The goal of this work is to calculate contact angles as a function of the molecular characteristics of the solid and the liquid. We use Kirkwood-Buff's mechanical route and decompose the normal and transverse components of the pressure tensor into solid and liquid regions. This decomposition leads to the emergence of a new force - the repulsion induced by the liquid displaced by the solid -. We found a neutral state where liquid/wall and displaced-liquid/liquid attractions are balanced. By expanding around this state, we could calculate the density profile within the hard-core van der Waals model at low isothermal compressibility, and establish a relation between the equilibrium contact angle and the microscopic properties of the liquid and solid. This work leads to reformulate Young's equation in a novel manner and sheds new light on the physics of wetting. The density profiles and contact angles obtained theoretically are supported by molecular dynamics simulations using the Lennard-Jones potential.

Dried blood spot (DBS) has risen in popularity due to the ease of sampling, storing, shipping and more. Despite those advantages, recovery of the dried blood in solution for analysis is still a bottleneck as it is manual, time-consuming and leads to high dilutions. To overcome those issues, we have developed a microfluidic chip allowing reversible opening, holding hermetically DBS and forcing the elution buffer through the thickness of DBS. The new technique, validated with clinical samples, is automated, fast, robust, precise, compatible with in-line analysis and leads to a highly concentrated extraction. Moreover, by using model experiments with fluorescein solutions, we show that the elution process is governed by an advection-diffusion coupling commonly known as Taylor dispersion. This new technique could open the way to a new generation of analytical devices to quantify analytes in DBS samples for a wide range of applications.

Abstract The book includes six chapters: - Chap 1 is an introduction, including the history of microfluidics, the present situation, the market and an attempt to envision the future. - Chap 2 concerns the physics of miniaturization, in natural and microfluidic systems. A description of basic physical laws, starting with intermolecular forces, including Van der Waals and electrostatic forces is given. The three main domains of fluidics at small scales (sub nanofluidic, nanofluidics, microfluidics and millifluidics) are discussed. - Chap 3 concerns the hydrodynamics of small systems, without free interface. The foundations of the governing equations are discussed. Then the notion of slippage at walls are presented for the cases of liquids and gases. Sections are devoted to the notions of hydrodynamic resistances and capaticances. Finally, inertial microfluidics, i.e. microfluidics or millifluidics at moderate Reynolds numbers, is presented. - Chap 4 concerns the hydrodynamics of microfluidics, in the presence of free interfaces. Bbubbles an droplets in microchannels. Basics of interfaces are shown, surface tension Laplace law, wetting. Surfactants are presented and various laws are discussed - Chap 5 concerns electrokinetic phenomena. Electrokinetic equations are given, leading to Debye layer, elecroosmosis, sedimentation potential, electrophoresis, along with the various methods of separation used in the field. - Chap 6 offers an introduction to microfabrication techniques. Photolithography is presented. Techniques dedicated to hard materials. Direct writing and 3D printing are shown. Soft lithography, and in particular those using PDMS (PolyDimethylSiloxane) is presented, with applications to valving, pumping, along with recent technological approaches.

As the COVID-19 pandemic winds down, it leaves behind the serious concern that future, even more disruptive pandemics may eventually surface. One of the crucial steps in handling the SARS-CoV-2 pandemic was being able to detect the presence of the virus in an accurate and timely manner, to then develop policies counteracting the spread. Nevertheless, as the pandemic evolved, new variants with potentially dangerous mutations appeared. Faced by these developments, it becomes clear that there is a need for fast and reliable techniques to create highly specific molecular tests, able to uniquely identify VOCs. Using an automated pipeline built around evolutionary algorithms, we designed primer sets for SARS-CoV-2 (main lineage) and for VOC, B.1.1.7 (Alpha) and B.1.1.529 (Omicron). Starting from sequences openly available in the GISAID repository, our pipeline was able to deliver the primer sets for the main lineage and each variant in a matter of hours. Preliminary in-silico validation showed that the sequences in the primer sets featured high accuracy. A pilot test in a laboratory setting confirmed the results: the developed primers were favorably compared against existing commercial versions for the main lineage, and the specific versions for the VOCs B.1.1.7 and B.1.1.529 were clinically tested successfully.

We succeeded in freeze-drying monodisperse microbubbles without degrading their performance, that is, their monodispersity in size and echogenicity. We used microfluidic technology to generate cryoprotected highly monodisperse microbubbles (coefficient of variation [CV] <5%). By using a novel retrieval technique, we were able to freeze-dry the microbubbles and resuspend them without degradation, that is, keeping their size distribution narrow (CV <6%). Acoustic characterization performed in two geometries (a centimetric cell and a millichannel) revealed that the resuspended bubbles conserved the sharpness of the backscattered resonance peak, leading to CVs ranging between 5% and 10%, depending on the geometry. As currently observed with monodisperse bubbles, the peak amplitudes are one order of magnitude higher than those of commercial ultrasound contrast agents. Our work thus solves the question of storage and transportation of highly monodisperse bubbles. This work might open pathways toward novel clinical non-invasive measurements, such as local pressure, impossible to carry out with the existing commercial ultrasound contrast agents.

