. In particular, nanowire FET sensors have been demonstrated to be much more sensitive to analytes, extending sensing capabilities to as low as attomolar concentrations without the need for labels. These devices have the potential to far surpass many current clinical alternatives in many important criteria, such as sensitivity, detection time, sample volumes, need for a label, and selectivity. However, in recent years it has become apparent that the technology has been suffering from lack of reliability, robustness, and repeatability of the devices in fluidic environments. These issues are the primary barriers preventing the maturation of the technology. Towards resolving some of these issues, this dissertation presents an iterative process of increasing the performance characteristics of nanoscale field-effect transistor biosensors. A top-down baseline silicon dioxide process with silicon-on-insulator wafers is presented, including methods for defining the biosensors at the nanoscale. This baseline process is then demonstrated for the detection of changes in pH and for detection of pyrophosphate. The CMOS compatible process presented allows for mass scale-up and for seamless integration with existing platforms. The next iteration of devices utilizes an atomic layer deposited high-k gate dielectric, aluminum oxide, for increased gate oxide capacitance. A high-k gate dielectric allows for similar electrical gate oxide thicknesses with higher physical oxide thicknesses, which results in lower leakages in fluid. This process is compared to the baseline silicon dioxide process. These process improvements result in increased sensitivity to pH, increased robustness in fluid, and reduced noise. The last device iteration replaces the aluminum oxide gate dielectric with hafnium oxide. HfO2 has a higher dielectric constant than Al2O3, is less susceptible to ion incorporation in fluid, has higher pH sensitivity, and is highly resistant to all forms of etching after annealed. This allows for the use of a wet etch of the fluid passivation layer, removing the possibility of damaging the fragile gate dielectric layer by dry etches such as reactive ion etching. Several critical steps were added for better characterization of gate dielectric layer, with special attention to the insulator-silicon interface. The HfO2 devices exhibited near Nernstian pH response with very low noise and good repeatability. Two of these stable devices were then employed simultaneously in a novel scheme that greatly amplifies pH response. Using the drastic differences in source-drain current for a 2 micron wide nanoplate device compared to a 100 nm wide nanowire device, the pH amplification scheme was shown to theoretically enable the detection of extremely low pH changes, down to 0.002 pH units. The devices were then used for the detection of microRNA analogues, short 20-25 base pair nucleotide molecules that have found use in the last decade as cancer biomarkers, down to 100 fM concentration levels. The process improvements in this work demonstrate significant progress towards catalyzing the transformation of such nanoscale bioFETs from mere proofs of concept into powerful, robust, and reliable tools for point-of-care diagnostics

Wearable Nano-Based Gas Sensors for Environmental Monitoring and Encountered Challenges in Optimization

With a rising emphasis on public safety and quality of life, there is an urgent need to ensure optimal air quality, both indoors and outdoors. Detecting toxic gaseous compounds plays a pivotal role in shaping our sustainable future. This review aims to elucidate the advancements in smart wearable (nano)sensors for monitoring harmful gaseous pollutants, such as ammonia (NH3), nitric oxide (NO), nitrous oxide (N2O), nitrogen dioxide (NO2), carbon monoxide (CO), carbon dioxide (CO2), hydrogen sulfide (H2S), sulfur dioxide (SO2), ozone (O3), hydrocarbons (CxHy), and hydrogen fluoride (HF). Differentiating this review from its predecessors, we shed light on the challenges faced in enhancing sensor performance and offer a deep dive into the evolution of sensing materials, wearable substrates, electrodes, and types of sensors. Noteworthy materials for robust detection systems encompass 2D nanostructures, carbon nanomaterials, conducting polymers, nanohybrids, and metal oxide semiconductors. A dedicated section dissects the significance of circuit integration, miniaturization, real-time sensing, repeatability, reusability, power efficiency, gas-sensitive material deposition, selectivity, sensitivity, stability, and response/recovery time, pinpointing gaps in the current knowledge and offering avenues for further research. To conclude, we provide insights and suggestions for the prospective trajectory of smart wearable nanosensors in addressing the extant challenges

