Magnetically-actuated artificial cilia for microfluidic propulsion

In this paper we quantitatively analyse the performance of magnetically-driven artificial cilia for lab-on-a-chip applications. The artificial cilia are fabricated using thin polymer films with embedded magnetic nano-particles and their deformation is studied under different external magnetic fields and flows. A coupled magneto-mechanical solid-fluid model that accurately captures the interaction between the magnetic field, cilia and fluid is used to simulate the cilia motion. The elastic and magnetic properties of the cilia are obtained by fitting the results of the computational model to the experimental data. The performance of the artificial cilia with a non-uniform cross-section is characterised using the numerical model for two channel configurations that are of practical importance: an open-loop and a closed-loop channel. We predict that the flow and pressure head generated by the artificial cilia can be as high as 18 microlitres per minute and 3 mm of water, respectively. We also study the effect of metachronal waves on the flow generated and show that the fluid propelled increases drastically compared to synchronously beating cilia, and is unidirectional. This increase is significant even when the phase difference between adjacent cilia is small. The obtained results provide guidelines for the optimal design of magnetically-driven artificial cilia for microfluidic propulsion.     

Efficient energy based modeling and experimental validation of liquid filling in planar micro-fluidic components and networks

This paper presents a model that describes how liquid flow fills micro-fluidic components and networks. As an alternative to computational fluid dynamic (CFD) simulations, we use a constrained energy minimization approach. This approach is based on two assumptions that hold in many micro-fluidic devices: (i) The length scales are small, and we consider slow filling rates, hence fluid momentum and viscous terms are small compared to surface tension forces, consequently the liquid/gas interfaces can be viewed as a succession of quasi-steady equilibrium configurations. (ii) Any equilibrium configuration corresponds to a surface tension energy minima which is constrained by the device shape and the volume of liquid in the device. The model is developed for planar micro-fluidic devices, is based on a fundamental physical principle, and shows accurate agreement with experimental data. It takes us only a few minutes to evaluate the model for a planar component of any shape using the Surface Evolver software, and this is significantly less then the computer run time required for CFD simulations. Moreover, once a library of component models has been created (which takes less than an hour of computer time) it then takes only seconds to simulate different network architectures with thousands of components. This fast "reconfigure the network and simulate in seconds" capability is essential for the design of truly complex networks that will enable the next generation of passive, micro-fluidic, lab-on-a-chip systems.     

Review on recent and advanced applications of monoliths and related porous polymer gels in micro-fluidic devices

This review critically summarises recent novel and advanced achievements in the application of monolithic materials and related porous polymer gels in micro-fluidic devices appearing within the literature over the period of the last 5 years (2005-2010). The range of monolithic materials has developed rapidly over the past decade, with a diverse and highly versatile class of materials now available, with each exhibiting distinct porosities, pore sizes, and a wide variety of surface functionalities. A major advantage of these materials is their ease of preparation in micro-fluidic channels by in situ polymerisation, leading to monolithic materials being increasingly utilised for a larger variety of purposes in micro-fluidic platforms. Applications of porous polymer monoliths, silica-based monoliths and related homogeneous porous polymer gels in the preparation of separation columns, ion-permeable membranes, preconcentrators, extractors, electrospray emitters, micro-valves, electrokinetic pumps, micro-reactors and micro-mixers in micro-fluidic devices are discussed herein. Procedures used in the preparation of monolithic materials in micro-channels, as well as some practical aspects of the micro-fluidic chip fabrication are addressed. Recent analytical/bioanalytical and catalytic applications of the final micro-fluidic devices incorporating monolithic materials are also reviewed.     

An integrated CMOS high voltage supply for lab-on-a-chip systems

Electrophoresis is a mainstay of lab-on-a-chip (LOC) implementations of molecular biology procedures and is the basis of many medical diagnostics. High voltage (HV) power supplies are necessary in electrophoresis instruments and are a significant part of the overall system cost. This cost of instrumentation is a significant impediment to making LOC technologies more widely available. We believe one approach to overcoming this problem is to use microelectronic technology (complementary metal-oxide semiconductor, CMOS) to generate and control the HV. We present a CMOS-based chip (3 mm x 2.9 mm) that generates high voltages (hundreds of volts), switches HV outputs, and is powered by a 5 V input supply (total power of 28 mW) while being controlled using a standard computer serial interface. Microchip electrophoresis with laser induced fluorescence (LIF) detection is implemented using this HV CMOS chip. With the other advancements made in the LOC community (e.g. micro-fluidic and optical devices), these CMOS chips may ultimately enable 'true' LOC solutions where essentially all the microfluidics, photonics and electronics are on a single chip.     

