KardiaTool: An Integrated POC Solution for Non-invasive Diagnosis and Therapy Monitoring of Heart Failure Patients

The aim of this work is to present KardiaTool platform, an integrated Point of Care (POC) solution for noninvasive diagnosis and therapy monitoring of Heart Failure (HF) patients. The KardiaTool platform consists of two components, KardiaPOC and KardiaSoft. KardiaPOC is an easy to use portable device with a disposable Lab-on-Chip (LOC) for the rapid, accurate, non-invasive and simultaneous quantitative assessment of four HF related biomarkers, from saliva samples. KardiaSoft is a decision support software based on predictive modeling techniques that analyzes the POC data and other patient's data, and delivers information related to HF diagnosis and therapy monitoring. It is expected that identifying a source comparable to blood, for biomarker information extraction, such as saliva, that is cost-effective, less invasive, more convenient and acceptable for both patients and healthcare professionals would be beneficial for the healthcare community. In this work the architecture and the functionalities of the KardiaTool platform are presented

Development of a lab-on-chip platform integrating electrochemical microsensors for the detection of water contaminants based on algal physiology monitoring

The monitoring of water quality has been of great importance in recent decades in order to find solutions to control water contamination, largely driven by agricultural and industrial activities. Although conventional methods such as chromatography, are very accurate and sensitive tools, increasing interest has been placed on promising techniques that can be used on site, are low cost, and offer the ability to perform rapid analysis. The present work is devoted to the development of lab on a chip component to the analysis of the toxicity of water. It consists of a portable system for detecting on-site and offers the possibility of a double complementary detection: optical and electrochemical. As the part dedicated to the electrochemical sensor has been previously validated, this study focused on the implementation of an electrochemical biosensor based on the use of an alga, for the detection of pollutants in water. The detection basic principle consists in monitoring changes in the metabolic activity of algae induced by the presence of herbicides. The seaweed response is different for each concentration of herbicide in an examined sample. Two herbicides selected affect the photosynthetic activity of the algae and consequently, induce changes in the amount of electro-active species produced by the alga: O2, H2O2 and H3O + / OH-. Before the development of the final component type Lab on Chip, detection principles as well as the electrode materials that will be integrated, have been validated using a simpler type of component, which was achieved through the silicon manufacturing technologies and which was characterized by simpler procedures.A silicon chip containing an electrochemical micro incorporating three electrodes was established. Once validated detecting materials and previously selected settings were used in the manufacture of components on Lab Chip. The Lab-on-Chip components were then used for the biological tests to detect the herbicides of interest. Special attention has been placed on monitoring like O2 indicator of the presence of herbicide, because this element is the most representative of changes of metabolic activity. An inhibiting effect on photosynthesis, concentration dependent of the herbicide been demonstrated. Detection of herbicidal was performed with great sensitivity and a range of covering the boundary concentration Maximum acceptable taxed by the Canadian Government.Le suivi de la qualité de l’eau a été d’une grande importance depuis ces dernières décennies afin de trouver des solutions de contrôler la contamination de l’eau, induite en grande partie par les activités agricoles et industrielles. Bien que les méthodes conventionnelles, comme la chromatographie, sont des outils très précis et sensibles, un intérêt grandissant a été placé sur des techniques prometteuses qui peuvent être utilisées sur site, sont bas coût, et offrent la possibilité d’effectuer des analyses rapides. Le travail présenté ici est dédié au développement de composant Laboratoire sur Puce pour l’analyse de la toxicité de l’eau. Il consiste en un système portable pour la détection sur site et offre la possibilité d’une double détection complémentaire : optique et électrochimique. Comme la partie dédiée au capteur électrochimique a préalablement été validée, cette étude est focalisée sur l’implémentation d’un biocapteur électrochimique basé sur l’utilisation d’une algue, pour la détection de polluants dans l’eau. Le principe basique de détection consiste au suivi de changements de l’activité métabolique d’algues induits par la présence d’herbicides. La réponse de l’algue est différente pour chaque concentration d’herbicide dans un échantillon examiné. Deux herbicides sélectionnés affectent l’activité photosynthétique de l’algue et par conséquent, induisent des modifications dans la quantité des espèces électroactives produites par l’algue : O2, H2O2 et H3O+/OH-. Avant le développement du composant final type Laboratoire sur Puce, les principes de détection aussi bien que les matériaux d’électrode qui vont être intégrés, ont été validés en utilisant un type de composant plus simple, qui a été réalisé grâce aux technologies de fabrication silicium et qui a été caractérisé par des procédures plus simples. Une puce sur silicium contenant un microsystème électrochimique intégrant trois électrodes a été mis en place. Une fois validés, les matériaux de détection et les configurations choisis précédemment ont été utilisés pour la fabrication des composants Laboratoire sur Puce. Les composants Laboratoire sur Puce ont été ensuite utilisés pour des tests biologiques afin de détecter les herbicides d’intérêt. Une attention spéciale a été placée sur le suivi de O2 comme indicateur de la présence d’herbicide, étant donné que cet élément est le plus représentatif de modifications de l’activité métabolique. Un effet d’inhibition sur la photosynthèse, dépendant de la concentration de l’herbicide a été démontré. La détection de l’herbicide a été réalisée avec une grande sensibilité et sur une gamme couvrant la limite de concentration maximale acceptable imposé par le gouvernement canadien

