Lab-on-a-chip technology is a rapidly growing research area. Joining together several disciplines, such as physics, biology and several instances of nanotechnologies. The aim of this research is mainly to produce chips that can do the same types of measurements as large lab equipment and measurement systems, but at a fraction of the size and cost. In this work a multifunctional measuring device have been developed. It can measure optical absorbance and fluorescence while performing a range of potentiometric techniques; including chronoamperometry, linear- and cyclic voltammetry. From all these measurements it is possible to calculate particle concentrations in fluid samples. The aim is to bring simpler and cheaper point of care devices to the public. Without larger losses in accuracy and reliability of the medicinal test. To do this our device is intended to be used with lab-chip, which are capable of amplifying the signals while reducing the sample size. Lab-chips could be used in several areas but the ones being designed with this device are made for biomedical purposes, applying suitable nanostructures and reagents to measure the presence of biomarkers. With these techniques, medicinal diagnostics can be made a few minutes after samples have been collected from patients. Much quicker and more direct than sending the samples to a lab and waiting hours if not days for the results. The measuring device or lab-chip reader will use two different lab-chips in the future. One that is optimised for optical absorbance and the other for fluorescence. Both will work with electrochemical measurements, but at present only the absorbance chip have been available for testing and that without any signal enhancing techniques. Assessment of the reader's capabilities was made with solutions of gold nanoparticles, TMB (tetramethylbenzidine), iron dissolved in PBS (Phosphate-buffed saline) and with a film made of PPV (Poly para-phenylenevinylene). The first two were used to test absorbance; while the iron and PBS have been used to test electrochemical system; and the PPV was coated on a glass substrate and used to test fluorescence. During the optical absorption test, it was found that the reader can distinguish between different concentrations of the various solutions. The results are promising and further removal of signal drifts will improve signals considerably. Fluorescence can be induced and measured with the device. This part of the system is, however, untested in general and future work will show if it is sufficient. The iron solution was tested with three different methods. chronopotentiometry, linear sweep voltammetry and cyclic voltammetry. It was however found that our measurements were distorted in comparison with the expected voltammogram for iron in PBS. Additional peaks were found in the voltammogram and it is believed that these are a result of oxidation of the electrodes on the lab-chip.

Noninvasive glucose monitoring has been the subject of considerable research because of the high number of diabetes patients who must monitor their glucose levels daily by taking blood samples. Among methods being evaluated for possible use in this application, near-infrared (NIR) spectroscopy has received significant attention because of available glucose absorption bands that can be observed in the presence of the large aqueous background found in tissue spectra. The objective of the research presented here is to evaluate the potential for implementing a noninvasive nocturnal hypoglycemic alarm with NIR spectroscopy. Such an alarm would be used by a diabetic to detect potentially dangerous occurrences of hypoglycemia during sleep. The approach used is to collect spectra continuously from the patient during the sleep period, followed by the application of pattern recognition methods to determine if a spectrum represents a blood glucose level that exceeds a hypoglycemic threshold. A reference spectrum is collected and a conventional finger-stick glucose concentration measurement is made at the start of the sleep period. The ratio is then taken of each subsequent spectrum to the collected reference, forming a differential spectrum corresponding to the signed difference in concentration relative to the reference. The identification of these differential spectra as "alarm" or "non-alarm" is performed with a classification model computed with piecewise linear discriminant analysis. This methodology is initially tested with in vitro laboratory data that simulated the glucose excursions that occur during sleep. The performance of the hypoglycemic alarm methodology in the presence of varying levels of urea, glyceryl triacetate, and L-lactate as potential spectral interferents is tested. The robustness of the methodology with respect to time is also evaluated. The thesis further discusses an experimental procedure to prepare tissue phantoms composed of two main proteins that exist in human skin tissue, keratin and collagen. A new methodology is developed to produce varying-thickness films that allowed the simulation of changes in the content of skin tissue proteins present within the optical path of the NIR measurement. The prepared films are incorporated into in vitro laboratory measurements in which varying levels of glucose, urea, keratin, and collagen are introduced in order to provide a test of the hypoglycemic alarm algorithm that simulates the spectral properties of human tissue. Finally, the hypoglycemic alarm algorithm is tested with in vivo data collected with rat animal models. Data are presented for single-day experiments performed with anesthetized rats, as well as for multiple-day experiments conducted with awake rats. The results obtained from both the in vitro and in vivo studies confirm that if high-quality spectral data are attainable, the alarm methodology can work effectively to identify hypoglycemic events while exhibiting a low rate of false detections.

