Development of an ultrafast quantitative heterogeneous immunoassay on pre-functionalized poly(dimethylsiloxane) microfluidic chips for the next-generation immunosensors

Although the reaction time for antigen-antibody binding has been greatly reduced in microchannels, other processes in heterogeneous immunoassays (HEIs), such as blocking and antigen adsorption have not benefited from miniaturization as a reduction in size to micro dimensions does not increase the speed of these processes significantly. The overall assay time of reported microfluidic HEIs has continued to be limited by these processes. In this study, we successfully develop an ultrafast quantitative HEI with pre-functionalized microfluidic poly(dimethylsiloxane) (PDMS) chips. The protein A functionalized PDMS surface is found to be highly effective in reducing the antigen adsorption time in microchannels. The functionalized surfaces can be stable at least for 2.5 months when stored at 4°C in a buffer solution consisting of 10 mM Tris, 0.05% bovine serum albumin, 0.05% Proclin 300, and 5% glycerol. In addition, the immunosorption process, which is substantially accelerated in micro scale, results in a significant reduction in nonspecific binding. The time of blocking step can therefore be reduced to a minimum or can be eliminated. The overall assay for detecting bovine immunoglobulin G is completed in 19 min with a limit of detection of 3.8 nM. The ultrafast analysis time and superior sensitivity demonstrated by this microfluidic HEI is promising for being used to develop the next-generation immunosensors.     

Valves for autonomous capillary systems

Autonomous capillary systems (CSs) are microfluidic systems inside which liquids move owing to capillary forces. CSs can in principle bring the high-performances of microfluidic-based analytical devices to near patient and environmental testing applications. In this paper, we show how wettable capillary valves can enhance CSs with novel functionalities, such as delaying and stopping liquids in microchannels. The valves employ an abruptly changing geometry of the flow path to delay a moving liquid filling front in a wettable microchannel. We show how to combine delay valves with capillary pumps, prevent shortcuts of liquid along the corners of microfluidic channels, stop liquids filling microchannels from a few seconds to over 30 min, trigger valves using two liquid fronts merging, and time a liquid using parallel microfluidic paths converging to a trigger valve. All together, these concepts should add functionality to passive microfluidic systems without departing from their initial simplicity of use. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Femtosecond laser-induced modification of surface wettability of PMMA for fluid separation in microchannels

The modification of polymer surface wettability is receiving increasing interest in recent years. As surface wettability affects the flowing resistance, and thus the separation ratio and/or mixing ratio of samples in different microchannels, the controlled modification of surface wettability is highly desirable. In this study, microfluidic channels with controlled surface wettability were achieved and fabricated using femtosecond (fs) laser direct ablation of polymethyl methacrylate at various fluences. Varied flow velocities and separation ratio of water in microfluidic channels have been successfully obtained through fs laser-induced modification in wetting characteristics of the microchannel surfaces. A concave flow front was observed in a microchannel with hydrophilic surface. Correspondingly, a convex flow front was observed with hydrophobic surface. For an untreated channel, a straight flow front was observed. These results would be attractive for various microfluidic chip applications, such as control of the reagent reaction through controlling liquid medium separation or control of mixing ratio in different channels.     

Experimental investigations of liquid flow in rib-patterned microchannels with different surface wettability

The effects of rib-patterned surfaces and surface wettability on liquid flow in microchannels were experimentally investigated in this study. Microchannels were fabricated on single-crystal silicon wafers by photolithographic and wet-etching techniques. Rib structures were patterned in the silicon microchannel, and the surface was chemically treated by trichlorosilane to create hydrophobic condition. Experiments with water as the working fluid were performed with these microchannels over a wide range of Reynolds numbers between 110 and 1914. The results for the rib-patterned microchannels showed that the friction factor with the hydraulic diameter based on the rib-to-upper-wall height was lower than that predicted from incompressible theory with the same height. The friction factor-Reynolds number products for the hydrophobic condition increased as Reynolds number increased in the laminar flow regime. The experimental results were also compared with the predictive expressions from the literature, and it was found that the experimental data for the small rib/cavity geometry was in good agreement with those in the literature.     

