Applications In Microfluidic Systems Research Articles

How to Prevent Bubbles in Microfluidic Channels.

Microfluidic technology has aroused wide applications, including analytical science, diagnostic technology, and micro-/nanofabrication. However, bubbles in microfluidic channels always bring out adverse impacts such as cell damage and device malfunction. To prevent bubble formation, numerical simulation and experiments were integrated to reveal the effect of the factors including the internal structure of the channel, internal wettability, and liquid flow rate. On one hand, the simulation results reveal that bubble formation can be prevented by these mentioned factors, the weight of which can be provided by a logistic regression model. In addition, the raised equilibrium equations can efficiently explain the influence of these factors on bubble prevention. On the other hand, the validity of the simulation was further verified by the prevention of bubbles in the water-flowing microchannels. Therefore, this work provides a promising strategy to prevent bubble formation in microchannels, which has wide applications in microfluidic systems.

Microfluidics for Biotechnology: Bridging Gaps to Foster Microfluidic Applications.

Microfluidics and novel lab-on-a-chip applications have the potential to boost biotechnological research in ways that are not possible using traditional methods. Although microfluidic tools were increasingly used for different applications within biotechnology in recent years, a systematic and routine use in academic and industrial labs is still not established. For many years, absent innovative, ground-breaking and “out-of-the-box” applications have been made responsible for the missing drive to integrate microfluidic technologies into fundamental and applied biotechnological research. In this review, we highlight microfluidics’ offers and compare them to the most important demands of the biotechnologists. Furthermore, a detailed analysis in the state-of-the-art use of microfluidics within biotechnology was conducted exemplarily for four emerging biotechnological fields that can substantially benefit from the application of microfluidic systems, namely the phenotypic screening of cells, the analysis of microbial population heterogeneity, organ-on-a-chip approaches and the characterisation of synthetic co-cultures. The analysis resulted in a discussion of potential “gaps” that can be responsible for the rare integration of microfluidics into biotechnological studies. Our analysis revealed six major gaps, concerning the lack of interdisciplinary communication, mutual knowledge and motivation, methodological compatibility, technological readiness and missing commercialisation, which need to be bridged in the future. We conclude that connecting microfluidics and biotechnology is not an impossible challenge and made seven suggestions to bridge the gaps between those disciplines. This lays the foundation for routine integration of microfluidic systems into biotechnology research procedures.

Bio-Inspired Design of Bi/Tridirectionally Anisotropic Sliding Superhydrophobic Titanium Alloy Surfaces.

Many biological surfaces with the multi-scale microstructure show obvious anisotropic wetting characteristics, which have many potential applications in microfluidic systems, biomedicine, and biological excitation systems. However, it is still a challenge to accurately prepare a metal microstructured surface with multidirectional anisotropy using a simple but effective method. In this paper, inspired by the microstructures of rice leaves and butterfly wings, wire electrical discharge machining was used to build dual-level (submillimeter/micrometer) periodic groove structures on the surface of titanium alloy, and then a nanometer structure was obtained after alkali-hydrothermal reaction, forming a three-level (submillimeter/micrometer/nanometer) structure. The surface shows the obvious difference of bidirectional superhydrophobic and tridirectional anisotropic sliding after modification, and the special wettability is easily adjusted by changing the spacing and angle of the inclined groove. In addition, the results indicate that the ability of water droplets to spread along parallel and perpendicular directions on the submillimeter groove structure and the different resistances generated by the inclined groove surface are the main reasons for the multi-anisotropic wettability. The research gives insights into the potential applications of metal materials with multidirectional anisotropic wetting properties.

Acoustic field design in microfluidic geometries via Huygens-Fresnel diffraction and deep neural networks

Creating defined nonuniform acoustic fields, with particle capture locations beyond the grids and lines that are typically generated, has a range of applications in microfluidic systems. In this work, we use a unique interaction between polydimethylsiloxane (PDMS) channel geometries and a travelling substrate wave to explore the creation of nonuniform acoustic fields for microscale pattering. Surface acoustic waves (SAWs) are ideal for generating high-frequency, microscale wavelengths, though conventionally generate particle pattering via the interference between opposing SAW transducers, creating a standing SAW. Our recent work, however, has shown that patterning can alternatively be created using only a single travelling SAW and channel boundaries via diffractive effects, where fringe spacing is a function of the channel wall orientation. Unique to SAW, this creates a condition where the channel shape directly impacts the acoustic field that results, and therefore the possibility of designing acoustic fields by defining the channel geometry. To solve this inverse problem, we implement a machine-learning approach based on a Deep Neural Networks (DNN) that can define channel geometries resulting in desired acoustic fields. This submitted work will introduce the mechanisms via which this diffractive patterning occurs and the implementation of the DNN design process.