Continuous and reversible mixing or demixing of nanoparticles by dielectrophoresis

Mixing and demixing (separation) are essential tasks in microfluidic devices, which seem to be contrary in nature. Accordingly, completely different strategies and devices are usually employed for their realization. We here present a microfluidic device which is capable of performing both these tasks as it can be operated in either mixing or demixing mode. The mixing and demixing processes are reversible and are accomplished by continuous operation of the device. An asymmetric S-shaped ridge extends over the full width of a microfluidic channel (200 μm) creating a constriction of 620 nm in height with an aspect ratio of 1 : 500. Appropriate AC and DC voltages generate electrodeless dielectrophoresis at the constriction as well as (linear) electrokinetic driving forces along the channel. These de/mixing parameters can be adapted in real time in such a way that continuous separation and mixing efficiencies of 85-100% can be achieved. As a proof of concept we demonstrate continuous mixing and demixing of polystyrene nanoparticles (20 and 100 nm). The experimental results are complemented by numerical simulations illustrating the particles' motion under the influence of the electrokinetic effects and thermal noise (diffusion). The monolithic one-step fabrication process by soft lithography (with PDMS in our case) will make integration and combination of several mixing and demixing functions into a more complex lab-on-a-chip device possible.     

Designing synthetic, pumping cilia that switch the flow direction in microchannels

Using computational modeling, we simulate the 3D movement of actuated cilia in a fluid-filled microchannel. The cilia are modeled as deformable, elastic filaments, and the simulations capture the complex fluid-structure interactions among these filaments, the channel walls, and the surrounding solution. The cilia are tilted with respect to the surface and are actuated by a sinusoidal force that is applied at the free ends. We find that these cilia give rise to a unidirectional flow in the system and by simply altering the frequency of the applied force we can controllably switch the direction of the net flow. The findings indicate that beating, synthetic cilia could be harnessed to regulate the fluid streams in microfluidic devices.     

Purification and enrichment of virus samples utilizing magnetic beads on a microfluidic system

This study reports a new microfluidic system with three integrated functional devices for pumping, mixing and separation of bio-samples by utilizing micro-electro-mechanical-systems technology. By using antibody-conjugated magnetic beads, the developed system can be used to purify and enrich virus samples such that the subsequent detection of viruses can be performed with a higher sensitivity. The target viruses were first captured by the antibody coated onto the magnetic beads by using a rotary micromixer which performed the incubation process. The viruses were then purified and enriched by a magnetic field generated by planar microcoils. The integrated microfluidic system can perform the whole purification and enrichment process automatically using a rotary micropump and appropriate microvalves. In addition, a numerical simulation was also employed to optimize the design of the microcoils and to investigate the magnetic field strength and distribution. The simulation results were consistent with experimental observations. Finally, the developed system was used to successfully perform the purification and enrichment of Dengue viruses. The detectable limit of Dengue viruses was found to be as low as 10(2) pfu ml(-1) by using this approach. Therefore, the integrated microsystem can perform incubation, transportation, mixing and purification of virus samples, possibly making it a promising platform for future biological and medical applications.     

A novel single-step fabrication technique to create heterogeneous poly(ethylene glycol) hydrogel microstructures containing multiple phenotypes of mammalian cells

In this study, a novel method for the one-step fabrication of stacked hydrogel microstructures using a microfluidic mold is presented. The fabrication of these structures takes advantage of the laminar flow regime in microfluidic devices, limiting the mixing of polymer precursor solutions. To create multilayered hydrogel structures, microfluidic devices were rotated 90 degrees from the traditional xy axes and sealed with a cover slip. Two discreet fluidic regions form in the channels, resulting in the multilayered hydrogel upon UV polymerization. Multilayered patterned poly(ethylene glycol) hydrogel arrays (60 mum tall, 250 mum wide) containing fluorescent dyes, fluorescein isothiocyanate, and tetramethylrhodamine isothiocyanate were created for imaging purposes. Additionally, this method was used to generate hydrogel layers containing murine fibroblasts and macrophages. The cell adhesion promoter, RGD, was added to hydrogel precursor solution to enhance fibroblast cell spreading within the hydrogel matrix in one layer, but not the other. We were able to successfully generate patterns of hydrogels containing multiple phenotypes by using this technique.     