Magnetofluidic spreading in microchannels

We investigate the spreading phenomena caused by the interaction between a uniform magnetic field and a magnetic fluid in microchannels. The flow system consists of two liquids: a ferrofluid and a mineral oil. The ferrofluid consists of superparamagnetic nanoparticles suspended in an oil-based carrier. Under a uniform magnetic field, the superparamagnetic particles are polarized and represent magnetic dipoles. The magnetization of the magnetic nanoparticles leads to a force resulting in the change of diffusion behavior inside the microchannel. Mixing due to secondary flow close to the interface also contributes to the spreading of the ferrofluid. The magnetic force acting on the liquid/liquid interface is caused by the mismatch of magnetization between the nanoparticles and surrounding liquid in a multiphase flow system. This paper examines the roles of magnetic force in the observed spreading phenomena. The effect of particles on the flow field is also considered. These phenomena would allow simple wireless control of a microfluidic system without changing the flow rates. These phenomena can potentially be used for focusing and sorting in cytometry.     

Functionalization of microfluidic devices for investigation of liquid crystal flows

Systematic studies of thermotropic liquid crystals in confinement, such as liquid crystals in microfluidic channels, require control of the anchoring conditions on the surfaces. Especially for the case of uniform planar anchoring, the standard method involves a mechanical treatment (rubbing) of the surface that is not applicable to microfluidic devices. In the present study, we report methods for the achievement of well-defined anchoring conditions for liquid crystals in microfluidic channels consisting of polydimethylsiloxane and glass. Various physico-chemical techniques enable to establish homeotropic, degenerate planar, uniform planar, and hybrid anchoring conditions on the surface of the channel walls. We characterize the treated surfaces in terms of wettability and liquid crystal anchoring and determine the director field in the microchannels for the different anchoring configurations using polarizing optical microscopy and fluorescence confocal polarization microscopy. The relevance of the surface anchoring for the flow behavior of the liquid crystal in the microchannel is demonstrated by studying the onset of defect-mediated chaotic-like flow at high Ericksen numbers for the different anchoring cases.     

Controlled Liquid–Air Interfaces and Interfacial Polymer Micromembranes in Microfluidic Channels

In this paper, we report on stable liquid–air interfaces and high-aspect-ratio polymer micromembranes with complex and controlled structures formed within microfluidic channels. Selective alkanethiol treatment on gold and copper surfaces is employed to create hydrophilic–hydrophobic boundaries between glass and these metal surfaces within microchannels. Robust liquid–air interfaces, featured with different 3-D structures, are formed at these boundaries. The process for creating these liquid–air interfaces is highly reproducible. Simulations are conducted to further study the liquid–air interfaces. The liquid–air interfaces are then utilized for interfacial polymerization. Two immiscible liquid phases containing the reagents react and generate polymer micromembranes within microfluidic channels. Formed following the hydrophilic–hydrophobic boundaries, these membranes have not only complex footprints on the substrates but also different configurations in the $z$ -direction. Here, we demonstrate high-quality and complex 3-D nylon micromembranes fabricated in microchannels using this method. $hfill$[2007-0294]      

New Generation of Digital Microfluidic Devices

This paper reports on the design, fabrication, and performance of micro-sized fluidic devices that use electrowetting to control and transport liquids. Using standard microfabrication techniques, new pumping systems are developed with significantly more capability than open digital microfluidic systems that are often associated with electrowetting. This paper demonstrates that, by integrating closed microchannels with different channel heights and using electrowetting actuation, liquid interfaces can be controlled, and pressure work can be done, resulting in fluid pumping. The operation of two different on-chip pumps and devices that can form water drops is described. In addition, a theory is presented to explain the details of single-electrode actuation in a closed channel. $hfill$[2008-0224]      

Guiding of emulsion droplets in microfluidic chips along shallow tracks defined by laser ablation

