Jmj Jaap den Toonder

Active micromixer based on artificial cilia

We propose a design for an active micromixer that is inspired by the motion of ciliated micro-organisms occurring in nature. The conceptual design consists of an array of individually addressable artificial cilia in the form of microactuators covering the channel wall. The microactuators can be set into motion by an external stimulus such as an electric or a magnetic field, inducing either a primary or secondary motion in the surrounding fluid. To validate the concept and to help to design the precise mixer configuration, we developed a computational fluid-structure model. This model is based on a fictitious domain method that couples the microactuator motion to the concomitant fluid flow, fully capturing the mutual fluid-structure interactions. The simulated flow patterns resulting from the motion of single and multiple actuated elements (in a microchannel filled with a Newtonian fluid) under the action of a time-periodic forcing function are analyzed using dynamical systems theory to quantify the mixing...

A direct simulation method for flows with suspended paramagnetic particles

A direct numerical simulation method based on the Maxwell stress tensor and a fictitious domain method has been developed to solve flows with suspended paramagnetic particles. The numerical scheme enables us to take into account both hydrodynamic and magnetic interactions between particles in a fully coupled manner. Particles are assumed to be non-Brownian with negligible inertia. Rigid body motions of particles in 2D are described by a rigid-ring description implemented by Lagrange multipliers. The magnetic force, acting on the particles due to magnetic fields, is represented by the divergence of the Maxwell stress tensor, which acts as a body force added to the momentum balance equation. Focusing on two-dimensional problems, we solve a single-particle problem for verification. With the magnetic force working on the particle, the proper number of collocation points is found to be two points per element. The convergence with mesh refinement is verified by comparing results from regular mesh problems with those from a boundary-fitted mesh problem as references. We apply the developed method to two application problems: two-particle interaction in a uniform magnetic field and the motion of a magnetic chain in a rotating field, demonstrating the capability of the method to tackle general problems. In the motion of a magnetic chain, especially, the deformation pattern at break-up is similar to the experimentally observed one. The present formulation can be extended to three-dimensional and viscoelastic flow problems.

Dynamics of magnetic chains in a shear flow under the influence of a uniform magnetic field

We numerically investigate dynamics of magnetic chains and flow characteristics in a two-dimensional shear flow under the influence of a magnetic field applied externally. A direct simulation method is employed to solve the particulate flow in the creeping flow regime, taking into account both magnetic and hydrodynamic interactions in a coupled manner. In a periodic channel, the dynamics of chains is found to be significantly influenced by the Mason number (the ratio of viscous force to magnetic force), the magnetic susceptibility, and the particle fraction. Below a critical Mason number, a chain rotates and reaches an equilibrium. Above the critical value, however, the chain continuously rotates as a rigid body. Thinning behavior in the wall shear stress is found above a threshold value of the Mason number. As for chain rupture in the shear flow, three regimes of the Mason number are found, showing three typical conformations of the chains: (i) complex chains with branches rather than linear chains, (ii) tilted linear chains broken in the middle, generating a slip zone between the upper and lower chains, and (iii) shortened chains rotating in the channel.

Cell types can be distinguished by measuring their viscoelastic recovery times using a micro-fluidic device

We introduce a simple micro-fluidic device containing an actuated flexible membrane, which allows the viscoelastic characterization of cells in small volumes of suspension by loading them in compression and observing the cell deformation in time. From this experiment, we can determine the characteristic time constant of recovery of the cell. To validate the device, two cell types known to have different cytoskeletal structures, 3T3 fibroblasts and HL60 cells, are tested. They show a substantially different response in the device and can be clearly distinguished on the basis of the measured characteristic recovery time constant. Also, the effect of breaking down the actin network, a main mechanical component of the cytoskeleton, by a treatment with Cytochalasin D, results in a substantial increase of the measured characteristic recovery time constant. Experimental variations in loading force, loading time, and surface treatment of the device also influence the measured characteristic recovery time constant significantly. The device can therefore be used to distinguish between cells with different mechanical structure in a quantitative way, and makes it possible to study changes in the mechanical response due to cell treatments, changes in the cell’s micro-environment, and mechanical loading conditions.