Els sensors químics tenen avui dia un renovat interès degut a les creixents necessitats actuals de la societat de disposar de més i millor informació analítica. No obstant, la manca de sensors ideals específics per a una espècie determinada va portar al nostre grup d'investigació a explorar les possibilitats de les llengües electròniques. Aquests sistemes analítics, bioinspirats en el sentit del gust, consideren un conjunt o matriu de sensors i/o biosensors amb selectivitat creuada, i no un únic sensor. La rica i abundant informació obtinguda és posteriorment tractada amb eines de calibratge multivariable per a extreure la informació analítica útil.La present tesi doctoral va començar enfocada en el desenvolupament, per primera vegada al grup, de llengües electròniques potenciomètriques basades en matrius de biosensors. Concretament, es va construir una llengua electrònica per a la determinació simultània d'urea, NH4+, K+ i Na+ en mostres clíniques. Es van fabricar i caracteritzar primer diferents biosensors d'urea basats en l'enzim ureasa i, un cop demostrada la seva idoneïtat per a ser implementats en una matriu, es van construir dos models de resposta diferents basats en xarxes neuronals artificials (XNA) i regressió per mínims quadrats parcials, respectivament. Els resultats obtinguts van mostrar una millor capacitat de predicció en el cas del model amb XNA, aconseguint determinar la urea sense necessitat d'eliminar les interferències alcalines.Amb l'experiència adquirida amb aquest primer sistema, es van iniciar i continuar altres aplicacions de les llengües electròniques potenciomètriques. Primerament, es va considerar la fabricació de matrius integrades de sensors potenciomètrics mitjançant la tècnica serigràfica (screen-printing), que permet la miniaturització i la producció massiva, en col·laboració amb el Centro de Investigación y Estudios Avanzados de Mèxic. Aquesta matriu serigrafiada va servir per a desenvolupar una llengua electrònica per a la quantificació simultània dels ions NH4+, K+ i Na+ en mostres mediambientals. També es va proposar l'ús per primera vegada d'una llengua electrònica per al monitoratge on-line de la composició de la solució nutritiva d'un hivernacle hidropònic, gràcies a una col·laboració amb investigadors de l'Institut de Recerca i Tecnologia Agroalimentària de la Generalitat de Catalunya. La idea era optimitzar una llengua electrònica per a la determinació simultània i en temps real dels ions fertilitzants NH4+, K+, NO3- i PO43-, i els ions salins Na+ i Cl-. Els resultats obtinguts van ser prou interessants com per seguir treballant en el tema. A més, es va explorar l'aplicabilitat de dues diferents llengües electròniques en el monitoratge mediambiental in-line amb transmissió de dades per radiofreqüència. La primera d'elles per a la determinació simultània i en temps real dels ions NH4+, K+, Na+, Cl- i NO3- en un reactor continu de tanc agitat que simulava les condicions de biodegradació naturals, i la segona, per a la determinació simultània i en temps real dels cations NH4+, K+ i Na+ en la presa mexicana d'Ignacio Ramírez. Els bons resultats obtinguts van permetre demostrar l'aplicabilitat de les llengües electròniques desenvolupades com a sistemes de mesura remota en aplicacions mediambientals. En totes aquestes aplicacions en camp, es va posar especial èmfasi en corregir l'efecte de la temperatura i les derives de la resposta dels elèctrodes.Finalment, i per tal de tornar a la línia de recerca inicial, es va desenvolupar amb èxit una nova llengua electrònica amb biosensors per a la quantificació d'urea, creatinina, NH4+, K+ i Na+ en mostres clíniques. En aquest cas els biosensors de creatinina desenvolupats estaven basats en l'enzim creatinina deiminasa i el model de resposta, que estava basat en XNA, va permetre la