We demonstrate controlled guiding of nanoliter emulsion droplets of polar liquids suspended in oil along shallow hydrophilic tracks fabricated at the base of microchannels located within microfluidic chips. The tracks for droplet guiding are generated by exposing the glass surface of polydimethylsiloxane (PDMS)-coated microscope slides via femtosecond laser ablation. The difference in wettability of glass and PDMS surfaces together with the shallow step-like transverse topographical profile of the ablated tracks allows polar droplets wetting preferentially the glass surface to follow the track. In this study, we investigate guiding of droplets of two different polar liquids (water/ethylene glycol) with and without surfactant suspended in an oil medium along surface tracks of different depths of 1, 1.5, and 2 \(\upmu\)m. The results of experiments are also verified with computational fluid dynamics simulations. Guiding of droplets along the tracks as a function of the droplet composition and size and the surface profile depth is evaluated by analyzing the trajectories of moving droplets with respect to the track central axis, and conditions for stable guiding are identified. The experiments and numerical simulations indicate that while the track topography plays a role in droplet guiding using 1.5- and 2-\(\upmu\)m deep tracks, for the case of the smallest track depth of 1 \(\upmu\)m, droplet guiding is mainly caused by surface energy modification along the track rather than the presence of a topographical step on the surface. Our results can be exploited to sort passively different microdroplets mixed in the same microfluidic chip, based on their inherent wetting properties, and they can also pave the way for guiding of droplets along reconfigurable tracks defined by surface energy modifications obtained using other external control mechanisms such as electric field or light.     

Selective Formation and Removal of Liquid Microlenses at Predetermined Locations Within Microfluidics Through Pneumatic Control

This paper reports on liquid (deionized water) microlenses that are intrinsically formed and integrated within microfluidics through pneumatic manipulation of fluids inside microchannels. Such microlenses are formed via liquid-air interfaces of liquid droplets, which are pinned at T-shaped junctions of channels. In addition to being tunable in focal lengths (a few hundreds of micrometers to infin) along the microchannels parallel to the substrate used, these microlenses can uniquely be repositioned, removed, and reformed at predetermined locations of the T-shaped junctions within microchannels on demand under pneumatic controls. The design and formation of a microfluidic channel network for the in situ formation are first described. Then, the pneumatic control of the fluids, including the formation, movement, and size control of a lens droplet, is discussed, and the in situ formation processes for single and multiple liquid microlenses are described. The in situ formation processes for a single microlens and a two-lens combination only take tens of seconds, eliminating various conventional microfabrication processes and multiple layers of materials. Finally, the detail of characterization of these microlenses is given.     

Liquid recirculation in microfluidic channels by the interplay of capillary and centrifugal forces

We demonstrate a technique to recirculate liquids in a microfluidic channel by alternating predominance of centrifugal and capillary forces to rapidly bring the entire volume of a liquid sample to within one diffusion length, δ, of the surface, even for sample volumes hundreds of times the product of δ and the geometric device area. This is accomplished by repetitive, random sampling of an on-disc sample reservoir to form a thin fluid layer of thickness δ in a microchannel, maintaining contact for the diffusion time, then rapidly exchanging the fluid layer for a fresh aliquot by disc rotation and stoppage. With this technique, liquid volumes of microlitres to millilitres can be handled in many sizes of microfluidic channels, provided the channel wall with greatest surface area is hydrophilic. We present a theoretical model describing the balance of centrifugal and capillary forces in the device and validate the model experimentally.     

Liquid flow through microchannels with grooved walls under wetting and superhydrophobic conditions

Recent developments in superhydrophobic surfaces have enabled significant reduction in the frictional drag for liquid flow through microchannels. There is an apparent risk when using such surfaces, however, that under some conditions the liquid meniscus may destabilize and, consequently, the liquid will wet the entire patterned surface. This paper presents analytical and experimental results that compare the laminar flow dynamics through microchannels with superhydrophobic walls featuring ribs and cavities oriented both parallel and transverse to the direction of flow under both wetting and non-wetting conditions. The results show the reduction in the total frictional resistance is much greater in channels when the liquid phase does not enter the cavity regions. Further, it is demonstrated that the wetting and non-wetting cavity results represent limiting cases between which the experimental data lie. Generalized expressions enabling prediction of the classical friction factor-Reynolds number product as a function of the relevant governing dimensionless parameters are also presented for both the superhydrophobic and wetting states. Experimental results are presented for a range of parameters in the laminar flow regime.     