Lipid nanoparticles (LNPs) for RNA and DNA delivery have attracted considerable attention for their ability to treat a broad range of diseases and to vectorize mRNA for COVID vaccines. LNPs are produced by mixing biomolecules and lipids, which self-assemble to form the desired structure. In this domain, microfluidics shows clear advantages: high mixing quality, low-stress conditions, and fast preparation. Studies of LNPs produced in micromixers have revealed, in certain ranges of flow rates, a degradation in performance in terms of size, monodispersity and encapsulation efficiency. In this study, we focus on the ring micromixer, which is well adapted to high throughput. We reveal three regimes, side-by-side, transitional and highly mixed, that control the mixing performance of the device. Furthermore, using cryo-TEM and biochemical analysis, we show that the mixing performances are strongly correlated to the characteristics of the LNPs we produce. We emphasize the importance of the flow-rate ratio and propose a physical criterion based on the onset of temporal instabilities for producing LNPs with optimal characteristics in terms of geometry, monodispersity and encapsulation yield. These criteria are generally applicable.

Coalescence is the most widely demonstrated mechanism for destabilizing emulsion droplets in microfluidic chambers. However, we find that depending on the channel wall surface functionalization, surface zeta potential, type of surfactant, characteristics of the oil as a dispersed phase, or even the presence of externally-induced stress, other different destabilization mechanisms can occur in subtle ways. In general, we observe four regimes leading to destabilization of concentrated emulsions: (i) coalescence, (ii) emulsion bursts, (iii) a combination of the two first mechanisms, attributed to the simultaneous occurrence of coalescence and emulsion bursts; and (iv) compaction of the droplet network that eventually destabilizes to fracture-like behavior. We correlate various physico-chemical properties (zeta potential, contact angle, interfacial tension) to understand their respective influence on the destabilization mechanisms. This work provides insights into possible ways to control or inflict emulsion droplet destabilization for different applications.

Aluminium salts such as aluminium chlorohydrate (ACH) are the active ingredients of antiperspirant products. Their mechanism of action involves a temporary and superficial plugging of eccrine sweat pores at the skin surface. We developed a microfluidic system that allows the real time observation of the interactions between sweat and ACH in conditions mimicking physiological sweat flow and pore dimensions. Using artificial sweat containing bovine serum albumin as a model protein, we performed experiments under flowing conditions to demonstrate that pore clogging results from the aggregation of proteins by aluminium polycations at specific location in the sweat pore. Combining microfluidic experiments, confocal microscopy and numerical models helps to better understand the physical chemistry and mechanisms involved in pore plugging. The results show that plugging starts from the walls of sweat pores before expanding into the centre of the channel. The simulations aid in explaining the influence of ACH concentration as well as the impact of flow conditions on the localization of the plug. Altogether, these results outline the potential of both microfluidic confocal observations and numerical simulations at the single sweat pore level to understand why aluminium polycations are so efficient for sweat channel plugging.

Are aluminium ions unavoidable in antiperspirants? To answer this question, we present confocal microscopy images of dendritic plugs appearing in sweat flowing across a microfluidic channel in the presence of aluminium salts. By comparing with numerical simulations, we identify the mechanisms forming this structured protein gel inside the pore.

To respond to the urgent need for COVID-19 testing, countries perform nucleic acid amplification tests (NAAT) for the detection of SARS-CoV-2 in centralized laboratories. Real-time RT-PCR (Reverse transcription-Polymerase Chain Reaction), used to amplify and detect the viral RNA., is considered, as the current gold standard for diagnostics. It is an efficient process, but the complex engineering required for automated RNA extraction and temperature cycling makes it incompatible for use in point of care settings [1]. In the present work, by harnessing progress made in the past two decades in isothermal amplification and paper microfluidics, we created a portable test, in which SARS-CoV-2 RNA is extracted, amplified isothermally by RT-LAMP (Loop-mediated Isothermal Amplification), and detected using intercalating dyes or fluorescent probes. Depending on the viral load in the tested samples, the detection takes between twenty minutes and one hour. Using a set of 16 pools of naso-pharyngal swab eluates, we estimated a limit of detection comparable to real-time RT-PCR (i.e. 1 genome copies per microliter of clinical sample) and no cross-reaction with eight major respiratory viruses currently circulating in Europe. We designed and fabricated an easy-to-use portable device called "COVIDISC" to carry out the test at the point of care. The low cost of the materials along with the absence of complex equipment will expedite the widespread dissemination of this device. What is proposed here is a new efficient tool to help managing the pandemics.