Magnetically actuated artificial cilia: the effect of fluid inertia

Natural cilia are hairlike microtubule-based structures that are able to move fluid on the micrometer scale using asymmetric motion. In this article, we follow a biomimetic approach to design artificial cilia lining the inner surfaces of microfluidic channels with the goal of propelling fluid. The artificial cilia consist of polymer films filled with superparamagnetic nanoparticles, which can mimic the motion of natural cilia when subjected to a rotating magnetic field. To obtain the magnetic field and associated magnetization local to the cilia, we solve the Maxwell equations, from which the magnetic body moments and forces can be deduced. To obtain the ciliary motion, we solve the dynamic equations of motion, which are then fully coupled to the Navier-Stokes equations that describe the fluid flow around the cilia, thus taking full account of fluid inertial forces. The dimensionless parameters that govern the deformation behavior of the cilia and the associated fluid flow are arrived at using the principle of virtual work. The physical response of the cilia and the fluid flow for different combinations of elastic, fluid viscous, and inertia forces are identified.     

Direct optical emission spectroscopy of liquid analytes using an electrolyte as a cathode discharge source (ELCAD) integrated on a micro-fluidic chip

Atomic emission detection of metallic species in aqueous solutions has been performed using a miniaturised plasma created within a planar, glass micro-fluidic chip. Detection was achieved using an Electrolyte as a Cathode Discharge source (ELCAD) in which the sample solution itself is used as the cathode for the discharge. To realise the ELCAD technique within a micro-fluidic device, a parallel liquid-gas flow was set up in a micro-channel and a glow discharge ignited between the flowing liquid sample surface and a metal wire anode. The detection of copper and sodium was achieved, using atmospheric pressure air as a carrier gas, by observation of atomic emission lines of copper at 324 nm, 327 nm, 511 nm, 515 nm and 522 nm and an atomic emission line of sodium at 589 nm using a commercially available miniaturised spectrometer. A total electrical power of less than 70 mW was required to sustain the discharge. A semi-quantitative, absolute detection limit of 17 nmol s(-1) was obtained for sodium with a sample flow rate of 100 microL min(-1) and an integration time of 100 ms in air at atmospheric pressure. The volume required for such detection is approximately 170 nL. Further analysis was performed with an Echelle spectrometer using both argon and air as a carrier gas. The geometry and flow rates used demonstrate the feasibility of integrating such micro-plasmas into other micro-fluidic devices, such as miniaturised CE devices, as a method of detection. The potential for using such micro-plasmas within highly portable miniaturised systems and mu-TAS devices is presented and discussed.     

Parallel mixing of photolithographically defined nanoliter volumes using elastomeric microvalve arrays

Portable microfluidic systems provide simple and effective solutions for low-cost point-of-care diagnostics and high-throughput biomedical assays. Robust flow control and precise fluidic volumes are two critical requirements for these applications. We have developed a monolithic polydimethylsiloxane (PDMS) microdevice that allows for storing and mixing subnanoliter volumes of aqueous solutions at various mixing ratios. Filling and mixing is controlled via two integrated PDMS microvalve arrays. The volumes of the microchambers are entirely defined by photolithography, hence volumes from picoliter to nanoliter can be fabricated with high precision. Because the microvalves do not require an energy input to stay closed, fluid can be stored in a highly portable fashion for several days. We have confirmed the mixing precision and predictability using fluorescence microscopy. We also demonstrate the application of the device for calibrating fluorescent calcium indicators. Due to the biocompatibility of PDMS, the device will have broad applications in miniaturized diagnostic assays as well as basic biological studies.     

