A Rapidly Stabilizing Water-Gated Field-Effect Transistor Based on Printed Single-Walled Carbon Nanotubes for Biosensing Applications

Biosensors are expected to revolutionize disease management through provision of low-cost diagnostic platforms for molecular and pathogenic detection with high sensitivity and short response time. In this context, there has been an ever-increasing interest in using electrolyte-gated field-effect transistors (EG-FETs) for biosensing applications owing to their expanding potential of being employed for label-free detection of a broad range of biomarkers with high selectivity and sensitivity while operating at sub-volt working potentials. Although organic semiconductors have been widely utilized as the channel in EGFETs, primarily due to their compatibility with cost-effective low-temperature solution-processing fabrication techniques, alternative carbon-based platforms have the potential to provide similar advantages with improved electronic performances. Here, we propose the use of inkjet-printed polymer-wrapped monochiral singlewalled carbon nanotubes (s-SWCNTs) for the channel of EG-FETs in an aqueous environment. In particular, we show that our EG-CNTFETs require only an hour of stabilization before producing a highly stable response suitable for biosensing, with a drastic time reduction with respect to the most exploited organic semiconductor for biosensors. As a proof-of-principle, we successfully employed our water-gated device to detect the well-known biotin-streptavidin binding event

Electrolyte-Gated Field Effect Transistors in Biological Sensing: A Survey of Electrolytes

Low operating voltages, rapid response, and high-throughput fabrication compatibility are key advantages for the development of electrolyte-gated field effect transistors (EGFETs) for biological sensing. Among the key components in EGFET biosensors, electrolyte materials are relatively less investigated, especially alternatives to water-based liquid electrolytes such as ionic liquids, ion gels, polyelectrolytes, and solid polymer electrolytes. These electrolytes enable portable devices and environmental stability superior to their water-based liquid alternatives. In this review, we offer an up-to-date evaluation of the state of EGFET research and gauge the strengths and limitations of high-performance electrolytes for use in EGFET biosensor applications as well as the potential for computer-aided design of such sensing platforms. The recent progress of EGFET biosensors for some popular analytes are reviewed and the performance of these alternative electrolytes in transistor biosensing is assessed. The challenges and opportunities for electrolytes in EGFETs are discussed for future research directions in this field

Hybrid Nanomaterials

Two of the hottest research topics today are hybrid nanomaterials and flexible electronics. As such, this book covers both topics with chapters written by experts from across the globe. Chapters address hybrid nanomaterials, electronic transport in black phosphorus, three-dimensional nanocarbon hybrids, hybrid ion exchangers, pressure-sensitive adhesives for flexible electronics, simulation and modeling of transistors, smart manufacturing technologies, and inorganic semiconductors

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

Water gated thin film-transistors: Ion sensing and modes of operation

This thesis investigates the ion sensing properties, and modes of operation, of water gated thin film transistors (WGTFTs).For ion sensing, suitable sensitisers (‘ionophores’) are integrated into the (WGTFT) architecture that lead to a membrane or interface potential in response to changing concentrations of the ionophore’s ‘primary’ ion, leading to a shift in transistor threshold voltage when a WGTFT is gated using a medium containing such ions. Quantitatively potential and threshold shift follow a modification of the Nernst equation. Hence measurement of TFT characteristics transduces ion concentration in the aqueous gate medium into a concentration-dependent WGTFT threshold shift ΔVT(c), similar as in the traditional ISFET (ion-selective field effect transistor). Here I report investigations on two aspects of ion-selective WGTFTs: (i) Previous studies on WGTFT ion sensors followed the design of ISFETs and conventional potentiometric ion sensors in so far that they introduced the ionophore within a permeable membrane that is distinct from the transducer. We have demonstrated a simplified ion- selective WGTFT architecture that requires no separate ion- selective membrane. Instead, we added a calcium-selective calix[4]arene ionophore directly to spin casting solutions of the organic semiconductor rrP3HT. We find that resulting WGTFTs cast from ionophore-doped rrP3HT solutions selectively respond to calcium cations dissolved in the gating water with similar characteristics as previous ion- selective WGTFTs. The ionophore-doped rrP3HT simultaneously acts as a semiconductor, and ion- sensitive layer, without the need for a separate ion- selective membrane. (ii) We have systematically compared the use of hole- vs electron transporting semiconductors in ion-selective WGTFTs. When using the same ion- selective membrane and otherwise identical device architecture to gate either a p-type (solution processed rrP3HT) or an n-type (spray pyrolysed ZnO) semiconductor, we find a systematic difference in WGTFT response characteristics: The hole transporter leads to super- Nernstian response, while the electron transporter shows sub- Nernstian response. We explain this by a capacitive amplification (or attenuation) mechanism based on the ratio of cationic to anionic electric double layer capacitances. A further study reported in this thesis is on the mode-of-operation in WGTFTs. When the common organic semiconductor ‘PBTTT’ is used in water- gated thin film transistors, it has so far been found to operate only in field effect (interfacial gating) mode. Electrochemical transistor (volumetric gating) mode, which is actuated by the penetration of waterborne ions into the bulk of the semiconducting film, enables significantly higher transistor currents. However, this has until now been prevented by the hydrophobicity of PBTTT, and could only be observed for derivatives of PBTTT with hydrophilic side chains. We report here for the first time the operation of PBTTT water-gated transistors in electrochemical mode, despite PBTTT’s hydrophobicity. This is enabled by a specific choice of the waterborne ion, which apart from its ionic character somewhat resemble typical PBTTT solvents and therefore can penetrate PBTTT bulk

