Microfluidic Stream Research Articles

Marangoni destabilization of bidimensional-confined gas–liquid co-flowing streams in rectangular microfluidic channels

In microchannels, the stability of a fluid jet injected into another immiscible fluid strongly depends on its degree of geometric confinement. When the width of the jet, w, is larger than the channel height, H, the surface tension driven Rayleigh–Plateau instability is suppressed so that the 2D (bidimensional)-confined jet is absolutely stable and never collapses into bubbles (or drops) in contrast to what occurs when w ≤ H [Dollet et al., “Role of the channel geometry on the bubble pinch-off in flow-focusing,” Phys. Rev. Lett. 100(3), 034504 (2008); Guillot et al., “Stability of a jet in confined pressure-driven biphasic flows at low Reynolds number in various geometries,” Phys. Rev. E 78(1), 016307 (2008)]. We here demonstrate both experimentally and theoretically that this picture is, indeed, no longer valid when Marangoni effects are considered. We experimentally show that the addition of small length alcohol molecules into the liquid phase destabilizes a 2D-confined gas–water microfluidic stream ( w > H), leading to the generation of steady non-linear waves and further to the production of bubbles. Using a simple hydrodynamic model, we show through a linear analysis that the destabilization of the gas stream may result from a Marangoni instability due to the fast adsorption of the alcohol molecules, which occurs on a timescale comparable to that of the microfluidic flow.

Intelligent polarization-sensitive holographic flow-cytometer: Towards specificity in classifying natural and microplastic fibers

Micron size fiber fragments (MFFs), both natural and synthetic, are ubiquitous in our life, especially in textile clothes, being necessary in modern society. In the Earth's aquatic ecosystem, microplastic fibers account for ~91% of microplastic pollution, thus deserving notable attention as one of the most alarming ecological problems. Accurate automatic identification of MFFs discharges in specific upstream locations is highly demanded. Computational microscopy based on Digital Holography (DH) and machine learning has been demonstrated to identify microplastics in respect to microalgae. However, DH is a non-specific optical tool, meaning it cannot distinguish different types of plastic materials. On the other hand, materials-specific assessments are pivotal to establish the environmental impact of different textile products and production processes. Spectroscopic assays can be employed to identify microplastics for their intrinsic specificity, although they are generally low-throughput and require large concentrations to enable effective measurements. Conversely, MFFs are usually finely dispersed within a water sample. Here we rely on a polarization-resolved holographic flow cytometer in a Lab-on-Chip (LoC) platform for analysing MFFs. We demonstrate that two important objectives can be achieved, i.e. adding material specificity through polarization analysis while operating in a microfluidic stream modality. Through a machine learning numerical pipeline, natural fibers (i.e. cotton and wool) can be clearly separated from synthetic microfilaments, namely PA6, PA6.6, PET, PP. Moreover, the proposed system can accurately distinguish between different polymers under investigation, thus fulfilling the specificity goal. We extract and select different features from amplitude, phase and birefringence maps retrieved from the digital holograms. These are shown to typify MFFs without the need for sample pre-treatment or large concentrations. The simplicity of the DH method for identifying MFFs in LoC-based flow cytometers could promote the use of polarization resolved field-portable analysis systems suitable for studying pollution caused by washing processes of synthetic textiles.

FlowSculpt: software for efficient design of inertial flow sculpting devices.

Flow sculpting is a powerful method for passive flow control that uses a sequence of bluff-body structures to engineer the structure of inertially flowing microfluidic streams. A variety of cross-sectional flow shapes can be created through this method, offering a new platform for flow manipulation or material fabrication useful in bioengineering, manufacturing, and chemistry applications. However, the inverse problem in flow sculpting - designing a device that produces a target fluid flow shape - remains challenging due to the complex, diverse, and enormous design space. Solutions to the inverse problem have been constrained to single-material fluid streams that are shaped into top-bottom symmetric shapes due to the bluff-body structures available in current libraries (pillars) that span the height of the channel. In this work, we introduce multi-material design and symmetry-breaking flow deformations enabled by half-height pillars, presented within an extremely fast simulation method for flow sculpting yielding a 34-fold reduction in runtime. The framework is deployed freely as a cross-platform application called "FlowSculpt". We detail its implementation and usage, and discuss the addition of enhanced search operations, which enable users to more easily design flow shapes that replicate their input drawings. With FlowSculpt, the microfluidics community can now quickly design flow shaping microfluidic devices on modest hardware, and easily integrate these complex physics into their research toolkit.

