Microfluidic device for continuous magnetophoretic separation of white blood cells

This paper presents a microfluidic device for magnetophoretic separation of red blood cells from blood under continuous flow. The separation method consists of continuous flow of a blood sample (diluted in PBS) through a microfluidic channel which presents on the bottom “dots” of ferromagnetic layer. By applying a magnetic field perpendicular on the flowing direction, the ferromagnetic “dots” generate a gradient of magnetic field which amplifies the magnetic force. As a result, the red blood cells are captured on the bottom of the microfluidic channel while the rest of the blood is collected at the outlet. Experimental results show that an average of 95% of red blood cells is trapped in the device.     

Microfluidic patterning of nanoparticle monolayers

A microfluidic technique was developed to pattern nanoparticle monolayer controllably in a tentative polydimethylsiloxane (PDMS) microchannel. It was found that nanoparticle monolayer could be achieved in a two-step fluidic process: nanoparticle sedimentation and DI water rinsing. When nanoparticle suspension flows through a tentative PDMS microchannel, the particles will settle down due to the gravity effect and the Brownian motion and be captured onto the amino-functionalized substrate via electrostatic attraction. Aggregation on the substrate followed by a necessary DI water rinsing transforms hill-like nanoparticle aggregates into monolayer. Removing the tentative PDMS microchannel, pattern of nanoparticle monolayer following the channel shape was obtained. Experimental results indicated that the final monolayered nanoparticle coverage decreases when the flowing velocity in the sedimentation and/or the rinsing steps increases. Based on the continuity essence of fluid flow, different flowing velocities could be realized in one microchannel by varying the channel size. Therefore, monolayer patterns with controllable coverage could be achieved by carefully designing the microchannel width. The present approach is believed to be a promising nanoparticle monolayer patterning technique.     

Microfluidic blood-plasma separation chip using channel size filtration effect

Microsystem Technologies - Blood separation is an essential first step when performing blood tests for clinical diagnosis purposes. Such tests are increasingly performed using microfluidic systems...     

Computational and performance analysis of a continuous magnetophoretic bioseparation chip with alternating magnetic fields

This paper presents the modeling and optimization of a magnetophoretic bioseparation chip for isolating cells, such as circulating tumor cells from the peripheral blood. The chip consists of a continuous-flow microfluidic platform that contains locally engineered magnetic field gradients. The high-gradient magnetic field produced by the magnets is spatially non-uniform and gives rise to an attractive force on magnetic particles flowing through a fluidic channel. Simulations of the particle–fluid transport and the magnetic force are performed to predict the trajectories and capture lengths of the particles within the fluidic channel. The computational model takes into account key forces, such as the magnetic and fluidic forces and their effect on design parameters for an effective separation. The results show that the microfluidic device has the capability of separating various cells from their native environment. An experimental study is also conducted to verify and validate the simulation results. Finally, to improve the performance of the separation device, a parametric study is performed to investigate the effects of the magnetic bead size, cell size, number of beads per cell, and flow rate on the cell separation performance.     

Blind separation of non-stationary sources using continuous density hidden Markov models

Blind source separation (BSS) has attained much attention in signal processing society due to its ‘blind’ property and wide applications. However, there are still some open problems, such as underdetermined BSS, noise BSS. In this paper, we propose a Bayesian approach to improve the separation performance of instantaneous mixtures with non-stationary sources by taking into account the internal organization of the non-stationary sources. Gaussian mixture model (GMM) is used to model the distribution of source signals and the continuous density hidden Markov model (CDHMM) is derived to track the non-stationarity inside the source signals. Source signals can switch between several states such that the separation performance can be significantly improved. An expectation-maximization (EM) algorithm is derived to estimate the mixing coefficients, the CDHMM parameters and the noise covariance. The source signals are recovered via maximum a posteriori (MAP) approach. To ensure the convergence of the proposed algorithm, the proper prior densities, conjugate prior densities, are assigned to estimation coefficients for incorporating the prior information. The initialization scheme for the estimates is also discussed. Systematic simulations are used to illustrate the performance of the proposed algorithm. Simulation results show that the proposed algorithm has more robust separation performance in terms of similarity score in noise environments in comparison with the classical BSS algorithms in determined mixture case. Additionally, since the mixing matrix and the sources are estimated jointly, the proposed EM algorithm also works well in underdetermined case. Furthermore, the proposed algorithm converges quickly with proper initialization.     

Microfluidic separation of magnetic particles with soft magnetic microstructures

This paper demonstrates simple and cost-effective microfluidic devices for enhanced separation of magnetic particles by using soft magnetic microstructures. By injecting a mixture of iron powder and polydimethylsiloxane (PDMS) into a prefabricated channel, an iron–PDMS microstructure was fabricated next to a microfluidic channel. Placed between two external permanent magnets, the magnetized iron–PDMS microstructure induces localized and strong forces on the magnetic particles in the direction perpendicular to the fluid flow. Due to the small distance between the microstructure and the fluid channel, the localized large magnetic field gradients result a vertical force on the magnetic particles, leading to enhanced separation of the particles. Numerical simulations were developed to compute the particle trajectories and agreed well with experimental data. Systematic experiments and numerical simulation were conducted to study the effect of relevant factors on the transport of superparamagnetic particles, including the shape of iron–PDMS microstructure, mass ratio of iron–PDMS composite, width of the microfluidic channel, and average flow velocity.     

