Walls Of Microfluidic Channel Research Articles

Direct electrification of silicon microfluidics for electric field applications

Microfluidic systems are widely used in fundamental research and industrial applications due to their unique behavior, enhanced control, and manipulation opportunities of liquids in constrained geometries. In micrometer-sized channels, electric fields are efficient mechanisms for manipulating liquids, leading to deflection, injection, poration or electrochemical modification of cells and droplets. While PDMS-based microfluidic devices are used due to their inexpensive fabrication, they are limited in terms of electrode integration. Using silicon as the channel material, microfabrication techniques can be used to create nearby electrodes. Despite the advantages that silicon provides, its opacity has prevented its usage in most important microfluidic applications that need optical access. To overcome this barrier, silicon-on-insulator technology in microfluidics is introduced to create optical viewports and channel-interfacing electrodes. More specifically, the microfluidic channel walls are directly electrified via selective, nanoscale etching to introduce insulation segments inside the silicon device layer, thereby achieving the most homogeneous electric field distributions and lowest operation voltages feasible across microfluidic channels. These ideal electrostatic conditions enable a drastic energy reduction, as effectively shown via picoinjection and fluorescence-activated droplet sorting applications at voltages below 6 and 15 V, respectively, facilitating low-voltage electric field applications in next-generation microfluidics.

Boost and Contraction of Flow by Herringbone Surface Design on the Microfluidic Channel Wall

AbstractThe handling of yield‐stress fluids typically involves a jammed‐to‐flow transition that is pivotal for many injection and transport technologies on different scales, such as additive manufacturing, injection molding, food rheology, and oil transport. For all of these applications, it is crucial to be able to tune the fluidization under constant load. The pressure‐driven flow of emulsions is reported within a microfluidic channel, one wall of which is patterned by a herringbone‐riblet roughness comprising a regular array of V‐shaped grooves. With respect to the pressure gradient, this pattern displays a convergent (divergent) orientation that provides a forward (backward) direction. At the tip of the herringbone pattern, the forward and backward flows are almost identical for a viscous Newtonian fluid and a diluted emulsion, whereas a surprising flow boost in the forward direction is observed as the emulsion approaches a jammed state. The flow boost is more effective at small herringbone angles and low pressure loads. 3D velocity profiles along the channel cross‐section unravel unexpected heterogeneous stress, band‐like distributed, with evidence of nonlocal correlations.

Margination of 2D Platelet Microparticles in Blood.

Margination describes the movement of particles toward the endothelial wall within blood vessels. While there have been several studies tracking the margination of spherical particles in blood, the behavior of anisotropic particle shapes is not well described. In this study 2D platelet particles which possess many attractive qualities for use as a drug delivery system, with their high surface area allowing for increased surface binding activity, were directly monitored and margination quantified. The margination propensity of 1 and 2 μm 2D platelet particles was contrasted to that of 2 μm spherical particles at apparent wall shear rates (WSRs) of 50, 100, and 200 s-1 by both directly tracking labeled particles using fluorescent microscopy as well as using small-angle X-ray scattering (SAXS). For fluorescence studies, margination was quantified using the margination parameter M, which describes the number of particles found closest to the walls of a microfluidic device, with an M-value of 0.2 indicating no margination. Increased margination was seen in 2D platelet particles when compared to spherical particles tested at all flow rates, with M-values of 0.39 and 0.31 seen for 1 and 2 μm 2D platelet particles, respectively, while 2 μm spherical particles had an M-value of 0.21. Similarly, margination was observed qualitatively using SAXS, with increased scattering seen for platelet particles near the microfluidic channel wall. For all particles, increased margination was seen at increasing shear rates.