The magnetic interaction of Janus magnetic particles suspended in a viscous fluid

We studied the magnetic interaction between circular Janus magnetic particles suspended in a Newtonian fluid under the influence of an externally applied uniform magnetic field. The particles are equally compartmentalized into paramagnetic and nonmagnetic sides. A direct numerical scheme is employed to solve the magnetic particulate flow in the Stokes flow regime. Upon applying the magnetic field, contrary to isotropic paramagnetic particles, a single Janus particle can rotate due to the magnetic torque created by the magnetic anisotropy of the particle. In a two-particle problem, the orientation of each particle is found to be an additional factor that affects the critical angle separating the nature of magnetic interaction. Using multiparticle problems, we show that the orientation of the particles has a significant influence on the dynamics of the particles, the fluid flow induced by the actuated particles, and the final conformation of the particles. Straight and staggered chain structures observed experimentally can be reproduced numerically in a multiple particle problem.

A microfluidic device based on an evaporation-driven micropump

In this paper we introduce a microfluidic device ultimately to be applied as a wearable sweat sensor. We show proof-of-principle of the microfluidic functions of the device, namely fluid collection and continuous fluid flow pumping. A filter-paper based layer, that eventually will form the interface between the device and the skin, is used to collect the fluid (e.g., sweat) and enter this into the microfluidic device. A controllable evaporation driven pump is used to drive a continuous fluid flow through a microfluidic channel and over a sensing area. The key element of the pump is a micro-porous membrane mounted at the channel outlet, such that a pore array with a regular hexagonal arrangement is realized through which the fluid evaporates, which drives the flow within the channel. The system is completely fabricated on flexible polyethylene terephthalate (PET) foils, which can be the backbone material for flexible electronics applications, such that it is compatible with volume production approaches like Roll-to-Roll technology. The evaporation rate can be controlled by varying the outlet geometry and the temperature. The generated flows are analyzed experimentally using Particle Tracking Velocimetry (PTV). Typical results show that with 1 to 61 pores (diameteru2009=u2009250xa0μm, pitchu2009=u2009500xa0μm) flow rates of 7.3u2009×u200910-3 to 1.2u2009×u200910-1xa0μL/min are achieved. When the surface temperature is increased by 9.4xa0°C, the flow rate is increased by 130xa0%. The results are theoretically analyzed using an evaporation model that includes an evaporation correction factor. The theoretical and experimental results are in good agreement.

Accurate quantification of magnetic particle properties by intra-pair magnetophoresis for nanobiotechnology

The application of magnetic particles in biomedical research and in-vitro diagnostics requires accurate characterization of their magnetic properties, with single-particle resolution and good statistics. Here, we report intra-pair magnetophoresis as a method to accurately quantify the field-dependent magnetic moments of magnetic particles and to rapidly generate histograms of the magnetic moments with good statistics. We demonstrate our method with particles of different sizes and from different sources, with a measurement precision of a few percent. We expect that intra-pair magnetophoresis will be a powerful tool for the characterization and improvement of particles for the upcoming field of particle-based nanobiotechnology.

