A high aspect ratio Fin-Ion Sensitive Field Effect Transistor: compromises towards better electrochemical bio-sensing

The development of next generation medicines demand more sensitive and reliable label free sensing able to cope with increasing needs of multiplexing and shorter times to results. Field effect transistor-based biosensors emerge as one of the main possible technologies to cover the existing gap. The general trend for the sensors has been miniaturisation with the expectation of improving sensitivity and response time, but presenting issues with reproducibility and noise level. Here we propose a Fin-Field Effect Transistor (FinFET) with a high heigth to width aspect ratio for electrochemical biosensing solving the issue of nanosensors in terms of reproducibility and noise, while keeping the fast response time. We fabricated different devices and characterised their performance with their response to the pH changes that fitted to a Nernst-Poisson model. The experimental data were compared with simulations of devices with different aspect ratio, stablishing an advantage in total signal and linearity for the FinFETs with higher aspect ratio. In addition, these FinFETs promise the optimisation of reliability and efficiency in terms of limits of detection, for which the interplay of the size and geometry of the sensor with the diffusion of the analytes plays a pivotal role.Comment: Article submitted to Nano Letter

Graphene inspired sensing devices

Graphene’s exciting characteristics such as high mechanical strength, tuneable electrical prop- erties, high thermal conductivity, elasticity, large surface-to-volume ratio, make it unique and attractive for a plethora of applications including gas and liquid sensing. Adsorption, the phys- ical bonding of molecules on solid surfaces, has huge impact on the electronic properties of graphene. We use this to develop gas sensing devices with faster response time by suspending graphene over large area (cm^2) on silicon nanowire arrays (SiNWAs). These are fabricated by two-step metal-assisted chemical etching (MACE) and using a home-developed polymer-assisted graphene transfer (PAGT) process. The advantage of suspending graphene is the removal of diffusion-limited access to the adsorption sites at the interface between graphene and its support. By modifying the Langmuir adsorption model and fitting the experimental response curves, we find faster response times for both ammonia and acetone vapours. The use of suspended graphene improved the overall response, based on speed and amplitude of response, by up to 750% on average. This device could find applications in biomedical breath analysis for diseases such lung cancer, asthma, kidney failure and more. Taking advantage of the mechanical strength of graphene and using the developed PAGT process, we transfer it on commercial (CMOS) Ion-Sensitive Field-Effect Transistor (ISFET) arrays. The deposition of graphene on the top sensing layer reduces drift that results from the surface modification during exposure to electrolyte while improving the overall performance by up to about 10^13 % and indicates that the ISFET can operate with metallic sensing membrane and not only with insulating materials as confirmed by depositing Au on the gate surface. Post- processing of the ISFET top surface by reactive ion plasma etching, proved that the physical location of trapped charge lies within the device structure. The process improved its overall performance by about 105 %. The post-processing of the ISFET could be applied for sensor performance in any of its applications including pH sensing for DNA sequencing and glucose monitoring.Open Acces

Understanding silicon nanowire field-effect transistors for biochemical sensing

There is an ever increasing need for inexpensive chemical and biochemical sensors for medical diagnostics, drug screening as well as environmental monitoring. State-of-the-art methods require either expensive or time-consuming labeling and are not suitable for large-scale integration. Advances in biotechnology, microfluidics and micro- and nanotechnology have led to various approaches of micro-analytical systems. In particular systems based on silicon field-effect transistors (Si FETs) have a great potential for biochemical sensing due to their potentially cheap fabrication in a CMOS-compatible process and simple electronic readout. Thereby, the gate oxide material of the FET is in direct contact with the analyte solution, leading to the ion-sensitive field-effect transistor (ISFET). The detection principle of ISFETs is based on the change of the transistor current caused by charges adsorbed at the sensor surface. It has been suggested recently that by downscaling the devices to the nanoscale, increased sensitivities can be expected. In particular, ISFETs based on silicon nanowires (Si NWs) are therefore intensively studied. Despite the achievements obtained in the last years, commercial products based on ISFETs are using the device as a pH sensor only. The reason for this development lies in the incomplete understanding of the complex interface between the electrolyte and the solid-state sensor as well as the difficulties related to the design of surfaces which selectively bind a targeted analyte. In this PhD project, we address these points by studying arrays of ISFETs based on silicon nanowires (Si NWs) fabricated by a top-down lithography approach and investigate their potential as an integrable sensing platform. First we characterize the devices and analyze their pH response. We find a response to pH at the fundamental (Nernst) limit, due to the special properties of the gate oxide materials used for the devices. We further demonstrate that the sensor signal is not affected by the width of the NWs, i.e. enhanced sensing is not observed for nanoscale devices. However, we reveal that the low-frequency noise of the devices decreases for increasing NW width, an aspect which has to be considered when ultimate integration is targeted. For the specific detection of ionic species, the sensor surface needs to be modified with functional groups, which selectively bind the target analyte. Unfortunately, the high pH sensitivity of oxide surfaces greatly complicates the detection of any target analyte other than pH. To circumvent this problem, we propose the use of an additional coating with a material with minimal sensitivity to pH. We find that gold is a promising candidate easily applied for this purpose. The gold layer allows immobilizing ligands via the well-established thiol-based chemistry thereby providing a platform suitable for surface functionalization. Using the additional gold layer, we demonstrate the successful detection of different ions such as sodium, calcium and fluoride ions with a differential setup having both functionalized and control NWs on the same sample. Furthermore, we find that the residual pH response of the gold layer still influences the detection of the targeted species by affecting the effective binding constant via the surface potential. To take this effect into account, an extended site binding model is proposed. Finally, we show that SiNWs have the potential to even monitor binding kinetics of ligand-protein systems and we obtain concentration dependent signals for a clinically relevant protein