Wrap-around sensors for electrical detection of particles in microfluidic channels

Microfluidic devices with integrated electrical sensors have been widely employed in the detection and characterization of particles suspended in liquids. Conventionally, electrical sensors in microfluidic devices are composed of electrodes all patterned on the same surface in a coplanar arrangement. While simplifying the fabrication of electrical sensors within microfluidic channels considerably, the use of coplanar electrodes leads to non-uniform electric fields within the channel and complicates scaling of electrical sensor networks by constraining the routing of different traces within the same plane. The alternative of integrating counter-facing parallel electrodes into microfluidic channels to alleviate those limitations requires a complex fabrication process. In this work, we present a robust and straightforward approach to creating 3D electrical sensors in microfluidic devices fabricated using soft lithography. By placing a blanket electrode on the microfluidic channel walls, our electrical sensor wraps around the flow channel to (i) provide higher sensitivity than their coplanar counterparts, (ii) extend the sensing volume beyond the vicinity of a surface and (iii) simplify the creation of electrical sensor networks with complex geometries by relaxing the routing constraints on traces. Practical implementation of 3D electrical sensors in microfluidic channels offers the potential to enhance the utility of electrical sensing without impacting the frugality of fluidic components in designing integrated microfluidic systems as quantitative platforms.

Microfluidic microcantilever as a sensitive platform to measure evaporation rate of picoliters of ethanol

Resonating microfluidic cantilevers are used for a broad range of biochemical sensing applications where a shift in the resonance frequency is used to detect minute changes in the cantilever mass. These multifunctional microfluidic microcantilevers open up opportunities for new ultrasensitive biochemical sensors wherein the target species in a carrier fluid bind to the inner functionalized walls of microfluidic channel, thereby changing the mass and hence the resonance frequency of the system for detection. In this paper, we develop computational models that predict the change in the resonance frequency as a function of change in mass for this hollow microcantilever system. We present computational models to simulate this process and validate the models using experimental data based on the evaporation of ethenol, a commonly available volatile compound. Specifically, a computational approach is presented in two variants; a one-dimensional structural beam element model, and a three-dimensional finite element model. The numerically predicted increase in the resonance frequencies due to a decrease in ethanol mass correlates well with experimental data. The models enable the determination of proof-of-concept and the rational design of novel resonant-based microfluidic microcantilever systems.

Longitudinal position dependence of the second-harmonic generation of optically trapped silica microspheres.

We report the design of a setup combining the simultaneous and independent optical trapping and second-harmonic generation (SHG) of 1 µm diameter silica microspheres with two independent laser beams. Optical trapping is achieved with a tightly focused continuous wave infrared laser beam whereas the SHG intensity from the trapped microparticles is obtained with a 810 nm femtosecond pulsed laser. The silica microparticles are dispersed in an aqueous solution, and a microfluidic channel flow is used to remove untrapped microparticles. We show by the perpendicular displacement of the optical trap from the microfluidic channel wall that it is possible to control the contribution of the channel wall/solution interface to the overall SHG intensity. Stable trapping and SHG detection of two microparticles is also demonstrated. Combining the independent trapping of centrosymmetrical silica microparticles with SHG offers new avenues for analytical studies like surface sensing or all-optical devices where the SHG intensity is controlled by the trapping beam.

A deep learning approach for designed diffraction-based acoustic patterning in microchannels

Acoustic waves can be used to accurately position cells and particles and are appropriate for this activity owing to their biocompatibility and ability to generate microscale force gradients. Such fields, however, typically take the form of only periodic one or two-dimensional grids, limiting the scope of patterning activities that can be performed. Recent work has demonstrated that the interaction between microfluidic channel walls and travelling surface acoustic waves can generate spatially variable acoustic fields, opening the possibility that the channel geometry can be used to control the pressure field that develops. In this work we utilize this approach to create novel acoustic fields. Designing the channel that results in a desired acoustic field, however, is a non-trivial task. To rapidly generate designed acoustic fields from microchannel elements we utilize a deep learning approach based on a deep neural network (DNN) that is trained on images of pre-solved acoustic fields. We use then this trained DNN to create novel microchannel architectures for designed microparticle patterning.

Femtosecond laser fabrication of silver nanostructures on glass for surface enhanced Raman spectroscopy

We report on an optimized fabrication protocol for obtaining silver nanoparticles on fused silica substrates via laser photoreduction of a silver salt solution. We find that multiple scans of the laser over the surface leads to a more uniform coverage of densely packed silver nanoparticles of approximately 50 nm diameter on the fused silica surface. Our substrates yield Raman enhancement factors of the order of 1011 of the signal detected from crystal violet. We use a theoretical model based on scanning electron microscope (SEM) images of our substrates to explain our experimental results. We also demonstrate how our technique can be extended to embedding silver nanoparticles in buried microfluidic channels in glass. The in situ laser inscription of silver nanoparticles on a laser machined, sub-surface, microfluidic channel wall within bulk glass paves the way for developing 3D, monolithic, fused silica surface enhance Raman spectroscopy (SERS) microfluidic sensing devices.

