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Microfluidics Mediated Production of Foams for Biomedical Applications
Laboratoire Microfluidique MEMS et nanostructures - Ilham Maimouni Cesare M. Cejas ,Janine Cossy ,Patrick Tabeling and Maria Russo
Micromachines - 11(1) 83 - doi.org/10.3390/mi11010083 - 2020
Within the last decade, there has been increasing interest in liquid and solid foams for several industrial uses. In the biomedical field, liquid foams can be used as delivery systems for dermatological treatments, for example, whereas solid foams are frequently used as scaffolds for tissue engineering and drug screening. Most of the foam functionalities are largely correlated to their mechanical properties and their structure, especially bubble/pore size, shape, and interconnectivity. However, the majority of conventional foaming fabrication techniques lack pore size control which can induce important inhomogeneities in the foams and subsequently decrease their performance. In this perspective, new advanced technologies have been introduced, such as microfluidics, which offers a highly controlled production, allowing for design customization of both liquid foams and solid foams obtained through liquid-templating. This short review explores both the fabrication and the characterization of foams, with a focus on solid polymer foams, and sheds the light on how microfluidics can overcome some existing limitations, playing a crucial role in their production for biomedical applications, especially as scaffolds in tissue engineering.
Stable liquid foams from a new polyfluorinated surfactant
Laboratoire Microfluidique MEMS et nanostructures - Maria Russo, Zacharias Amara, Johan Fenneteau, Pauline Chaumont-Olive, Ilham Maimouni, Patrick Tabeling and Janine Cossy
Chem. Comm. - 56 5807-5810 - doi.org/10.1039/D0CC02182B - 2020
Liquid foams exhibiting long-term stability are a key-challenge in material design. Based on this perspective, new pyridinium polyfluorinated surfactants were synthesized from simple building blocks enabling unusually stable liquid foams. While the batch-generated foams were used for qualitative foaming evaluation, microfluidics allowed a quantitative insight into the aging effects of monodisperse foams.
Microfluidic model of the platelet-generating organ: beyond bone marrow biomimetics
Laboratoire Microfluidique MEMS et nanostructures - Antoine Blin, Anne Le Goff, Aurélie Magniez, Sonia Poirault-Chassac, Bruno Teste, Géraldine Sicot, Kim Anh Nguyen, Feriel S. Hamdi, Mathilde Reyssat & Dominique Baruch
Nature - Scientific Reports 6 21700 - DOI: 10.1038/srep21700 - 2019
We present a new, rapid method for producing blood platelets in vitro from cultured megakaryocytes based on a microfluidic device. This device consists in a wide array of VWF-coated micropillars. Such pillars act as anchors on megakaryocytes, allowing them to remain trapped in the device and subjected to hydrodynamic shear. The combined effect of anchoring and shear induces the elongation of megakaryocytes and finally their rupture into platelets and proplatelets. This process was observed with megakaryocytes from different origins and found to be robust. This original bioreactor design allows to process megakaryocytes at high throughput (millions per hour). Since platelets are produced in such a large amount, their extensive biological characterisation is possible and shows that platelets produced in this bioreactor are functional.
Universal diagram for the kinetics of particle deposition in micro channels
Laboratoire Microfluidique MEMS et nanostructures - C.M. Cejas, F. Monti, M. Truchet, J.-P. Burnouf, P. Tabeling
Phys. Rev. E - 98 62606 - - 2019
Universal diagram for the kinetics of particle deposition in micro channels.
Foam as a self-assembling amorphous photonic band gap material
Laboratoire Microfluidique MEMS et nanostructures - View ORCID ProfileJoshua Ricouvier, Patrick Tabeling, and Pavel Yazhgur
Phys. Fluids - 116 (19) 9202-9207 - doi.org/10.1073/pnas.1820526116 - 2019
We show that slightly polydisperse disordered 2D foams can be used as a self-assembled template for isotropic photonic band gap (PBG) materials for transverse electric (TE) polarization. Calculations based on in-house experimental and simulated foam structures demonstrate that, at sufficient refractive index contrast, a dry foam organization with threefold nodes and long slender Plateau borders is especially advantageous to open a large PBG. A transition from dry to wet foam structure rapidly closes the PBG mainly by formation of bigger fourfold nodes, filling the PBG with defect modes. By tuning the foam area fraction, we find an optimal quantity of dielectric material, which maximizes the PBG in experimental systems. The obtained results have a potential to be extended to 3D foams to produce a next generation of self-assembled disordered PBG materials, enabling fabrication of cheap and scalable photonic devices.