Mise en place d'une plateforme Laboratoire Sur Puce intégrant des microcapteurs électrochimiques pour la mesure des polluants dans l'eau basée sur le suivi physiologique d'algues

Le suivi de la qualité de l'eau a été d'une grande importance depuis ces dernières décennies afin de trouver des solutions de contrôler la contamination de l'eau, induite en grande partie par les activités agricoles et industrielles. Bien que les méthodes conventionnelles, comme la chromatographie, sont des outils très précis et sensibles, un intérêt grandissant a été placé sur des techniques prometteuses qui peuvent être utilisées sur site, sont bas coût, et offrent la possibilité d'effectuer des analyses rapides. Le travail présenté ici est dédié au développement de composant Laboratoire sur Puce pour l'analyse de la toxicité de l'eau. Il consiste en un système portable pour la détection sur site et offre la possibilité d'une double détection complémentaire : optique et électrochimique. Comme la partie dédiée au capteur électrochimique a préalablement été validée, cette étude est focalisée sur l'implémentation d'un biocapteur électrochimique basé sur l'utilisation d'une algue, pour la détection de polluants dans l'eau. Le principe basique de détection consiste au suivi de changements de l'activité métabolique d'algues induits par la présence d'herbicides. La réponse de l'algue est différente pour chaque concentration d'herbicide dans un échantillon examiné. Deux herbicides sélectionnés affectent l'activité photosynthétique de l'algue et par conséquent, induisent des modifications dans la quantité des espèces électroactives produites par l'algue : O2, H2O2 et H3O+/OH-. Avant le développement du composant final type Laboratoire sur Puce, les principes de détection aussi bien que les matériaux d'électrode qui vont être intégrés, ont été validés en utilisant un type de composant plus simple, qui a été réalisé grâce aux technologies de fabrication silicium et qui a été caractérisé par des procédures plus simples. Une puce sur silicium contenant un microsystème électrochimique intégrant trois électrodes a été mis en place. Une fois validés, les matériaux de détection et les configurations choisis précédemment ont été utilisés pour la fabrication des composants Laboratoire sur Puce. Les composants Laboratoire sur Puce ont été ensuite utilisés pour des tests biologiques afin de détecter les herbicides d'intérêt. Une attention spéciale a été placée sur le suivi de O2 comme indicateur de la présence d'herbicide, étant donné que cet élément est le plus représentatif de modifications de l'activité métabolique. Un effet d'inhibition sur la photosynthèse, dépendant de la concentration de l'herbicide a été démontré. La détection de l'herbicide a été réalisée avec une grande sensibilité et sur une gamme couvrant la limite de concentration maximale acceptable imposé par le gouvernement canadien.Water quality assessment has attracted wide attention during the last decades in order to find ways to control contamination of water bodies induced, in a big part, by agricultural and industrial activities. Although conventional techniques, such as chromatography are highly accurate and sensitive tools, increasing interest has been placed lately to powerful alternative techniques that can be used on field, are cost-effective and offer the possibility of conducting rapid analysis. The present work was therefore dedicated to the development of a lab-on-chip device for water toxicity analysis. It consists in a portable system for on-site detection and aims at offering the possibility of conducting double complementary detection: optical and electrochemical. Since the optical sensor is already validated, this study focused on the implementation of the algal-based, electrochemical biosensor for detection water contaminants. The basic detection principle consists in monitoring disturbances in metabolic activities of algae induced by the presence of the herbicides. Algal response is different for each herbicide concentration in the examined sample. The two selected herbicides affect algal photosynthetic activity and consequently induce modifications in the quantity of electroactive species, O2, H2O2 and H3O+/OH- ions related to pH, produced by algae. Prior to the development of the final lab-on-chip device, the detection principle as well as the electrode materials that were going to be integrated were validated using a simpler device that was implemented using a silicon-based fabrication technology and was characterized using simpler procedures. A silicon chip containing the integrated three-electrode electrochemical microsystem was fabricated. The performance of the microsystem was evaluated through electrochemical characterization and calibration was performed. Once validated, the aforementioned materials and configurations were used for the fabrication of the lab-on-chip devices. The lab-on-chip devices were further used in bioassays to detect the herbicides of interest. Special emphasis was placed on O2 monitoring as indicator of the presence of herbicide, as it is the element the most representative of variations in metabolic activities. A concentration-dependent inhibition effect of the herbicide on photosynthesis was demonstrated. Herbicide detection was achieved with a greater sensitivity and a range covering the limit of maximum acceptable concentration imposed by Canadian government