Micro- and nano-devices for electrochemical sensing

Electrode miniaturization has profoundly revolutionized the field of electrochemical sensing, opening up unprecedented opportunities for probing biological events with a high spatial and temporal resolution, integrating electrochemical systems with microfluidics, and designing arrays for multiplexed sensing. Several technological issues posed by the desire for downsizing have been addressed so far, leading to micrometric and nanometric sensing systems with different degrees of maturity. However, there is still an endless margin for researchers to improve current strategies and cope with demanding sensing fields, such as lab-on-a-chip devices and multi-array sensors, brain chemistry, and cell monitoring. In this review, we present current trends in the design of micro-/nano-electrochemical sensors and cutting-edge applications reported in the last 10 years. Micro- and nanosensors are divided into four categories depending on the transduction mechanism, e.g., amperometric, impedimetric, potentiometric, and transistor-based, to best guide the reader through the different detection strategies and highlight major advancements as well as still unaddressed demands in electrochemical sensing

Nitric oxide an pH measurement with AlGaN/GaN based ISFETs

This thesis deals with the optimization of aluminum-gallium nitride/gallium nitride (AlGaN/GaN) ion sensitive field effect transistors (ISFETs), including the material parameters associated with fabrication, and the implementation of these optimized sensors for the detection of nitric oxide (NO), specifically aimed at biological detection. As the sensors will be used in fluidic environments, requirements regarding the chemical and mechanical stability of passivation can be quite demanding. It was demonstrated that polyimide exhibits the best passivation properties for these transistors in comparison to the well-known ‘hard passivation’ materials Si3N4 or SiO2. In order to employ polyimide as the insulation, a unique ECR (Electron Cyclotron Resonance) plasma process was developed to enable patterning while protecting the active sensor area of each of the AlGaN/GaN devices. This active area is the so-called two-dimensional electron gas (2DEG), which is spontaneously formed between AlGaN and GaN. The ECR plasma step delivers the essential anisotropic polyimide etching to insulate each ISFET with no measureable damage to the 2DEG. Furthermore, it was demonstrated that a contamination free surface was attained through the use of this fabrication process, providing good device functionality from the initial measurement-state of the ISFET, without the need of the additional cleaning procedures. A number of new technological processes were developed involving AlGaN/GaN ISFET gate area functionalization to enable NO measurement. A complete analysis of the sensor performance based on these functionalization methods showed tungsten trioxide and graphene functionalization techniques to be the most useful and compatible. These experiments also verify NO sensitivity in the presence of known interfering substances. Additionally, the possibility to make simultaneous pH and NO measurements was demonstrated via a suitable reduction of pH sensitivity of the functionalized transistors. Preliminary biocompatibility tests were demonstrated using L929 (mouse fibroblast) cells. Finally, a miniaturized AlGaN/GaN ISFET array was developed. A sensor size reduction and pitch size of 10 µm x 10 µm and 100 µm x 100 µm, respectively, was employed to improve precision for in vitro cell culture or tissue related experiments. With both the large-scale devices, as well as those miniaturized for the ISFET array, sensitivities of up to 57.0 mV/pH (values extremely near the theoretical Nernstian limit of 58.2 mV/pH at 20 °C) could be achieved. By combining the sensors with this achieved pH sensitivity and the NO sensors in the small-scale ISFET arrays, future work could enable simultaneous NO and pH measurement on a single chip across a local gradient in physiological applications.Diese Arbeit befasst sich mit der Optimierung von Aluminium-Gallium-Nitrid/Gallium-Nitrid (AlGaN/GaN) -Ionen-sensitiven-Feldeffekttransistoren (ISFETs), einschließlich der zur Prozessierung notwendigen Materialparameter, so wie die Implementierung dieser optimierten Sensoren zur Detektion von Stichstoffmonoxid (NO), im Speziellen für biologische Anwendungen. Durch den angestrebten Einsatz der Transistoren in Flüssigkeiten werden an die chemische und mechanische Stabilität der Passivierung hohe Anforderungen gestellt. Im Vergleich mit den bekannten 