Separation detection of different circulating tumor cells in the blood using an electrochemical microfluidic channel modified with a lipid-bonded conducting polymer

Different circulating tumor cells (CTCs) in blood were separated and detected through the decoration of anti-cancer drug on the target cells, along with chemical modification of the microfluidic channel walls using a lipid attached covalently to the conducting polymer. The working principle of the electrochemical microfluidic device was evaluated with experimental parameters affecting on the separation, in terms of mass and surface charge of target species, fluid flow rate, AC amplitude, and AC frequency. The separated CTCs were selectively detected via the oxidation of daunomycin adsorbed specifically at the cells using an electrochemical sensor installed at the channel end. The fluorescence microscopic examination also confirmed the separation of CTCs in the channel. To evaluate the reliability of the method, blood samples from 37 cancer patients were tested. The device was able to separate the CTCs with 92.0 ± 0.5 % efficiency and 90.9% detection rate.

Temperature Gradients Drive Bulk Flow Within Microchannel Lined by Fluid-Fluid Interfaces.

Surface tension gradients induce Marangoni flow, which may be exploited for fluid transport. At the micrometer scale, these surface-driven flows can be quite significant. By introducing fluid-fluid interfaces along the walls of microfluidic channels, bulk fluid flows driven by temperature gradients are observed. The temperature dependence of the fluid-fluid interfacial tension appears responsible for these flows. In this report, the design concept for a biocompatible microchannel capable of being powered by solar irradiation is provided. Using microscale particle image velocimetry, a bulk flow generated by apparent surface tension gradients along the walls is observed. The direction of flow relative to the imposed temperature gradient agrees with the expected surface tension gradient. The phenomenon's ability to replace bulky peripherals, like traditional syringe pumps, on a diagnostic microfluidic device that captures and detects leukocyte subpopulations within blood is demonstrated. Such microfluidic devices may be implemented for clinical assays at the point of care without the use of electricity.

Hyperactivated stallion spermatozoa fail to exhibit a rheotaxis-like behaviour, unlike other species

The journey of spermatozoa through the female genital tract is facilitated by rheotaxis, or the cell’s preference to swim against a flow, as well as thigmotaxis, the wall tracking behaviour, which guides them to the site of fertilisation. The aim of this study was to characterise the rheotactic and thigmotactic response of stallion sperm within a microfluidic channel. Stallion sperm rheotaxis was assessed within the microfluidic channel with regard to: (i) A range of flow velocities, (ii) Varying media viscosity and (iii) Sperm hyperactivation. Sperm distribution across the microfluidic channel was also studied and compared to human and ram sperm. Stallion sperm progressed furthest at a velocity range of 10–30 µm/s, with an optimum velocity of 20 µm/s. A flow viscosity of 2.5cP or greater reduced sperm rheotaxis (P < 0.05). Stallion sperm that were hyperactivated were unable to exhibit rheotaxis within the microfluidic channel, whereas, both hyperactivated human and ram sperm did exhibit positive rheotaxis under the same conditions. The number of sperm swimming near the microfluidic channel walls was higher than in the microfluidic channel centre (P < 0.05). This is the first study to illustrate that stallion sperm are rheotactically responsive and increasing viscosity reduces this response. We also demonstrated that sperm are predominantly inclined to swim along a surface and uniquely, hyperactivated stallion sperm are non-progressive and do not exhibit a rheotactic response unlike other species.

