New Microfluidic System for Electrochemical Impedance Spectroscopy Assessment of Cell Culture Performance: Design and Development of New Electrode Material

Electrochemical impedance spectroscopy (EIS) is widely accepted as an effective and non-destructive method to assess cell health during cell-culture. However, there is a lack of compact devices compatible with microfluidic integration and microscopy that could provide the real-time and non-invasive monitoring of cell-cultures using EIS. In this paper, we reported the design and characterization of a modular EIS testing system based on a patented technology. This device was fabricated using easily processable methodologies including screen-printing of the impedance electrodes and molding or micromachining of the cell culture chamber with an easy assembly procedure. Accordingly, to obtain processable, biocompatible and sterilizable electrode materials that lower the impact of interfacial impedance on TEER (Transepithelial electrical resistance) measurements, and to enable concomitant microscopy observations, we optimized the formulation of the electrode inks and the design of the EIS electrodes, respectively. First, electrode materials were based on carbon biocompatible inks enriched with IrOx particles to obtain low interfacial impedance electrodes approaching the performances of classical non-biocompatible Ag/AgCl second-species electrodes. Secondly, we proposed three original electrode designs, which were compared to classical disk electrodes that were optically compatible with microscopy. We assessed the impact of the electrode design on the response of the impedance sensor using COMSOL Multiphysics. Finally, the performance of the impedance spectroscopy devices was assessed in vitro using human airway epithelial cell cultures

Development of a multiparametric (bio)sensing platform for continuous monitoring of stress metabolites

There is a growing need for real-time monitoring of metabolic products that could reflect cell damages over extended periods. In this paper, we report the design and development of an original multiparametric (bio)sensing platform that is tailored for the real-time monitoring of cell metabolites derived from cell cultures. Most attractive features of our developed electrochemical (bio)sensing platform are its easy manufacturing process, that enables seamless scale-up, modular and versatile approach, and low cost. In addition, the developed platform allows a multiparametric analysis instead of single-analyte analysis. Here we provide an overview of the sensors-based analysis of four main factors that can indicate a possible cell deterioration problem during cell-culture: pH, hydrogen peroxide, nitric oxide/nitrite and lactate. Herein, we are proposing a sensors platform based on thick-film coupled to microfluidic technology that can be integrated into any microfluidic system using Luer-lock connectors. This platform allows obtaining an accurate analysis of the secreting stress metabolites during cell/tissues culture

Wettability Switching Techniques on Superhydrophobic Surfaces

The wetting properties of superhydrophobic surfaces have generated worldwide research interest. A water drop on these surfaces forms a nearly perfect spherical pearl. Superhydrophobic materials hold considerable promise for potential applications ranging from self cleaning surfaces, completely water impermeable textiles to low cost energy displacement of liquids in lab-on-chip devices. However, the dynamic modification of the liquid droplets behavior and in particular of their wetting properties on these surfaces is still a challenging issue. In this review, after a brief overview on superhydrophobic states definition, the techniques leading to the modification of wettability behavior on superhydrophobic surfaces under specific conditions: optical, magnetic, mechanical, chemical, thermal are discussed. Finally, a focus on electrowetting is made from historical phenomenon pointed out some decades ago on classical planar hydrophobic surfaces to recent breakthrough obtained on superhydrophobic surfaces

Développement de microsystèmes EWOD sur surfaces hydrophobes et superhydrophobes (application à la spectrométrie de masse)

Ce travail s'inscrit dans le contexte du développement des laboratoires sur puce. La principale application visée au cours de cette thèse concerne la spectrométrie de masse. Nous avons opté pour une microfluidique discrète par électromouillage sur diélectrique (EWOO). Le premier prototype réalisé est un microsystème comportant deux plans hydrophobes (base et capot) et dédié à l'analyse MALDI. Le déplacement d'un mélange de peptides et d'une goutte de matrice a permis d'effectuer une analyse MALDI. Le second prototype, original, a consisté à réaliser un capot en silicium nanostructuré, permettant de réaliser une analyse par Désorption/lonisation sur nanostructures (DIOS). Cette technique présente comme intérêts, contrairement à l'analyse MALDI, de s'affranchir de la matrice et d'annuler le bruit pour les basses masses. De plus, traitées hydrophobes, ces surfaces nanostructurées présentent un caractère superhydrophobe. L'ensemble des opérations microfluidiques élémentaires ainsi que l'analyse biologique ont été validées. Enfin, l'électromouillage sur des surfaces superhydrophobes, a été étudié. Les meilleurs résultats de la littérature font état d'une relaxation partielle de la goutte. Nous avons pu nous placer à l'état de l'art en réalisant le premier effet EWOO totalement réversible (angle de contact variant de 161 à 134 @ 150 V TRMS) sur surfaces superhydrophobes (nanofils de silicium obtenus par croissance). Nous présentons une interprétation du phénomène ainsi que les premiers éléments d'un modèle théorique. En parallèle, un premier microsystème dédié à la culture de cellules en goutte ainsi qu'un cache (breveté) en silicium pour imagerie MALDI ont été développés.LILLE1-BU (590092102) / SudocSudocFranceF

Validation and integration of an effervescent reaction for fluid actuation in a microfluidic device

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Validation and integration of an effervescent reaction for fluid actuation in a microfluidic platform

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Quantitative biological assays with on-chip calibration using versatile architecture and collapsible chambers

International audienceA new microfluidic device composed of pneumatically actuated multiple collapsible chambers arranged in an X-Y architecture has been developed. Elementary fluidic functions such as fluid transfer, volumes calibration , mixing, aliquoting and linear dilutions can be parallelized, achieving automatically and rapidly complex operations. The ultimate aim is to perform fully integrated quantitative assays such as complete enzymatic assays and Elisa assays by using existing kits and an on-chip calibration. Both objectives require to manipulate a high range of volumes (from 1 L to 100 L) while keeping an excellent accuracy. Furthermore, quantitative assays have to be highly repeatable to be relevant. This challenge has been successfully addressed by combining three original characteristics. First, a versatile architecture has been designed allowing to be adapted to any quantitative protocol. Then, a hyper elastic membrane with a high elongation rate and switching between two polymer solid layers has been used to control precisely the fluid volumes at each inlet and outlet chambers. Finally, repeatability was obtained by including linear dilutions to generate a standard curve and to calibrate the system

Stretchable microfluidic integrating linear dilutions for quantitative multi-step assays

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A stand-alone and portable microfluidic platform for quantitative multi-step assays

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Integration of a dilution range using collapsible chambers in a X-Y architecture

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