Electrolyte Gated Metal Oxide Transistors

L’invention du transistor a significativement affectée le progrès technique et scientifique de notre société. Depuis plus de 50 ans, les transistors sont utilisés comme composants actifs dans les circuits électroniques, pour réaliser des amplificateurs ou des interrupteurs par exemple. La plus fascinante des directions futures pour le développement des transistors consiste en leur utilisation dans des dispositifs électroniques flexibles, légers et biocompatibles. Les oxydes métalliques semi-conducteurs ont été intensivement étudiés au cours des dernières décennies pour des applications dans les transistors, du fait de la grande mobilité de leurs porteurs de charges (∼1– 100 cm2V-1s-1), de leur importante transparence optique, de leur stabilité chimique ainsi que de leur faible coût de fabrication. Les oxydes métalliques sont divisés entre les oxydes de transition et ceux post-transition, dépendamment des métaux, qui possèdent différentes configurations électroniques et donc différentes conductivités. Dans cette thèse, nous allons nous concentrer sur les deux principaux représentants des oxydes métalliques de transition et post-transition, i.e., le TiO2 et le SnO2, utilisés comme matériaux de canal dans des transistors utilisant un électrolyte comme diélectrique à la grille. Le TiO2 et le SnO2 sont abondants et biointégrables, possèdent une large bande interdite (3-4 eV), et peuvent être utilisés comme canal de transistor pour de nombreuses applications différentes. Remplacer le diélectrique conventionnel dans les transistors à couche minces par un électrolyte donne l’opportunité de décroître le voltage auquel le transistor est opéré du fait de la haute capacitance de la double couche électrique (autour de 10 μF/cm2) qui se forme à l’interface entre l’électrolyte et le semi-conducteur. Cette capacitance élevée permet l’accumulation d’une importante densité de porteurs de charges dans le canal et rend donc possible la transition entre un état isolant et un état semi-conducteur voire métallique. Les transistors utilisant un électrolyte comme diélectrique à la grille (EGTs) peuvent être employés comme éléments de matrice active pour les écrans à faible puissance ou encore intégrés dans des textiles ou d’autres matériaux flexibles. Les EGTs peuvent aussi être utilisés dans d'autres applications prometteuses que sont telles les capteurs chimiques ou biologiques, du fait de leur haute sensibilité aux ions et de leur compatibilité avec les électrolytes aqueux. Le coeur de cette thèse est dévoué à une meilleure compréhension des mécanismes d’opération d’une importante classe de transistors à couche minces, i.e. les transistors à oxydes métalliques v utilisant un électrolyte comme diélectrique à la grille, afin d’optimiser leurs performances et de développer des agencements géométriques pour permettre d’obtenir des transistors à haute performance. Les EGTs consistent en un canal en oxyde métallique et en une électrode de grille en contact avec un électrolyte. L’application d’un voltage à la grille entraîne la formation d’une double couche électrique au niveau de l’interface entre le canal et l’électrolyte, qui permet de moduler la densité des porteurs de charges dans le canal. Les mécanismes de dopage et la modulation de la densité des porteurs de charges dans les EGTs ont été étudiés par caractérisation électrique des transistors, par voltammétrie cyclique (CV) ainsi que par spectroscopie d’impédance électrochimique. Des transistors SnO2 et TiO2 utilisant des liquides ioniques à la grille ont été fabriqués sur des substrats en silicone. Une méthode de gravure non conventionnelle utilisant le parylène a été utilisée pour étudier le rôle joué par l’extension des interfaces électrolyte/semi-conducteur et électrode/semi-conducteur sur le dopage ainsi que sur les processus de transport des porteurs de charges. Le chevauchement entre les électrodes métalliques et le semi-conducteur, qui est en contact avec l’électrolyte, affecte le processus d’injection des charges. La gravure a entraîné l’augmentation de la densité des porteurs de charges d’un à deux ordres de magnitude dans les deux oxydes métalliques. De plus, les EGTs à SnO2 ont été fabriqués sur des substrats flexibles en polyimide. Les transistors EGTs à SnO2 flexibles possèdent de bonnes propriétés électriques lorsqu’ils sont pliés selon différents rayons de courbure et ils pourraient posséder un fort potentiel pour des applications dans le domaine de l’électronique flexible. Les effets de la structure et de la morphologie des semi-conducteurs sur les performances des transistors ont été étudiés. Dans ce but, des films de TiO2 poreux à très forte densité ont été fabriqués par traitement à partir d’une solution ainsi que par évaporation par faisceau d’électrons. Les EGTs à TiO2 faits par évaporation possédaient un courant plus élevé ainsi qu’un ratio on/off plus haut du fait d’une meilleure qualité de la structure. Les effets des gros cations [EMIM] et des petits cations Li+ sur les mécanismes de dopage ont été étudiés en utilisant deux électrolytes [EMIM][TFSI] et [EMIM][TFSI] mélangé avec un sel de lithium. Les relativement gros cations [EMIM] ne peuvent pas pénétrer à l’intérieur du maillage cristallin du TiO2. L’intercalation