Biocompatible magnetic nanocomposite microcapsules as microfluidic one-way diffusion blocking valves with ultra-low opening pressure

A one-of-a-kind biocompatible magnetic nanocomposite microcapsule is developed as an in-line passive valve that can be integrated with micropumps and microfluidics. The magnetic nanocomposites act as the core for building a valve that utilizes the magnetic force attraction for sealing the microfluidic channels. The nanocomposites, molded with commercial microtubings, are prepared by incorporating Fe3O4 nanoparticles into polyethylene-glycol (PEG). Parylene-C provides a flexible, biocompatible shell and moisture barrier for the microcapsule that enables deformation and sealing to the microfluidic channel wall. The highly customizable valve design offers easy scalability and simplicity for integration into microfluidic systems. The presented magnetically-responsive microcapsule demonstrates reliable performance as a passive one-way valve that exhibits unique features and capabilities including effective flow-rectification with steady flows, extremely low leakage flows from backpressures at a rate of 4.7 nL/min kPa−1, successfully blocking 99.96% of the diffusion, and extremely low inlet flow opening pressure of 2.1 kPa.

Additive manufacturing of three-dimensional (3D) microfluidic-based microelectromechanical systems (MEMS) for acoustofluidic applications.

Three-dimensional (3D) printing now enables the fabrication of 3D structural electronics and microfluidics. Further, conventional subtractive manufacturing processes for microelectromechanical systems (MEMS) relatively limit device structure to two dimensions and require post-processing steps for interface with microfluidics. Thus, the objective of this work is to create an additive manufacturing approach for fabrication of 3D microfluidic-based MEMS devices that enables 3D configurations of electromechanical systems and simultaneous integration of microfluidics. Here, we demonstrate the ability to fabricate microfluidic-based acoustofluidic devices that contain orthogonal out-of-plane piezoelectric sensors and actuators using additive manufacturing. The devices were fabricated using a microextrusion 3D printing system that contained integrated pick-and-place functionality. Additively assembled materials and components included 3D printed epoxy, polydimethylsiloxane (PDMS), silver nanoparticles, and eutectic gallium-indium as well as robotically embedded piezoelectric chips (lead zirconate titanate (PZT)). Electrical impedance spectroscopy and finite element modeling studies showed the embedded PZT chips exhibited multiple resonant modes of varying mode shape over the 0-20 MHz frequency range. Flow visualization studies using neutrally buoyant particles (diameter = 0.8-70 μm) confirmed the 3D printed devices generated bulk acoustic waves (BAWs) capable of size-selective manipulation, trapping, and separation of suspended particles in droplets and microchannels. Flow visualization studies in a continuous flow format showed suspended particles could be moved toward or away from the walls of microfluidic channels based on selective actuation of in-plane or out-of-plane PZT chips. This work suggests additive manufacturing potentially provides new opportunities for the design and fabrication of acoustofluidic and microfluidic devices.

Laser polishing and 2PP structuring of inside microfluidic channels in fused silica

This study presents the development of post-processing steps for microfluidics fabricated with selective laser etching (SLE) in fused silica. In a first step, the SLE surface—even inner walls of microfluidic channels—can be smoothed by laser polishing. In addition, two-photon polymerization (2PP) can be used to manufacture polymer microstructures and microcomponents inside the microfluidic channels. The reduction in the surface roughness by laser polishing is a remelting process. While heating the glass surface above softening temperature, laser radiation relocates material thanks to the surface tension. With laser polishing, the RMS roughness of SLE surfaces can be reduced from 12 µm down to 3 nm for spatial wavelength λ < 400 µm. Thanks to the laser polishing, fluidic processes as well as particles in microchannels can be observed with microscopy. A manufactured microfluidic demonstrates that SLE and laser polishing can be combined successfully. By developing two-photon polymerization (2PP) processing in microchannels we aim to enable new applications with sophisticated 3D structures inside the microchannel. With 2PP, lenses with a diameter of 50 µm are processed with a form accuracy rms of 70 nm. In addition, this study demonstrates that 3D structures can be fabricated inside the microchannels manufactured with SLE. Thanks to the combination of SLE, laser polishing and 2PP, research is pioneering new applications for microfluidics made of fused silica.

