Methods for counting particles in microfluidic applications

Microfluidic particle counters are important tools in biomedical diagnostic applications such as flow cytometry analysis. Major methods of counting particles in microfluidic devices are reviewed in this paper. The microfluidic resistive pulse sensor advances in sensitivity over the traditional Coulter counter by improving signal amplification and noise reduction techniques. Nanopore-based methods are used for single DNA molecule analysis and the capacitance counter is useful in liquids of low electrical conductivity and in sensing the changes of cell contents. Light-scattering and light-blocking counters are better for detecting larger particles or concentrated particles. Methods of using fluorescence detection have the capability for differentiating particles of similar sizes but different types that are labeled with different fluorescent dyes. The micro particle image velocimetry method has also been used for detecting and analyzing particles in a flow field. The general limitation of microfluidic particle counters is the low throughput which needs to be improved in the future. The integration of two or more existing microfluidic particle counting techniques is required for many practical on-chip applications.     

Numerical simulation of the motion of granular material using object-oriented techniques

The objective of this contribution is to present a numerical simulation method to model the motion of a packed bed on a moving grate or in a rotary kiln using object-oriented techniques. The packed bed can be described as granular material consisting of a large number of particles. The method chosen is the Lagrangian time-driven method and it uses the position, the orientation, the velocity and the angular velocity of particles as independent variables. These are obtained by time integration of the three-dimensional dynamics equations which were derived from the classical Newtonian mechanics approach based on the second law of Newton for the translation and rotation of each particle in the granular material. This includes keeping track of all forces and moments acting on each particle at every time-step. Particles are treated as contacting visco-elastic bodies which can overlap each other. Contact forces depend on the overlap geometry, material properties and dynamics of particles and include normal and tangential components of repulsion force with visco-elastic models for energy dissipation through internal and surface friction. The resulting equations of particle motion are solved by the Gear predictor–corrector scheme of fifth-order accuracy.The simulation method is based on object-oriented methodologies and programmed in the programming language C++. This approach supports objects which can be used for three-dimensional particles of various shapes and sizes and for walls as boundaries. The programming modules are implemented in the TOSCA (tools of object-oriented software for continuum mechanic applications) software package which allows for a high degree of flexibility and for shortening the duration of the software development process. As methods for particle motion may deal with particles of different sizes and materials, the approach allows to describe transport processes in technical applications.     

Soft medical robotics: clinical and biomedical applications,challenges, and future directions

Bioinspired soft robotics allow for safer clinical interactions with human patients but conventional, hard robots, which are often built with rigid materials and complex control systems, compromise tissue integrity, freedom of movement, conformability, and overall human bio-compatibility. Soft, compliant materials intrinsically reduce mechanical complexity, accommodate their usage environment, and provide great practical potential for medical device developments. Previous review papers have generally covered the topics of materials, manufacturing processes, actuator modeling and control, and current trends. Here, we focus on recent developments in soft robotic applications for the medical field including advances in cardiac devices, surgical robots, and soft rehabilitation and assistance devices. In medical applications, soft robotic devices not only expedite the evolution of minimally invasive surgery but also improve the bio-compatibility of rehabilitation and assistance devices. Here, we evaluate design requirements, mechanisms, achievements and challenges in these key areas. Of particular note, this paper concludes with a discussion on advances in 3D printing and adapting neural networks for modeling and control frameworks that have facilitated the development of faster and less expensive soft medical devices.     

Transport of drug particles in micropumps through novel actuation

Micropumps with various types of actuations have been used in lab-on-a-chip devices. In order to control the delivery of drug particles both in space and time and avoid clogging, other types of actuation mechanisms may be needed. In this study, a valveless micropump with novel actuation is proposed to transport particles for biomedical and environmental applications. The transport of drug particles through the designed valveless micropump is carried out through computational fluid dynamics combined with discrete particle transport methods. After convergence studies, the effects of actuation frequency, particle size and the resident times on the particle transport are investigated. Interestingly, both the actuation frequency and particle size have a strong effect in terms of resident times and the spatial distribution of the transported particles through the designed micropump. Based on the results obtained, the relationship between actuation frequency, fluid flow, and particle transport through the designed micropump is presented. The computational analysis presented demonstrates that it is possible to optimize the proposed valveless micropump design for specific delivery of drug particles for separation and sorting applications.     

