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1. Reducing Unspecific Protein Adsorption in Microfluidic Papers Using Fiber-Attached Polymer Hydrogels.

Author

von Stockert AR, Luongo A, Langhans M, Brandstetter T, Rühe J, Meckel T, and Biesalski M

Subjects
Adsorption, Hydrogels, Paper, Microfluidics, Polymers
Abstract

Microfluidic paper combines pump-free water transport at low cost with a high degree of sustainability, as well as good availability of the paper-forming cellulosic material, thus making it an attractive candidate for point-of-care (POC) analytics and diagnostics. Although a number of interesting demonstrators for such paper devices have been reported to date, a number of challenges still exist, which limit a successful transfer into marketable applications. A strong limitation in this respect is the (unspecific) adsorption of protein analytes to the paper fibers during the lateral flow assay. This interaction may significantly reduce the amount of analyte that reaches the detection zone of the microfluidic paper-based analytical device (µPAD), thereby reducing its overall sensitivity. Here, we introduce a novel approach on reducing the nonspecific adsorption of proteins to lab-made paper sheets for the use in µPADs. To this, cotton linter fibers in lab-formed additive-free paper sheets are modified with a surrounding thin hydrogel layer generated from photo-crosslinked, benzophenone functionalized copolymers based on poly-(oligo-ethylene glycol methacrylate) (POEGMA) and poly-dimethyl acrylamide (PDMAA). This, as we show in tests similar to lateral flow assays, significantly reduces unspecific binding of model proteins. Furthermore, by evaporating the transport fluid during the microfluidic run at the end of the paper strip through local heating, model proteins can almost quantitatively be accumulated in that zone. The possibility of complete, almost quantitative protein transport in a µPAD opens up new opportunities to significantly improve the signal-to-noise (S/N) ratio of paper-based lateral flow assays.

Published
2021
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2. Folding a focalized acoustical vortex on a flat holographic transducer: Miniaturized selective acoustical tweezers

Author

Olivier Bou Matar, Michael Baudoin, Antoine Riaud, Jean Louis Thomas, J.-C. Gerbedoen, Nikolay Smagin, Institut d’Électronique, de Microélectronique et de Nanotechnologie - UMR 8520 (IEMN), Centrale Lille-Institut supérieur de l'électronique et du numérique (ISEN)-Université de Valenciennes et du Hainaut-Cambrésis (UVHC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF), Acoustique Impulsionnelle & Magnéto-Acoustique Non linéaire - Fluides, Interfaces Liquides & Micro-Systèmes - IEMN (AIMAN-FILMS - IEMN), Centrale Lille-Institut supérieur de l'électronique et du numérique (ISEN)-Université de Valenciennes et du Hainaut-Cambrésis (UVHC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF)-Centrale Lille-Institut supérieur de l'électronique et du numérique (ISEN)-Université de Valenciennes et du Hainaut-Cambrésis (UVHC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF), Puissance - IEMN (PUISSANCE - IEMN), Fudan University [Shanghai], State Key Laboratory of ASIC and System, School of Microelectronics, Fudan University, Transduction, Propagation et Imagerie Acoustique - IEMN (TPIA - IEMN), Institut d’Électronique, de Microélectronique et de Nanotechnologie - Département Opto-Acousto-Électronique - UMR 8520 (IEMN-DOAE), Centrale Lille-Institut supérieur de l'électronique et du numérique (ISEN)-Université de Valenciennes et du Hainaut-Cambrésis (UVHC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF)-Centrale Lille-Institut supérieur de l'électronique et du numérique (ISEN)-Université de Valenciennes et du Hainaut-Cambrésis (UVHC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF)-Institut d’Électronique, de Microélectronique et de Nanotechnologie - UMR 8520 (IEMN), Acoustique pour les nanosciences (INSP-E3), Institut des Nanosciences de Paris (INSP), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), AcknowledgmentsWe acknowledge the platform 'WaveSurf' from Université Polytechnique Hauts-de-France for performing the measurements with the laser interferometer. We also acknowledge A. Vlandas for critical reading of the manuscript and valuable advices that helped us improve its overall quality. Funding: This work was supported by SATT Nord. Author contributions: M.B., A.R., and J.-L.T. designed the research. M.B. and J.-C.G. built the setup and performed the experiments. M.B. and A.R. performed the numerical simulations. O.B.M., J.-C.G., and N.S. performed the field measurements with the interferometer. M.B., O.B.M., A.R., and J.-L.T. analyzed and interpreted the results. M.B., O.B.M., J.-C.G., A.R., and J.-L.T. wrote the paper. All authors approved the final version of the manuscript. Competing interests: J.-L.T., O.B.M., A.R., and M.B. are inventors on a patent application related to this work filed with the European Patent Office (application no. EP17198204.4, submitted 25 October 2017). All other authors declare that they have no competing interests. Data and materials availability: All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials. Additional data related to this paper may be requested from the authors., RENATECH, Baudoin, Michael, Médecine Personnalisée, Pharmacogénomique, Optimisation Thérapeutique (MEPPOT - U1147), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Acoustique Impulsionnelle & Magnéto-Acoustique Non linéaire - Fluides, Interfaces Liquides & Micro-Systèmes - IEMN (AIMAN-FILMS-IEMN), Centrale Lille-Institut supérieur de l'électronique et du numérique (ISEN)-Université de Valenciennes et du Hainaut-Cambrésis (UVHC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF)-Centrale Lille-Institut supérieur de l'électronique et du numérique (ISEN)-Université de Valenciennes et du Hainaut-Cambrésis (UVHC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF)-INSA Institut National des Sciences Appliquées Hauts-de-France (INSA Hauts-De-France)-Institut d’Électronique, de Microélectronique et de Nanotechnologie - UMR 8520 (IEMN), Centrale Lille-Institut supérieur de l'électronique et du numérique (ISEN)-Université de Valenciennes et du Hainaut-Cambrésis (UVHC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF)-Centrale Lille-Institut supérieur de l'électronique et du numérique (ISEN)-Université de Valenciennes et du Hainaut-Cambrésis (UVHC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF)-INSA Institut National des Sciences Appliquées Hauts-de-France (INSA Hauts-De-France), Institut d’Électronique, de Microélectronique et de Nanotechnologie (IEMN) - UMR 8520 ( IEMN ), Ecole Centrale de Lille-Institut supérieur de l'électronique et du nunérique (ISEN)-Université de Valenciennes et du Hainaut-Cambresis ( UVHC ) -Université de Lille-Centre National de la Recherche Scientifique ( CNRS ), Université Paris Sorbonne Cité, INSERM UMR-S1147, Institut des Nanosciences de Paris ( INSP ), and Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Centre National de la Recherche Scientifique ( CNRS )

