Rosaria Ferrigno

French National Centre for Scientific Research, Lutetia Parisorum, Île-de-France, France

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Publications (64)248.71 Total impact

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    ABSTRACT: Enrichment of rare cell populations such as Circulating Tumor Cells (CTCs) is a critical step before performing analysis. This paper presents a polymeric microfluidic device with integrated thick Carbon-PolyDimethylSiloxane composite (C-PDMS) electrodes designed to carry out dielectrophoretic (DEP) trapping of low abundance biological cells. Such conductive composite material presents advantages over metallic structures. Indeed, as it combines properties of both the matrix and doping particles, C-PDMS allows the easy and fast integration of conductive microstructures using a soft-lithography approach while preserving O2 plasma bonding properties of PDMS substrate and avoiding a cumbersome alignment procedure. Here, we first performed numerical simulations to demonstrate the advantage of such thick C-PDMS electrodes over a coplanar electrode configuration. It is well established that dielectrophoretic force ( ) decreases quickly as the distance from the electrode surface increases resulting in coplanar configuration to a low trapping efficiency at high flow rate. Here, we showed quantitatively that by using electrodes as thick as a microchannel height, it is possible to extend the DEP force influence in the whole volume of the channel compared to coplanar electrode configuration and maintaining high trapping efficiency while increasing the throughput. This model was then used to numerically optimize a thick C-PDMS electrode configuration in terms of trapping efficiency. Then, optimized microfluidic configurations were fabricated and tested at various flow rates for the trapping of MDA-MB-231 breast cancer cell line. We reached trapping efficiencies of 97% at 20 μl/h and 78.7% at 80 μl/h, for 100 μm thick electrodes. Finally, we applied our device to the separation and localized trapping of CTCs (MDA-MB-231) from a red blood cells sample (concentration ratio of 1:10). F D E P
    Full-text · Article · Sep 2015 · Biomicrofluidics
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    ABSTRACT: To determine the octanol–water partition coefficient (log Kow or log D), a microfluidic method is developed to reduce time and coast of analyze. A double Y serpentine microfluidic chip is fabricated used soft lithography facilities. To generate a biphasic parallel flow, hydrophilic microchannels walls are generated by oxygen plasma treatment. Epifluorescence microscopy is used to measure the intensity of fluorescence molecules in microchannel. Using microfluidic parallel diluter this intensity show a strong linear correlation with molecule concentration in solution. The equilibrium between phases is reached in less than 5 s. To validate this microsystem, we have determined the log D of fluorescein natrium molecule. The obtained results compare well with previous measurements using traditional shake-flask or microfluidic drops flow methods, with a relative difference to the literature less than 3%. Rapid microfluidic partition coefficient determination is useful for studying liquid–liquid partition of organic pollutant.
    Full-text · Article · Oct 2014 · Fluid Phase Equilibria
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    ABSTRACT: This paper reports the use of a recent composite material, noted hereafter i-PDMS, made of carbonyl iron microparticles mixed in a PolyDiMethylSiloxane (PDMS) matrix, for magnetophoretic functions such as capture and separation of magnetic species. We demonstrated that this composite which combine the advantages of both components, can locally generate high gradients of magnetic field when placed between two permanent magnets. After evaluating the magnetic susceptibility of the material as a function of the doping ratio, we investigated the molding resolution offered by i-PDMS to obtain microstructures of various sizes and shapes. Then, we implemented 500 μm i-PDMS microstructures in a microfluidic channel and studied the influence of flow rate on the deviation and trapping of superparamagnetic beads flowing at the neighborhood of the composite material. We characterized the attraction of the magnetic composite by measuring the distance from the i-PDMS microstructure, at which the beads are either deviated or captured. Finally, we demonstrated the interest of i-PDMS to perform magnetophoretic functions in microsystems for biological applications by performing capture of magnetically labeled cells.