Particle squeezing in narrow confinements

Many lab-on-a-chip applications require processing of droplets, cells, and particles using narrow confinements. The physics governing the process of a particle squeezing through narrow confinement is complex. Various models and applications have been developed in this area in recent years. In the present paper, we review the physics, modeling approaches, and designs of narrow confinements for the control of deformable droplets, cells, and particles. This review highlights the interdisciplinary nature of the problem, since the experimental, analytical, and numerical methods used in studies of particle squeezing through narrow confinements come from various fields of science and technology.     

Enhancing microcantilever capability with integrated AC electroosmotic trapping

Microcantilevers are finding wide applications in detecting biochemical agents. However, their usage has been limited to highly concentrated samples to ensure sufficient deposition of agents onto cantilevers. A pre-concentration or enrichment step will expand their application range to more dilute, practical samples and real-time detection. This paper reports the integration of in-situ particle concentrators on microcantilevers. Only a thin metal layer on microcantilevers is required to generate microfluidic convection of particles from solution bulk onto microcantilever surfaces, greatly enriching local particle counts and enhancing sensitivity of the system. A working prototype is presented in the paper. Preliminary experiments concentrating latex particles were conducted and the particle concentration effect has been experimentally verified using AFM probes as microcantilevers. As ACEO concentrator has no dependence on particle properties, the method is expected to be applicable to bio-particles collection.     

Microfluidic systems for diagnostic applications: a review

Because of intensive developments in recent years, the microfluidic system has become a powerful tool for biological analysis. Entire analytic protocols including sample pretreatment, sample/reagent manipulation, separation, reaction, and detection can be integrated into a single chip platform. A lot of demonstrations on the diagnostic applications related to genes, proteins, and cells have been reported because of their advantages associated with miniaturization, automation, sensitivity, and specificity. The aim of this article is to review recent developments in microfluidic systems for diagnostic applications. Based on the categories of various fluid-manipulating mechanisms and biological detection approaches, in-depth discussion of the microfluidic-based diagnostic systems is provided. Moreover, a brief discussion on materials and manufacturing techniques will be included. The current excellent integration of microfluidic systems and diagnostic applications suggests a solid foundation for the development of practical point-of-care devices.     

Nanoparticles in polymer-matrix composites

Regarding the development of nanoparticles for polymer matrix composites the particle/agglomerate size and particle/agglomerate distribution in the composites, respectively, is often crucial. This is exemplarily shown for, e.g. optical applications with measurements of refractive index and transmittance. Classical blending techniques, where nanoparticles are dispersed in polymers or resins, are compared to a combination of a special gas-phase synthesis method with subsequent in-situ deposition of nanoparticles in high-boiling liquids. The particles/agglomerates were characterized regarding particle size and particle size distribution using transmission electron microscopy and dynamic light scattering. Additionally, important material properties like mechanical properties, relevant for application, or like viscosity, relevant for processing, are determined. It is shown, that with in-situ dispersed nanoparticles synthesized in a microwave plasma process composites with finely dispersed particles/agglomerates are attainable.     

Liquid wicking behavior in paper-like materials: mathematical models and their emerging biomedical applications

Paper-like materials have found widespread applications in various fields, especially recently emerging applications in biomedicine as paper-based devices, where liquid wicking behavior plays a significant role. Although tremendous experimental evidence has indicated that fluid control is a key technology to improve the performance of these paper-based devices, the underlying mechanisms of liquid wicking behavior in paper-like materials remain unclear. Numerical and mathematical techniques provide effective strategy and great potential in understanding the liquid flowing process in the complex fibrous structure of paper-like materials. In this review, we first present the basic physical process and key factors of liquid wicking behavior in paper-like materials. Furthermore, we review various macroscopic and mesoscopic mathematical models on fluid flow in porous materials, focusing on each model’s advantages and challenges, and summarize their related biomedical applications. The aims are to better understand the underlying mechanisms of liquid wicking behavior in paper-like materials through mathematical models and to provide guidance in the design and optimization of paper-based biomedical devices.     

Diamagnetic particle focusing using ferromicrofluidics with a single magnet

Focusing particles into a tight stream is critical to many applications such as microfluidic flow cytometry and particle sorting. Current magnetic field-induced particle focusing techniques rely on the use of a pair of repulsive magnets, which makes the device integration and operation difficult. We develop herein a new approach to focusing nonmagnetic particles in ferrofluid flow through a T-microchannel using a single permanent magnet. Particles are deflected across the suspending ferrofluid by negative magnetophoresis and confined by a water flow to the center plane of the microchannel, leading to a focused particle stream flowing near the bottom channel wall. Such three-dimensional diamagnetic particle focusing is demonstrated in a sufficiently diluted ferrofluid through both the top and side views of the microchannel. As the suspended particles can be visualized in bright field, this magnetic focusing method is expected to find applications to label-free (i.e., no magnetic or fluorescent labeling) cellular focusing in lab-on-a-chip devices.     

