Desarrollo y caracterización de sensores químicos de estado sólido para aplicaciones biomédicas

Consultable des del TDXTítol obtingut de la portada digitalitzadaEl trabajo realizado para la tesis se ha centrado en el desarrollo y el estudio de multi-sensores químicos basados en silicio para aplicaciones biomédicas. Dicho trabajo se divide en tres partes: En la primera parte se han fabricado sensores de silicio basados en transistores de efecto de campo sensibles a iones (ISFET). El dispositivo tiene forma de aguja e incluye dos sensores ISFETs, un pseudo-electrodo de referencia de platino y un sensor de temperatura basado en una resistencia de platino. Los ISFETs se han caracterizado eléctricamente como transistores MOSFET y químicamente como sensores de pH, con resultados satisfactorios, lo que ha demostrado la viabilidad de las tecnologías de fabricación. Se han desarrollado MEMFETs selectivos al ión potasio depositando sobre el ISFET una membrana polimérica de PVC que contiene la valinomicina como ionóforo. Los sensores mostraron una respuesta de 50 mV/década aproximadamente, en un rango de actividad del ión K+ que va desde 10-4 M hasta 10-1 M. Debido a su gran volumen, el electrodo de referencia estándar no es práctico para trabajar con ISFETs. Por ello se ha estudiado la realización de medidas diferenciales utilizando además del MEMFET de potasio, un ISFET de referencia (REFET) y el pseudo electrodo de platino integrado en el dispositivo permitiendo así la substitución del electrodo de referencia. El REFET se ha fabricado depositando una membrana polimérica de PVC inerte. Para mejorar la adherencia de la membrana a la superficie del REFET se ha realizado un proceso de silanización de la superficie, consistente en modificar químicamente la superficie del dieléctrico, de modo que se crean enlaces mediante los cuales la membrana queda bien adherida al dispositivo. Se ha caracterizado también el sensor de temperatura basado en una resistencia de platino integrado en la aguja. Los resultados obtenidos son muy lineales y repetitivos, con un valor del coeficiente de temperatura de la resistencia TRC de 26873 ppm/C. En la segunda parte de la tesis, se han desarrollado microelectrodos de estado sólido sensibles al ión hidrógeno en forma de aguja de silicio, basados en membranas poliméricas, utilizando como ionóforos el Chromoionoforo I (ETH 5294) y el Tri-n-dodecilamino (TDDA). Se ha depositado sobre los microelectrodos de platino un nuevo material polimérico conductor; el polipirrol dopado con el anión cobaltabisdicarballuro [3,3'-Co(1,2-C2B9H11)2]- mediante la técnica de electropolimerización. Este polímero actúa como capa intermedia entre el platino y la membrana. El empleo de esta etapa intermedia aumenta considerablemente la adherencia de la membrana PVC sobre la superficie del transductor y por tanto el tiempo de vida. Las características de respuesta de los microelectrodos son muy satisfactorias. Los dispositivos presentan una sensibilidad nernstiana en un rango de respuesta amplio (pH 3.5-11.0). Los coeficientes de selectividad potenciometricos obtenidos ponen de manifiesto la buena selectividad de los microelectrodos al ión hidrógeno en presencia de iones como potasio, sodio y litio. La ultima parte de este trabajo ha sido dirigida a la búsqueda de soluciones a dificultades que han sido encontradas en la utilización química de los MEMFETs sensibles al ión K+. En este sentido, se ha estudiado la modificación del óxido de silicio utilizado en la puerta del ISFET con el fin de variar su selectividad a iones específicos. Para ello se han fabricado estructuras capacitivas sensibles al ión potasio utilizando membranas inorgánicas basadas en la técnica de implantación iónica del ión aluminio y potasio en el oxido de silicio. Las estructuras han sido caracterizadas mediante la técnica capacidad-tensión (C-V) a alta frecuencia. Las características de respuesta obtenidas tanto en cuanto a sensibilidad como a selectividad han sido aceptables y comparables con las halladas en la bibliografía.The thesis work