Ιnvestigation of the electrochemical performance of nanostructured electrodes containing TiO2 for the detection of Hg

89 σ.H παρούσα μελέτη στοχεύει στην ανάπτυξη ενός κατάλληλου ηλεκτροδίου εργασίας για την ανίχνευση ιχνών υδραργύρου (Hg2+) και στην εξεύρεση ενός τρόπου σταθεροποίησης νανοσωματιδίων χρυσού (Αu NPs) στην επιφάνεια του ηλεκτροδίου αυτού. Χρησιμοποιήθηκε υαλώδης άνθρακας σαν υπόστρωμα για τη χημική απόθεση από ατμό στρώματος TiO2. Διερευνήθηκε, λοιπόν, η καταλληλότητα της επίστρωσης TiO2 ως μέσου σταθεροποίησης των νανοσωματιδίων χρυσού καθώς και ως υλικού για την ανίχνευση του Hg2+ μέσω ηλεκτροχημικών διεργασιών. Νανοσωματίδια χρυσού αποτέθηκαν με τη βοήθεια ηλεκτροχημικών μεθόδων, όπως η κυκλική βολταμετρία και η χρονοαμπερομετρία, στα ηλεκτρόδια υαλώδους άνθρακα με την επίστρωση TiO2. Τα τελικά ηλεκτρόδια ενεργοποιήθηκαν σε διάλυμα H2SO4. Η ηλεκτρονική μικροσκοπία σάρωσης (SEM), η μικροσκοπία ατομικής δύναμης (AFM) καθώς και η ανάλυση με περίθλαση ακτίνων Χ (XRD) χρησιμοποιήθηκαν για το χαρακτηρισμό των δειγμάτων που προέκυψαν μετά την απόθεση του στρώματος TiO2 στο υπόστρωμα υαλώδους άνθρακα όπως και αυτών που προέκυψαν μετά την ηλεκτραπόθεση των νανοσωματιδίων χρυσού. Για την ανίχνευση του Hg2+, διεξήχθη Ανοδική Αναδιαλυτική Βολταμετρία Τετραγωνικού Κύματος (SWASV) και χρησιμοποιήθηκαν τα AuNPs/TiO2 τροποποιημένα ηλεκτρόδια υαλώδους άνθρακα. Τα αποτελέσματα της μελέτης έδειξαν ότι το TiO2 δεν αποτελεί υλικό κατάλληλο για την ανίχνευση του Hg2+ μέσω της τεχνικής αυτής.The objective of this study is to fabricate a working electrode for the detection of mercury (Hg2+) and find a way to stabilize the gold nanoparticles (Αu NPs) on the surface of the electrode. Glassy carbon was selected as the substrate and TiO2 was the coating deposited on the glassy carbon substrate by chemical vapor deposition. Investigation was thus held, to find out whether the TiO2 coating is the appropriate stabilizing agent for the gold nanoparticles and a reliable electrode material for the detection of Hg2+ through electrochemical methods. Gold nanoparticles were electrodeposited on the TiO2 coated glassy carbon substrates by cyclic voltammetry and chronoamperometry and then activated in H2SO4. Scanning Electron Microscopy (SEM), Atomic Force Microscopy (AFM) and X-ray Diffraction (XRD), were used not only for the characterization of the TiO2 coated GC disks but also for the AuNPs/TiO2 modified GC electrodes. For the detection of Hg2+, Square Wave Anodic Stripping Voltammetry was carried out, by using the resulted Au NPs/ TiO2 modified glassy carbon electrodes. The outcome of this study is that TiO2 is not the appropriate coating for the Hg2+ detection through this technique.Αλίκη Ι. Τσόπελ