'harten' Passivierungsmaterialien wie Si3N4 oder SiO2 konnte gezeigt werden, dass Polyimid die besten Isolationseigenschaften aufweist. Um Polyimid als Passivierung einzusetzen, musste aber ein neuartiger ECR (Electron Cyclotron Resonance) Plasmaprozess entwickelt werden, der einerseits die AlGaN/GaN-Elemente strukturiert und gleichzeitig den aktiven Sensorbereich schützt. Dabei handelt es sich um das sogenannte zweidimensionale Elektronengas (2DEG), das sich spontan zwischen der AlGaN- und GaN-Schicht ausbildet. Der ECR Plasmaschritt ermöglicht das notwendige anisotrope Ätzen zur Isolierung der ISFETs gegeneinander ohne eine messbare Degeneration des 2DEG. Dieser Prozess hinterlässt eine kontaminationsfreie Oberfläche und somit sofort messbare ISFETs, was vorher benötigte Reinigungsschritte überflüssig macht. Um die Detektion von NO zu erlauben, wurde eine Reihe neuer technologischer Prozesse entwickelt, wie etwa die entsprechende Gate-Funktionalisierung der AlGaN/GaN-ISFETs. Wolframtrioxid und Graphen stellten sich bei der vollständigen Analyse des Sensorverhaltens als die Besten der untersuchten Funktionalisierungen heraus. Beim Nachweis der NO-Sensitivität gegenüber bekannten störenden Substanzen, konnte über die Verringerung der pH-Sensitivität des funktionalisierten Transistors, eine gleichzeitige Messung des pH-Wertes und NO durchgeführt werden. Mit Hilfe von L929-Zellen (Maus-Fibroblasten) wurden darüber hinaus die ersten Tests zur Biokompatibilität des Systems durchgeführt. Um die Genauigkeit für in vitro Zellkulturen oder Gewebe-basierte Experimente zu erhöhen, wurde ein miniaturisiertes AlGaN/GaN-ISFET-Array entwickelt, mit einer Miniaturisierung und einem Pitch von 10 mm x 10 mm bzw. 100 mm x 100 mm. Mit einzelnen Sensoren wie auch den miniaturisierten Arrays kann eine Sensitivität von bis zu 57.0 mV/pH (nahe am theoretischen Nernst'schen Verhalten mit 58.2 mV/pH bei 20 °C) erreicht werden. Die Kombination von miniaturisierten Arrays und der Verringerung der pH-Sensitivität könnte in zukünftigen Arbeiten eine simultane NO- sowie pH-Messung auf einem Chip über einen lokalen Gradienten physiologischer Anwendungen ermöglichen

Flexible Thermoelectric Generators and 2-D Graphene pH Sensors for Wireless Sensing in Hot Spring Ecosystem

abstract: Energy harvesting from ambient is important to configuring Wireless Sensor Networks (WSN) for environmental data collecting. In this work, highly flexible thermoelectric generators (TEGs) have been studied and fabricated to supply power to the wireless sensor notes used for data collecting in hot spring environment. The fabricated flexible TEGs can be easily deployed on the uneven surface of heated rocks at the rim of hot springs. By employing the temperature gradient between the hot rock surface and the air, these TEGs can generate power to extend the battery lifetime of the sensor notes and therefore reduce multiple batteries changes where the environment is usually harsh in hot springs. Also, they show great promise for self-powered wireless sensor notes. Traditional thermoelectric material bismuth telluride (Bi2Te3) and advanced MEMS (Microelectromechanical systems) thin film techniques were used for the fabrication. Test results show that when a flexible TEG array with an area of 3.4cm2 was placed on the hot plate surface of 80°C in the air under room temperature, it had an open circuit voltage output of 17.6mV and a short circuit current output of 0.53mA. The generated power was approximately 7mW/m2. On the other hand, high pressure, temperatures that can reach boiling, and the pH of different hot springs ranging from 9 make hot spring ecosystem a unique environment that is difficult to study. WSN allows many scientific studies in harsh environments that are not feasible with traditional instrumentation. However, wireless pH sensing for long time in situ data collection is still challenging for two reasons. First, the existing commercial-off-the-shelf pH meters are frequent calibration dependent; second, biofouling causes significant measurement error and drift. In this work, 2-dimentional graphene pH sensors were studied and calibration free graphene pH sensor prototypes were fabricated. Test result shows the resistance of the fabricated device changes linearly with the pH values (in the range of 3-11) in the surrounding liquid environment. Field tests show graphene layer greatly prevented the microbial fouling. Therefore, graphene pH sensors are promising candidates that can be effectively used for wireless pH sensing in exploration of hot spring ecosystems.Dissertation/ThesisDoctoral Dissertation Exploration Systems Design 201