has been focused on the development and the study of chemical multi-sensors based on silicon for biomedical applications. The work is divided in three parts: In the first part we fabricated sensors based on ion-sensitive field-effect transistors (ISFET). The device has the form of a needle and includes two ISFET sensors, a platinum pseudo-reference electrode and a temperature sensor based on a platinum resistor. The ISFETs have been characterised both electrically as MOSFET transistors and chemically as pH sensors with good results, thus demonstrating the viability of the fabrication technologies. Potassium selective MEMFET devices have been obtained by solvent-casting a poly(vinyl chloride) (PVC) plasticized potassium-sensitive membrane, containing valinomycin as ionophore, on the insulator gate. Linear responses have been obtained in a range of K+ activity between 10-4 M and 10-1 M approximately, with an almost Nerntsian sensitivity (50 ± 2 mV per decade). To make useful measurements with ISFETs in their final application, the use of conventional reference electrodes, which are big and fragile, should be avoided. This can be done if a differential setup is used, with two ISFETs that show different sensitivities to the measuring ion. In that case, a metallic quasi-reference electrode can be used. The electrical potential at the electrode-electrolyte interface is unstable, but it is measured by the differential ISFET pair as a common mode voltage and is eliminated. For the differential measurement one of the ISFETs has to be made insensitive to the measuring ion (reference-ISFET or REFET). In this work we used the platinum pseudo electrode integrated in the device. The REFET has been fabricated by depositing a polymeric PVC inert membrane. To improve the adherence of the membrane to the surface of the REFET, a surface functionalization process has been realized. The temperature sensor based on a platinum resistance integrated in the needle has been also characterized. The response of the resistance with the temperature is highly linear and repetitive with a resistance temperature coefficient of 26873 ppm/C. In the second part of the work, we have developed hydrogen selective solid state microelectrodes based on silicon needle. The microelectrodes are based on an hydrogen selective PVC membrane containing either Chromoionophore I (ETH 5294) or Tri-n-dodecylamine (TDDA) ionophores. A novel electrodeposited conductive polymer, Polypyrrole (PPy) doped with Cobaltabis(dicarbollide) ions ([3.3-Co(1.2C2B9H11)2]), has been used as a solid internal contact layer between the solid surface (Pt) and the polymeric sensitive membrane. The presence of this polypyrrole layer greatly increases the stability of the microelectrodes. The potenciometric response characteristics of the microelectrodes are very satisfactory. The devices exhibited excellent selectivity to Hydrogen against common interfering cations, as potassium, sodium and lithium, in background solutions. The pH response shows also a good linearity in a wide pH range (3.5-11.0), with Nernstian slopes. The last part of this work has been directed to the research of solutions to the difficulties that have been found in the chemical utilization of the potassium sensitive MEMFETs. We have studied the modification of the silicon dioxide on the ISFET gate to change its selectivity to specific ions. In this way we have obtained potassium-sensitive capacitive structures by ion implantation of K+ and Al+ ions into silicon dioxide on silicon with low energy in order to reduce the damage to the substrate during the process of implantation. As this method is compatible with the standard CMOS process, these results can be considered as promising for its application to the production of ISFET devices sensitive to potassium. The structures have been characterized by means of the capacity-tension (C-V) method at high frequency. The characteristics of response obtained (sensibility and selectivity) have been acceptable and comparable with those found in the bibliography