Hydrodynamics of active particles confined in a periodically tapered channel

Active particles in diverse circumstances encounter confined channels with asymmetric bounding walls. In the present work, employing the squirmer model, we analyze the trajectory of a single and a pair of active particles in a two-dimensional periodically tapered channel with asymmetric bounding walls through a combined analytical-numerical approach. Assuming Stokes equations for the flow inside the channel, both puller and pusher types of squirmers are treated. We illustrate through phase diagrams how for different projection angles of the squirmer the associated swimming trajectories are non-trivially altered for various tapering angles of the channel. The phase diagram characterizes the trajectory of the squirmer as trapped or escaped depending on these angles. It is observed that for a fixed projection angle, the swimmer exhibits a transition in the swimming state at a critical tapering of the channel. Correspondingly, the combination of the projection and tapering angles may serve as a control mechanism guiding the swimmer for relevant applications in micro-fluidic systems. We further investigate the stability of the individual squirmer trajectory in the presence of a second squirmer, which hints at the development of parallel or coordinated swimming motion inside the channel. The results indicate that the tapering of the channel acts as a decisive parameter in the mutual attraction or repulsion and navigates the collective swimming state of the squirmers.

Application of level-set method in simulation of normal and cancer cells deformability within a microfluidic device

Application of microfluidic systems for the study of cellular behaviors has been a flourishing area of research in the past decade. In the process of probing cell biomechanics the passage of a cell through a narrow microchannel or a small pore has attracted much attention during the recent years. And the study of cellular deformability and transportability using these systems with enhanced resolution and accuracy has opened a new paradigm for high-throughput characterization of both healthy and diseased cell populations.Here we use the level-set method to explore the relationship between the transit time and mechanical properties of normal white blood cells (WBCs) and breast cancer epithelial cells (MCF7) under different microenvironmental parameters (i.e., pressure difference, cell size, effective cell surface tension, constriction size and taper angle) in a 2-D computational domain by considering the cell as a viscous drop. The novel biomechanical relations are obtained for each cell type by the Response Surface Method (RSM), relating microenvironmental parameters to the dimensionless entry time of the normal and cancer cells. Our results revealed that MCF7 cells show asignificantly different behavior (a bifurcating behavior when the pressure difference of inlet/outlet increases) in regards to the dimensionless entry time as a function of microchannel taper angle in comparison with the WBC. These results suggest that the microenvironmental parameters have a significant effect on the transportability of the cells and different cells have different behaviors in response to a specific microenvironmental parameter. Finally, it can be claimed that this method can be also utilized to distinguish between benign and cancerous cells or even to probe tumor heterogeneity toward high throughput cell cytometry.

Direct ink writing combined with metal-assisted chemical etching of microchannels for the microfluidic system applications

Microchannels are critical components of the microfluidic systems. But the low efficiency and high cost of conventional machining methods severely hinder the wide applications of microchannels. Here, we have reported a facile and low-cost strategy for the fabrication of microchannels on silicon substrate based on direct marker pen ink writing (DIW) and metal-assisted chemical etching (MaCE). Firstly, ink patterns were directly written on the bare silicon substrate by DIW without any polymer resist. They were utilized as stable mask in subsequent step, and can be easily removed by ethanol when not needed. Then, Ag nanofilms were deposited on the spaces between ink patterns by electroless deposition. Finally, silicon microchannels were fabricated by MaCE. During MaCE process, the Ag nanofilm was acted as catalyst and hydrogen peroxide-hydrofluoric acid solution was used as etching solution. The mask effect of ink patterns in the DIW-MaCE fabrication strategy was studied, and the effects of etching time, Ag nanofilm thickness, and etchant concentration on the formation of microchannels structures were also investigated. The microchannels structures were also fabricated to demonstrate the applications in microfluidics. We have introduced diamond tips of multi-probe microfabrication equipment to control the geometry and size of ink patterns in this study, and thus the final microchannels structures can be optimized during MaCE. The proposed DIW-MaCE strategy is facile and cost-effective for the fabrication of microchannels, and the microchannels structures are promising for extending the microfluidics and microsensors devices applications.