Lab-on-Chip Prototype for the Detection of Coronary Artery Disease Biomarkers

We report an easy-to-use Lab-on-Chip (LoC) device able to detect soluble, circulating biomarkers in plasma that are relevant to Coronary Artery Disease (CAD). The LoC prototype is developed within the SMARTool European project and is intended to be used for Point-of-Care (PoC) testing of patients with CAD, facilitating more rapid and efficient monitoring and treatment decisions. A LoC prototype is presented, enabling chemiluminescent assays to be performed on chip targeting biomarkers relevant to CAD. In parallel, a robust technology for electrostatically actuated, capillary burst valve for PoC applications, integrated in potentially disposable, thermoplastic devices is reported. The devices were fabricated using easily scalable fabrication techniques and can be used to perform multistep assays on single-use microfluidic devices

Final capping passivation layers for long-life microsensors in real fluids

International audienceFinal capping insulation layer is a critical step in the microfabrication process that determines the lifetime of analytical microsensors in real fluids. Actual processes encounter considerable limitations as (i) organic passivation layers do not provide a satisfying long-term protection against liquids and (ii) inorganic passivation processes (dielectric materials deposition and patterning) are very aggressive for the underlying layers, imposing severe constraints on the integration of sensitive materials. We present here a low temperature deposition process of high quality silicon nitride Si3N4 using ICP-CVD technique combined with a lift-off based process to pattern conformal deposition, in order to avoid harsh treatments such as wet or dry etching. High-density SiNx films with low H content (5 x 10 20 at/cm 3) were synthesized at 100°C with controlled uniformity (5%), refractive index (2.025 at 830 nm), etch rate in buffered hydrofluoric acid (8 nm/min), residual stress (-500 MPa), breakdown field (3.9 MV/cm) and dielectric constant (6.0). In order to validate the compatibility of this passivation process with long-term fluids analysis, microelectrodes were fabricated and their lifetime in natural seawater was evaluated. Their active surfaces were defined by patterning the insulation layer. Special care was given to their accurate estimation through the modelling of chronoamperometric curves. Reproducible and stable electrochemical response was obtained for months (> 50 days), demonstrating a considerably extended lifetime in harsh liquid media

Integration of tungsten layers for the mass fabrication of WO3-based pH-sensitive potentiometric microsensors

International audience(W/WO3 –Ag/AgCl) and (Pt/IrO2 – Ag/AgCl) potentiometric microdevices were developed for pH measurement in liquid phase using a (Pt – Pt – Ag/AgCl) electrochemical microcells (ElecCell) silicon-based technological platform. A special emphasis was placed on the mass fabrication of the W/WO3 microelectrode using sputtering deposition and oxygen plasma processes. Compared to the Pt/IrO2-based one, the W/WO3-based microelectrodes showed lower performances regarding the pH measurement. Nevertheless, since W/WO3 microelectrodes yielded quasi-Nernstian sensitivity (around 55 mV/pH) in the [2-12] pH range, tungsten oxide WO3 can be considered as a good candidate for the mass fabrication of pH microsensors using silicon technologies, even if important temporal drift (at least 6 millivolts per hour) and high hysteresis (around 50 mV) were also evidenced

PEDOT-modified electrochemical microsensors: a versatile probe for the detection of antioxidant biomarkers