Microfluidic systems for the analysis of viscoelastic fluid flow phenomena in porous media

In this study, two microfluidic devices are proposed as simplified 1-D microfluidic analogues of a porous medium. The objectives are twofold: firstly to assess the usefulness of the microchannels to mimic the porous medium in a controlled and simplified manner, and secondly to obtain a better insight about the flow characteristics of viscoelastic fluids flowing through a packed bed. For these purposes, flow visualizations and pressure drop measurements are conducted with Newtonian and viscoelastic fluids. The 1-D microfluidic analogues of porous medium consisted of microchannels with a sequence of contractions/expansions disposed in symmetric and asymmetric arrangements. The real porous medium is in reality, a complex combination of the two arrangements of particles simulated with the microchannels, which can be considered as limiting ideal configurations. The results show that both configurations are able to mimic well the pressure drop variation with flow rate for Newtonian fluids. However, due to the intrinsic differences in the deformation rate profiles associated with each microgeometry, the symmetric configuration is more suitable for studying the flow of viscoelastic fluids at low De values, while the asymmetric configuration provides better results at high De values. In this way, both microgeometries seem to be complementary and could be interesting tools to obtain a better insight about the flow of viscoelastic fluids through a porous medium. Such model systems could be very interesting to use in polymer-flood processes for enhanced oil recovery, for instance, as a tool for selecting the most suitable viscoelastic fluid to be used in a specific formation. The selection of the fluid properties of a detergent for cleaning oil contaminated soil, sand, and in general, any porous material, is another possible application.     

Surface polishing of quartz-based microfluidic channels using CO<Subscript>2</Subscript> laser

Recently, microgrinding using a polycrystalline diamond tool has been introduced to fabricate microchannels and structures from quartz (fused silica). Compared to wet or dry etching processes, the grinding process is very simple and time-efficient for prototyping. However, the roughness of the machined surface remains an issue, because the surface is covered with many small cracks. Poor surface roughness can affect fluid flow in the microfluidic channels. To reduce the surface roughness of microchannels generated by a grinding process, this study presents the laser polishing of quartz and investigates the effects of the translational speed and pitch of a laser spot on the surface roughness and shape accuracy of microchannels.     

Numerical investigation on drag reduction with superhydrophobic surfaces by lattice-Boltzmann method

The mechanism of drag reduction by using superhydrophobic surfaces whose contact angle is greater than 150° is still an open problem that needs to be investigated. The main purpose of this paper is to reveal how the pressure drop can be decreased. The lattice-Boltzmann method (LBM) is employed to investigate fluid flows through channels with different wettability conditions and topographical surfaces. The drag reduction by superhydrophobic surfaces is determined based on numerical experiments. For the smooth-surface flow, a very thin gas film is observed between the fluid and the superhydrophobic wall; hence, the liquid/solid interface is replaced by the gas/liquid interface. For the rough-surface flow, liquid sweeps over the grooves and the contact area is reduced; therefore, the friction is decreased rapidly. Additionally, the effects of surface wettability and surface roughness are analyzed as well. It is found that introducing roughness elements has a positive effect for reducing the pressure drop for the hydrophobic-surface flow, but has a negative effect for the hydrophilic-surface flow.     

A deformable surface model for real-time water drop animation

A water drop behaves differently from a large water body because of its strong viscosity and surface tension under the small scale. Surface tension causes the motion of a water drop to be largely determined by its boundary surface. Meanwhile, viscosity makes the interior of a water drop less relevant to its motion, as the smooth velocity field can be well approximated by an interpolation of the velocity on the boundary. Consequently, we propose a fast deformable surface model to realistically animate water drops and their flowing behaviors on solid surfaces. Our system efficiently simulates water drop motions in a Lagrangian fashion, by reducing 3D fluid dynamics over the whole liquid volume to a deformable surface model. In each time step, the model uses an implicit mean curvature flow operator to produce surface tension effects, a contact angle operator to change droplet shapes on solid surfaces, and a set of mesh connectivity updates to handle topological changes and improve mesh quality over time. Our numerical experiments demonstrate a variety of physically plausible water drop phenomena at a real-time rate, including capillary waves when water drops collide, pinch-off of water jets, and droplets flowing over solid materials. The whole system performs orders-of-magnitude faster than existing simulation approaches that generate comparable water drop effects.     