Self-adaptive flexible valve as passive flow regulator

Valves are widely used in fluidic channel systems to regulate flows. In many applications, maintaining a constant flow rate under varying input conditions is critical. However, current active or passive valves suffer from several drawbacks, such as complex structures, complicated fabrication processes, and complex operational procedures. This paper presents a novel design concept for fluidic channels using a simple structure that can serve as self-adaptive passive valves to regulate flow under external pressure. The design relies on embedding a cantilever-like flap inside a channel to provide a self-regulated closed-loop control of the flow. The flap can passively deform to adapt to the variation of the fluid pressure. A theoretical model is developed and validated by finite-element simulations to understand the flow characteristics of this design. Based on the theoretical model, we provide the design rules for obtaining valves with desired pressure-flow rate responses. Furthermore, by integrating the quantitative design tool and 3D printing, a valve that can maintain a constant flow rate over a certain pressure range is designed, fabricated, and characterized. With support from systematic analysis and rapid manufacturing techniques, the valve design proposed here can open routes for applications in microfluidic systems and drug infusion systems.

Manabu Tokeshi (Ed.): Applications of microfluidic systems in biology and medicine.

Manabu Tokeshi (Ed.): Applications of microfluidic systems in biology and medicine.

Quadri-directionally anisotropic droplets sliding surfaces fabricated by selective laser texturing of aluminum alloy plates

A periodic array patterned superhydrophobic surface consisted of asymmetric multi-directional stairway units was prepared by selective laser texturing of aluminum alloy plate, which was endowed for the first time with the quadri-directionally anisotropic droplets sliding characteristic. Through the layer-by-layer subtractive laser ablation procedure, the unique unequal tread depths of the micron-sized stairway-structure in four directions were ingeniously constructed. The achieved surface with an arbitrary desired sliding angle in any of the four directions constructed a transitional superhydrophobic state between Wenzel’s and Cassie’s states of the supported water droplets. The comprehensive mechanism of the supernatural quadri-directional anisotropy was verified to be mainly summarized into the synergy and balance between the droplet’s resistance effect of gravity force and the pinning-effect controlled adhesion force. The two obstructive effects were verified to be in exact accordance with each other on the movement of water droplets. The quadri-directionally anisotropic sliding droplets characteristic induced by the simple but powerful selective laser texturing method can provide a fresh cognition of anisotropic wettability and enormous potential applications in microfluidic systems for biochemical separation.

Cover Image, Volume 39, Issue 5

The cover image is based on the Original Article Rolling circle amplification and its application in microfluidic systems for E. coli O157:H7 detections by Xudong Cao, Yuqian Jiang, Zhenyu Qiu et al., https://doi.org/10.1111/jfs.12671

Passive fluidic micro-sensor with all-optical readout realized using a direct laser writing technique

In this Letter, we report on design and realization of solvent-sensitive microstructures based on three-dimensional periodic lattices fabricated in a polymeric photoresist. Sensing is based on reversible size change in polymeric microstructures upon immersion in wetting and non-wetting solvents. Its readout is achieved purely optically by observing modification of a Moiré pattern formed by grating-like deformable and rigid polymeric structures. A compact micro-sensor using these principles was realized using a direct laser writing technique in the photoresist. High sensitivity and easy optical readout of the sensor were demonstrated. In the future, sensors based on similar principles may find applications in microfluidic systems, such as lab-on-a-chip.

Application of microfluidic systems for neural differentiation of cells

Neural differentiation of stem cells is an important issue in development of central nervous system. Different methods such as chemical stimulation with small molecules, scaffolds, and microRNA can be used for inducing the differentiation of neural stem cells. However, microfluidic systems with the potential to induce neuronal differentiation have established their reputation in the field of regenerative medicine. Organization of microfluidic system represents a novel model that mimic the physiologic microenvironment of cells among other two and three dimensional cell culture systems. Microfluidic system has patterned and well-organized structure that can be combined with other differentiation techniques to provide optimal conditions for neuronal differentiation of stem cells. In this review, different methods for effective differentiation of stem cells to neuronal cells are summarized. The efficacy of microfluidic systems in promoting neuronal differentiation is also addressed.