Fibrin-Targeted Polymerized Shell Microbubbles as Potential Theranostic Agents for Surgical Adhesions
Laboratoire Microfluidique MEMS et nanostructures - Catherine A. Gormley, Benjamin J. Keenan, Jo Ann Buczek-Thomas,† Amanda C. S. N. Pessoa, Jiang Xu, Fabrice Monti, Patrick Tabeling, R. Glynn Holt, Jon O. Nagy, and Joyce Y. Wong
Langmuir - 35(31) 10061–10067 - doi: 10.1021/acs.langmuir.8b03692 - 2019
The development of new therapies for surgical adhesions has proven to be difficult as there is no consistently effective way to assess treatment efficacy in clinical trials without performing a second surgery, which can result in additional adhesions. We have developed lipid microbubble formulations that use a short peptide sequence, CREKA, to target fibrin, the molecule that forms nascent adhesions. These targeted polymerized shell microbubbles (PSMs) are designed to allow ultrasound imaging of early adhesions for diagnostic purposes and for evaluating the success of potential treatments in clinical trials while acting as a possible treatment. In this study, we show that CREKA-targeted microbubbles preferentially bind fibrin over fibrinogen and are stable for long periods of time (~48 h), that these bound microbubbles can be visualized by ultrasound, and that neither these lipid-based bubbles nor their diagnostic-ultrasound-induced vibrations damage mesothelial cells in vitro. Moreover, these bubbles show the potential to identify adhesionlike fibrin formations and may hold promise in blocking or breaking up fibrin formations in vivo.

Deposition kinetics of bi- and tridisperse colloidal suspensions in microchannels under the van der Waals regime
Laboratoire Microfluidique MEMS et nanostructures - Cesare M. Cejas, Lucrezia Maini, Fabrice Montia and Patrick Tabeling
Soft Matter - 15 7438-7447 - doi.org/10.1039/C9SM01098J - 2019
We investigate the kinetics of irreversible adsorption under the van der Waals regime, i.e. weakly Brownian polydisperse colloidal suspensions injected into shallow microchannels at high ionic strengths, where each suspension is represented by populations of particles with different particle sizes. We find that each population size of the particle in the suspension can be treated independently using an analytical solution based on the advection–diffusion equation and that the distribution of the adsorbed particles along the channel axis behaves according to a power law. The experimental measurements agree with Langevin simulations and are well accounted for by theory valid in the van der Waals regime. Operating in the van der Waals regime permits the present study to confirm the use of microfluidics as an effective in situ method to measure the Hamaker constant of particles under aqueous conditions.

Droplet generation at Hele-Shaw microfluidic T-junction
Laboratoire Microfluidique MEMS et nanostructures - I. Chakraborty, J. Ricouvier, P. Yazghur, P. Tabeling, A. Leshansky
Phys. Fluids - 31(2) 22010 - DOI: 10.1063/1.5086808 - 2019
Flow and fracture near the sol–gel transition of silica nanoparticle suspensions
Laboratoire Microfluidique MEMS et nanostructures - Gustavo E. Gimenes a and Elisabeth Bouchaudbc
Soft Matter - 14 8036-8043 - DOI:10.1039/C8SM01247D - 2018
We analyze the evolution of the mechanical response of a colloidal suspension to an external tensile stress, from fracture to flow, as a function of the distance from the sol–gel transition. We cease to observe cracks at a finite distance from the transition. In an intermediate region where the phenomenon is clearly hysteretic, we observe the coexistence of both flow and fracture. Even when cracks are observed, the material in fact flows over a distance that increases in the vicinity of the transition.
