Laboratoire d’analyse et d’architecture des systèmes
C.MAGNANI, C.MONTIS, G.MANGIAPIA, A.F.MINGOTAUD, C.MINGOTAUD, C.ROUX, P.JOSEPH, D.BERTI, B.LONETTI
IMRCP, UNIFI, Forschungszentrum, MILE
Revue Scientifique : Colloids and Surfaces B: Biointerfaces, Vol.168, pp.18-28, Août 2018 , N° 18144
In recent years, there has been a growing interest in the formation of copolymers-lipids hybrid self-assemblies, which allow combining and improving the main features of pure lipids-based and copolymer-based systems known for their potential applications in the biomedical field. In this contribution we investigate the self-assembly behavior of dipalmitoylphosphatidylcholine (DPPC) mixed with poly(butadiene-b-ethyleneoxide) (PBD-PEO), both at the micro- and at the nano-length scale. Epifluorescence microscopy and Laser Scanning Confocal microscopy are employed to characterize the morphology of micron-sized hybrid vesicles. The presence of fluid-like inhomogeneities in their membrane has been evidenced in all the investigated range of compositions. Furthermore, a microfluidic set-up characterizes the mechanical properties of the prepared assemblies by measuring their deformation upon flow: hybrids with low lipid content behave like pure polymer vesicles, whereas objects mainly composed of lipids show more variability from one vesicle to the other. Finally, the structure of the nanosized assemblies is characterized through a combination of Dynamic Light Scattering, Small Angle Neutron Scattering and Transmission Electron Microscopy. A vesicles-to-wormlike transition has been evidenced due to the intimate mixing of DPPC and PBD-PEO at the nanoscale. Combining experimental results at the micron and at the nanoscale improves the fundamental understanding on the phase behavior of copolymer-lipid hybrid assemblies, which is a necessary prerequisite to tailor efficient copolymer-lipid hybrid devices.
O.LIOT, M.SOCOL, L.GARCIA, J.THIERY, A.FIGAROL, A.F.MINGOTAUD, P.JOSEPH
MILE, IPBS, IMRCP
Revue Scientifique : Journal of Physics: Condensed Matter, Vol.30, N°23, 23400p., Avril 2018 , N° 18148
This paper presents experimental results about transport of dilute suspensions of nano-objects in silicon-glass micrometric and sub-icrometric channels. Two kinds of objects are used: solid, rigid latex beads and spherical capsule-shaped, soft polymersomes. They are tracked using fluorescence microscopy. Three parameters are studied: confinement (ratio between particle diameter and channel depth), Brownian diffusion and particle nature. The aim of this work is to understand how these different parameters affect the transport of suspensions in narrow channels and to understand the different mechanisms at play. Concerning the solid beads we observe the appearance of two regimes, one where the experimental mean velocity is close to the expected one and another where this velocity is lower. This is directly related to a competition between confinement, Brownian diffusion and advection. These two regimes are shown to be linked to the homogeneity of particles distribution in the channel depth, which we experimentally deduce from velocity distributions. This inhomogeneity appears during the entrance process into the sub-micrometric channels, as for hydrodynamic separation or deterministic lateral displacement. Concerning the nature of the particles we observed a shift of transition towards the second regime likely due to the relationships between shear stress and polymersomes mechanical properties which could reduce the inhomogeneity imposed by the geometry of our device.
J.CACHEUX, M.BRUT, A.BANCAUD, P.CORDELIER, T.LEICHLE
MEMS, M3, MILE, CRCT-INSERM
Revue Scientifique : ACS Sensors, Vol.3, N°3, pp.606-611, Mars 2018 , N° 18096
In this work, we demonstrate that the analysis of spatially resolved nanofluidic-embedded biosensors permits the fast and direct discrimination of single-nucleotide difference (SND) within oligonucleotide sequences in a single step interaction. We design a sensor with a linear dimension much larger than the channel depth in order to ensure that the reaction over the whole sensor is limited by the convection rate. Thus, the targets are fully collected, inducing a nonuniform spatial hybridization profile. We also use the nanoscale height of the channel, which enables us to minimize the amount of labeled molecules flowing over the sensor and hence to reduce the fluorescence background, to carry out real-time hybridization detection by fluorescence microscopy. Taken together, these design rules allow us to show that the spatial hybridization profile depends on the duplex affinity, and we speculate that the on and off-rate constants can be inferred during target injection, which is not possible in local analysis where the dissociation step through rinsing must be conducted. We finally manage to discriminate a GT mismatch on a microRNA sequence by optimizing the interaction temperature and the probe design after a few minutes of interaction in a single step protocol. This work may be applied to any biosensing transduction scheme with spatial resolution, e.g., surface plasmon resonance imaging, integrated into nanofluidic channels for applications where high oligonucleotide sequence selectivity and short analysis times are required.