determinació simultània de les cinc espècies, deixant el sistema a punt per a passar a estudis en hospitals. / Chemical sensors have nowadays a renewed interest due to the increasing current needs of the society for having more and better analytical information. However, the lack of specific ideal sensors for a determinate species brought to our research group to explore the possibilities of the electronic tongues. These analytical systems, bio inspired in the sense of taste, consider a set or array of sensors and/or biosensors with cross selectivity, and not only one sensor. The rich obtained information is later treated with tools of multivariable calibration to extract the useful analytical information.The present doctoral thesis started focusing on the development of potentiometric electronic tongues based on arrays of biosensors for the first time in our group. Precisely, an electronic tongue was constructed for the simultaneous determination of urea, NH4+, K+ and Na+ in clinical samples. Firstly, different urea biosensors based on the enzyme urease were manufactured and characterized. Once demonstrated their suitability to be implemented in an array, two different models of response based on artificial neural networks (ANN) and partial least squares were constructed. The results showed a better capacity of prediction in the case of the model with ANN, which allowed the determination of urea concentration without the need of eliminating the alkaline interferences.With the experience acquired with this first system, other applications of the potentiometric electronic tongues were studied. Firstly, the construction of integrated arrays of potentiometric sensors by using the screen-printing technique was considered in collaboration with the Centro de Investigación y Estudios Avanzados of Mexico. This technique allows the miniaturization and the massive production of arrays. This array served to develop an electronic tongue for the simultaneous quantification of NH4+, K+ i Na+ ions in environmental samples. Also, the use of an electronic tongue was proposed for the first time in the monitoring of the nutrient solution composition produced by a hydroponic greenhouse, thanks to collaboration with researchers of the Institut de Recerca i Tecnologia Agroalimentària of the Generalitat de Catalunya. The idea was to optimize an electronic tongue for the simultaneous real-time determination of the fertilizer ions NH4+, K+, NO3- and PO43-, and the saline ions Na+ and Cl-. The obtained results were so interesting to continue working on the subject. Moreover, the applicability of two different electronic tongues was explored in environmental in-line monitoring with data transmission for radio frequency. The first of them was used for the simultaneous real-time determination of NH4+, K+, Na+, Cl- and NO3- ions in a continuous stirred-tank reactor that simulated the natural biodegradation conditions; and the second one, for the simultaneous real-time determination of the cations NH4+, K+ and Na+ in the Ignacio Ramírez Mexican dam. The good results obtained allowed to demonstrate the applicability of the developed electronic tongues as systems for remote measurement in environmental applications. In all these applications carried out of the laboratory, special attention was paid in compensating for temperature effects and response drifts.Finally, and in order to come back to the initial-research line, a new electronic tongue was successfully developed using biosensors for the quantification of urea, creatinine, NH4+, K+ and Na+ in clinical samples. In this case creatinine biosensors were based on the enzyme creatinine deiminase and the model of response based on XNA allowed the simultaneous determination of the five species, leaving the system ready to be used in hospital studies.