de petits cations comme le Li+ a été rendue possible à la fois dans les films denses et dans les films mésoporeux de TiO2 par réduction de la vitesse de balayage dans les mesures courant/voltage. vi Les mécanismes de transport des charges des transistors utilisant un électrolyte comme diélectrique à la grille ont été étudiés et une corrélation entre la capacitance de la double couche, la densité des porteurs de charges, la mobilité des électrons, la tension seuil et le ratio on/off a été démontrée. Nous pensons que nos transistors à oxydes métalliques utilisant un électrolyte comme diélectrique à la grille sont prometteurs pour de l’électronique flexible, produite sur de grandes surfaces et à faible coût. ---------- The invention of the transistor has significantly affected the technological and scientific progress of our society. For over 50 years, transistors have been used as the active components, such as amplifiers or switches, in electronic circuits. The most fascinating future direction for transistor development is towards flexible, lightweight and biocompatible electronics. Metal oxide semiconductors have been intensively investigated over the past decades for transistor applications, due to their high charge carrier mobility (∼1– 100 cm2V-1s-1), high optical transparency, chemical stability and low-manufacturing cost. Metal oxides are divided into transition and post transition oxides, depending on the metals, which possess different electron configurations and, accordingly, different conductivity. In this Thesis we focus on two main representatives of transition and post transition metal oxides, i.e., TiO2 and SnO2, as the channel materials in electrolyte gated transistors. TiO2 and SnO2 are abundant and bio friendly, with high band gap (3-4 eV) and can be utilized as transistor channel for many different applications. Replacing the conventional dielectric in thin film transistors with electrolyte gives the opportunity to decrease the transistor operating voltage due to the high capacitance of the electrical double layer (around 10 μF/cm2) that form at the electrolyte/semiconductor interface. This high capacitance allows accumulation of high charge carrier density in the channel thus making possible a transition from an insulating state to semiconducting or metallic one. Electrolyte gated transistors (EGTs) can be utilized as backplanes for low powered displays and integrated into textiles or flexible materials. Other exciting applications of EGTs are chemical sensors or biosensors, due to the high sensitivity to ions and compatibility with aqueous electrolytes. The core of this thesis is devoted to a better understanding of the operational mechanisms of an important class of thin film transistors, i.e. electrolyte gated metal oxide transistors, to optimize their performance and to develop the appropriate device geometry for high performance transistors. EGTs consist of metal oxide channel and a gate electrode in contact with an electrolyte. The application of a gate electrical bias leads to the formation of an electrical double layer at the channel/electrolyte interface, which permits to modulate the charge carrier density in viii the channel. The doping mechanisms and the charge carrier density modulation in EGTs were investigated by transistor electrical characterization, cyclic voltammetry (CV) and electrochemical impedance spectroscopy. Ionic liquid gated SnO2 and TiO2 transistors were fabricated on silicon substrates. Parylene patterning was utilized to investigate the role played by the extension of the electrolyte/semiconductor and electrode/semiconductor interfaces on the doping and charge carrier transport processes. The overlap between the metal electrodes and the semiconductor, which is in contact with the electrolyte, affects the charge injection process. By patterning the charge carrier density was increased on one or two order of magnitude in both metal oxide materials. Moreover, SnO2 EGTs were fabricated on flexible polyimide substrate. EGT SnO2 flexible transistors possessed good electrical properties under bending at different radius and could have high potential in flexible electronics. The effect of structure and morphology of semiconductors on transistor performance was demonstrated. For this purpose, porous and highly dense films of TiO2 were fabricated by solution processing and by electron beam evaporation. Evaporated TiO2 EGT showed higher current and higher on/off ratio due to better structural quality. The effect of big [EMIM] and small Li+ cation on doping mechanisms was investigated by using two electrolytes [EMIM][TFSI] and [EMIM][TFSI] mixed with a lithium salt. The relatively large [EMIM] cation cannot enter the crystal lattice of TiO2. The intercalation of small cation such as Li+ was possible both in mesoporous and dense TiO2 films by decreasing the sweeping rate in current / voltage measurements. The charge transport mechanism of electrolyte gated transistors was investigated and a correlation between capacitance of the double layer, charge carrier density, electron mobility, threshold voltage and on/off ratio was demonstrated. We believe that our electrolyte gated metal oxide transistors are promising for low cost, flexible and large area electronics