    Full-text · Article · Sep 2014 · Biomicrofluidics
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    ABSTRACT: Microfluidic technology has opened new possibilities for the crystallization of biological macromolecules during the past decade. Microfluidic systems offer numerous advantages over conventional crystal growth methods. They enable easy handling of nanovolumes of solutions, extreme miniaturization, and parallelization of crystallization assays, especially for high throughput screening applications. Our goal was to design a versatile, low cost, and easy-to-use crystallization chip based on counter-diffusion that is compatible with on-chip crystallographic characterization. The ChipX is a microfluidic chip made of cyclic olefin copolymer. It was used to grow crystals of biomolecules and perform complete X-ray diffraction analyses on synchrotron sources. Our results demonstrate that accurate crystallographic data can be collected at room temperature directly from ChipX microfluidic devices for both experimental SAD phasing and structure refinement.
    Full-text · Article · Jun 2013 · Crystal Growth & Design
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    ABSTRACT: This paper reports the use of a recent composite material, i-PDMS, made of carbonyl iron microparticles mixed in a PolyDiMethylSiloxane (PDMS) matrix, for magnetophoretic functions such as capture and separation. Indeed, we demonstrated that this composite can locally generate high magnetic field gradients when placed between two permanent magnets. We first investigated the molding resolution offered by i-PDMS to obtain microstructures of various sizes and shapes. Then, we implemented 500 }im i-PDMS microstructures in a microfluidic channel and studied the influence of flow rate on the trapping and deviation of paramagnetic beads flowing at the neighborhood of the composite material. Copyright © (2013) by the Chemical and Biological Microsystems Society All rights reserved.
    No preview · Article · Jan 2013
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    ABSTRACT: An alternative strategy to integrate electrochemical cells composed of two and three electrodes into total COC polymeric microsystems is presented. Results based on in-situ amperometric and potentiometric measurements are shown (C) 2012 Elsevier Ltd....Selection and/or peer-review under responsibility of the Symposium Cracoviense Sp. z.o.o.
    Full-text · Article · Dec 2012 · Procedia Engineering
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    ABSTRACT: This paper demonstrates the potential use of a new microfluidic device embedding thick electrodes for cell lysis and cell separation applications. The system consists of a microfluidic channel featuring conductive walls made of a polydimethylsiloxane (PDMS) matrix mixed with carbon nanoparticles. Cell lysis was performed electrically by applying square pulses across the channel width, which was monitored by fluorimetry. Lysed and unlysed cells showed different dielectrophoretic behavior under appropriate experimental conditions, which suggests that the developed device is suitable to perform both cell lysis and subsequent sorting of viable and dead cells.
    No preview · Article · Aug 2012 · Conference proceedings: ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference
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    ABSTRACT: We have developed a method for studying cellular adhesion by using a custom-designed microfluidic device with parallel non-connected tapered channels. The design enables investigation of cellular responses to a large range of shear stress (ratio of 25) with a single input flow-rate. For each shear stress, a large number of cells are analyzed (500-1500 cells), providing statistically relevant data within a single experiment. Besides adhesion strength measurements, the microsystem presented in this paper enables in-depth analysis of cell detachment kinetics by real-time videomicroscopy. It offers the possibility to analyze adhesion-associated processes, such as migration or cell shape change, within the same experiment. To show the versatility of our device, we examined quantitatively cell adhesion by analyzing kinetics, adhesive strength and migration behaviour or cell shape modifications of the unicellular model cell organism Dictyostelium discoideum at 21 °C and of the human breast cancer cell line MDA-MB-231 at 37 °C. For both cell types, we found that the threshold stresses, which are necessary to detach the cells, follow lognormal distributions, and that the detachment process follows first order kinetics. In addition, for particular conditions' cells are found to exhibit similar adhesion threshold stresses, but very different detachment kinetics, revealing the importance of dynamics analysis to fully describe cell adhesion. With its rapid implementation and potential for parallel sample processing, such microsystem offers a highly controllable platform for exploring cell adhesion characteristics in a large set of environmental conditions and cell types, and could have wide applications across cell biology, tissue engineering, and cell screening.