Rolling circle amplification and its application in microfluidic systems for Escherichia coli O157:H7 detections

AbstractRolling circle amplification (RCA) has been widely used to enhance detection signals as its long single‐stranded RCA products can provide multiple binding sites for signal probes for sensitive detections. In the current study, we employ atomic force microscopy (AFM) to monitor the RCA products during the course of the RCA process over time. Subsequently, the results of the RCA obtained from the AFM study are combined with those from the conventional electrophoresis method to optimize RCA reactions for rapid and sensitive detection. We show that there appears to be an inhomogeneous RCA initiation phase in early to mid‐stage of the RCA reaction where some chains grow faster while others grow slower or remain dormant, an observation that has not been reported in the literature. Furthermore, we demonstrate that the RCA can significantly enhance detection signals by up to 100‐fold. We also show that the Escherichia coli O157:H7 detection with the RCA can be carried out in different food matrices with excellent detection sensitivities and specificities. In conclusion, these results suggest that a microfluidic device in combination with RCA signal enhancement is a simple and robust approach to sensitive whole‐cell detection in food samples.Practical applicationsThe current research has exciting potentials for applications in sensitive detections of food samples for food safety inspections.

Review on structure, function and applications of microfluidic systems

Microfluidic is the use of special properties of fluids in very small volumes such as Picoliter Nanoliter or Microliter The flow of these fluids is regulated in the micro channels These canals are made in very small dimensions and the material of these microchannels is basically polydimethylsiloxane PDMS This technology is widely used in medical and tissue engineering and research and diagnostic fields The microfluidic device is made up of glass silicon or the like in which the micro channels are inserted into the chip Different methods such as photolithography and so on are used to make these types of chips each with many advantages and disadvantages The microfluidic device has several components each of which has a special function The microfluidic systems have many advantages that make this technology much to be considered

Flexibility of Micromagnetic Flagella in the Presence of an Oscillating Field

Magnetic microbeads have recently been the subject of much study because of their potential applications in microfluidic systems which facilitate mixing [1], labeling [2], separation [3] and transport [4] in lab-on-achip devices. It has been proposed that rotating superparamagnetic beads chains can enhance the mixing efficiency in microfluidic devices [5] and the magnetic micro-bead chain that is subjected to an oscillating field can be used to design a micro-swimmer [6]. To manipulate the micro-beads chain swimming in the low-Reynolds number environment, various magnetic actuation methods have been employed to obtain the higher propulsive efficiency for the locomotion in the viscous fluid. A flexible flagellum is arguably the simplest mechanism to duplicate as it is a one-dimensional structure. However, a challenge to create the stable planar beating motion for propulsion generation is to fabricate the magnetic flagellum simultaneously flexible and stable structure at a microscale. In order to effectively use an oscillating magnetic flagellum as a tail of a microswimmer, the measurement of the bending rigidity for the flexible micro-chains is essential. In this study, the curvatures and the bending rigidity of distorted chains with different lengths subjected to an external field with various controlling parameters (such as the field intensity and frequency) were probed to evaluate the flexibility of the magnetic flagellum. The magnetic flagellum is obtained by combining the self-assembling ability of micro-sized superparamagnetic particles composed the iron oxide magnetite (Fe 3 O 4 ) embedded in polystyrene microspheres suspended in distilled water. Properties of the commercially available micro-beads are density ρ=1500 kg/m3, diameter d = 4.5 μm, initial magnetic susceptibility χ = 1.6, and without magnetic hysteresis or remanence, which could be magnetized under an applying external field and completely demagnetized when the field is removed. Firstly, the magnetic beads magnetized by a homogeneous static field $H_{d}$ tended to aggregate and form the linear flagellum, and a dynamical sinusoidal field $H_{y}$ with a maximum amplitude $H_{p}$ and an adjustable frequency $f$, that is, $H_{y} = H_{p} { sin(2}\pi {ft)}$, were then applied in a direction perpendicular to $H_{d}$. Thus, the planar beating motion is created to form the dynamic flexible flagellum. In order to accurately obtain the chain flexibility and bending rigidity, we model the waggling chains as continuous elastic flagella and analytically derive their curvatures as a function of magnetic field strength. The maximum dimensionless curvature (denoted as $C_{max})$ of the chain is given as $C_{max}=d/R, R$ represents the flagellum’s radius of curvature. The bending rigidity κ of the waggling chain is measured from the S-shape of the chain by using the equation given as [4]: $C_{max}= {(Bd/4)(}\pi {/3}\kappa\mu _{0})^{0.5}$ Where the $\mu _{0}$ represents the vacuum permeability, $B$ is the overall magnetic field strength. Figure 1 shows the most significant deformed shapes for the flexible flagella of various lengths subjected to the increasing field strength. It can be seen that all the chains bend to S-shape for all values of applying field strength, and the deformation increases slightly with an increase in the perpendicular dynamic field intensity H p for each flagellum. On the other hand, the influences of flagellum strengths are not consistent. By examining figure 1 carefully, we found the increase of the length doesn’t enhance the deformation significantly. On the contrary, the longer length as flagellum consisting of 16 particles (denoted as P16) behaves more insignificant S-shape than the counterpart of the P15 chain because of the more significant constraint from the stronger hydrodynamic drag acting on a longer chain. The further inspection of the interesting finding can be done by the examination of figure 2, which shows the geometrical relation between the flagellum’s radius of curvature $R$ and the diameter $d$ of the magnetic bead. It can be seen that for all lengths of flagella the maximum curvature of the flagellum increases linearly with the intensity of the applied field. In addition, the value of $C_{max}$ of the flagellum firstly gets higher then declines with the increase of the length, which indicates the magnetic flagellum subjected to an oscillating field would have the most flexible structure at the certain length. The further discussions are shown in full paper demonstrating the effects of the other controlling parameters on $C_{max}$ and the bending rigidity κ.