Sensing harmful ions in water by using water-gated thin-film transistor sensors

This thesis demonstrates the development of a worthy approach to detect harmful waterborne analytes in significantly low concentrations in water by using water-gated thin-film transistors (WGTFTs) as potentiometric ion sensors. The successful gating of a thin-film transistor with water to be the gate medium in 2010 paved the way for a new sensor technology, WGTFTs, to detect waterborne analytes in water gate media. WGTFT sensors have been applied to detect waterborne analytes (e.g. K+, Na+ and Ca2+) with the help of organic macrocyclic ionophores (sensitisers) incorporated within the membrane in WGTFT’s architecture. The response characteristics of such WGTFT sensors underwent the Nikolsky-Eisenman (modified Nernstian) law, with a limit-of-detection (LoD) in the range of 100 nM – 1 µM. This limit is insufficient to monitor drinking water against harmful or toxic ions. Accordingly, ion-exchange sorbents such as zeolites and resin were exploited in this work to sensitise the WGTFTs. These sorbents were embedded within a PVC membrane as a sensitiser and located in the transistor’s gate medium, which separated the sample solution (containing an analyte ion) and a reference solution (free of analyte ion) in the composition of WGTFT sensors. Radioactive- 137Cs is rare in nature but finds its way into water supplies and then into humans and animals due to nuclear accidents. The sensitisation of the WGTFT sensor with Cs+-selective mordenite zeolite as an ion-exchange ionophore enabled the detection of Cs+ in very low concentrations. The response of such Cs+- WGTFT sensor followed the Langmuir adsorption isotherm with high stability constant and an exceedingly low LoD (33 pM). Such response characteristics enabled us to determine very low LoD. The LoD of a Cs+- WGTFT sensor is much lower than the potability limit of Cs+ in drinking water (7.5 nM), which has not been obtained by organic macrocyclic sensitisers. Pb2+ and Cu2+ are common drinking water pollutants deposited in water resulting from the use of these metals in manufacturing water pipes. To detect these cations in low concentrations, clinoptilolite zeolite was used to sensitise the WGTFT in a similar manner used in previous Cs+- WGTFT sensors. The threshold shifted in response to increasing Pb2+ or Cu2+ concentrations following the Langmuir-Freundlich characteristic. Hence, the LoDs were much lower than the action levels of the lead-and-copper rule recommended by the Environmental Protection Agency for drinking water. Such WGTFT sensors achieved respective Pb2+ and Cu2+ LoDs of 0.9 nM and 14 nM against 72 nM and 20.5 µM as action levels with high selectivity for these metal cations, even with the presence of other interfering cations in the water sample. Therefore, these features qualify clinoptilolite-sensitised WGTFTs for the monitoring of the lead-and-copper rule. WGTFTs sensitised with another class of ion-exchange sorbents, La- loading of PurometTM MTS9501 resin, demonstrated excellent response to fluoride (F-) anion in a low dynamic range, following the Langmuir-Freundlich adsorption isotherm. This process enabled picomolar LoD and extremely low c1/2 concentration. A successful routine was suggested to restrict the interferant from co-solutes. Although, the LoD of F- was much below practical requirements, this work provides a template for further studies using resins as sensitisers in applications where an extremely low LoD is crucial

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