Subjects
[PHYS.PHYS.PHYS-FLU-DYN]Physics [physics]/Physics [physics]/Fluid Dynamics [physics.flu-dyn], [PHYS.PHYS.PHYS-CLASS-PH]Physics [physics]/Physics [physics]/Classical Physics [physics.class-ph], Materials science, Acoustics, Microfluidics, Holography, FOS: Physical sciences, Physics - Classical Physics, Applied Physics (physics.app-ph), 02 engineering and technology, 01 natural sciences, law.invention, Engineering, [ PHYS.PHYS.PHYS-CLASS-PH ] Physics [physics]/Physics [physics]/Classical Physics [physics.class-ph], law, 0103 physical sciences, Tweezers, Miniaturization, Piezoelectric substrate, 010306 general physics, Research Articles, [ PHYS.MECA.ACOU ] Physics [physics]/Mechanics [physics]/Acoustics [physics.class-ph], Applied Physics, Multidisciplinary, Fluid Dynamics (physics.flu-dyn), SciAdv r-articles, Classical Physics (physics.class-ph), Physics - Applied Physics, Physics - Fluid Dynamics, [PHYS.PHYS.PHYS-FLU-DYN] Physics [physics]/Physics [physics]/Fluid Dynamics [physics.flu-dyn], 021001 nanoscience & nanotechnology, Vortex, [PHYS.MECA.ACOU]Physics [physics]/Mechanics [physics]/Acoustics [physics.class-ph], Folding (chemistry), Transducer, [ PHYS.PHYS.PHYS-FLU-DYN ] Physics [physics]/Physics [physics]/Fluid Dynamics [physics.flu-dyn], [PHYS.PHYS.PHYS-CLASS-PH] Physics [physics]/Physics [physics]/Classical Physics [physics.class-ph], [PHYS.MECA.ACOU] Physics [physics]/Mechanics [physics]/Acoustics [physics.class-ph], 0210 nano-technology, Research Article
Abstract

Selective manipulation of micrometric objects in a standard microscopy environment is possible with miniaturized acoustical tweezers., Acoustical tweezers based on focalized acoustical vortices hold the promise of precise contactless manipulation of millimeter down to submicrometer particles, microorganisms, and cells with unprecedented combined selectivity and trapping force. Yet, the widespread dissemination of this technology has been hindered by severe limitations of current systems in terms of performance and/or miniaturization and integrability. Here, we unleash the potential of focalized acoustical vortices by developing the first flat, compact, paired single electrode focalized acoustical tweezers. These tweezers rely on spiraling transducers obtained by folding a spherical acoustical vortex on a flat piezoelectric substrate. We demonstrate the ability of these tweezers to grab and displace micrometric objects in a standard microfluidic environment with unique selectivity. The simplicity of this system and its scalability to higher frequencies open tremendous perspectives in microbiology, microrobotics, and microscopy.