    Full-text · Article · Mar 2012 · Biomicrofluidics
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    ABSTRACT: This paper reports on the integration of thick carbon-polydimethylsiloxane (C-PDMS) electrodes in microfluidic systems for electrokinetic operations. The C-PDMS material, obtained by mixing carbon nanopowder and PDMS, preserves PDMS processing properties such as O2 plasma activation and soft-lithography patternability in thick or 3D electrodes. Conductivity in the order of 10 S m−1 was reached for a carbon concentration of 25 wt%. To evaluate the adhesion between PDMS and C-PDMS, we prepared bi-material strips and carried out a manual pull test. The cohesion and robustness of C-PDMS were also evaluated by applying a large range of electric field conditions from dc to ac (300 kHz). No damage to the electrodes or release of carbon was noticed. The use of such a material for electrokinetic manipulation was validated on polystyrene particles and cells. Here, we demonstrate that C-PDMS seems to be a valuable technological solution for electrokinetic in microfluidic and particularly for biological applications such as cell electrofusion, lysis and trapping, which are favored by uniform lateral electric fields across the microchannel section.
    No preview · Article · Aug 2011 · Journal of Micromechanics and Microengineering
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    A.Zebda · C. Innocent · L. Renaud · M. Cretin · F. Pichot · R. Ferrigno · S. Tingry

    Full-text · Chapter · Aug 2011
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    ABSTRACT: This paper presents an alternative approach to create low-cost and patternable carbon electrodes suitable for microfluidic devices. The fabrication and the electrochemical performances of electrodes made of Polydimethylsiloxane doped with commercially available carbon black (C-PDMS) are described. Conductivity and electrochemical measurements performed on various carbon to PDMS ratios showed that electrodes with suitable electrochemical properties were obtained with a ratio of 25 %.
    No preview · Article · Feb 2011 · Electroanalysis
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    ABSTRACT: This paper reports on the integration and evaluation of robust, thick Carbon-PDMS nanocomposite electrodes (C-PDMS), integrated in PDMS microfluidic systems to carry out electric field induced fusion of biological cells. Such material preserves PDMS processing properties and sustains a large range of electric field intensities and frequencies without any carbon release. Polystyrene particles, yeasts and HEK-293 cells were manipulated in devices consisting of C-PDMS walls bounded to a glass plate. Different collective behaviors were observed such as alignment in chains parallel to the electric field and in circulating bands tilted with respect to the electric field direction. An AC electrofusion protocol was also tested.
    Full-text · Article · Oct 2010
  • A. Zebda · L. Renaud · M. Cretin · C. Innocent · R. Ferrigno · S. Tingry
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    ABSTRACT: Simulation and experimental data are combined to optimize the electrode geometry of a membraneless laminar flow glucose biofuel cell. The design of the cell is based on a Y-shaped microfluidic channel that exploits the laminar flow of fluids. Glucose is oxidized by the glucose oxidase enzyme at the anode whereas oxygen is reduced by the laccase enzyme at the cathode. The energy output level of the microfluidic biofuel cell is limited by the reaction-depletion boundary layer at the electrode surfaces. To optimize the electrochemical characteristics of the device, our approach involves the reduction of both electrode length and spacing between anode and cathode in the microchannel. Computational fluids dynamics and electrochemical measurements show that the current density and power density are 3 times higher by decreasing the electrode length from 10 to 0.5 mm. The device delivers a power density of 0.33 mW cm−2 for a cell voltage of 0.22 V in buffered solutions at 300 μL min−1 flow rate. Moreover, the electrical performances are increased by generating up to 0.55 mW cm−2 for a cell voltage of 0.3 V when ohmic losses in the electrolyte are decreased by reducing the distance between cathode and anode in the microchannel.