AlGaN/GaN sensors for direct monitoring of fluids and bioreactions

AlGaN/GaN based pH-sensors have been characterized and further developed for the in situ monitoring of cell reactions. Generally, good proliferation of different cell lines was observed on AlGaN and GaN surfaces without using any kind of thin films of organic material for improving of the cellular adhesion and biocompatibility. NG108-15 nerve cells were chosen for the investigation of the sensor response on cell activity. In an open setup with contact to normal atmosphere, the monitoring of the spontaneous cell activity (“breathing”) was recorded. By titration in complex electrolytes, it was demonstrated that these sensors are able to monitor complex cell reactions on different neuroinhibitors. Numerical simulations as well as simplified analytical calculations of ion fluxes give strong evidence that the signal in the cell-transistor coupling experiments is primarily generated by the Na+ flux. In conclusion, the AlGaN/GaN-ISFETs show stable operation under physiological conditions, exhibit a very good signal resolution and are suitable for long-time monitoring of cell reactions on different stimuli.In dieser Arbeit wurden AlGaN/GaN-Heterostrukturen, die ein hohes Potenzial für pH-Sensoren aufweisen, charakterisiert und weiterentwickelt für die elektronische Erfassung von Zellreaktionen. Dazu wurden NG108-15 Nervenzellen auf den Sensoroberflächen kultiviert und deren Antwort auf Stimulierung mit verschiedenen Neuroinhibitoren aufgezeichnet. Zunächst wurde ein Messaufbau für das Erfassen extrazellularer Potenzialänderungen entworfen und das bestehende Chipdesign sowie die Herstellungstechnologie weiterentwickelt. Für die Auswahl optimaler Sensoren für die Transistor-Zell-Kopplung wurden sowohl mittels PIMBE und MOCVD gewachsene Heterostrukturen charakterisiert bezüglich ihrer elektronischen Transporteigenschaften und ihres Verhaltens als pH-Sensor. Auf AlGaN- und GaN-Oberflächen konnte eine sehr gute Kultivierung verschiedener Zelllinien erzielt werden ohne die sie sonst übliche Verwendung organischer Zwischenschichten zur Erhöhung von Adhäsion (z.B. Fibroplasten). Der Einfluss verschiedener Technologie- und sensorrelevanter Behandlungsschritte auf die Oberflächeneigenschaften der AlGaN/GaN-Sensoren wurde untersucht und die Medienstabilität bzw. Wechselwirkungen wurden analysiert. In einem offenen Setup mit Gasaustausch zur Umgebung wurde eine spontane Zellaktivität erfasst ("Zellatmung"), die in einem abgeschlossenen Setup aufgrund des reduzierten Gasaustausches nicht auftrat. Weiterhin wurde die Empfindlichkeit des Sensors auf Potenzialänderungen durch Na+ and K+ Ionen und deren Reaktionen mit Neurotoxinen bestätigt. Durch Titration in komplexe Elektrolyte und durch Kultivierung von NG108-15 Nervenzellen auf der Sensoroberfläche wurde demonstriert, dass die Sensoren in der Lage sind, komplexe Zellreaktionen zu erfassen. Berechnungen mit Hilfe von Simulationen und vereinfachten analytischen Beschreibungen für die Ionenflüsse belegten, dass bei der Zell-Transistor-Kopplung das Sensorsignal im Wesentlichen durch die Na+ Flüsse erzeugt wird. Die experimentellen Beobachtungen und die theoretischen Modellierung zeigte dafür eine gute Übereinstimmung. Zusammenfassend wurde in dieser Arbeit gezeigt, dass AlGaN/GaN-ISFETs stabil unter physiologischen Bedingungen arbeiten, sehr gute Signalauflösung ermöglichen und für Langzeitmessungen mit lebenden Zellen geeignet sind

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

Field-Effect Sensors

This Special Issue focuses on fundamental and applied research on different types of field-effect chemical sensors and biosensors. The topics include device concepts for field-effect sensors, their modeling, and theory as well as fabrication strategies. Field-effect sensors for biomedical analysis, food control, environmental monitoring, and the recording of neuronal and cell-based signals are discussed, among other factors