Modulated fluorescence detection with microelectromagnetic traps

Modulation of magnetic fields in microelectromagnetic traps (METs) is used to enhance signal to noise gains for quantification of magnetic particles captured from a microfluidic analyte stream.

Influences of Detection Pinhole and Sample Flow on Thermal Lens Detection in Microfluidic Systems

Thermal lens microscopy (TLM), due to its high temporal ( $${\sim }\mathrm{ms}$$ ) and spatial resolution ( $${\sim }\upmu \mathrm{m}$$ ), has been coupled to lab-on-chip chemistry for detection of a variety of compounds in chemical or biological fields. Due to the very short optical path length (usually below 100 $$\upmu \mathrm{m}$$ ) in a microchip, the sensitivity of TLM is unfortunately still 10 to 100 times lower than conventional TLS with 1 cm sample length. Optimization of the TLM optical configuration was made with respect to different pinhole aperture-to-beam size ratios for the best signal-to-noise ratio. In the static mode, the instrumental noise comes mainly from the shot noise of the probe beam when the chopper frequency is over 1 kHz or from the flicker noise of the probe beam at low frequencies. In the flowing mode, the flow-induced noise becomes dominant when the flow rate is high. At a given flow rate, fluids with a higher density and/or a higher viscosity will cause larger flow-induced noise. As an application, a combined microfluidic flow injection analysis ( $$\upmu \mathrm{FIA}$$ )–TLM device was developed for rapid determination of pollutants by colorimetric reactions. Hexavalent chromium [Cr(VI)] was measured as a model analyte. Analytical signals for 12 sample injections in 1 min have been recorded by the $${\upmu }$$ FIA–TLM. For injections of sub- $$\upmu $$ L samples into the microfluidic stream in a $$50\,\upmu \mathrm{m}$$ deep microchannel, a limit of detection of $$4\,\mathrm{ng}{\cdot }\mathrm{mL}^{-1}$$ was achieved for Cr(VI) in water at 60 mW excitation power.

Electrochemical dissolved oxygen removal from microfluidic streams for LOC sample pretreatment.

Current water quality monitoring for heavy metal contaminants largely results in analytical snapshots at a particular time and place. Therefore, we have been interested in miniaturized and inexpensive sensors suitable for long-term, real-time monitoring of the drinking water distribution grid, industrial wastewater effluents, and even rivers and lakes. Among the biggest challenges for such sensors are the issues of in-field device calibration and sample pretreatment. Previously, we have demonstrated use of coulometric stripping analysis for calibration-free determination of copper and mercury. For more negatively reduced metals, O2 reduction interferes with stripping analysis; hence, most electroanalysis techniques rely on pretreatments to remove dissolved oxygen (DO). Current strategies for portable DO removal offer limited practicality, because of their complexity, and often cause inadvertent sample alterations. Therefore, we have designed an indirect in-line electrochemical DO removal device (EDOR), utilizing a silver cathode to reduce DO in a chamber that is fluidically isolated from the sample stream by an O2-permeable membrane. The resulting concentration gradient supports passive DO diffusion from the sample stream into the deoxygenation chamber. The DO levels in the sample stream were determined by cyclic voltammetry (CV) and amperometry at a custom thin-layer cell (TLC) detector. Results show removal of 98% of the DO in a test sample at flow rates approaching 50 μL/min and power consumption as low as 165 mW h L(-1) at steady state. Besides our specific stripping application, this device is well-suited for LOC applications where miniaturized DO removal and/or regulation are desirable.

3A1-I03 開放空間での多点微小水流を用いた細胞操作手法の開発(バイオマニピュレーション)

3A1-I03 開放空間での多点微小水流を用いた細胞操作手法の開発(バイオマニピュレーション)

A Bio-Manipulation Method Based on the Hydrodynamic Force of Multiple Microfluidic Streams

This paper proposes a multiple microfluidic streambased manipulation (MMSM) system for bio-objects. It uses micro hydrodynamics and lab on chip (LOC) technology. Our method can implement the functions of micro manipulation and micro assembly of bio-objects in an open space without contact. Compared to other conventional bio-micro-manipulation and assembly methods, this system manipulates micro objects by controlling multiple microfluidic streams onto them from various directions. The advantages of this method are that it performs open space, multifunction, multi-scale, multi-degree-of-freedom, and non-invasive 3D manipulation. These microfluidic streams are generated simultaneously from multiple orifices. By regulating the parameters of the microfluidic stream, such as the position and number of operating orifices and the flow rate, the direction and velocity of the object can be controlled. To verify this principle, we design an open-space fluidic system for on-chip manipulation and calculated velocity and direction of the microfluidic stream using CFD simulation. Then the prototype microchip with an array of nine orifices is fabricated from glass. In experiments, demonstrations of rectilinear motion of a single cell andmicro particle are observed. The results presented in this paper show that this MMSM is capable of biomicromanipulation and micro assembly of bio-objects.

