Microbubbles are widely used for biomedical applications, ranging from imagery to therapy. In these applications, microbubbles can be functionalized to allow targeted drug delivery or imaging of the human body. However, functionalization of the microbubbles is quite difficult, due to the unstable nature of the gas/liquid interface. In this paper, we describe a simple protocol for rapid functionalization of microbubbles and show how to use them inside a microfluidic chip to develop a novel type of biosensor. The microbubbles are functionalized with biochemical ligand directly at their generation inside the microfluidic chip using a DSPE-PEG-Biotin phospholipid. The microbubbles are then organized inside a chamber before injecting the fluid with the bioanalyte of interest through the static bubbles network. In this proof-of-concept demonstration, we use streptavidin as the bioanalyte of interest. Both functionalization and capture are assessed using fluorescent microscopy thanks to fluorescent labeled chemicals. The main advantages of the proposed technique compared to classical ligand based biosensor using solid surface is its ability to rapidly regenerate the functionalized surface, with the complete functionalization/capture/measurement cycle taking less than 10 min.
Objective Primary hemostasis involves in-flow interactions between platelets and sub-endothelial matrix at the wall of the damaged vessel. Assessing primary hemostasis defects would benefit from evaluation of the whole sequence of processes involved in platelet plug formation. We propose a novel label-free approach based on characterization of shear-dependent kinetics to evaluate the early stages of primary hemostasis. We developed a quartz crystal microbalance (QCM) biosensor to measure the amount of platelet deposited over time. With experiments and numerical simulations, we investigated the relevance of this approach and its limitations.
Primary haemostasis is a complex dynamic process, which involves in-flow interactions between platelets and sub-endothelial matrix at the area of the damaged vessel wall. It results in a first haemostatic plug, which stops bleeding, before coagulation ensues and consolidates it. The diagnosis of primary haemostasis defect would benefit from evaluation of the whole sequence of mechanisms involved in platelet plug formation in flow. This work proposes a new approach that is based on characterization of the shear-dependent kinetics that enables the evaluation of the early stages of primary haemostasis. We used a label-free method with a quartz crystal microbalance (QCM) biosensor to measure the platelet deposits over time onto covalently immobilized type I fibrillar collagen. We defined three metrics: total frequency shift, lag time, and growth rate. The measurement was completed at four predefined shear rates prevailing in small vessels (500, 770, 1000 and 1500 s(-1)) during five minutes of perfusion with anticoagulated normal whole blood. The rate of the frequency shift over the first five minutes was strongly influenced by shear rate conditions, presenting a maximum around 770 s(-1), and varying by a factor larger than three in the studied shear rate range. To validate the biosensor signal, the total frequency shift was compared to results obtained by atomic force microscopy (AFM) on final platelet deposits. The results show that shear-dependent kinetic assays are promising as an advanced method for screening of primary haemostasis.
Shear bulk acoustic type of resonant biosensors, such as the quartz crystal microbalance (QCM), give access to label-free in-liquid analysis of surface interactions. The general understanding of the sensing principles was inherited from past developments in biofilms measurements and applied to cells while keeping the same basic assumptions. Thus, the biosensor readouts are still quite often described using 'mass' related terminology. This contribution aims to show that assessment of cell deposits with acoustic biosensors requires a deep understanding of the sensor transduction mechanism. More specifically, the cell deposits should be considered as a structured viscoelastic load and the sensor response depends on both material and topological parameters of the deposits. This shifts the paradigm of acoustic biosensor away from the classical mass loading perspective. As a proof of the concept, we recorded QCM frequency shifts caused by blood platelet deposits on a collagen surface under different rheological conditions and observed the final deposit shape with atomic force microscopy (AFM). The results vividly demonstrate that the frequency shift is highly impacted by the platelet topology on the bio-interface. We support our findings with numerical simulations of viscoelastic unstructured and structured loads in liquid. Both experimental and theoretical studies underline the complexity behind the frequency shift interpretation when acoustic biosensing is used with cell deposits.
The discovery of topological phases of matter, initially driven by theoretical advances in quantum condensed matter physics, has been recently extended to classical wave systems, reaching out to a wealth of novel potential applications in signal manipulation and energy concentration. Despite the fact that wave propagation in many realistic media (metals at optical frequencies, polymers at ultrasonic frequencies) is inherently dispersive, topological wave transport in photonic and phononic crystals has so far been limited to ideal situations and proof-of-concept experiments involving dispersionless media. Here, we report the first experimental demonstration of topological edge states in a classical water wave system supporting highly dispersive wave propagation, in the intermediate regime of gravity-capillary waves. We use a stochastic method to rigorously take into account the inherent dispersion and devise a water wave crystal insulator supporting valley-selective transport at topological domain walls. Our measurements, performed with a high-speed camera under stroboscopic illumination, unambiguously demonstrate the possibility of valley-locked transport of water waves.