Rapid method for design and fabrication of passive micromixers in microfluidic devices using a direct-printing process

We developed a facile and rapid one-step technique for design and fabrication of passive micromixers in microfluidic devices using a direct-printing process. A laser printing mechanism was dexterously adopted to pattern the microchannels with different gray levels using vector graphic software. With the present method, periodically ordered specific bas-relief microstructures can be easily fabricated on transparencies by a simple printing process. The size and shape of the resultant microstructures are determined by the gray level of the graphic software and the resolution of the laser printer. Patterns of specific bas-relief microstructures on the floor of a channel act as obstacles in the flow path for advection mixing, which can be used as efficient mixing elements. The mixing effect of the resultant micromixer in microfluidic devices was evaluated using CCD fluorescence spectroscopy. We found that the mixing performance depends strongly on the gray level values. Under optimal conditions, fast passive mixing with our periodic ordered patterns in microfluidic devices has been achieved at the very early stages of the laminar flow. In addition, fabrication of micromixers using the present versatile technique requires less than an hour. The present method is promising for fabrication of micromixers in microfluidic devices at low cost and without complicated devices and environment, providing a simple solution to mixing problems in the micro-total-analysis-systems field.     

Passive and Active Mixing in Microfluidic Devices

In microfluidics the Reynolds number is small, preventing turbulence as a tool for mixing, while diffusion is that slow that time does not yield an alternative. Mixing in microfluidics therefore must rely on chaotic advection, as well-known from polymer technology practice where on macroscale the high viscosity makes the Reynolds numbers low and diffusion slow. The mapping method is used to analyze and optimize mixing also in microfluidic devices. We investigate passive mixers like the staggered herringbone micromixer (SHM), the barrier embedded micromixer (BEM) and a three-dimensional serpentine channel (3D-SC). Active mixing is obtained via incorporating particles that introduce a hyperbolic flow in e.g. two dimensional serpentine channels. Magnetic beads chains-up in a flow after switching on a magnetic field. Rotating the field creates a physical rotor moving the flow field. The Mason number represents the ratio of viscous forces to the magnetic field strength and its value determines the fate of the rotor: a single, an alternating single and double, or a multiple part chain-rotor results. The type of rotor determines the mixing quality with best results in the alternating case where crossing streamlines introduce chaotic advection. Finally, an active mixing device is proposed that mimics the cilia in nature. The transverse flow induced by their motion indeed enhances mixing at the microscale.     

Progress in the realisation of an autonomous environmental monitoring device for ammonia

Progress in the development of a micro-fluidic system for colorimetric monitoring of ammonia in drinking and wastewater is described. The ultimate goal is to have a miniaturised instrument that can produce accurate, reliable measurements, is easy to operate, has minimal power consumption, and can operate autonomously for a year. In this study, the indophenol reaction is incorporated into a simple, reliable analytical micro-fluidic system. Absorbance measurements for the blue ammonia-indophenol complex formed in the micro-fluidic system are shown. A key issue is the limiting stability of hypochlorite, a reagent used in the assay. The effects of hypochlorite concentration and impurities on the stability of hypochlorite are investigated and discussed. Decomposition is shown to be very dependent on the presence of heavy-metal impurities. With low levels of these catalytic metals and careful storage, hypochlorite has been shown to be stable for over a year.     

Feedback control system simulator for the control of biological cells in microfluidic cross slots and integrated microfluidic systems

Control systems for lab on chip devices require careful characterisation and design for optimal performance. Traditionally, this involves either extremely computationally expensive simulations or lengthy iteration of laboratory experiments, prototype design, and manufacture. In this paper, an efficient control simulation technique, valid for typical microchannels, Computed Interpolated Flow Hydrodynamics (CIFH), is described that is over 500 times faster than conventional time integration techniques. CIFH is a hybrid approach, utilising a combination of pre-computed flows and hydrodynamic equations and allows the efficient simulation of dynamic control systems for the transport of cells through micro-fluidic devices. The speed-ups achieved by using pre-computed CFD solutions mapped to an n-dimensional control parameter space, significantly accelerate the evaluation and improvement of control strategies and chip design. Here, control strategies for a naturally unstable device geometry, the microfluidic cross-slot, have been simulated and optimal parameters have been found for proposed devices capable of trapping and sorting cells.     