Microfluidic probes for use in life sciences and medicine

Microfluidic probes (MFPs) combine the concepts of microfluidics and of scanning probes and constitute a contact-free and channel-free microfluidic system. Whereas classically the sample is introduced into the microfluidic device, with a MFP, the microfluidic stream is applied to the sample. MFPs use hydrodynamic flow confinement instead of walls to constrain a microfluidic stream between the MFP tip and a substrate. Because MFPs are free to move, they can be used to process large areas and samples in a selective manner. The development of MFP technology is recent and has numerous potential applications in several fields, most notably in the life sciences. In this review, we discuss the concept of MFPs and highlight their application in surface biopatterning, controlling the cellular microenvironments, local processing of tissue slices, and generating concentration gradients of biochemicals. We hope that this manuscript will serve as an interdisciplinary guide for both engineers as they further develop novel MFPs and applications and for life scientists who may identify novel uses of the MFP for their research.

Free-Surface Microfluidics/Surface-Enhanced Raman Spectroscopy for Real-Time Trace Vapor Detection of Explosives

The dominant physical transport processes are analyzed in a free-surface microfluidic and surface-enhanced Raman spectroscopy (SERS) chemical detection system. The analysis describes the characteristic fluid dynamics and mass transport effects occurring in a microfluidic detection system whose analyte absorption and concentration capability is designed to operate on principles inspired by canine olfaction. The detection system provides continuous, real-time monitoring of particular vapor-phase analytes at concentrations of 1 ppb. The system is designed with a large free-surface-to-volume ratio microfluidic channel which allows for polar or hydrophilic airborne analytes to readily be partitioned from the surrounding gas phase into the aqueous phase for detection. The microfluidic stream can concentrate certain molecules by up to 6 orders of magnitude, and SERS can enhance the Raman signal by 9-10 orders of magnitude for molecules residing in the so-called SERS "hot spots", providing extremely high detection sensitivity. The resulting vibrational spectra are sufficiently specific to identify the detected analyte unambiguously. Detection performance was demonstrated using a nominal 1 ppb, 2,4-dinitrotoluene (2,4-DNT) vapor stream entrained within N(2) gas. Applications to homeland security arise from the system's high sensitivity and its ability to provide highly reproducible, continuous chemical detection monitoring with minimal sampling requirements.

Errata: Passive regulation of volume-flow ratio for microfluidic streams with different hydrophilicity and viscosity

The corresponding author of this paper is: Professor Youn Tae Kim, Department of IT Fusion Technology, Chosun University, 375 Seosk-dong, Dong-gu, Gwangju 501–759, Korea E-mail: petruskim@chosun.ac.kr Fax: +82-62-233-6896

Passive regulation of volume-flow ratio for microfluidic streams with different hydrophilicity and viscosity

Biochemical solutions have a wide range of hydrophilicity (contact angle and surface tension) and viscosity. A critical challenge is that microfluidic systems typically need expensive or complex pumps to control the various parallel biochemical streams. In this study, without using any pumps, we present a simple scheme that controls the ratio of the volumetric flow rate (VFR) of the parallel streams that have highly different hydrophilicity and viscosity. We accomplish this process by using capillarity to drive and merge two streams, and by regulating relative flow resistance to control the VFR ratio. Our results will significantly simplify the control of the VFR ratio for the various biochemical solutions that are used in microfluidic applications.