Published
2019

3. Developing a MEMS device with built-in microfluidics for biophysical single cell characterization

Author

Chann Lagadec, Dominique Collard, Hiroyuki Fujita, Manabu Ataka, Gregoire Perret, Momoko Kumemura, Yuki Takayama, Samuel Meignan, Mehmet C. Tarhan, Stanislav L. Karsten, Institut d’Électronique, de Microélectronique et de Nanotechnologie - UMR 8520 (IEMN), Centrale Lille-Institut supérieur de l'électronique et du numérique (ISEN)-Université de Valenciennes et du Hainaut-Cambrésis (UVHC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF), Physique-IEMN (PHYSIQUE-IEMN), Centrale Lille-Institut supérieur de l'électronique et du numérique (ISEN)-Université de Valenciennes et du Hainaut-Cambrésis (UVHC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF)-Centrale Lille-Institut supérieur de l'électronique et du numérique (ISEN)-Université de Valenciennes et du Hainaut-Cambrésis (UVHC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF), Laboratory for Integrated Micro Mechatronics Systems (LIMMS), The University of Tokyo (UTokyo)-Centre National de la Recherche Scientifique (CNRS), Kyushu Institute of Technology (Kyutech), The University of Tokyo (UTokyo), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Plasticité Cellulaire et Cancer - U908 (CPAC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Physique - IEMN (PHYSIQUE - IEMN), IEMN, Collection, and Acknowledgments:Authors would like to thank the VLSI Design and Education Center (VDEC, The Universityof Tokyo, Japan) for the mask production, IRCL (Institut pour la Recherche sur le Cancer de Lille, France) forhosting SMMiL-E facilities and V. Menon for critical reading of the paper. Y.T. thanks the University of Lille andthe SIRIC ONCO-Lille, and M.C.T. thanks Région Hauts-de-France for financial support.

Subjects
0301 basic medicine, Materials science, lcsh:Mechanical engineering and machinery, [SPI.NANO] Engineering Sciences [physics]/Micro and nanotechnologies/Microelectronics, Microfluidics, microfluidics, single cell analysis, 02 engineering and technology, Capacitive displacement sensor, Article, Displacement (vector), 03 medical and health sciences, [SPI]Engineering Sciences [physics], [SPI.MECA.BIOM] Engineering Sciences [physics]/Mechanics [physics.med-ph]/Biomechanics [physics.med-ph], lcsh:TJ1-1570, Electrical measurements, Electrical and Electronic Engineering, [SPI.NANO]Engineering Sciences [physics]/Micro and nanotechnologies/Microelectronics, ComputingMilieux_MISCELLANEOUS, Microelectromechanical systems, [SDV.IB] Life Sciences [q-bio]/Bioengineering, Microchannel, biophysical cell characterization, business.industry, MEMS design, Mechanical Engineering, [SPI.MECA.BIOM]Engineering Sciences [physics]/Mechanics [physics.med-ph]/Biomechanics [physics.med-ph], 021001 nanoscience & nanotechnology, Characterization (materials science), 030104 developmental biology, Control and Systems Engineering, Optoelectronics, [SDV.IB]Life Sciences [q-bio]/Bioengineering, 0210 nano-technology, business, Actuator, bioMEMS
Abstract

This study combines the high-throughput capabilities of microfluidics with the sensitive measurements of microelectromechanical systems (MEMS) technology to perform biophysical characterization of circulating cells for diagnostic purposes. The proposed device includes a built-in microchannel that is probed by two opposing tips performing compression and sensing separately. Mechanical displacement of the compressing tip (up to a maximum of 14 &micro, m) and the sensing tip (with a quality factor of 8.9) are provided by two separate comb-drive actuators, and sensing is performed with a capacitive displacement sensor. The device is designed and developed for simultaneous electrical and mechanical measurements. As the device is capable of exchanging the liquid inside the channel, different solutions were tested consecutively. The performance of the device was evaluated by introducing varying concentrations of glucose (from 0.55 mM (0.1%) to 55.5 mM (10%)) and NaCl (from 0.1 mM to 10 mM) solutions in the microchannel and by monitoring changes in the mechanical and electrical properties. Moreover, we demonstrated biological sample handling by capturing single cancer cells. These results show three important capabilities of the proposed device: mechanical measurements, electrical measurements, and biological sample handling. Combined in one device, these features allow for high-throughput multi-parameter characterization of single cells.