    No preview · Article · Aug 2010 · Sensors and Actuators B Chemical
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    C Vézy · K Stephan · T Livache · A Roget · C Rivière · J.-P Rieu · R Ferrigno
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    ABSTRACT: The combination of microfluidic and electrochemistry for the generation of surface anisotropy of functionalized pyrrole is described. By using co-electropolymerization of pyrrole and pyrrole-biotin in a microfluidic environment, we have created a surface density gradient of pyrrole-biotin on gold electrodes as revealed by fluorescence. The combination of fast electropolymerization and microfluidic allows the transfer of a local volume anisotropy to a surface anisotropy with a tuneable slope of the gradient.
    Full-text · Article · Aug 2010 · Electrochemistry Communications
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    ABSTRACT: The objective of this work was to develop and characterize a poly(dimethylsiloxane) device with an integrated active cooling function able to carry out capillary electrophoresis separations. Polymer-based microdevices are indispensable to recent advances in biomedical analysis. In particular, they have been applied to many microfluidic platforms owing to their low cost, ease of fabrication, and versatility in preparing complex microstructures. However, when applied to capillary electrophoresis separations, polymer microfluidic structures present an inherent disadvantage compared to glass and Si structures; they have a lower thermal conductivity than glass and Si. Although miniaturized devices allow operation at high electric fields, they face separation efficiency limitations due to Joule heating. There is, therefore, a strong need of developing capillary electrophoresis microfluidic structures with active cooling in order to operate at a higher electric field and potentially increase separation efficiency in these microdevices. A poly(dimethylsiloxane)/glass hybrid microfluidic capillary electrophoresis system is presented, where Joule heating was minimized by using an integrated active cooling function. Two poly(dimethylsiloxane) slabs with embedded microfluidic structures were irreversibly sealed on both sides of a thin glass slide. The top poly(dimethylsiloxane) slab was used to carry out capillary electrophoresis separations, whereas the bottom poly(dimethylsiloxane) slab was employed to cool down the buffer solution used during the capillary electrophoresis separation. As demonstrated on current versus voltage plots and on capillary electrophoresis electropherograms, capillary electrophoresis separation was able to be operated at a higher electric field when using the cooling function. The cooling rate was adjustable by varying the flow rate and the initial temperature of the liquid flowing in the cooling microfluidic structure.
    No preview · Article · Jan 2010 · Experimental Heat Transfer
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    ABSTRACT: A microfluidic glucose/O2 biofuel cell, delivering electrical power, is developped based on both laminar flow and biological enzyme strategies. The device consists of a Y-shaped microfluidic channel in which fuel and oxidant streams flow laminarly in parallel at gold electrode surfaces without convective mixing. At the anode, the glucose is oxidized by the enzyme glucose oxidase whereas at the cathode, the oxygen is reduced by the enzyme laccase, in presence of specific redox mediators. Such cell design protects the anode from interfering parasite reaction of O2 at the anode and works with different streams of oxidant and fuel for optimal operation of the enzymes. The dependence of pH and nature of mediator on the current is evaluated in order to determine the optimum conditions to high current densities. The maximum power density delivered by the assembled biofuel cell reaches 70 mW·cm−2 at 0.28 V with 10 mM glucose at 23 °C. The microfluidic approach reported here demonstrates the feasibility of advanced microfabrication techniques to build an efficient microfluidic glucose/O2 biofuel cell device.
    No preview · Article · Sep 2009 · Sensor Letters
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    ABSTRACT: This paper describes two configurations that integrate electrochemical detection into microfluidic devices. The first configuration is a low-cost approach based on the use of PCB technology. This device was applied to electrochemiluminescence detection. The second configuration was used to carry out amperometric quantification of electroactive species using a serial dilution microfluidic system.