Functional Biodegradable Nanocomposites

Concern around environmental issues facing society has grown significantly in recent years. Reduction in damages resulting from both industrial and domestic waste has become a key topic as a means to address environmental problems and the exhaustion of natural resources. Likewise, the use of materials of polymeric origin in applications such as tissue regeneration, controlled release of medicines, packaging, soil remediation, etc., makes the development of materials biodegradable in biological media increasingly important. Recently, significant progress has been achieved in the creation of biodegradable polymeric formulations with functionalities similar to those of non-biodegradable polymers, both of natural and of synthetic origin, extending their applicability to fields such as food packaging, electronics, production of health-related materials, agriculture, etc. In this context, biodegradable nanocomposites offer new and exciting possibilities. This book deals with the development of functional polymer nanocomposites that can undergo biodegradation in different media, including biological systems, soils, landfills, etc. Original and review articles covering aspects of polymer science and technology, such as synthesis, processing, characterization, properties, and applications of functional biodegradable nanocomposites for different applications, are included in this book

Silica and Silicon Based Nanostructures

Silica and silicon-based nanostructures are now well-understood materials for which the technologies are mature. The most obvious applications, such as electronic devices, have been widely explored over the last two decades. The aim of this Special Issue is to bring together the state of the art in the field and to enable the emergence of new ideas and concepts for silicon and silica-based nanostructures

Flexible sensors—from materials to applications

Flexible sensors have the potential to be seamlessly applied to soft and irregularly shaped surfaces such as the human skin or textile fabrics. This benefits conformability dependant applications including smart tattoos, artificial skins and soft robotics. Consequently, materials and structures for innovative flexible sensors, as well as their integration into systems, continue to be in the spotlight of research. This review outlines the current state of flexible sensor technologies and the impact of material developments on this field. Special attention is given to strain, temperature, chemical, light and electropotential sensors, as well as their respective applications

Electronic Devices for the Combination of Electrically Controlled Drug Release, Electrostimulation, and Optogenetic Stimulation for Nerve Tissue Regeneration