Adsorption kinetics of proteins in plastic microfluidic channels: Real-time monitoring of lysozyme adsorption by pulsed streaming potentials

A proof-of-concept study is presented illustrating the real-time monitoring of lysozyme (Ly) adsorption on the surface of microchannels made with cyclic olefin copolymer (COC). The signal arises from changes in the surface charge upon adsorption of Ly which is monitored by pulsed streaming potentials. Because streaming potentials are electrochemical potentials resulting from the pressure-driven flow of the liquid and the surface charge of the microchannel, this approach is ideal for microfluidics. Initial adsorption rates showed a linear correlation with the bulk concentration of [Ly] in the range between 7.0 and 350 nM. Fitting of the adsorption isotherms allowed the estimation of equilibrium and rate constants of adsorption. The influence of phosphate ions on the adsorption kinetics of Ly was also investigated. Unlike the steady flow used in conventional streaming potential measurements, the present approach incorporates pulsed flow and the ability to inject finite samples into the microfluidic stream. The pulsed flow allows the use of non-reference electrodes which removes the need for special electrolytes to stabilize the electrode potentials. Likewise, the injection permits monitoring of adsorption and desorption events in real time. The label-free monitoring of these events and the high sensitivity of the adsorption kinetics of Ly to solution species found in this work indicates that this method could be applicable to study protein–protein interactions.

Controlled transport of magnetic particles using soft magnetic patterns

Inspired by magnetic bubble memory technology, we demonstrate the temporal and spatial manipulation of superparamagnetic beads guided by soft magnetic patterns in a rotating magnetic field. Soft magnetic structures allow complex and repetitive tasks to be performed. As a demonstration, we show cyclic capture and release of antibodies from different microfluidic streams.

From Microdroplets to Microfluidics: Selective Emulsion Separation in Microfluidic Devices

Microdroplets show great promise as a new high-throughput technology in chemistry, biochemistry, and molecular biology. Microdroplets can be generated at rates in excess of several thousands per second and accurately formulated using minute amounts of small molecules, DNA, proteins, or cells. Furthermore, integrated active elements can be used to control individual droplets. With the technology for creating, dividing, fusing, interrogating, and even sorting microdroplets already developed, one of the main problems to be resolved is how to access their contents. Droplets are naturally self-contained microreactors that prevent sample loss, diffusion, and cross-contamination, general issues that afflict traditional microfluidics. However, the isolated nature of droplets prevents physical access of their contents on-chip. Even though this does not represent a problem for many of the applications that have already been demonstrated, it limits the integration of microdroplets with other platforms. Analytical techniques such as mass spectrometry, capillary electrophoresis, and liquid chromatography have been successfully integrated with continuous-flow microfluidic devices, but their integration with microdroplets remains challenging. If the contents of microdroplets could be readily extracted on demand, the carrier fluid discarded, and the microdroplets converted into a continuous stream, microfluidic functionality could be combined with the advantages of microdroplets. In this paper we present a technology that bridges the fields of microdroplets and continuous-flow microfluidics by extracting on-chip the contents of microdroplets and incorporating them into a continuous stream. The extraction is achieved through electrocoalescence: droplets are forced to coalesce with an aqueous stream by application of an electric field across the channel. The extraction is controlled through the voltage applied at microfabricated electrodes on each side of the channel and can be performed in a continuous or discrete fashion. The discrete collection of droplets can be controlled by an external electrical signal related to the contents of the droplets. As a proof of principle, we have implemented a fluorescence intensity based detection system to control the collection of the droplets, resulting in a device capable of selectively incorporating the contents of droplets of interest to a continuous microfluidic stream. We used flow-focusing to generate microdroplets. An aqueous stream was focused between two oil streams as they pass through a junction. Shear forces make the aqueous thread break up into monodisperse droplets. Droplet size and frequency were controlled by a combination of channel dimensions and flow rates. We used a mixture of fluorous oil (FC-77) and 1H,1H,2H,2H-perfluorooctanol (70:30 by weight) as the carrier phase. The oil and aqueous flows at the flow-focusing device were adjusted to generate the desired droplet frequency, typically ranging from 10–250 Hz. The flow of the lateral aqueous phase was adjusted so an interface was held in the region between the electrodes without overflow in either direction. Figure 1a shows a scheme of a typical device where droplets flow parallel to a stream of water between two electrodes. In the absence of an electric field, the droplets are not perturbed by the presence of the aqueous stream and follow the geometrically determined flow lines. Figure 1b and c show micrographs of such a device in operation. Droplets of a dye generated at the flow-focusing device flow past the

Dynamic Microfluidic Photomasking

This paper presents a novel microfluidic photomasking strategy. Laminar microfluidic streaming is exploited to achieve photomasking with dynamic spatial control. Two light-absorbing streams hydrodynamically focus a transparent stream to define a line of light transmission. A device incorporating two such microfluidic layers, which are aligned orthogonally, enables light transmission only where the transparent streams overlap. Control of fluid flow in the microfluidic layers enables dynamic spatial control of the exposed region. The dynamic microfluidic photomasking strategy is tested through transmitted light microscopy and applied to microfabrication via photoresist patterning. When applied to microfabrication in a frontal photopolymerization mode, this method affords both planar and depthwise control of feature geometry.