    No preview · Article · Sep 2009 · Conference proceedings: ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference
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    ABSTRACT: A microfluidic glucose/O2 biofuel cell, delivering electrical power, is developed based on both laminar flow and biological enzyme strategies. The device consists of a Y-shaped microfluidic channel in which fuel and oxidant streams flow laminarly in parallel at gold electrode surfaces without convective mixing. At the anode, the glucose is oxidized by the enzyme glucose oxidase whereas at the cathode, the oxygen is reduced by the enzyme laccase, in the presence of specific redox mediators. Such cell design protects the anode from interfering parasite reaction of O2 at the anode and works with different streams of oxidant and fuel for optimal operation of the enzymes. The dependence of the flow rate on the current is evaluated in order to determine the optimum flow that would provide little to no mixing while yielding high current densities. The maximum power density delivered by the assembled biofuel cell reaches 110 μW cm−2 at 0.3 V with 10 mM glucose at 23 °C. This research demonstrates the feasibility of advanced microfabrication techniques to build an efficient microfluidic glucose/O2 biofuel cell device.
    No preview · Article · Sep 2009 · Journal of Power Sources
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    ABSTRACT: Microfluidic devices were designed to perform on micromoles of biological macromolecules and viruses the search and the optimization of crystallization conditions by counter-diffusion, as well as the on-chip analysis of crystals by X-ray diffraction. Chips composed of microchannels were fabricated in poly-dimethylsiloxane (PDMS), poly-methyl-methacrylate (PMMA) and cyclo-olefin-copolymer (COC) by three distinct methods, namely replica casting, laser ablation and hot embossing. The geometry of the channels was chosen to ensure that crystallization occurs in a convection-free environment. The transparency of the materials is compatible with crystal growth monitoring by optical microscopy. The quality of the protein 3D structures derived from on-chip crystal analysis by X-ray diffraction using a synchrotron radiation was used to identify the most appropriate polymers. Altogether the results demonstrate that for a novel biomolecule, all steps from the initial search of crystallization conditions to X-ray diffraction data collection for 3D structure determination can be performed in a single chip.
    Full-text · Article · Jun 2009 · Lab on a Chip
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    ABSTRACT: A Y-shaped microfluidic channel is applied for the first time to the construction of a glucose/O2 biofuel cell, based on both laminar flow and biological enzyme strategies. During operation, the fuel and oxidant streams flow parallel at gold electrode surfaces without convective mixing. At the anode, the glucose oxidation is performed by the enzyme glucose oxidase whereas at the cathode, the oxygen is reduced by the enzyme laccase, in the presence of specific redox mediators. Such cell design protects the anode from an interfering parasite reaction of O2 at the anode and offers the advantage of using different streams of oxidant and fuel for optimal performance of the enzymes. Electrochemical characterizations of the device show the influence of the flow rate on the output potential and current density. The maximum power density delivered by the assembled biofuel cell reached 110 μW cm−2 at 0.3 V with 10 mM glucose at 23 °C. The microfluidic approach reported here demonstrates the feasibility of advanced microfabrication techniques to build an efficient microfluidic glucose/O2 biofuel cell device.
    No preview · Article · Mar 2009 · Electrochemistry Communications

Publication Stats

2k Citations
248.71 Total Impact Points

Institutions

  • 2008-2015
    • French National Centre for Scientific Research
      Lutetia Parisorum, Île-de-France, France
  • 2007-2014
    • University of Lyon
      • Institute for Nanotechnologies of Lyon
      Lyons, Rhône-Alpes, France
  • 2006-2014
    • Claude Bernard University Lyon 1
      • Institut des nanotechnologies de Lyon
      Villeurbanne, Rhône-Alpes, France
  • 2009-2011
    • Idaho National Laboratory
      Arco, Idaho, United States
  • 2002-2005
    • Harvard University
      • Department of Chemistry and Chemical Biology
      Cambridge, Massachusetts, United States
  • 1997-2002
    • École Polytechnique Fédérale de Lausanne
      • Laboratory of Physical and Analytical Electrochemistry
      Lausanne, Vaud, Switzerland