A novel technique based on Bloch surface waves sustained by one-dimensional photonic crystals to probe mass transport in a microfluidic channel

We report on the use of an optical sensing platform based on Bloch surface waves sustained by one-dimensional photonic crystals as a novel optical tool to probe in real time the fluid flow at a boundary wall of a microfluidic channel under dynamic conditions. Understanding how fluid flow interacts with wall surfaces is crucial for a broad range of biological processes and engineering applications, such as surface wave biosensing. The proposed platform provides nanometric resolution with respect to the distance from the boundary wall sensor's surface. Here, for the first time, we report on the experimental investigation on the temporal evolution of the interface between two fluids with different refractive indices under convective and diffusive conditions. The temporal evolution of the fluids interface in proximity of the wall is recovered. From the data analysis, the diffusion coefficients of glucose and glycerol in water are measured and found in good agreement with the literature. Tuning the one-dimensional photonic crystals geometry and the Bloch surface wave's dispersion has the potential to probe the fluid flow in an extremely wide range of distances from the microfluidic channel wall.

Dissipative particle dynamics of diffusion-NMR requires high Schmidt-numbers.

We present an efficient mesoscale model to simulate the diffusion measurement with nuclear magnetic resonance (NMR). On the level of mesoscopic thermal motion of fluid particles, we couple the Bloch equations with dissipative particle dynamics (DPD). Thereby we establish a physically consistent scaling relation between the diffusion constant measured for DPD-particles and the diffusion constant of a real fluid. The latter is based on a splitting into a centre-of-mass contribution represented by DPD, and an internal contribution which is not resolved in the DPD-level of description. As a consequence, simulating the centre-of-mass contribution with DPD requires high Schmidt numbers. After a verification for fundamental pulse sequences, we apply the NMR-DPD method to NMR diffusion measurements of anisotropic fluids, and of fluids restricted by walls of microfluidic channels. For the latter, the free diffusion and the localisation regime are considered.

Study of Surface Charge Instabilities by EOF Measurements on a Chip: A Real-Time Hysteresis and Peptide Adsorption Based Methodology.

This paper describes the measurement of the electroosmotic mobility (EOF) in a Wheatstone fluidic bridge (μFWB) as a direct probe of the surface instability. The variation of EOF known as one major contribution of the electrokinetic migration has been determined with a real-time measurement platform after different conditionings on chips. We also scan the pH of the background electrolytes with three different ionic strengths to evaluate the dependencies of the EOF as a function of the pH. A hysteresis methodology has been developed for probing the surface charge instabilities. EOF mobility has been recorded during on-a-chip electrophoresis to estimate the effect of such instability on the analytical performance. As expected, our experimental curves show that a decrease in the ionic strength increases the surface charge stability of the hybrid microchip. This result demonstrates that ionic exchanges between the surface and the fluid are clearly involved in the stability of the surface charge. With this original method based on real-time EOF measurement, the surface state can be characterized after hydrodynamic and electrophoresis sequences to mimic any liquid conditioning and separation steps. Finally, as a demonstrative application, isotherms of the adsorption of insulin have been recorded showing the change in surface charge by unspecific adsorption of this biomolecule onto the microfluidic channel's wall. These methodologies and findings could be particularly relevant to investigating various analytical pathways and to understanding the molecular mechanisms at solid/liquid interfaces.

White Blood Cell Mechanics Mediate Glucocorticoid- and Catecholamine-Induced Demargination