[ES] La capacidad de las células madre para proliferar formando distintas células especializadas les otorga la potencialidad de servir de base para terapias efectivas para patologías cuyo tratamiento era inimaginable hasta hace apenas dos décadas. Sin embargo, esta capacidad se encuentra mediada por estímulos fisiológicos, químicos, y eléctricos, específicos y complejos, que dificultan su traslación a la rutina clínica. Por ello, las células madre representan un campo de estudio en el que se invierten amplios esfuerzos por parte de la comunidad científica. En el ámbito de la regeneración nerviosa, para modular su desarrollo y diferenciación el tratamiento farmacológico, la electroestimulación, y la estimulación optogenética son técnicas que están consiguiendo prometedores resultados. Es por ello por lo que en la presente tesis se ha desarrollado un conjunto de sistemas electrónicos para permitir la aplicación combinada de estas técnicas in vitro, con perspectiva a su aplicación in vivo. Hemos diseñado una novedosa tecnología para la liberación eléctricamente controlada de fármacos. Esta tecnología está basada en nanopartículas de sílice mesoporosa y puertas moleculares de bipiridina-heparina. Las puertas moleculares son electroquímicamente reactivas, y encierran los fármacos en el interior de las nanopartículas, liberándolos ante un estímulo eléctrico. Hemos caracterizado esta tecnología, y la hemos validado mediante la liberación controlada de rodamina en cultivos celulares de HeLa. Para la combinación de liberación controlada de fármacos y electroestimulación hemos desarrollado dispositivos que permiten aplicar los estímulos eléctricos de forma configurable desde una interfaz gráfica de usuario. Además, hemos diseñado un módulo de expansión que permite multiplexar las señales eléctricas a diferentes cultivos celulares. Además, hemos diseñado un dispositivo de estimulación optogenética. Este tipo de estimulación consiste en la modificación genética de las células para que sean sensibles a la radiación lumínica de determinada longitud de onda. En el ámbito de la regeneración de tejido mediante células precursoras neurales, es de interés poder inducir ondas de calcio, favoreciendo su diferenciación en neuronas y la formación de circuitos sinápticos. El dispositivo diseñado permite obtener imágenes en tiempo real mediante microscopía confocal de las respuestas transitorias de las células al ser irradiadas. El dispositivo se ha validado irradiando neuronas modificadas con luz pulsada de 100 ms. También hemos diseñado un dispositivo electrónico complementario de medida de irradiancia con el doble fin de permitir la calibración del equipo de irradiancia y medir la irradiancia en tiempo real durante los experimentos in vitro. Los resultados del uso de los bioactuadores en procesos complejos y dinámicos, como la regeneración de tejido nervioso, son limitados en lazo abierto. Uno de los principales aspectos analizados es el desarrollo de biosensores que permitiesen la cuantización de ciertas biomoléculas para ajustar la estimulación suministrada en tiempo real. Por ejemplo, la segregación de serotonina es una respuesta identificada en la elongación de células precursoras neurales, pero hay otras biomoléculas de interés para la implementación de un control en lazo cerrado. Entre las tecnologías en el estado del arte, los biosensores basados en transistores de efecto de campo (FET) funcionalizados con aptámeros son realmente prometedores para esta aplicación. Sin embargo, esta tecnología no permitía la medición simultánea de más de una biomolécula objetivo en un volumen reducido debido a las interferencias entre los distintos FETs, cuyos terminales se encuentran inmersos en la solución. Por ello, hemos desarrollado instrumentación electrónica capaz de medir simultáneamente varios de estos biosensores, y la hemos validado mediante la medición simultánea de pH y la detección preliminar de serotonina y glutamato.[CA] La capacitat de les cèl·lules mare per a proliferar formant diferents cèl·lules especialitzades els atorga la potencialitat de servir de base per a teràpies efectives per a patologies el tractament de les quals era inimaginable fins fa a penes dues dècades. No obstant això, aquesta capacitat es troba mediada per estímuls fisiològics, químics, i elèctrics, específics i complexos, que dificulten la seua translació a la rutina clínica. Per això, les cèl·lules mare representen un camp d'estudi en el qual s'inverteixen amplis esforços per part de la comunitat científica. En l'àmbit de la regeneració nerviosa, per a modular el seu desenvolupament i diferenciació el tractament farmacològic, l'electroestimulació, i l'estimulació optogenética són tècniques que estan aconseguint prometedors resultats. És per això que en la present tesi s'ha desenvolupat un conjunt de sistemes electrònics per a permetre l'aplicació combinada d'aquestes tècniques in vitro, amb perspectiva a la seua aplicació in vivo. Hem dissenyat una nova tecnologia per a l'alliberament elèctricament controlat de fàrmacs. Aquesta tecnologia està basada en nanopartícules de sílice mesoporosa i portes moleculars de bipiridina-heparina. Les portes moleculars són electroquímicament reactives, i tanquen els fàrmacs a l'interior de les nanopartícules, alliberant-los davant un estímul elèctric. Hem caracteritzat aquesta tecnologia, i l'hem validada mitjançant l'alliberament controlat de rodamina en cultius cel·lulars de HeLa. Per a la combinació d'alliberament controlat de fàrmacs i electroestimulació hem desenvolupat dispositius que permeten aplicar els estímuls elèctrics de manera configurable des d'una interfície gràfica d'usuari. A més, hem dissenyat un mòdul d'expansió que permet multiplexar els senyals elèctrics a diferents cultius cel·lulars. A més, hem dissenyat un dispositiu d'estimulació optogenètica. Aquest tipus d'estimulació consisteix en la modificació genètica de les cèl·lules perquè siguen sensibles a la radiació lumínica de determinada longitud d'ona. En l'àmbit de la regeneració de teixit mitjançant cèl·lules precursores neurals, és d'interés poder induir ones de calci, afavorint la seua diferenciació en neurones