We describe in this work an advanced microfluidic chip for the capture of bioanalyte on the surface of droplets arranged in a dense array. We show the procedure for generating, functionalizing, and arranging the droplets inside the device for capturing a specific bioanalyte. Then, we demonstrate the capacity of the array to capture analyte from a cross-flowing liquid, using a biotin/streptavidin model. The paper also proposes to use the droplets array, after integration with acoustic detection, as a regenerable detection interface for bioanalyte sensing. We model the arrangement of droplet in dense array and show that they present a larger effective capture surface and shorter capture distance than standard flat surface biosensor of the same footprint. As the droplets can be easily evacuated and replaced inside the device analysis chamber, the proposed biosensor would allow biointerface regeneration and chain measurement without dismounting the device.
The contribution focuses on the development of microresonant sensor solution integrated in microfluidic platform for the haemostasis assessment at realistic rheological flow conditions similar to the one in blood vessels. A multi-parameter sensor performs real time analysis of interactions between immobilized collagen and platelets. The detection and characterization of such interactions at controlled flow rates provide information to evaluate the dynamic of each step of primary haemostasis. The microresonant sensor concept was developed and is described in the contribution.
Resonant biosensors are known for their high accuracy and high level of miniaturization. However, their fabrication costs prevent them from being used as disposable sensors and their effective commercial success will depend on their ability to be reused repeatedly. Accordingly, all the parts of the sensor in contact with the fluid need to tolerate the regenerative process which uses different chemicals (H3PO4, H2SO4 based baths) without degrading the characteristics of the sensor. In this paper, we propose a fluidic interface that can meet these requirements, and control the liquid flow uniformity at the surface of the vibrating area. We study different inlet and outlet channel configurations, estimating their performance using numerical simulations based on finite element method (FEM). The interfaces were fabricated using wet chemical etching on Si, which has all the desirable characteristics for a reusable biosensor circuit. Using a glass cover, we could observe the circulation of liquid near the active surface, and by using micro-particle image velocimetry (μPIV) on large surface area we could verify experimentally the effectiveness of the different designs and compare with simulation results.
This work reports on the design, the modeling, the simulation, the integration strategy and the preliminary test results of a new variable capacitor using large variation of permittivity obtained by tuning the density of oil-in-water droplet produced with a microfluidic circuit.
The convergence of Micro Electro Mechanical Systems (MEMS) and optics was, at the end of the last century, a fertile ground for a new breed of technological and scientific achievements. The weightlessness of light has been identified very early as a key advantage for micro-actuator application, giving rise to optical free-space MEMS devices. In parallel to these developments, the past 20 years saw the emergence of a less pursued approach relying on guided optical wave, where, pushed by the similarities in fabrication process, researchers explored the possibilities offered by merging integrated optics and MEMS technology. The interest of using guided waves is well known (absence of diffraction, tight light confinement, small size, compatibility with fiber optics) but it was less clear how they could be harnessed with MEMS technology. Actually, it is possible to use MEMS actuators for modifying waveguide properties (length, direction, index of refraction) or for coupling light between waveguide, enabling many new devices for optical telecommunication, astronomy or sensing. With the recent expansion to nanophotonics and optomechanics, it seems that this field still holds a lot of promises.
Pillar-based phononic crystals exhibit some unique wave phenomena due to the interaction between surface acoustic modes of the substrate and local resonances supported by pillars. In this paper, we extend the investigations by taking into account the presence of a liquid medium. We particularly demonstrate that local resonances dramatically decrease the phase velocity of Scholte-Stoneley wave, which leads to a slow wave at the solid/fluid interface. Moreover, we show that increasing the height of pillars introduces a new set of branches of interface modes and drastically affects the acoustic energy localization. Indeed, while some modes display a highly confined pressure between pillars, others exponentially decay in the fluid or only propagate in the solid without disturbing the fluid pressure. These theoretical results, performed by finite element method, highlight a new acoustic wave confinement suitable in various applications such as acoustophoresis, lab on chip and microfluidics.
We generated silicone oil micro-droplet in deionized water with a microfluidic T-junction devices made on silicon-glass with different cross-sections (depth and width) of the continuous phase and the dispersed phase micro-channels. We experimentally show that the size of the droplet decreases when the width or the velocity of the dispersed phase micro-channel decreases but is almost insensitive to the channel depth. For describing the observed behaviour, we proposed a modified mechanism of droplet formation consisting of three stages, each with start and end precisely identified. Based on this mechanism, we developed an analytical model for obtaining the droplet diameter in dripping regime when there is partial wetting at the channel boundary. This model is in better agreement with the experiments than other analytical models from the literature, suggesting the effect of channel wetting is significant. We also discuss the use of the capillary number in models, and suggests that the velocity would be a better metrics for comparing different T-junction geometry. In the experiment, the generated droplet diameter is varied between 28 μm and 196 μm. Keywords: Analytical model, capillary number, dripping regime, droplet generation, microfluidics, oil-in-water, T-Junction.