Mechanical Behavior of High-Performance Concrete under Thermal Effect

Several studies on the behavior of concrete at high temperatures are the subject of recent concerns, following the latest fires in various European tunnels. In these extreme conditions, significant degradations of concrete structures can be observed (peeling, cracking, breaking of the structure). A priori prediction of concrete behavior during this type of stress is therefore essential and is not possible without a good understanding of the different mechanisms of concrete damage at high temperatures. These mechanisms are often considered as the main causes of cracking and peeling of concrete subjected to high temperatures. Therefore, a fire can strongly modify the behavior of concrete and jeopardize the stability of concrete. In case of fires, it is necessary to know the instantaneous and residual behavior of concrete subjected to temperatures up to 1000°C. In this work we present a study of the mechanical performance of high-temperature high-performance concrete (HPC) exposed to four maximum temperatures, 200, 400, 600, and 900°C. The results obtained show that the mechanical strength at 28 days increases with the degree of temperature compared with that measured at 20°C. On the contrary, a clear decrease is observed between 600 and 900°C

Effect of Curing Temperature in the Alkali-Activated Brick Waste and Glass Powder mortar and Their Influence of Mechanical resistances

In this study, compressive strength values were measured at different curing times(7,14 and 28 days).The alkali-activation of the brick and glass powder body with potassium water glass having a silicate modulus of 3. Compressive strengths, flexural strength and specific fracture energy of the specimens stored at 40° C and 60° C are evaluated at 28-days. The study demonstrates that the storage temperature of specimens and the content of the alkaline solution have a significant influence on all mechanical properties of the studied materials. Keywords: brick waste, glass powder, curing temperature, alkali-activated

Influence of Local Sand on the Physicomechanical Comportment and Durability of High Performance Concrete

This research consists of incorporating the crushed sand (CS) in the composition of a concrete and studies the effect of its gradual replacement by the sand dune (SD) on sustainability of high performance concrete (HPC) in aggressive environments. The experimental study shows that the parameters of workability of HPC are improved when the CS is partially replaced by the SD (<2/3). However, a high content of SD (>1/3) additional quantities of water is needed to meet the workability properties. The mechanical strengths decrease by adding the SD to CS, but they reach acceptable values with CS in moderate dosages. The HPC performances are significantly better than the control concrete made up with the same aggregates. The specification tests of durability show that the water absorbing coefficients by capillarity increase after adding SD to the CS

Human olfactory receptor 17-40 as active part of a nanobiosensor: A microscopic investigation of its electrical properties

Increasing attention has been recently devoted to protein-based nanobiosensors. The main reason is the huge number of possible technological applications, going from drug detection to cancer early diagnosis. Their operating model is based on the protein activation and the corresponding conformational change, due to the capture of an external molecule, the so-called ligand. Recent measurements, performed with different techniques on human 17-40 olfactory receptor, evidenced a very narrow window of response in respect of the odour concentration. This is a crucial point for understanding whether the use of this olfactory receptor as sensitive part of a nanobiosensor is a good choice. In this paper we investigate the topological and electrical properties of the human olfactory receptor 17-40 with the objective of providing a microscopic interpretation of available experiments. To this purpose, we model the protein by means of a graph able to capture the mean features of the 3D backbone structure. The graph is then associated with an equivalent impedance network, able to evaluate the impedance spectra of the olfactory receptor, in its native and activated state. We assume a topological origin of the different protein electrical responses to different ligand concentrations: In this perspective all the experimental data are collected and interpreted satisfactorily within a unified scheme, also useful for application to other proteins.Comment: 6 pages, 6 figures, DOI:10.1039/c1ra0002

An Estimate of a Frequency Characterizing the Electrochemical Stability of a Gold Electrode Modified by MHDA Thiol in Different Ways

A theoretical investigation aimed at estimating a characteristic frequency in the medium-low frequency domain in which the impedance response of a given interface measured by electrochemical impedance spectroscopy (EIS) is almost constant, constitutes the basic idea of this work. A theoretical model was subsequently applied to the data resulting from EIS measurements performed on gold electrodes modified by various ways of 16-mercaptohexadecanoic acid (MHDA) thiol functionalization. Analysis of these data revealed a direct relationship between the way the substrate was modified and this characteristic frequency. This work is licensed under a Creative Commons Attribution 4.0 International License