Discrimination between Single Escherichia coli Cells Using Time-Resolved Confocal Spectroscopy

We describe a technique for rapidly discriminating between single-cell populations within a flowing microfluidic stream. Single-cell time-correlated single-photon counting (scTCSPC) as well as photon burst spectroscopy are used to characterize individual Escherichia coli cells expressed with either green, cyano, or yellow fluorescent protein. The approach utilizes standard confocal fluorescence microscopy incorporating femtoliter detection volumes. The measured burst width characteristics are predominately governed by the fluorescence quantum yield and absorption cross section of the proteins used. It is these characteristics which were used to distinguish between cells with high precision. By utilizing scTCSPC individual fluorescence lifetimes originating from single cells could also be determined. Average fluorescence lifetimes are determined using standard deconvolution procedures. The simplicity of the approach for obtaining well-defined burst width distributions is expected to be extremely valuable for single-cell sorting experiments.

Long-term microfluidic cultures of myotube microarrays for high-throughput focal stimulation.

We have developed a microfluidic cell culture method that allows for the formation of linear isolated myotubes organized in a parallel microarray. Attachment and spreading of cells are confined within microtracks of cell-adherent proteins separated by a protein-repellent coating. Signaling molecules or other molecules of interest can be focally delivered to the myotubes using heterogeneous microfluidic streams. We have used the method to focally deliver agrin (a molecule implicated as a postsynaptic organizer), which leads to localized acetylcholine receptor clustering. These techniques can be modified to accommodate other cell types and can be adapted to virtually any bioactive molecule such as signaling factors or drugs. This protocol features two major techniques that can be utilized simultaneously or independently to (i) micropattern cells using surface chemical modification and (ii) use a microfluidic platform for culturing and focal stimulation of cells with molecules of interest. Device design, fabrication and assembly can be completed in 3 days.

Nanofluidic Injection and Heterogeneous Kinetics of Organomercaptan Surface Displacement Reactions on Colloidal Gold in a Microfluidic Stream

Colloidal gold is developed as a molecular capture reagent in hybrid nanofluidic-microfluidic devices for mass-limited sample analysis. Two fluorescent organomercaptans are injected through a nanocapillary array membrane and subsequently captured at the surface of 19-nm-diameter colloidal Au nanoparticles. The surface displacement kinetics are monitored via quenching of the organomercaptan fluorescence by the metallic particles coupled to a distance-time conversion based on fluid velocity in the microfluidic channel using the point of mixing as the zero of time. The adsorbate concentration, colloid concentration, and fluid velocity are varied to determine the surface displacement rate constants for these heterogeneous reactions in the microfluidic device. Surface displacement rate constants are approximately 10(4) M(-1) s(-1) for a small organic molecule and for an octapeptide. These values are similar to values determined in macroscale measurements made with a traditional fluorometer and are 1 order of magnitude larger than values reported for adsorption of organomercaptans on planar Au, indicating faster kinetics in the colloid-adsorbate system. These results highlight the utility of colloidal Au nanoparticles as molecular carriers for the sequestration of analytes, allowing the manipulation of mass-limited samples and ultimately the capture and delivery of selected analytes from a microfabricated device to an off-line detector.

Combinatorial mixing of microfluidic streams.

We have devised a microfluidic mixer design that produces all the mixture combinations of a given number of dilutions of the input compounds. As proof of the concept, we present a device that generates four titrations of two dye solutions, blue and yellow, and combinatorially mixes the blue titrations with the yellow titrations to deliver the sixteen mixture combinations in separate outlet microchannels. Our device features four different flow levels made by stacking nine laser-cut Mylar laminates. The fluidic network has a symmetric design that guarantees that the flow rates are the same at all the outlets, with deviations attributable to imperfections in the fabrication, assembly, or perfusion processes. Design rules for scaling up the number of compounds and/or dilutions are presented. The mixing scheme has broad applicability in high-throughput combinatorial testing applications such as drug screening, cell-based biochemical assays, lab-on-a-chip devices, and biosensors.