Micro fl uidic actuators based on temperature-responsive hydrogels
Laboratoire Microfluidique MEMS et nanostructures - Loïc D'Eramo, Benjamin Chollet, Marie Leman, Ekkachai Martwong, Mengxing Li, Hubert Geisler, Jules Dupire, Margaux Kerdraon, Clémence Vergne, Fabrice Monti, Yvette Tran and Patrick Tabeling
Microsystems & Nanoengineering - 4 17069 - doi:10.1038/micronano.2017.69 - 2018
The concept of using stimuli-responsive hydrogels to actuatefluids in microfluidic devices is particularly attractive, but limitations,in terms of spatial resolution, speed, reliability and integration, have hindered its development during the past two decades. By patterning and grafting poly(N-isopropylacrylamide) PNIPAM hydrogel films on plane substrates with a 2μm horizontal resolution and closing the system afterward, we have succeeded in unblocking bottlenecks that thermo-sensitive hydrogel technology has
been challenged with until now. In this paper, we demonstrate, for thefi rst time with this technology, devices with up to 7800
actuated micro-cages that sequester and release solutes, along with valves actuated individually with closing and opening switching
times of 0.6 ± 0.1 and 0.25± 0.15 s, respectively. Two applications of this technology are illustrated in the domain of single cell
handling and the nuclear acid amplification test (NAAT) for the Human Synaptojanin 1 gene, which is suspected to be involved in several neurodegenerative diseases such as Parkinson’s disease. The performance of the temperature-responsive hydrogels we
demonstrate here suggests that in association with their moderate costs, hydrogels may represent an alternative to the actuation orhandling techniques currently used in microfluidics, that are, pressure actuated polydimethylsiloxane (PDMS) valves and droplets

Influence of outer-layer finite-size effects on the dewetting dynamics of a thin polymer film embedded in an immiscible matrix
Laboratoire Microfluidique MEMS et nanostructures - M. S. Chebil, J. D. McGraw, T. Salez,C. Sollogoub and G. Miquelard-Garnier
Soft Matter - 14 6256-6263 - https://doi.org/10.1039/C8SM00592C - 2018
In capillary-driven fluid dynamics, simple departures from equilibrium offer the chance to quantitatively model the resulting relaxations. These dynamics in turn provide insight on both practical and fundamental aspects of thin-film hydrodynamics. In this work, we describe a model trilayer dewetting experiment elucidating the effect of solid, no-slip confining boundaries on the bursting of a liquid film in a viscous environment. This experiment was inspired by an industrial polymer processing technique, multilayer coextrusion, in which thousands of alternating layers are stacked atop one another. When pushed to the nanoscale limit, the individual layers are found to break up on time scales shorter than the processing time. To gain insight on this dynamic problem, we here directly observe the growth rate of holes in the middle layer of the trilayer films described above, wherein the distance between the inner film and solid boundary can be orders of magnitude larger than its thickness. Under otherwise identical experimental conditions, thinner films break up faster than thicker ones. This observation is found to agree with a scaling model that balances capillary driving power and viscous dissipation with a no-slip boundary condition at the solid substrate/viscous environment boundary. In particular, even for the thinnest middle-layers, no finite-size effect related to the middle film is needed to explain the data. The dynamics of hole growth is captured by a single master curve over four orders of magnitude in the dimensionless hole radius and time, and is found to agree well with predictions including analytical expressions for the dissipation.

Optimizing Hyperuniformity in Self-Assembled Bidisperse Emulsions
Laboratoire Microfluidique MEMS et nanostructures - Joshua Ricouvier, Romain Pierrat, Rémi Carminati, Patrick Tabeling, and Pavel Yazhgur
Phys. Rev. Lett. - 119 208001 - doi.org/10.1103/PhysRevLett. - 2017
We study long range density fluctuations (hyperuniformity) in two-dimensional jammed packings of bidisperse droplets. Taking advantage of microfluidics, we systematically span a large range of size and concentration ratios of the two droplet populations. We identify various defects increasing long range density fluctuations mainly due to organization of local particle environment. By choosing an appropriate bidispersity, we fabricate materials with a high level of hyperuniformity. Interesting transparency properties of these optimized materials are established based on numerical simulations.
Roughness of oxide glass subcritical fracture surfaces
Laboratoire Microfluidique MEMS et nanostructures - Gael Pallares , Frederic Lechenault, Matthieu George, Elisabeth Bouchaud, Cédric Ottina, Cindy L. Rountree, Matteo Ciccotti ,
Phys. Chem. - 101 (3) 1279-1288 - DOI : 10.1111/jace.15262 - 2017
An original setup combining a very stable loading stage, an atomic force microscope and an environmental chamber, allows to obtain very stable sub-critical fracture propagation in oxide glasses under controlled environment, and subsequently to finely characterize the nanometric roughness properties of the crack surfaces. The analysis of the surface roughness is conducted both in terms of the classical root mean square roughness to compare with the literature, and in terms of more physically adequate indicators related to the self-affine nature of the fracture surfaces. Due to the comparable nanometric scale of the surface roughness, the AFM tip size and the instrumental noise, a special care is devoted to the statistical evaluation of the metrologic properties. The 2 roughness amplitude of several oxide glasses was shown to decrease as a function of the stress intensity factor, to be quite insensitive to the relative humidity and to increase with the degree of heterogeneity of the glass. The results are discussed in terms of several modeling arguments concerning the coupling between crack propagation, material's heterogeneity, crack tip plastic deformation and water diffusion at the crack tip. A synthetic new model is presented combining the predictions of a model by Wiederhorn et al. [1] on the effect of the material's heterogeneity on the crack tip stresses with the self-affine nature of the fracture surfaces.