C.CHEN, P.JOSEPH, S.GEOFFROY, M.PRAT, P.DURU
IMFT, MILE, LMDC
Revue Scientifique : Journal of Fluid Mechanics, Vol.837, pp.703-728, Février 2018 , N° 18069
The objective of the present work is to study the drying of a quasi-2D model porous medium, thereafter called micromodel, initially filled with a pure liquid. The micromodel consists of cylinders measuring 50 µm in both height and diameter, radially arranged as a set of neighbouring spirals and sandwiched between two horizontal, flat plates. As drying proceeds, air invades the pore space and elongated liquid films trapped by capillary forces form along the spirals. These films consist of " chains " of liquid bridges connecting neighbouring cylinders. They provide an hydraulic connectivity between the central, bulk liquid cluster and the external rim of the cylinders pattern, where evaporation is taking place during a first constant evaporation-rate drying stage. The first goal of the present paper is to describe experimentally the phase distribution during drying, notably the liquid films evolution, which controls the evaporation kinetics (e.g. the depinning of the films from the external rim signs the end of the constant evaporation rate period). Then, a visco-capillary model for the drying process is presented. It is based on numerical simulations of a liquid film capillary shape and of the viscous flow within a film. The model shows a reasonably good agreement with the experimental data. Thus, the present study is a step towards direct modelling of the films effect on the drying of more complex porous media (e.g. packing of beads) and should be of interest for multiphase flow applications in porous media, involving transport within liquid films.
B.CHAMI, M.SOCOL, R.MALBEC, A.BANCAUD
Affiche/Poster : MICROFLUIDICS2017 - Ecole thématique ( ) 2017 du 25 juin au 30 juin 2017, Carcans Maubuisson (France), Février 2018, 1p. , N° 17515
H.RANCHON, J.CACHEUX, B.REIG, O.LIOT, P.TEERAPANICH, T.LEICHLE, P.JOSEPH, A.BANCAUD
MILE, MEMS, TEAM
Revue Scientifique : Langmuir, Vol.34, N°4, pp.1394-1399, Janvier 2018 , N° 18012
We investigate the pressure-driven transport of particles 200 or 300 nm in diameter in shallow microfluidic channels ∼1 μm in height with a bottom wall characterized by a high roughness amplitude of ∼100 nm. This study starts with the description of an assay to generate cracks in hydrophilic thin polymer films together with a structural characterization of these corrugations. Microfluidic chips of variable height are then assembled on top of these rough surfaces, and the transport of particles is assessed by measuring the velocity distribution function for a set of pressure drops. We specifically detect anomalous transport properties for rough surfaces. The maximum particle velocity at the centerline of the channel is comparable to that obtained with smooth surfaces, but the average particle velocity increases nonlinearly with the flow rate. We suggest that the change in the boundary condition at the rough wall is not sufficient to account for our data and that the occurrence of contacts between the particle and the surface transports the particle away from the wall and speeds up its motion. We finally draw perspectives for the separation by field-flow fractionation.