Towards Artificial Visual Sensory System: Organic Optoelectronic Synaptic Materials and Devices

Developing an artificial visual sensory system requires optoelectronic materials and devices that can mimic the behavior of biological synapses. Organic/polymeric semiconductors have emerged as promising candidates for optoelectronic synapses due to their tunable optoelectronic properties, mechanic flexibility, and biological compatibility. In this review, we discuss the recent progress in organic optoelectronic synaptic materials and devices, including their design principles, working mechanisms, and applications. We also highlight the challenges and opportunities in this field and provide insights into potential applications of these materials and devices in next-generation artificial visual systems. By leveraging the advances in organic optoelectronic materials and devices, we can envision its future development in artificial intelligence.     

The CellCard System: a novel approach to assessing compound selectivity for lead prioritization of G protein-coupled receptors

Advances in high throughput screening technologies have led to the identification of many small molecules, "hits", with activities toward the target of interest. And, as the screening technologies become faster and more robust, the rate at which the molecules are identified continues to increase. This evolution of high throughput screening technologies has generated a significant strain on the laboratories involved with the downstream profiling of these hits using cell-based assays. The CellCard System, by enabling multiple targets and/or cell lines to be assayed simultaneously within a single well, provides a platform on which selectivity screening can be quickly and robustly performed. Here we describe two case studies using the beta-lactamase and beta-galactosidase reporter gene systems to characterize G protein-coupled receptor agonist activity. Using these examples we demonstrate how the implementation of this technology enables assay miniaturization without micro-fluidic devices as well as how the inclusion of intra-well controls can provide a means of data quality assessment within each well.     

Superior mechanical properties of dense and porous organic/inorganic hybrid thin films

The intrinsic mechanical properties of a given material strongly depend upon its chemical nature: the organics tend to be soft, but tough, while the inorganic materials are hard but brittle and are prone to fracture. The later characteristic gets even worse for porous materials and is of major concern in the microelectronics industry as porous organosilicates (mainly inorganic) will constitute the insulating layers in future electronic devices. In this paper, we demonstrate that significantly tougher organosilicate glass thin-films prepared by sol–gel process, can be obtained by introducing carbon bridging units between silicon atoms present in the organosilicate network. A fracture energy value of 15 J/m² was measured, surprisingly higher than that for dense silicon dioxide (10 J/m²), suggesting mechanical properties that lie somewhere in between those of conventional glasses and organic polymers. We also found that the Young’s modulus follows a linear decay when porosity is introduced, a unique property when compared to traditional organosilicates. As a result, crack resistant films were obtained at high levels of porosity, opening potential applications in the fields of low-k materials for future integrated circuits, membranes, sensors, waveguides, fuel cells and micro-fluidic channels.     

A microfluidic device for self-synchronised production of droplets

The primary requirement for a mixing operation in droplet-based microfluidic devices is an accurate pairing of droplets of reaction fluids over an extended period of time. In this paper, a novel device for self-synchronous production of droplets has been demonstrated. The device uses a change in impedance across a pair of electrodes introduced due to the passage of a pre-formed droplet to generate a second droplet at a second pair of electrodes. The device was characterised using image analysis. Droplets with a volume of ~23.5 ± 3.1 nl (i.e.~93% of the volume of pre-formed droplets) were produced on applying a voltage of 500 V. The synchronisation efficiency of the device was 83%. As the device enables self-synchronised production of droplets, it has a potential to increase the reliability and robustness of mixing operations in droplet-based microfluidic devices.     

Recent applications of AC electrokinetics in biomolecular analysis on microfluidic devices

AC electrokinetics is a generic term that refers to an induced motion of particles and fluids under nonuniform AC electric fields. The AC electric fields are formed by application of AC voltages to microelectrodes, which can be easily integrated into microfluidic devices by standard microfabrication techniques. Moreover, the magnitude of the motion is large enough to control the mass transfer on the devices. These advantages are attractive for biomolecular analysis on the microfluidic devices, in which the characteristics of small space and microfluidics have been mainly employed. In this review, I describe recent applications of AC electrokinetics in biomolecular analysis on microfluidic devices. The applications include fluid pumping and mixing by AC electrokinetic flow, and manipulation of biomolecules such as DNA and proteins by various AC electrokinetic techniques. Future prospects for highly functional biomolecular analysis on microfluidic devices with the aid of AC electrokinetics are also discussed.