Paper-based RNA detection and multiplexed analysis for Ebola virus diagnostics
Laboratoire Microfluidique MEMS et nanostructures - Laura Magro, Béatrice Jacquelin, Camille Escadafal, Pierre Garneret, Aurélia Kwasiborski, Jean-Claude Manuguerra, Fabrice Monti, Anavaj Sakuntabhai, Jessica Vanhomwegen, Pierre Lafaye & Patrick Tabeling
Scientific Reports - 1347 (2017) - https://doi.org/10.1038/s41598-017-00758-9 - 2017
The most performing techniques enabling early diagnosis of infectious diseases rely on nucleic acid detection. Today, because of their high technicality and cost, nucleic acid amplification tests (NAAT) are of benefit only to a small fraction of developing countries population. By reducing costs, simplifying procedures and enabling multiplexing, paper microfluidics has the potential to considerably facilitate their accessibility. However, most of the studies performed in this area have not quit the lab. This letter brings NAAT on paper closer to the field, by using clinical samples and operating in a resource-limited setting. We first performed isothermal reverse transcription and Recombinase Polymerase Amplification (RT-RPA) of synthetic Ribonucleic Acid (RNA) of Ebola virus using paper microfluidics devices. We further applied this method in Guinea to detect the presence of Ebola virus in human sample RNA extracts, with minimal facilities (carry-on detection device and freeze-dried reagents on paper). RT-RPA results were available in few minutes and demonstrate a sensitivity of 90.0% compared to the gold-standard RT-PCR on a set of 43 patient samples. Furthermore, the realization of a nine-spot multilayered device achieving the parallel detection of three distinct RNA sequences opens a route toward the detection of multiple viral strains or pathogens.
In situ targeted activation of an anticancer agent using ultrasound-triggered release of composite droplets
Laboratoire Microfluidique MEMS et nanostructures - Bezagu M, Clarhaut J, Renoux B, Monti F, Tanter M, Tabeling P, Cossy J, Couture O, Papot S, Arseniyadis S.
Eur J Med Chem. - 42 44014 - doi: 10.1016/j.ejmech.2017.03.057 - 2017
The efficiency of a drug is usually highly dependent on the way it is administered or delivered. As such, targeted-therapy, which requires conceiving drug-delivery vehicles that will change their state from a relatively stable structure with a very slow leak-rate to an unstable structure with a fast release, clearly improves the pharmacokinetics, the absorption, the distribution, the metabolism and the therapeutic index of a given drug. In this context, we have developed a particularly effective double stimuli-responsive drug-delivery method allowing an ultrasound-induced release of a monomethylauristatin E-glucuronide prodrug and its subsequent activation by a β-glucuronidase. This led to an increase of cytotoxicity of about 80% on cancer cells.
Microfluidic step-emulsification in axisymmetric geometry
Laboratoire Microfluidique MEMS et nanostructures - Chakraborty, J. Ricouvier, P. Yazhgur, P. Tabelingb and A. M. Leshansky
Lab. Chip - 17 3609-3620 - DOI: 10.1039/C7LC00755H - 2017
Biphasic step-emulsification (Z. Li et al., Lab Chip, 2015, 15, 1023) is a promising microfluidic technique for high-throughput production of μm and sub-μm highly monodisperse droplets. The step-emulsifier consists of a shallow (Hele-Shaw) microchannel operating with two co-flowing immiscible liquids and an abrupt expansion (i.e., step) to a deep and wide reservoir. Under certain conditions the confined stream of the disperse phase, engulfed by the co-flowing continuous phase, breaks into small highly monodisperse droplets at the step. Theoretical investigation of the corresponding hydrodynamics is complicated due to the complex geometry of the planar device, calling for numerical approaches. However, direct numerical simulations of the three dimensional surface-tension-dominated biphasic flows in confined geometries are computationally expensive. In the present paper we study a model problem of axisymmetric step-emulsification. This setup consists of a stable core-annular biphasic flow in a cylindrical capillary tube connected co-axially to a reservoir tube of a larger diameter through a sudden expansion mimicking the edge of the planar step-emulsifier. We demonstrate that the axisymmetric setup exhibits similar regimes of droplet generation to the planar device. A detailed parametric study of the underlying hydrodynamics is feasible via inexpensive (two dimensional) simulations owing to the axial symmetry. The phase diagram quantifying the different regimes of droplet generation in terms of governing dimensionless parameters is presented. We show that in qualitative agreement with experiments in planar devices, the size of the droplets generated in the step-emulsification regime is independent of the capillary number and almost insensitive to the viscosity ratio. These findings confirm that the step-emulsification regime is solely controlled by surface tension. The numerical predictions are in excellent agreement with in-house experiments with the axisymmetric step-emulsifier.