A Highly Sensitive Potentiometric Amphetamine Microsensor Based on All-Solid-State Membrane Using a New Ion-Par Complex, [3,3′-Co(1,2-closo-C2B9H11)2]− C9H13NH+

In the present work a highly sensitive ion-selective microelectrode for the detection of amphetamine is presented. For this purpose, a novel ion-par complex based on the metallocarborane, cobalt bis(dicarbollide) anion ([3,3′-Co(1,2-C2B9H11)2]−) coupled to amphetamonium cation has been prepared as the active site for amphetamine recognition. The prepared ion-par complex was incorporated to a PVC-type sensitive membrane. It was then drop-casted on the top of a gold microelectrode previously modified with a solid contact layer of polypyrrole. This novel amphetamine microsensor has provided excellent and quick response within the range 10−5 M to 10−3 M of amphetamine concentration, a limit of detection of 12 µM and a slope of 60.1 mV/decade. It was also found to be highly selective toward some potential interference compounds when compared to amphetamine.The authors acknowledge the financial support from the European Union’s Horizon 2020 research and innovation programme entitled MicroMole and HEARTEN grant agreement No. 653626 and No. 643694 respectivel

Lime-treatment of sand improved by bentonite addition.

peer reviewe

Development of an ImmunoFET for Analysis of Tumour Necrosis Factor- (alfa) in Artificial Saliva: Application for Heart Failure Monitoring

Assessing tumour necrosis factor-(alfa) (TNF-(alfa)) levels in the human body has become an essential tool to recognize heart failure (HF). In this work, label-free, rapid, easy to use ImmunoFET based on an ion-sensitive field effect transistor (ISFET) was developed for the detection of TNF-(alfa) protein. Monoclonal anti-TNF-(alfa) antibodies (anti-TNF-(alfa) mAb) were immobilized on an ISFET gate made of silicon nitride (Si3N4) after salinization with 11-(triethoxysilyl) undecanal (TESUD). The obtained ISFET functionalized with the mAbs (ImmunoFET) was used to detect TNF-(alfa) protein in both phosphate buffer saline (PBS) and artificial saliva (AS). The change in the threshold voltage of the gate (DVT) showed approximately linear dependency on the concentration of the antigens in the range 5-20 pg/mL for both matrixes. The cross-selectivity study showed that the developed ImmunoFET demonstrated to be selective towards TNF-(alfa), when compared to other HF biomarkers such as N-terminal pro-brain natriuretic peptide (NT-proBNP), interleukin-10 (IL-10), and cortisol, even if further experiments have to be carried out for decreasing possible unspecific absorption phenomena. To the best of our knowledge, this is the first ImmunoFET that has been developed based on Si3N4 for TNF-(alfa) detection in AS by electrical measurement

Highly Sensitive Electrochemical BioMEMS for TNF-α Detection in Humansaliva: Heart Failure

Abstract Prediction of disease progression using saliva as a diagnostic medium has roused the interest of scientific researchers in the 10 last past years. Potentially important biomarkers are increased in saliva during local and systemic inflammation. In the present study we have developed a highly sensitive biosensor for TNF-α detection in human saliva of patients suffering from heart failure. Therefore, a fully integrated electrochemical BioMEMS was developed in order to increase the sensitivity of detection, decrease the time of analysis, and to simultaneously detect varying cytokine biomarkers using eight gold working microelectrodes (WE). The monoclonal antibodies (mAb) anti-human Tumor Necrosis Factor alpha (anti-TNF-α) were immobilized onto gold microelectrodes through functionalization with carboxyl diazonium. Cyclic voltammetry (CV) was applied during the microelectrode functionalization process to characterize the gold microelectrode surface properties. Finally, electrochemical impedance spectroscopy (EIS) characterized the modified gold microelectrodes, and the detection range of TNF-α cytokines was from 1pg/mL to 15 pg/mL