On the direct employment of dipolar particle interaction in microfluidic systems

This review article will summarize recent developments in the employment of dipolar coupled magnetic particle structures. We will discuss the basics of magnetic dipolar particle interaction in static and rotating magnetic fields. In dependence on the magnetic fields employed, agglomerates of different dimensionality may form within the carrier liquid. The stability and formation dynamics of these particle structures will be presented. Furthermore, we will review recent microfluidic applications based on the interaction of magnetic particles and present methods for surface patterning with micron-sized and nano-sized particles which employ dipolar particle coupling.     

Aggregation dynamics of particles in a microchannel due to an applied magnetic field

Functionalized magnetic microspheres have promising applications in different microfluidic devices including MEMS-scale biosensors. These particles exhibit magnetic field-induced aggregation, which can be harnessed to achieve several practical tasks in microfluidic devices. For this, the particle aggregation needs to be well characterized. Herein, a numerical simulation and experimental validation of particle-chaining is presented. Simulations show that the particle aggregation time scales linearly with a group parameter. The predicted growth of one- two- and three-particle chains with time shows a similar trend as that found in the experiments. The results of the study could help predicting the performance of magnetic aggregate-based lab-on-a-chip devices.     

Streamline generation code for particle dynamics description in numerical models of turbulence

Streamline Version 4 is a versatile Fortran 77 & C++ program for calculating charged test particle trajectories or field-lines for user-specified fields using the test-particle method. The user has the freedom to specify any type of field (analytical, tabulated in files, time dependent, etc.) and maintains complete control over initial conditions of trajectories/field-lines and boundary conditions of specified fields. The structure of Streamline was redesigned from previous versions in order to know not only particle or field-lines positions and velocities at each step of the simulations, but also the instantaneous field values as seen by particles. This was made to compute the instantaneous value of the particle’s magnetic moment, but other applications are possible too. Accuracy tests of the code are shown for different cases, i.e., particles moving in constant magnetic field, magnetic plus constant electric field and wave field. In addition in the last part of the paper we concentrate our discussion on the study of velocity space diffusion of charged particles in turbulent slab fields, paying attention to the discretization of the fields and the temporal discretization of the dynamical equations. The diffusion of charged particles is a very common topic in plasma physics and astrophysics since it plays an important role in many different phenomena such as stochastic particle acceleration, diffusive shock acceleration, solar energetic particle propagation, and the scattering required for the solar modulation of galactic cosmic rays.     

Electrochemical detection techniques in micro- and nanofluidic devices

Electrochemical techniques are widely used in microfluidic and nanofluidic devices because they are suitable for miniaturization, have better sensitivity compared to optical detection techniques, and their components can be reliably microfabricated. In addition to the detection and quantification of analytes, electrochemical techniques can be used to monitor processes such as biological cell death and protein/DNA separations/purifications. Such techniques are combined with micro- and nanofluidic devices with point-of-care (POC) applications in mind, where cost, footprint, ease of use, and independence from peripheral equipment are critical for a viable design. A large variety of electrode materials and device configurations have been employed to meet these requirements. This review introduces the reader to the major electrochemical techniques, materials, and fabrication methods for working and reference electrodes, and to surface modifications of electrodes to facilitate electrochemical measurements, in the context of micro- and nanofluidic devices. The continuing development of these techniques holds promise for the next-generation lab-on-a-chip devices, which can realize the goals of this technology such as POC clinical analysis.     

Ultra-thin films and multigate devices architectures for future CMOS scaling

The nanoelectronics industry is facing historical challenges to scale down CMOS devices to meet demands for low voltage, low power, high performance and increased functionality. Using new materials and devices architectures is necessary. HiK gate dielectrics and metal gates have been introduced and have shown their ability to reduce power consumption. Fully depleted ultra-thin SOI devices are a good alternative to bulk for low power applications. Multigate devices are the current goal in device architecture...     