A.NAILLON, P.JOSEPH, M.PRAT
Revue Scientifique : Physical Review Letters, Vol.120, N°3, 034502p., Janvier 2018 , N° 18026
The stress generation on pore walls due to the growth of a sodium chloride crystal in a confined aqueous solution is studied from evaporation experiments in microfluidic channels in conjunction with numerical computations of crystal growth. The study indicates that the stress build-up on the pore walls as the result of the crystal growth is a highly transient process taking place over a very short period of time (in less than 1s in our experiments). The analysis makes clear that what matters for the stress generation is not the maximum supersaturation at the onset of the crystal growth but the supersaturation at the interface between the solution and the crystal when the latter is about to be confined between the pore walls. It is shown that the stress generation can be characterized with a simple stress diagram involving the pore aspect ratio and the Damkhöler number characterizing the competition between the precipitation reaction kinetics and the ion transport towards the growing crystal. This opens up the route for a better understanding of the damage of porous materials induced by salt crystallization, an important issue in earth sciences, reservoir engineering and civil engineering.
J.LACROIX, S.PELOFY, MC.BLATCHE, M.J.PILLAIRE, S.HUET, C.CHAPUIS, J.S.HOFFMAN, A.BANCAUD
MILE, I2C, TOUCAN, Rennes
Revue Scientifique : Small, Vol.12, N°43, pp.5963-5970, Décembre 2017, DOI 10.1002/smll.201503795 , N° 16314
DNA replication is essential to maintain genome integrity in S phase of the cell division cycle. Accumulation of stalled replication forks is a major source of genetic instability, and likely constitutes a key driver of tumorigenesis. The mechanisms of regulation of replication fork progression have therefore been extensively investigated, in particular with DNA combing, an optical mapping technique that allows the stretching of single molecules and the mapping of active region for DNA synthesis by fluorescence microscopy. DNA linearization in nanochannels has been successfully used to probe genomic information patterns along single chromosomes, and has been proposed to be a competitive alternative to DNA combing. Yet this conjecture remains to be confirmed experimentally. Here, two complementary techniques are established to detect the genomic distribution of tracks of newly synthesized DNA in human cells by optical mapping in nanochannels. Their respective advantages and limitations are compared, and applied them to detect deregulations of the replication program induced by the antitumor drug hydroxyurea. The developments here thus broaden the field of applications accessible to nanofluidic technologies, and can be used in the future as part for molecular diagnostics in the context of high throughput cancer drug screening.
O.LIOT, S.AKASH, P.BACCHIN, P.DURU, J.MORRIS, P.JOSEPH
MILE, LGC, IMFT, Levich Institute
Rapport LAAS N°17438, Décembre 2017, 7p.
Blockage of pores by particles is found in numerous industrial and natural processes, including filtration and oil extraction. We present experimental results of filtration through a linear array of ten channels with one dimension which is sub-micron. These silicon-glass nanoslits serve as model pores, through which a dilute dispersion of Brownian polystyrene spheres flows. The clog growth rate at fixed differential pressure is shown to systematically increase with the number of saturated (entirely clogged) pores, indicating that there is an interaction or " cross-talk " between the pores. This observation is interpreted using a model proposed here, based on the concept that the residual permeability allows a clog to act as a filter. A clogged pore is thus the source of a local increase of particle concentration adjacent to the pore, which then diffuses towards other pores. This phenomenon, evidenced and modelled here in one dimension, should be at play in two-dimensional membranes.
R.MALBEC, B.CHAMI, H.NGO, A.DIDELOT, F.GARLAN, S.GARRIGOU, V.TALY, L.AESCHBACH, E.TROFIMENKO, V.DION, A.BOUTONNET, F.GINOT, A.BANCAUD
MILE, Paris Descartes, Univ de Lausanne, Picometrics Technologies
Manifestation avec acte : International Electron Devices Meeting ( IEDM ) 2017 du 02 décembre au 06 décembre 2017, San Francisco (USA), Décembre 2017, 4p. , N° 17502
Circulating cell-free DNA (cfDNA) is a powerful cancer biomarker for establishing targeted therapies or monitoring patients' treatment. However, current cfDNA characterization is severely limited by its low concentration, requiring the extensive use of amplification techniques. Here we report that the µLAS technology allows us to quantitatively characterize the size distribution of purified cfDNA in a few minutes, even when its concentration is as low as 1 pg/µL. Moreover, we show that DNA profiles can be directly measured in blood plasma with a minimal conditioning process to speed up considerably speed up the cfDNA analytical chain.