The application of microfluidic systems in clinical diagnostics

Currently, clinical laboratories are developing towards two different directions. One is centralized laboratory with automated pipelines, and the other is highly integrated portable detection system.The latter evolved from an early single test device gradually to an integrated platform based on microfluidic technology, which can operate multiple steps and tests simultaneously. The microfluidic system is further developed to a miniaturized device which can perform biochemical, immune, microbial and cytological tests. With the medical reform process in China, the microfluidic systems will appear in the primary health unit or even families. This review concludes the current application of microfluidic technology in clinical diagnostics and its future trends.(Chin J Lab Med, 2018, 41: 631-633) Key words: Microchip analytical procedures; Microfluidics; Clinical laboratory techniques

An Effective Capillary Valve Based on Micro-hole Array for Microfluidic Systems.

With the development of microfluidic systems for portable devices where the capillary force as the driving force drove the liquid in a microchannel. An effective capillary microvalve based on a micro-hole array is proposed in this paper for the purpose of good performance, and programmable control, and easy-to-fabricate. The Wenzel model was used to slow down the velocity of fluid flow. The microvalve was made by a hot-embossing and hot-bonding process. The valve function was assessed by liquid flowing experiments. The results showed that the valve employs an abruptly changing contact angle to slow down the fluid flow. The controlling time is approximately 177 - 213 s. The best control effect was obtained when the contact angle equaled to 90°. The effect of the roughness of the microvalve was also evaluated. Therefore, this work has a great potential and broad prospect for both research and applications in microfluidic systems, such as the portable devices in the medical testing field.

Advances in microfluidic devices made from thermoplastics used in cell biology and analyses.

Silicon and glass were the main fabrication materials of microfluidic devices, however, plastics are on the rise in the past few years. Thermoplastic materials have recently been used to fabricate microfluidic platforms to perform experiments on cellular studies or environmental monitoring, with low cost disposable devices. This review describes the present state of the development and applications of microfluidic systems used in cell biology and analyses since the year 2000. Cultivation, separation/isolation, detection and analysis, and reaction studies are extensively discussed, considering only microorganisms (bacteria, yeast, fungi, zebra fish, etc.) and mammalian cell related studies in the microfluidic platforms. The advantages/disadvantages, fabrication methods, dimensions, and the purpose of creating the desired system are explained in detail. An important conclusion of this review is that these microfluidic platforms are still open for research and development, and solutions need to be found for each case separately.

Rhodamine based turn-on fluorescent sensor for Hg2+ and its application of microfluidic system and bioimaging

In this paper, a new rhodamine derivative bearing thiazole and thiocarbonyl moieties 1 was synthesized and its sensing behaviors toward various metal ions were investigated by fluorescence spectroscopies and UV/Vis. The ring-opening process of spirolactam enables the selective fluorescence enhancement and colorimetric change for Hg2+ in CH3CN-HEPES buffer (0.01 M, pH 7.4) (3:7, v/v). The selectivity and sensitivity of 1 towards Hg2+ lead to sensor 1 applied to microfluidic device and even used to functions Hg2+ sensing in Hela cells.