Particle focusing in a contactless dielectrophoretic microfluidic chip with insulating structures

The focusing of biological and synthetic particles in microfluidic devices is a crucial step for the construction of many microstructured materials as well as for medical applications. The present study examines the feasibility of using contactless dielectrophoresis (cDEP) in an insulator-based dielectrophoretic (iDEP) microdevice to effectively focus particles. Particles 10?μm in diameter were introduced into the microchannel and pre-confined hydrodynamically by funnel-shaped insulating structures near the inlet. The particles were repelled toward the center of the microchannel by the negative DEP forces generated by the insulating structures. The microchip was fabricated based on the concept of cDEP. The electric field in the main microchannel was generated using electrodes inserted into two conductive micro-reservoirs, which were separated from the main microchannel by 20-μm-thick insulating barriers made of polydimethylsiloxane (PDMS). The impedance spectrum of the thin insulating PDMS barrier was measured to investigate its capacitive behavior. Experiments employing polystyrene particles were conducted to demonstrate the feasibility of the proposed microdevice. Results show that the particle focusing performance increased with increasing frequency of the applied AC voltage due to the reduced impedance of PDMS barriers at high frequencies. When the frequency was above 800?kHz, most particles were focused into a single file. The smallest width of focused particles distributed at the outlet was about 13.1?μm at a frequency of 1?MHz. Experimental results also show that the particle focusing performance improved with increasing applied electric field strength and decreasing inlet flow rate. The usage of the cDEP technique makes the proposed microchip mechanically robust and chemically inert.     

Application of polydopamine in biomedical microfluidic devices

Polydopamine (PDA) is a bioinspired material with tremendous potential for applications involving surface modifications. By simply immersing the substrate in the dopamine monomer solution, we are able to apply a hydrophilic and biofunctional PDA coating that adheres strongly to any surface, including (super)hydrophobic surface, with unprecedented ease. Using PDA, almost any materials can be immobilized on the surface in a single step by mixing them with the dopamine monomer solution. This review provides a comprehensive coverage of the applications of PDA in the device fabrication, surface modification, and biofunctionalization of biomedical microfluidic devices. While discussing the advantages and limitations of PDA, we pay special attention to its unique properties that specifically benefit biomedical microfluidic devices. We also discuss other potential applications of PDA beyond the current development. Through this review, we hope to promote PDA and encourage a broader adoption of PDA by the microfluidic community.     

Metamaterial band theory： fundamentals ＆ applications

Remarkable progress has been made over the past decade in controlling light propagation and absorption in compact devices using nanophotonic structures and metamaterials. From sensing and modulation, to on-chip communication and light trapping for solar cells, new device applications and opportunities motivate the need for a rigorous understanding of the modal properties of metamaterials over a broad range of frequencies. In this review, we provide an overview of a metamaterial band theory we have developed that rigorously models the behavior of metamaterials made of dispersive materials such as metals. The theory extends traditional photonic band theory for periodic dielectric structures by coupling the mechanical motion of electrons in the metal directly to Maxwell＇s equations. The solution for the band structures of metamaterials is then reduced to a standard matrix eigenvalue problem that nevertheless fully takes into account the dispersive properties of the constituent materials. As an application of the metamaterial band theory, we show that one can develop a perturbation formalism based on this theory to physically explain and predict the effect of dielectric refractive index modulation or metallic plasma frequency variation in metamaterials. Furthermore, the metamaterial band theory also provides an intuitive physical picture of the source of modal material loss, as well as a rigorous upper bound on the modal material loss rate of any plasmonic, metamaterial structure. This in turn places fundamental limits on the broadband operation of such devices for applications such as photodetection and absorption.     

Production of uniform droplets using membrane, microchannel and microfluidic emulsification devices

This review provides an overview of major microengineering emulsification techniques for production of monodispersed droplets. The main emphasis has been put on membrane emulsification using Shirasu Porous Glass and microsieve membrane, microchannel emulsification using grooved-type and straight-through microchannel plates, microfluidic junctions and flow focusing microfluidic devices. Microfabrication methods for production of planar and 3D poly(dimethylsiloxane) devices, glass capillary microfluidic devices and single-crystal silicon microchannel array devices have been described including soft lithography, glass capillary pulling and microforging, hot embossing, anisotropic wet etching and deep reactive ion etching. In addition, fabrication methods for SPG and microseive membranes have been outlined, such as spinodal decomposition, reactive ion etching and ultraviolet LIGA (Lithography, Electroplating, and Moulding) process. The most widespread application of micromachined emulsification devices is in the synthesis of monodispersed particles and vesicles, such as polymeric particles, microgels, solid lipid particles, Janus particles, and functional vesicles (liposomes, polymersomes and colloidosomes). Glass capillary microfluidic devices are very suitable for production of core/shell drops of controllable shell thickness and multiple emulsions containing a controlled number of inner droplets and/or inner droplets of two or more distinct phases. Microchannel emulsification is a very promising technique for production of monodispersed droplets with droplet throughputs of up to 100?l?h^?1.     

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.