Cluster formation and growth in microchannel flow of dilute particle suspensions

The lifetime of microfluidic devices depends on their ability to maintain flow without interruption. Certain applications require microdevices for transport of liquids containing particles. However, microchannels are susceptible to blockage by solid particles. Therefore, in this study, the phenomenon of interest is the formation and growth of clusters on a microchannel surface in the flow of a dilute suspension of hard spheres. Based on the present experiments, aggregation of clusters was observed for particle-laden flows in microchannels with particle void fraction as low as 0.001 and particle diameter to channel height ratio as low as 0.1. The incipience and growth of a single cluster is discussed, and the spatial distribution and time evolution of clusters along the microchannel are presented. Although the cluster size seems to be independent of location, more clusters are found at the inlet/outlet regions than in the microchannel center. Similarly as for an individual cluster, as long as particle–cluster interaction is the dominant mode, the total cluster area in the microchannel grows almost linearly in time. The effects of flow rate, particle size, and concentration are also reported.     

Fabrication of microchannels in single crystal diamond for microfluidic systems

A growth of single crystal diamond (SCD) microchannels on HPHT diamond substrate has been carried out successfully by a simple and novel method. Firstly, aluminum film was patterned on SCD diamond substrate surface by magnetron sputtering, photolithography and dry etching techniques. Secondly, the aluminum patterns were transferred onto diamond substrate via inductively coupled plasma etching to form grooves on diamond surface. Finally, microchannels were achieved by epitaxial lateral overgrowth of SCD on the surface of prepared substrate by microwave plasma chemical vapor deposition system. After that, fluorescent liquid was introduced to check hollowness of the microchannels. This work provides a simple and time saving method to fabricate SCD microchannels for microfluidic system, which offers a great potential for hard environment applications.     

Microfluidic two-phase interactions under variable liquid to cross-flow gas momentum flux ratios

Volume of fluid (VOF) and large eddy simulations (LES) are coupled to investigate the microfluidic two-phase interactions during the liquid emergence into the cross-flow gas in a super-hydrophobic micro-channel. Spatio-temporal evolution of the gas/liquid interface is presented for nine different cases of the liquid to gas momentum flux ratios, gas/liquid Reynolds numbers and gas/liquid Weber numbers. With increased momentum of the gas flow, the liquid topology is found deflected towards the downstream. Under variable gas resistance effects, the liquid flow emerging through the square pore may or may not develop a circular cross-section governed by the axis-switching phenomenon. At strong gas inertia, vortex shedding in the downstream of the liquid generates vorticular ligaments in the wake region. Shearing effects on the liquid surface are increased at higher liquid injection velocities and/or gas densities. Depending on the competing effects of the viscous diffusion versus gas/liquid inertia, different combinations of the interactions among the three building blocks of the fluid flow problems (boundary layer, shear layer and wake) are described in microfluidics scales. The complexity of the liquid topology is found correlated with the occurrence of the phenomena such as the Kelvin–Helmholtz (KH) instability, the horseshoe vortex system, stationary/shedding vortices in the wake of the liquid topology as well as their interaction with the micro-channel wall boundary layers.     

Separation of highly viscous fluid threads in branching microchannels

We experimentally study the transport properties of threads made of high-viscosity fluids flowing in a sheath of miscible, low-viscosity fluids in bifurcating microchannels. A viscous filament is generated using a square hydrodynamic focusing section by injecting a ‘thick’ fluid into the central channel and a ‘thin’ fluid from the side channels. This method allows us to produce miscible fluid threads of various sizes and lateral positions in a straight channel and enables the systematic study of the downstream thread’s response to flow partitioning in branching microfluidic networks at low Reynolds numbers. A phase diagram detailing the various flow patterns observed at the first bifurcation, including thread folding, transport, and fouling, is presented along with transition lines. We also examine the role of viscous buckling instabilities on thread behavior and the formation of complex viscous mixtures and stratifications at the small scale. This work shows the possibility to finely control thread trajectory and stability as well as manipulate the structural arrangement of high-viscosity multiphase flows in complex microfluidic systems.