i la formació de circuits sinàptics. El dispositiu dissenyat permet obtindré imatges en temps real mitjançant microscòpia confocal de les respostes transitòries de les cèl·lules en ser irradiades. El dispositiu s'ha validat irradiant neurones modificades amb llum polsada de 100 ms. També hem dissenyat un dispositiu electrònic complementari de mesura d'irradiància amb el doble fi de permetre el calibratge de l'equip d'irradiància i mesurar la irradiància en temps real durant els experiments in vitro. Els resultats de l'ús dels bioactuadors en processos complexos i dinàmics, com la regeneració de teixit nerviós, són limitats en llaç obert. Un dels principals aspectes analitzats és el desenvolupament de biosensors que permeteren la quantització de certes biomolècules per a ajustar l'estimulació subministrada en temps real. Per exemple, la segregació de serotonina és una resposta identificada amb l'elongació de les cèl·lules precursores neurals, però hi ha altres biomolècules d'interés per a la implementació d'un control en llaç tancat. Entre les tecnologies en l'estat de l'art, els biosensors basats en transistors d'efecte de camp (FET) funcionalitzats amb aptàmers són realment prometedors per a aquesta aplicació. No obstant això, aquesta tecnologia no permetia el mesurament simultani de més d'una biomolècula objectiu en un volum reduït a causa de les interferències entre els diferents FETs, els terminals dels quals es troben immersos en la solució. Per això, hem desenvolupat instrumentació electrònica capaç de mesurar simultàniament diversos d'aquests biosensors i els hem validat amb mesurament simultani del pH i la detecció preliminar de serotonina i glutamat.[EN] The stem cells' ability to proliferate to form different specialized cells gives them the potential to serve as the basis for effective therapies for pathologies whose treatment was unimaginable until just two decades ago. However, this capacity is mediated by specific and complex physiological, chemical, and electrical stimuli that complicate their translation to clinical routine. For this reason, stem cells represent a field of study in which the scientific community is investing a great deal of effort. In the field of nerve regeneration, to modulate their development and differentiation, pharmacological treatment, electrostimulation, and optogenetic stimulation are techniques that are achieving promising results. For this reason, we have developed a set of electronic systems to allow the combined application of these techniques in vitro, with a view to their application in vivo. We have designed a novel technology for the electrically controlled release of drugs. This technology is based on mesoporous silica nanoparticles and bipyridine-heparin molecular gates. The molecular gates are electrochemically reactive and entrap the drugs inside the nanoparticles, releasing them upon electrical stimulus. We have characterized this technology and validated it by controlled release of rhodamine in HeLa cell cultures. For combining electrostimulation and controlled drug release we have developed devices that allow applying the different electrical stimuli in a configurable way from a graphical user interface. In addition, we have designed an expansion module that allows multiplexing electrical signals to different cell cultures. In addition, we have designed an optogenetic stimulation device. This type of stimulation consists of genetically modifying cells to make them sensitive to light radiation of a specific wavelength. In tissue regeneration using neural precursor cells, it is interesting to be able to induce calcium waves, favoring the cell differentiation into neurons and the formation of synaptic circuits. The designed device enable the obtention of real-time images through confocal microscopy of the transient responses of cells upon irradiation. The device has been validated by irradiating modified neurons with 100 ms pulsed light stimulation. We have also designed a complementary electronic irradiance measurement device to allow calibration of the irradiator equipment and measuring irradiance in real time during in vitro experiments. The results of using bioactuators in complex and dynamic processes, such as nerve tissue regeneration, are limited in an open loop. One of the main aspects analyzed is the development of biosensors that would allow quantifying of specific biomolecules to adjust the stimulation provided in real time. For instance, serotonin secretion is an identified response of neural precursor cells elongation, among other biomolecules of interest for the implementation of a closed-loop control. Among the state-of-the-art technologies, biosensors based on field effect transistors (FETs) functionalized with aptamers are promising for this application. However, this technology did not allow the simultaneous measurement of more than one target biomolecule in a small volume due to interferences between the different FETs, whose terminals are immersed in the solution. This is why we have developed electronic instrumentation capable of simultaneously measuring several of these biosensors, and we have validated it with the simultaneous pH measurement and the preliminary detection of serotonin and glutamate.Monreal Trigo, J. (2023). Electronic Devices for the Combination of Electrically Controlled Drug Release, Electrostimulation, and Optogenetic Stimulation for Nerve Tissue Regeneration [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/19384

Carbon Nanotubes

Since their discovery in 1991, carbon nanotubes have been considered as one of the most promising materials for a wide range of applications, in virtue of their outstanding properties. During the last two decades, both single-walled and multi-walled CNTs probably represented the hottest research topic concerning materials science, equally from a fundamental and from an applicative point of view. There is a prevailing opinion among the research community that CNTs are now ready for application in everyday world. This book provides an (obviously not exhaustive) overview on some of the amazing possible applications of CNT-based materials in the near future