International audienceThe development of low-cost biosensors that enable a sensitive, selective and reliable determination of analytes has received considerable attention. In this context, electrochemistry represents a powerful tool for dealing with the detection of chemical species. Indeed, microelectrodes can be integrated using silicon-based technologies, and are compatible with the use of electrocatalytic conductive polymers. One of them, the poly(3,4-ethylenedioxythiophene) (PEDOT), was shown to exhibit optimized properties for bioanalysis: low oxidation potential, good stability, high electrical conductivity, good detection selectivity and biocompatibility. As a result, PEDOT was used for the determination of different molecules of biological interest such as antioxidant biomarkers. Among them, ascorbic (AA) and uric (UA) acids were widely studied since they are associated with oxidative stress and related pathologies. In previous works, we demonstrated the integration of (Au-Pt-Ag/AgCl) electrochemical microcells (ElecCell) for the bioelectrochemical detection, as well as the catalytic behaviour of PEDOT towards the simultaneous determination of AA and UA acid in aqueous solutions and blood serum. This paper presents the integration of (Au/PEDOT-Pt-Ag/AgCl) ElecCell microdevices for the detection of antioxidant markers (fig. 1). First, it deals with the optimization of the PEDOT electrodeposition process on integrated gold microelectrodes. Then, more attention is brought to the dopamine (Dop) analysis, a well-known neurotransmitter coexisting usually with AA and UA in biological samples. Thus, using PEDOT-modified ElecCell microdevices, the selective determination of dopamine was achieved in presence of both ascorbic and uric acids (fig. 2). Excellent catalytic properties were thus evidenced for their simultaneous detection with high sensibilities (around 0.85, 3.0 and 1.65 pA.cm-2 .M-1 for AA, UA and Dop respectively) and low detection limits (< 500 nM) (fig. 3 and 4). Such results intend to demonstrate that silicon-based, PEDOT-modified electrochemical microsensors are convenient probes for the practical determination of antioxidant biochemical markers in biological samples. Fig. 1: Details of the (Au/PEDOT-Pt-Ag/AgCl) Fig 2: Differential pulse voltammogramm of ElecCell microdevice an equimolar solution (1 mM) of AA, UA and Dop Fig. 3: Differential pulse voltammogramms for Fig. 4: Calibration curves of AA, UA and Dop different concentrations of dopamine (0.1-300 M

Light emitting devices and integrated electrochemical sensors on lab-on-chip for toxicity bioassays based on algal physiology

International audienceIn the frame of water toxicity analysis, a portable, glass-based, lab-on-chip was developed, integrating three-electrode electrochemical microsensors and organic light-emitting diodes (OLED). The basic detection principle consists in monitoring electrochemically O2-related, algal metabolism in presence of herbicides. Thus, aiming on Diuron herbicide detection, a concentration-dependent inhibition effect on photosynthetic oxygen production rate was evidenced in the [0-1 M] range. Finally, OLED-based integrated system demonstrates higher detection characteristics than those using external white light source (sensitivity: 0.48 versus 0.26 nA/s/M) and is highly promising for further integration of optical and electrochemical sensors enabling double complementary detection

Microalgae electrochemical microbiosensor for water toxicity analysis

International audienceThe goal of our research lies in developing a three-electrode electrochemical microbiosensor integrated on a lab on chip platform used in environmental applications and more specifically water toxicity analysis. It consists in fabricating a portable system for on-site detection of herbicides in water. The detection is performed by measuring the disturbances in photosynthetic and metabolic activities of algae caused by traces of herbicides. The system offers the possibility of conducting double complementary detection, electrochemical and optical, by measuring current variations reflecting the biochemical phenomena and fluorescence emitted by algae respectively. The electrochemical system enables a real-time parallel monitoring of multiple electro-active species taking part in metabolic activities of algae and more particularly O2, H2O2 and OH-pH-related ions. Electrodes and fluidic part including measurement chambers and channels were integrated on glass substrate in order to obtain a system compatible with optical technologies (Fig. 1). Platinum and platinum black (Bl Pt) working microelectrodes were fabricated for H2O2 and dissolved O2 whereas W/WO3 and IrOx microelectrodes were used for pH monitoring. A Pt counter microelectrode and an Ag/AgCl reference microelectrode were then integrated in the structure. Electrodes exhibited high sensitivity for H2O2 detection and low detection limits (50nM). pH electrodes demonstrated a linear Nernstian response over a wide pH range (59 mV/pH). The performances of the Pt and Bl Pt sensors for O2 detection were evaluated and compared by recording the oxygen reduction current during algae photosynthesis and respiration. Variations in photosynthetic activity of algae were determined in presence of different concentrations of Diuron herbicide by comparing oxygen production rates (Fig. 2). Fig.1: Lab-on-chip electrochemical biosensor Fig. 2 : Algal response to pollutan