Advances in 3D neuronal cell culture

In this contribution, the authors present our advances in three-dimensional (3D) neuronal cell culture platform technology contributing to controlled environments for microtissue engineering and analysis of cellular physiological and pathological responses. First, a micromachined silicon sieving structure is presented as key parameter for a modified version of a planar tissue culture, allowing seeding of single neurons in pyramidal shaped pores by a hydrodynamic sieve flow. Second, a nanogroove–hydrogel interface is presented as a more biomimetic in vivo representation of neuronal tissues, where 3D culturing is required to reproduce the layered tissue organization, which is observed in the microenvironment of the brain. To further our understanding of uniquely nanopatterned interfaces, the authors evaluated 3D neuronal outgrowth into Matrigel atop of primary cortical cell (CTX) cultured on nanogrooves. The interface facilitates conformation of cell somas and aligned outgrowth in 3D with outgrowth alignment preserved in Matrigel up to 6u2009μm above the nanogrooved substrate, which has a pattern height of just 108u2009nm. Finally, with the view to incorporate these guided culture interfaces in our previously designed hybrid Polydimethylsiloxane bioreactor, the authors have also explored 3D cellular culture matrix as a variable in such systems. By analyzing the effect of different gel matrices (Matrigel, PuraMatrix, and collagen-I) on the neuron model cell line SH-SY5Y, the authors bring together the ability to guide neuronal growth in spatially standardized patterns and within a bioreactor potentially coupled to an array of single cells that could facilitate readout of such complex cultures by integration with existing technologies (e.g., microelectrode arrays). Various combinations of these novel techniques can be made and help to design experimental studies to investigate how changes in cell morphology translate to changes in function but also how changes in connectivity relate to changes in electrophysiology. These latest advancements will lead to the development of improved, highly organized in vitro assays to understand, mimic, and treat brain disorders.

Monocytic Cells Become Less Compressible but More Deformable upon Activation

Aims Monocytes play a significant role in the development of atherosclerosis. During the process of inflammation, circulating monocytes become activated in the blood stream. The consequent interactions of the activated monocytes with the blood flow and endothelial cells result in reorganization of cytoskeletal proteins, in particular of the microfilament structure, and concomitant changes in cell shape and mechanical behavior. Here we investigate the full elastic behavior of activated monocytes in relation to their cytoskeletal structure to obtain a better understanding of cell behavior during the progression of inflammatory diseases such as atherosclerosis. Methods and Results The recently developed Capillary Micromechanics technique, based on exposing a cell to a pressure difference in a tapered glass microcapillary, was used to measure the deformation of activated and non-activated monocytic cells. Monitoring the elastic response of individual cells up to large deformations allowed us to obtain both the compressive and the shear modulus of a cell from a single experiment. Activation by inflammatory chemokines affected the cytoskeletal organization and increased the elastic compressive modulus of monocytes with 73–340%, while their resistance to shape deformation decreased, as indicated by a 25–88% drop in the cell’s shear modulus. This decrease in deformability is particularly pronounced at high strains, such as those that occur during diapedesis through the vascular wall. Conclusion Overall, monocytic cells become less compressible but more deformable upon activation. This change in mechanical response under different modes of deformation could be important in understanding the interplay between the mechanics and function of these cells. In addition, our data are of direct relevance for computational modeling and analysis of the distinct monocytic behavior in the circulation and the extravascular space. Lastly, an understanding of the changes of monocyte mechanical properties will be important in the development of diagnostic tools and therapies concentrating on circulating cells.

Magnetic particle actuation in stationary microfluidics for integrated lab-on-chip biosensors

The aging population and increases in chronic diseases put high pressure on the healthcare system, which drives a need for easy-to-use and cost-effective medical technologies. In-vitro diagnostics (IVD) plays a large role in delivering healthcare and, within the IVD market, decentralized diagnostic testing, i.e. point-of-care testing (POCT), is a growing segment. POCT devices should be compact and fully integrated for maximum ease of use. A new class of POCT technologies is appearing based on actuated magnetic particles. The use of magnetic particles has important advantages: they have a large surface-to-volume ratio, are conveniently biofunctionalized, provide a large optical contrast, and can be manipulated by magnetic fields. In this chapter, we review the use of magnetic particles actuated by magnetic fields to realize integrated lab-on-chip diagnostic devices wherein several assay process steps are combined, e.g. to mix fluids, capture analytes, concentrate analytes, transfer analytes, label analytes, and perform stringency steps. We focus on realizations within the concept of stationary microfluidics and we discuss efforts to integrate different magnetically actuated assay steps, with the vision that it will become possible to realize biosensing systems in which all assay process steps are controlled and optimized by magnetic forces.