Paper Microfluidics for Nucleic Acids Amplification Testing (NAAT) of Infectious Diseases
Laboratoire Microfluidique MEMS et nanostructures - Magro L1, Escadafal C, Garneret P, Jacquelin B, Kwasiborski A, Manuguerra JC, Monti F, Sakuntabhai A, Vanhomwegen J, Lafaye P, Tabeling P.
Lab. Chip - 17(14) 2347-2371 - doi: 10.1039/c7lc00013h. - 2017
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.
Microfluidic actuators based on temperature-responsive hydrogels
Laboratoire Microfluidique MEMS et nanostructures - Joshua Ricouvier, Romain Pierrat, Rémi Carminati, Patrick Tabeling, Pavel Yazhgur
Phys. Rev. Lett. - 119 (20) 208001 - DOI:10.1103/PhysRevLett.119.208001 - 2017
We study long range density fluctuations (hyperuniformity) in two-dimensional jammed packings of bidisperse droplets. Taking advantage of microfluidics, we systematically span a large range of size and concentration ratios of the two droplet populations. We identify various defects increasing long range density fluctuations mainly due to organization of local particle environment. By choosing an appropriate bidispersity, we fabricate materials with a high level of hyperuniformity. Interesting transparency properties of these optimized materials are established based on numerical simulations.
Particle deposition kinetics of colloidal suspensions in microchannels at high ionic strength
Laboratoire Microfluidique MEMS et nanostructures - Cesare M. Cejas, Fabrice Monti, Marine Truchet, Jean-Pierre Burnouf, and Patrick Tabeling
Langmuir - 33 (26) 6471–6480 - DOI: 10.1021/acs.langmuir.7b01394 - 2017
Despite its considerable practical importance, the deposition of real Brownian particles transported in a channel by a liquid, at small Reynolds numbers, has never been described at a comprehensive level. Here, by coupling microfluidic experiments, theory, and numerics, we succeed in unravelling the problem for the case of straight channels at high salinity. We discover a broad regime of deposition (the van der Waals regime) in which particle–wall van der Waals interactions govern the deposition mechanism. We determine the range of existence of the regime, for which we calculate the concentration profiles, retention profiles, and deposition kinetics analytically. The retention profiles decay as the inverse of the square root of the distance from the entry, and the deposition kinetics are given by the expression , where S is a dimensionless deposition function, A is the Hamaker constant, and ξL is a dimensionless parameter characterizing fluid flow properties. These findings are well supported by numerics. Experimentally, we find that the retention profiles behave as x–0.5±0.1 (where x is the distance from the channel entry) over three decades in scale, as predicted theoretically. By varying the flow conditions (speed, geometry, surface properties, and concentration) so as to cover four decades in ξL and taking the Hamaker constant as a free parameter, we accurately confirm the theoretical expression for the deposition kinetics. Operating in the van der Waals regime enables control of the deposition rates via surface chemistry. From a surface science perspective, working in the van der Waals regime enables us to measure the Hamaker constants of thousands of particles in a few minutes, a task that would take a much longer time to perform with standard AFM.
In situ targeted activation of an anticancer agent using ultrasound-triggered release of composite droplets
Laboratoire Microfluidique MEMS et nanostructures - Bezagu M, Clarhaut J, Renoux B, Monti F, Tanter M, Tabeling P6, Cossy J, Couture O, Papot S, Arseniyadis S
- 142 44014 - DOI: 10.1016/j.ejmech.2017.03.057 - 2017
The efficiency of a drug is usually highly dependent on the way it is administered or delivered. As such, targeted-therapy, which requires conceiving drug-delivery vehicles that will change their state from a relatively stable structure with a very slow leak-rate to an unstable structure with a fast release, clearly improves the pharmacokinetics, the absorption, the distribution, the metabolism and the therapeutic index of a given drug. In this context, we have developed a particularly effective double stimuli-responsive drug-delivery method allowing an ultrasound-induced release of a monomethylauristatin E-glucuronide prodrug and its subsequent activation by a β-glucuronidase. This led to an increase of cytotoxicity of about 80% on cancer cells.

42 publications.