Abstract In order to respond to the urgent request of massive testing, developed countries perform nucleic acid amplification tests (NAAT) of SARS-CoV-2 in centralized laboratories. Real-time RT - PCR (Reverse transcription - Polymerase Chain Reaction) is used to amplify the viral RNA and enable its detection. Although PCR is 37 years old, it is still considered, without dispute, as the gold standard. PCR is an efficient process, but the complex engineering required for automated RNA extraction and temperature cycling makes it incompatible for use in point of care settings. In the present work, by harnessing progress made in the past two decades in DNA amplification, microfluidics and membrane technologies, we succeeded to create a portable test, in which SARS-CoV-2 RNA is extracted, amplified isothermally by RT - LAMP (Loop-mediated Isothermal Amplification), and detected using intercalating dyes or highly fluorescent probes. Depending on the viral load, the detection takes between twenty minutes and one hour. Using pools of naso-pharyngal clinical samples, we estimated a sensitivity comparable to RT-qPCR (up to a Cycle threshold of 39, equivalent to <0.1 TCID50 per mL) and a 100% specificity, for other human coronaviruses and eight respiratory viruses currently circulating in Europe. We designed and fabricated an easy-to-use portable device called “COVIDISC” to carry out the test at the point of care. The low cost of the materials along with the absence of complex equipment paves the way towards a large dissemination of this device. The perspective of a reliable SARS-CoV-2 point of care detection, highly performing, that would deliver on-site results in less than one hour, with a self-testing potential, opens up a new efficient approach to manage the pandemics.

Solid foams with micrometric pores are used in different fields (filtering, 3D cell culture, etc.), but today, controlling their foam geometry at the pore level, their internal structure, and the monodispersity, along with their mechanical properties, is still a challenge. Existing attempts to create such foams suffer either from slow speed or size limitations (above 80 μm). In this work, by using a temperature-regulated microfluidic process, 3D solid foams with highly monodisperse open pores (PDI lower than 5%), with sizes ranging from 5 to 400 μm and stiffnesses spanning 2 orders of magnitude, are created for the first time. These features open the way for exciting applications, in cell culture, filtering, optics, etc. Here, the focus is set on photonics. Numerically, these foams are shown to open a 3D complete photonic bandgap, with a critical index of 2.80, thus compatible with the use of rutile TiO2. In the field of photonics, such structures represent the first physically realizable self-assembled FCC (face-centered cubic) structure that possesses this functionality.

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.

Surface interactions are an interplay of van der Waals adhesion forces with electrostatic charges. In colloidal deposition, at low ionic strengths, the Debye layer is sufficiently large to prevent particles from approaching the surface. It is only with the addition of higher salt concentrations, typically above 0.1 M, that surface charges are screened for interactions to take place via van der Waals-adhesion forces. This is true for repulsive charges, when both surfaces have similar charges and signs of the zeta potential are the same. However, with attractive charges, where zeta potential signs are opposite, the result is also opposite. By combining microfluidic experiments, theory, and numerical simulations, results show that when charges are attractive, particle deposition instead increases at low ionic strengths (at greater Debye lengths), at rates controlled by van der Waals forces but assisted by electrostatic forces. We propose a mechanism where particles approach the wall, mobilized by electrostatic attraction, up to a distance where van der Waals forces come into play, collecting the particles at the wall, which electrostatic forces alone are unable to achieve, owing to hindered diffusion. The present work thus allows us to understand the different mechanisms that govern deposition in the case where surface charges are opposite.

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.

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.

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.

To-date, despite remarkable applications in optoelectronics and tremendous amount of theoretical, computational and experimental efforts, there is no technological pathway enabling the fabrication of 3D photonic band gaps in the visible range. The resolution of advanced 3D printing technology does not allow to fabricate such materials and the current silica-based nanofabrication approaches do not permit the structuring of the desired optical material. Materials based on colloidal self-assembly of polymer spheres open 3D complete band gaps in the infrared range, but, owing to their critical index, not in the visible range. More complex systems, based on oriented tetrahedrons, are still prospected. Here we show, numerically, that FCC foams (Kepler structure) open a 3D complete band gap with a critical index of 2.80, thus compatible with the use of rutile TiO2. We produce monodisperse solid Kepler foams including thousands of pores, down to 10 um, and present a technological pathway, based on standard technologies, enabling the downsizing of such foams down to 400 nm, a size enabling the opening of a complete band gap centered at 500 nm.

We proposed the combined numerical and experimental study of the dynamics of droplets generation at shallow microfluidic T-junction, where the flow is strongly confined in the vertical direction. The numerical simulation is performed by employing quasi-2D Hele-Shaw approximation with an interface capturing procedure based on coupled Level-Set and Volume-of-Fluid methods. We investigate the effect of the capillary number, Ca, the channel geometry (cross section aspect ratio, χ), and the flow rate (disperse-to-continuous phases) ratio, Γ, on the dynamics of the droplet breakup. Depending on Ca, three distinct flow regimes are identified: squeezing, tearing and jetting. In the squeezing regime at low Ca, the size of the generated droplets depends on χ and Γ, while it is almost insensitive to Ca in agreement to previous studies. In the tearing regime at moderate Ca, the droplet size decreases as ∼Ca−1/3, while it is only a weak function of χ and Γ. Finally, in the jetting regime, the steady co-flow of both phases takes place at high enough Ca. The numerical predictions based on the Hele-Shaw flow approximation are in excellent agreement with our in-house experimental results, demonstrating that the proposed approach can be effectively used for computationally inexpensive and adequately accurate modeling of biphasic flows in shallow microfluidic devices.