Ce travail de thèse porte sur la réalisation et la validation d'un capteur pour la mesure d'impédance en cytométrie de flux associée à un dispositif microfluidique pour des cellules sanguines dans la gamme de fréquences (100 kHz-10 MHz). Un premier chapitre introduit les propriétés électriques et diélectriques des tissus vivants. Les effets de chaque élément des cellules sur l'impédance globale mesurée sont décrits, ainsi que les modèles associés. Un état de l'art, sur les mesures de l'échelle macroscopique à la mesure unitaire de cellules, est exposé dans le second chapitre. Les mesures en cytométrie de flux et l'utilisation possible des actionneurs à ondes acoustiques de surface (SAW) y sont aussi étudiées. Le troisième chapitre concerne la modélisation analytique et la simulation par la méthode des éléments finis de cellules unitaires par des microélectrodes de différentes géométries. Les résultats de cette section ont permis de déterminer les meilleures géométries, leurs sensibilités, et leurs réponses. La fabrication du capteur est étudiée dans le quatrième chapitre. Les contraintes liées à la faisabilité par les techniques de micro-fabrication et la biocompatibilité des matériaux y sont développées. Des premiers tests de validation sur les écoulements y sont effectués. Le cinquième et dernier chapitre est centré sur la mesure de cellules et particules. Des tests de calibration ont été réalisés pour déterminer le facteur de forme des électrodes et les impédances parasites. Les mesures suivantes sur des cellules et particules ont permis de valider les résultats obtenus en simulation, ainsi que la discrimination des particules testées en fonction de leurs dimensions / This thesis focuses on the implementation and validation of a microfluidic bioimpedance sensor for cytometric measures in the frequency range ( 100kHz - 10MHz ) of biological cells ( blood cells) combined with a microfluidic device. The first chapter introduces the electrical and dielectric properties of living tissues and summarizes the state of the art. The effects of each element of the cells on the overall measured impedance are described, as well as the associated models. A state of the art, on the bioimpedance macroscopic measurements unit cell is outlined in the second chapter. Measurements by flow cytometry and the possible use of surface acoustic wave (SAW) devices as actuators are also studied. The third chapter deals with analytical modeling and simulation by the finite element method of unit cells by microelectrodes of different geometries. 3D simulations were done showing the best configuration for the electrodes design. The results of this section were used to determine the best geometry, their sensibilities, and their answers. The sensor design is described in the fourth chapter. Technological constraints related to its micro- fabrication techniques feasibility and biocompatibility of materials are developed. Flows validation tests were done and are described. The fifth and final chapter focuses on the measurement of cells and particles. In a first step, calibration tests were carried out to determine the form factor of the electrodes and the parasitic impedances. Measurements on cells and particles were used to validate the results obtained in simulation, as well as discrimination based particles tested their dimensions

As the science and technology advance, people are looking for new discoveries to solve the existing problems and improve the quality of life. In this processes of development, nanoscience and nanotechnology have attracted technologists' attention and turned out to be one of the most promising technologies that could have a revolutionary impact. Znic Oxide (ZnO) nanostructures, in particular nanowires (NWs), have the potential to be one of such revolutionary material. ZnO is a piezoelectric, transparent and semiconducting material. With a direct band gap of 3.37eV and large excitation binding energy (60meV), ZnO exhibits near-UV emission, and transparent conductivity. ZnO NWs, with all of the properties of bulk ZnO, have other properties that are distinct to nanoscale material. All of these make ZnO NWs a very unique material that has many potential applications in system miniaturization. System-on-package (SOP) technology is a new concept developed to solve the integration problem in microelectronic industry. SOP technology paradigm provides system-level miniaturization in a package size that makes today's hand-held devices into multi-functional systems, with applications ranging from computing, wireless communications, health care to personal security. The SOP is a system miniaturization technology that ultimately integrates nanoscale thin film components for batteries, thermal structures, active and passive components in low cost organic packaging substrates, leading to micro to nanoscale modules and systems. The goal of this research is to investigate and utilize the unique properties of ZnO NWs and apply them to the fabrication of devices that can be integrated with SOP platform. The issues include developing techniques to manipulate and align ZnO NWs; developing contact preparation method to improve the contact conductance for the fabrication of ZnO NW based devices. Also, the investigation of the oxygen diffusion coefficient in ZnO NWs is carried out, which serves as the basis of ZnO NWs for sensing applications. Two practical applications, which include fabricating and characterizing SOP compatible ZnO NW based bio-sensor and SOP compatible ZnO NW based nano-generator, are evaluated. Finally the remaining work beyond the scope of the thesis is outlined.