After treatment with glucocorticoids (e.g. dexamethasone) or catecholamines (e.g. epinephrine), the white blood cell (WBC) count substantially increases. This is primarily due to WBCs shifting from the marginated to circulating pools (Nakagawa et al., Circulation, 2008) and is traditionally attributed to down-regulation of adhesion molecule expression (Weber et al., J Leukoc Biol, 2004).Recent research has described how mechanical properties determine the radial position of blood cells within the intravascular space (Reasor et. al, Ann Biomed Eng., 2013). In addition, because WBC demargination occurs rapidly (e.g.,<15 min after IV epinephrine infusion (Dimitrov et al., J Immunol. 2010)) on a timescale that may be shorter than that expected for alterations in gene expression, we hypothesized that alterations in WBC mechanical properties upon exposure to glucocorticoids or catecholamines mediate demargination.To that end, we developed an in vitro microfluidic system as a simplified microvasculature model (Fig 1A), which our laboratory has expertise in (Tsai et al., J Clin Invest., 2008 and Rosenbluth et al., Biophys J. , 2006). In the absence of confounding factors such as WBC release from bone marrow or endothelial interactions, this type of assay is ideally suited to determine the role of glucocorticoid and catecholamine treatment on the demargination of WBCs. By flowing whole blood into similar non-functionalized microfluidic devices, other groups have demonstrated that non-activated WBCs marginate to the microfluidic channel wall, which is likely due to their mechanical properties (Jain et al., PLoS One, 2009). Human whole blood was incubated at 37° C with acridine orange (WBC stain) and either dexamethasone or epinephrine at physiologically relevant concentrations. The blood was then flowed through our microfluidics at physiologic shear rates while confocal videomicroscopy was used to image the center plane of the channel. We developed custom analysis software that extracts the position of individual WBCs from a series of confocal images and plots histograms of their locations, tracking over 10,000 WBCs per experiment (Fig 1B). Overall, we found that both dexamethasone and epinephrine (to a slightly lesser extent) cause WBCs to demarginate from the walls of the vessel compared to control conditions (Fig 1C). This glucocorticoid and catecholamine-induced movement of WBCs toward the microchannel center mimics in vivo demargination and our reductionist microfluidic approach strongly suggests that alterations in WBC mechanics play a key role in this process. [Display omitted] Indeed, using computational modeling, we confirmed that a reduction in the mechanical stiffness of WBCs is sufficient by itself to explain the observed demargination (Fig 2A) (Kumar et al., Phys Rev Lett., 2012). Using a range of WBC stiffnesses, our simulations revealed that decreases in WBC stiffness correlated with the degree of demargination. To corroborate our microfluidic data, we also directly measured WBC stiffness using atomic force microscopy. WBCs treated with dexamethasone were significantly softer (p< 0.0002) than control WBCs (Fig 2B), supporting our hypothesis that the demargination phenomenon is related to the biophysical changes in WBCs. Experiments measuring the stiffness of epinephrine-treated cells as well as experiments evaluating how these drugs affect the actin cytoskeleton are currently underway. [Display omitted] Overall, our data suggest that WBC mechanics play a major role in glucocorticoid- and catecholamine-induced demargination and that the underlying mechanisms may, at least in part, be biophysical in nature. This novel finding may have important implications in other hematologic processes such as WBC margination and recruitment during inflammatory responses or hematopoietic stem cell mobilization and homing. Disclosures:No relevant conflicts of interest to declare.

Relaxation characteristics of a compliant microfluidic channel under electroosmotic flow

We investigate the effect of electroosmotic flow on the temporal response of an initially deformed microfluidic channel wall as it relaxes to its undeformed state. Our results reveal that the electrokinetic effects significantly alter not just the quantitative response of the relaxation dynamics but also the qualitative nature of the relaxation profiles. Furthermore, the electrokinetics brings about a preferential asymmetry to the nature of the dynamical evolution of the relaxation characteristics. Overall, we unveil a rich interplay between the pertinent physico-chemical interactions, the compliance of the deformable channel walls and the geometry of the fluidic confinement, bearing non-trivial consequences towards optimal control of electroosmotic flow in narrow channels with deformable confining boundaries.

A Simple Separation Method with a Microfluidic Channel Based on Alternating Current Potential Modulation

A simple separation and detection system based on an electrochemical potential modulated microchannel (EPMM) device was developed for the first time. The application of alternating current (AC) potential to the microfluidic separation channel walls, which were composed of screen printed carbon electrodes, resulted in the oscillation and fluctuation of analytes and in the formation of a perfect flat flow front. These events resulted in an increase in the effective concentration and in the fine separation of samples. The performance of the EPMM device was examined through the analysis of endocrine disruptors (EDs) and heavy metal ions (HMIs) as model compounds. The analytical parameters that affected the separation and detection of EDs and HMIs were studied in terms of AC amplitude, AC frequency, flow rate, buffer concentration, pH, detection potential, and temperature. The separation efficiency was evaluated through measurements of the theoretical plate number (N), the retention time, and the half-peak width. Linear calibration plots for the detection of EDs and HMIs were obtained between 0.15 and 250.0 nM (detection limit 86.4 ± 2.9 pM) and between 0.01 and 10.0 nM (detection limit 9.5 ± 0.3 pM), respectively. The new device was successfully demonstrated with authentic and real samples.