We present a simple yet efficient technique to obtain membrane with precise thickness by the etching of silicon in anisotropic etchant. This technique uses a mechanical holder to protect the front side of the wafer and a light signal to monitor from a distance the thickness of a reference hole in the etched wafer. The original feature in our set-up is that we measure the absorption of the light in two different bands of wavelength. one where the silicon is highly absorbant and the other where it is not, to improve the robustness of the measurement. This principle allows for effectively compensating for the fluctuation in the light source intensity, and provide real-time information on the membrane thickness, removing the incertitude inherent in the usual timed etch. We present the application of this technique to the manufacturing of thick single-crystal stiffener used to prevent the warp of stacked thin films presenting a gradient of stress.
We present an experimental study of a new regime of monodisperse micro-droplet generation that we named the balloon regime. A dispersion of oil in water in a T-junction microfluidic system was studied. Several microfluidic devices having different cross-sections of the continuous and the dispersed phases micro-channels were tested. This new regime appears only for low- dispersed phase velocity. The micro-droplet size is mainly related to the geometry of the T-junction micro-channels especially its width and depth, and independent of the continuous and dispersed phases velocities. In our experiments, the velocities of the continuous and the dispersed phases \(\overline v_{\rm c}\) and \(\overline v_{\rm d}\) respectively, have been varied in a wide range: \(\overline v_{\rm c}\) from 0.5 to 500 mm/s, and \(\overline v_{\rm d}\) from 0.01 to 30 mm/s. We show that the continuous phase only controls the micro-droplet density, while the dispersed phase linearly changes the frequency of the micro-droplet generation. Another particularity of the present regime, which differentiates it from all other known regimes, is that the micro-droplet retains its circular shape throughout its formation at the T junction, and undergoes no deformation due to the drag forces. We propose a mechanism to explain the formation of micro-droplets in this new regime.
We present an experimental study of the effect of the dispersed phase velocity on the regime of droplet generation in a T-junction microfluidic configuration. Silicone oil with a large interfacial tension (100 mN/m) was dispersed in deionized water. In addition to the known regimes of droplet generation (dripping, squeezing and jetting regimes), we present a new regime of monodisperse droplet generation that we named balloon regime. This regime appears to be linked to the injection of the dispersed phase at lower velocity through a narrow channel. In our experiments, the velocities of the continuous and the dispersed phases vc and vd respectively, have been varied in a wide range: vc from 0.93 to 50 cm/s, and vd from 0.01 to 3 cm/s. In this new regime, the diameter of the micro-droplets generated is constant and is not related to the velocity of the continuous phase, which just acts as the carrier of the micro-droplet. A comparison between the balloon and the dripping regimes is presented. In the balloon regime and contrary to the dripping regime, the droplet formed keeps a circular shape throughout its formation at the T-junction, without any deformation due to drag forces. To explain the formation of the micro-droplets in the balloon regime, we propose a mechanism based on the stability of the micro-droplets shape.
Effect of substrate temperature on lanthanide oxide material Gd2O3 thin films deposited by e-beam evaporation has been reported in the present work. Optical properties and surface morphology of as deposited films have been measured using spectrophotometry and atomic force microscopy respectively. Optical constants such as refractive index, extinction coefficient, band gap and Urbach energy have been determined by analysis of experimentally recorded absorption, transmittance and reflection data in wavelength range 200-800nm. Optical band gap energy shows decreasing while Urbach energy shows increasing behavior with increasing temperature. Extinction coefficient and refractive index with varying wavelengths are also calculated. Surface topographies of all samples are studied by atomic force microscope (AFM) and root mean square (RMS) value of roughness is observed increasing with increasing substrate temperature.
We describe a novel type of MEMS optical switch based on moving waveguide which has merits inherited from both MEMS and integrated optics technologies. It provides an expandable 2 times 2 switching capability, a first in this category of switches. The switch is built by assembling independently optimized latching silicon actuator and soft polymer waveguides. The actuator is based on two new structures: a microhinge, dubbed the fork hinge, and a latching structure using a precompressed microspring. The mechanical switching speed was measured below 0.5 ms. The complex polymer waveguide structure was thoroughly characterized to obtain all the components of the optical loss. This analysis allowed us to estimate robustly the insertion loss of the assembled optical switch below 3 dB and to identify the possibilities to improve this figure.