Esta tesis doctoral se centra en el aprovechamiento de varias metodologías basadas en técnicas electroquímicas y analíticas para la detección del estrés oxidativo en medios complejos biológicos, en partículas, proteínas y medios complejos biológicos. 1. Modificación covalente de aminoácidos en proteínas redox y no redox por métodos electroquímicos, químicos o mediante irradiación ultrasónica, y estudios de cinética de la transferencia electrónica sobre electrodos serigrafiados de carbón. 2. Estudios metabolómicos de medios de cultivo celular complejos y desarrollo de sensores y biosensores para la identificación, determinación y detección de biomarcadores relacionados con el metabolismo celular y el estrés oxidativo.

Les électrodes modifiées avec cyclodextrines ayant des grandes performances analytiques représentent une alternative intéressante pour le développement de (bio)capteurs électrochimiques dans un domaine attractif de la recherche pour différentes applications, et notamment les analyses pharmaceutiques et biomédicales. Le but de cette étude a été de développer de nouvelles électrodes modifiées avec β-cyclodextrine pour des applications biomédicales et pharmaceutiques. L'influence de la β-cyclodextrine a été étudiée en solution et à la surface d’électrodes.L'influence de la β-cyclodextrine en solution aqueuse sur le comportement électrochimique de certaines substances pharmaceutiques (l’acide ascorbique, l'acide urique, la caféine, la théophylline, l'aminophylline et l'acétaminophène) a été étudiée en utilisant des méthodes électrochimiques et spectrales, mettant en évidence la formation de complexes d'inclusion.Diverses techniques ont été utilisées pour la modification des électrodes avec β-cyclodextrine: l'incorporation de la β-cyclodextrine dans la pâte de carbone et le piégeage dans des films polymères de polyéthylèneimine. Ces capteurs ont permis la détermination simultanée de l'acide ascorbique et de l'acide urique. Les électrodes modifiées ont été aussi appliquées pour le dosage de l'acide ascorbique dans deux produits pharmaceutiques et pour l’évaluation quantitative de l'acide ascorbique et de l'acide urique dans l’urine humaine avec de bonnes performances.Deux types de biocapteurs basés sur une nouvelle nanostructure de graphène ont été élaborés avec de l'oxyde réduit de graphène, de β-cyclodextrine et de tyrosinase en utilisant la méthode couche par couche et l’électropolymérisation. Les nouveaux nanocomposites ont été caractérisés par des techniques spectrales, microscopiques et électrochimiques. Les biocapteurs optimisés ont été appliquées avec succès pour la détermination du catéchol et de la dopamine dans des produits pharmaceutiques et des échantillons biologiques avec une bonne récupération.La solubilisation dans l'eau de certains nouveaux fluorophores (quatre nouvelles tétrazines) en utilisant la -cyclodextrine et de nanoparticules d'or modifiées avec β-cyclodextrine a été signalée. Les assemblages supramoléculaires redox ont été caractérisés dans l'eau par analyses électrochimiques et de fluorescence. L'immobilisation de tétrazines sur différents types d'électrodes modifiées par polypyrrole-cyclodextrine a été également réalisée et examinée par techniques électrochimiques, spectroscopiques et microscopiques.Une autre contribution originale est la combinaison de la lithographie avec de nanosphères utilisant des billes de latex avec différents diamètres (900 et 100 nm), avec l’électropolymérisation du monomère pyrrole-Ru(II). Des micro et nanostructures très organisées ont été réalisées en présentant de meilleures6propriétés pour le film photosensible de poly [Ru(II)-pyrrole]. Par ailleurs, le film de poly [Ru(II)-pyrrole] a été modifié avec d'autres types de dérivés de pyrrole qui présentent de propriétés de complexation utiles pour l’immobilisation des biomolécules à la surface de l'électrode. / The cyclodextrin modified electrodes with enhanced analytical performances represent an attractive promise for the future development of electrochemical (bio)sensors and remain a very active field of research for a wide range of applications in many areas, including pharmaceutical and biomedical analysis. The aim of this study was to develop novel cyclodextrin modified electrodes for pharmaceutical and biomedical applications. The β-cyclodextrin influence was investigated both in solution and immobilized at the electrode surface.The influence of β-cyclodextrin on the electrochemical behavior of some pharmaceuticals (ascorbic acid, uric acid, caffeine, theophylline, aminophylline, and acetaminophen) in aqueous solutions was studied by using electrochemical and spectral methods, which highlighted the inclusion complexes formation.Various techniques were used for the electrode