Published
2018

4. Paper microfluidics for nucleic acid amplification testing (NAAT) of infectious diseases

Author

Pierre Garneret, Patrick Tabeling, Beatrice Jacquelin, Fabrice Monti, Anavaj Sakuntabhai, Pierre Lafaye, Laura Magro, Aurélia Kwasiborski, Camille Escadafal, Jessica Vanhomwegen, Jean-Claude Manuguerra, Laboratoire Microfluidique, MEMS, Nanostructures (MMN), Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Cellule d'Intervention Biologique d'Urgence - Laboratory for Urgent Response to Biological Threats (CIBU), Institut Pasteur [Paris], HIV, Inflammation et persistance, Génétique fonctionnelle des Maladies infectieuses - Functional Genetics of Infectious Diseases, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Ingénierie des Anticorps (plate-forme) - Antibody Engineering (Platform), Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], P. T., J. C. M. and P. L. initiated the collaboration. L. M., P. G., B. J. and C. E. prepared the manuscript with the assistance of P. T. L. M., F. M. and P. T. brought expertise on paper microfluidics and technological developments. J. C. M., A. S., C. E., A. K., J. V. and P. L. helped on more biological points of view: isothermal amplifications and sample preparations., Institut Pasteur [Paris] (IP), HIV, Inflammation et persistance - HIV, Inflammation and Persistence, and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Paper, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, Microfluidics, Biomedical Engineering, Loop-mediated isothermal amplification, Bioengineering, Nanotechnology, 02 engineering and technology, Biology, 01 natural sciences, Biochemistry, Communicable Diseases, law.invention, Domain (software engineering), law, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Lab-On-A-Chip Devices, Nucleic Acid Amplification Tests, Humans, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, 010401 analytical chemistry, General Chemistry, Nucleic acid amplification technique, Equipment Design, Lab-on-a-chip, Microfluidic Analytical Techniques, 021001 nanoscience & nanotechnology, Data science, 0104 chemical sciences, 3. Good health, Molecular Diagnostic Techniques, Low and middle income countries, Nucleic acid, 0210 nano-technology, Nucleic Acid Amplification Techniques
Abstract

International audience; The diagnosis of infectious diseases is entering a new and interesting phase. Technologies based on paper microfluidics, coupled to developments in isothermal amplification of Nucleic Acids (NAs) raise opportunities for bringing the methods of molecular biology in the field, in a low setting environment. A lot of work has been performed in the domain over the last few years and the landscape of contributions is rich and diverse. Most often, the level of sample preparation differs, along with the sample nature, the amplification and detection methods, and the design of the device, among other features. In this review, we attempt to offer a structured description of the state of the art. The domain is not mature and there exist bottlenecks that hamper the realization of Nucleic Acid Amplification Tests (NAATs) complying with the constraints of the field in low and middle income countries. In this domain however, the pace of progress is impressively fast. This review is written for a broad Lab on a Chip audience.

Published
2017

5. Modeling carbon dioxide transport in PDMS-based microfluidic cell culture devices

Author

Antti-Juhana Mäki, Joose Kreutzer, Mikko Peltokangas, Pasi Kallio, S. Auvinen, Tampere University, Department of Automation Science and Engineering, Department of Materials Science, Research group: Paper Converting and Packaging, BioMediTech, and Integrated Technologies for Tissue Engineering Research (ITTE)

Subjects
Materials science, Computer simulation, Concentration Response, Applied Mathematics, General Chemical Engineering, Microfluidics, Nanotechnology, General Chemistry, 217 Medical engineering, Industrial and Manufacturing Engineering, Finite element method, chemistry.chemical_compound, Silicone, chemistry, Cell culture, Concentration gradient, Biological system, Carbon dioxide transport
Abstract

Maintaining a proper pH level is crucial for successful cell culturing. Mammalian cells are commonly cultured in incubators, where the cell culture medium is saturated with a mixture of air and 5% carbon dioxide (CO2). Therefore, to keep cell culture medium pH in an acceptable level outside these incubators, a suitable CO2 concentration must be dissolved in the medium. However, it can be very difficult to control and measure precisely local concentration levels. Furthermore, possible undesired concentration gradients generated during long-term cell culturing are almost impossible to detect. Therefore, we have developed a computational model to estimate CO2 transport in silicone-based microfluidic devices. An extensive set of experiments was used to validate the finite element model. The model parameters were obtained using suitable measurement set-ups and the model was validated using a fully functional cell cultivation device. The predictions obtained by the simulations show very good responses to experiments. It is shown in this paper how the model helps to understand the dynamics of CO2 transport in silicone-based cell culturing devices possessing different geometries, thus providing cost-effective means for studying different device designs under a variety of experimental conditions without the need of actual testing. Finally, based on the results from the computational model, an alternative strategy for feeding CO2 is proposed to accelerate the system performance such that a faster and more uniform CO2 concentration response is achieved in the area of interest. acceptedVersion

Published
2015