modification with β-cyclodextrin, such as: the incorporation in carbon paste and the entrapment in polymeric films (polyethylenimine). These sensors allowed the simultaneous determination of ascorbic and uric acids. The modified electrodes were also applied for the dosage of ascorbic acid in two pharmaceutical products and for the ascorbic and uric acids quantification in human urine with good performances.Two types of biosensors based on a new nanostructured graphene framework were developed with reduced graphene oxide, β-cyclodextrin and tyrosinase by using either layer by layer method or electropolymerization. These new nanocomposites were characterized by spectral, microscopic and electrochemical techniques. The optimized biosensors were successfully applied for catechol and dopamine determination in pharmaceutical products, serum and urine samples with good recoveries.The solubilization in water of some new fluorophores (four new synthesized tetrazines) by using -cyclodextrin and gold nanoparticles modified with β-cyclodextrin was reported. The redox supramolecular assemblies were characterized in water by electrochemical and fluorescence measurements. The immobilization of tetrazines onto various types of electrodes modified with polypyrrole-cyclodextrin was also achieved and examined by electrochemical, microscopic and spectroscopic techniques.Another original contribution is the combination of nanosphere lithography by using latex beads with different diameters (900 and 100 nm), with the electropolymerization of a Ru(II)-pyrrole monomer. The achievement of highly organized micro and nanostructures showed enhanced features for the photosensitive electrogenerated poly-[RuII-pyrrole] films. Furthermore, poly-[RuII-pyrrole] film was modified with other types of pyrrole derivatives presenting complexation properties in order to immobilize biomolecules at the electrode surface.

No description available.

Optofluidics is a new branch within photonics which attempts to unify concepts from optics and microfluidics. Unification of photonics and microfluidics enable us to carry out analysis of fluids through highly sensitive optical sensing device. These optical sensing devices are contained within a microchip, wherein light is made to pass through analyte (fluids of few nanoliters). The interaction between light and fluid gives rise to highly sensitive diagnostic systems. In this work the fabrication and performance characterization of a fluorescent green OLED for optofluidic applications is presented. The effect of thickness variation of hole injection (CuPc) and hole blocking (BCP) layers on the performance of fluorescent green organic light emitting diodes (OLEDs) have been studied. Even though these two organic layers have opposite functions, yet there is a particular combination of their thicknesses when they function in conjunction and luminous efficiency and power efficiency are maximized. The optimum thickness of CuPc layer, used as hole injection layer and BCP used as hole blocking layer were found to be 18 nm and 10 nm respectively. It is with this delicate adjustment of thicknesses, charge balancing was achieved and luminous efficiency and power efficiency were optimized. Such OLEDs with higher luminance can be monolithically integrated with other optical and fluidic components on a common substrate and can function as monolithically integrated internal source of light in optofluidic sensors. In this work the analysis of a fully integrated optofluidic lab-on-a-chip sensor for refractive index and absorbance based sensing using fluorescent green organic light emitting diode (OLED) as a light source is also presented. This device consists of collinear input and output waveguides which are separated by a microfluidic channel. When light is passed through the analyte contained in the fluidic gap an optical power loss due to absorption of light takes place. Apart from absorption a mode-mismatch between collinear input and output waveguide also occurs. The degree of mode-mismatch, quantum of optical power loss due to absorption of light by the fluid forms the basis of our analysis. Detection of minutest change in refractive index and changes in concentration of species contained in the analyte is indicative of sensitivity. Various parameters which influence the sensitivity of the sensor are mode spot size, refractive index of the fluid, molar concentration of the species contained in the analyte, width of the fluidic gap, waveguide geometry. By correlating various parameters, an optimal fluidic gap distance corresponding to a particular mode spot size to achieve the best sensitivity for refractive index based sensing and absorbance based sensing have been determined.

No description available.