Microfluidic counterflow centrifugal elutriation system for sedimentation-based cell separation

We present a centrifugal microfluidic system for precise cell/particle sorting using the concept of counterflow centrifugal elutriation (CCE). A conventional CCE system uses a rotor device incorporating a flow-through separation chamber, in which the balance of centrifugal and counterflow drag forces exerted on particles is gradually shifted by changing the flow rate and/or the rotation speed. In the present system, both the centrifugal and the fluid forces are generated through microdevice rotation in order to significantly simplify the setup of the conventional CCE. In addition, the density gradient of the medium is employed to elute particles/cells of different sedimentation velocities stepwise from the separation chamber instead of changing the rotation speed. We successfully separated polymer particles with diameters of 1.0–5.0 μm using a branched loading channel for focusing particles to the center of the separation chamber. We also demonstrated the sorting of blood cells for biological applications. This system may provide a versatile means for cell/particle sorting in a general biological laboratory and function as a unit operation in various centrifugal microfluidic platforms for biochemical experiments and clinical diagnosis.     

Microfluidic mixing using pulsating flows

Mixing of biological species in microfluidic channels is challenging since the mixing process is limited by the small mass diffusion coefficient of the species and by the dominance of viscous effects, captured by the low value of Reynolds number characteristic of laminar liquid flow in microchannels. This paper investigates the use of pulsating flows to enhance mixing in microflows. The dependence of the degree of mixing on various dimensionless groups is investigated. These dimensionless numbers are Strouhal number, pulse amplitude divided by base velocity, Reynolds number, location along the mixing channel normalized by the channel width, channel cross section aspect ratio, and phase difference between the inlet streams. The degree of mixing, observed to experience both spatial fluctuations down the mixing channel and temporal fluctuations over a pulsation cycle at the quasi-stationary state, is shown to be most sensitive to changes in pulsation amplitude and frequency. For a fixed pulsation amplitude and Reynolds number, the degree of mixing has a peak value for a certain Strouhal number above and below which the degree of mixing decreases. Increasing the pulsation amplitude improves mixing with the behavior becoming asymptotic at large pulsation amplitudes. The temporal fluctuations in the degree of mixing over a cycle at the quasi-stationary state decrease and the average degree of mixing increases downstream the mixing channel. The fluctuations are also smaller at higher values of the Strouhal number and are generally larger for larger pulsation amplitudes. This study also takes into account the rate of work input required to overcome viscous effects. While this power input is independent of the pulsation frequency, it exhibits a parabolic dependence on the pulsation amplitude. Finally, considering the dependence of the degree of mixing (mean and standard deviation), mixing length, and energy consumption on these dimensionless groups, examples of the trade-off that has to be made in choosing the operating conditions based on different constraints are presented.     

Microfluidic mixing using PDMS-based microporous structures

We showed that efficient mixing of fluid flows at microscales can be achieved by a simple type of micromixers based on microporous structures. We used sugar particles as templates for fabricating the microporous structures. We quantitatively studied the relation between the mixing performance and the characteristics of the microporous structures, and showed that permeability is the key indicator of the mixing performance. By visualizing the flow inside the microstructures using confocal microscope, we also found that flow passage having repetitive and sudden contraction–expansion is the chief factor leading to mixing enhancement.     

Enhancing nanoparticle deposition using actuated synthetic cilia

We use computational modeling to probe the utility of actuated synthetic cilia lining walls of a microfluidic channel for enhancing the deposition of nanoparticles dispersed in a viscous fluid filling the channel. We demonstrate that elastic cilia actuated by a sinusoidal force applied to their free ends generate circulatory secondary flows facilitating nanoparticle transport. We identify optimal operational conditions in which the effect of cilia beating on particle deposition is maximized. Our simulations also reveal that cilia transition to a three-dimensional beating pattern when the actuation force exceeds a critical value. This transition is associated with buckling instability experienced by elastic cilia. Our findings guide the optimal design of ciliated microfluidic systems for uses such as deposition of particulates onto sensory surfaces and microfluidic mixing.     

Microfluidic devices easily created using an office inkjet printer

Although various processes have been used for producing microfluidic devices, many of them are not so simple that ordinary end-users can produce the devices by themselves. However, in this study, microfluidic devices were easily produced using an office inkjet printer. As the components of the device, channels, manifolds, and mixers were created by printing their shapes on glass slides using the printer. A syringe pump could control the flow of fluid through the manifolds and mixers. In addition, resistivity of the device to acidic and basic solutions was tested.     

Microfluidic chips for cells capture using 3-D hydrodynamic structure array

Microfluidic chips were designed and fabricated to capture cells in a relative small volume to generate the desired concentration needed for analysis. The microfluidic chips comprise three-dimensional (3-D) cell capture structures array fabricated in PDMS. The capture structure includes two layers. The first layer consists of spacers to create small gap between the upper layer and glass. The second layer is a sharp corner U-shaped compartment with sharp corners at the fore-end. And another type capture structure with Y-shaped fluidic guide has been designed. It was demonstrated that the structures can capture cells in theory, using Darcy–Weisbach equation and COMSOL Multiphysics. Then yeast cell was chosen to test the performance of the chips. The chip without fluid guides captured ~1.44 × 10⁵ cells and the capture efficiency was up to 71 %. And the chip with fluid guides captured ~5.0 × 10⁴ cells and the capture efficiency was ~25 %. The chip without fluid guides can capture more cells because the yeast cells in the chip without fluid guides are subject to larger hydrodynamic drag force.     

Cleaning of structured templates from nanoparticle accumulation using silicone

Polydimethylsiloxan (PDMS) turned out to be a simple and cost efficient material for the removal of nanoparticles from patterned surfaces. After molding the particle-laden surface using liquid silicone, surface cleaning is realized by curing the PDMS comprising the encapsulated particles and subsequent removal. The method is proven for silicon, SiO₂ and gold surfaces occupied by carbon and Polytetrafluorethylen (PTFE or Teflon) particles. Samples up to 2?inch wafers were successfully cleaned. The effect of PDMS on the surface energy is verified by contact angle measurements showing a clear change in wetting for H₂O. This effect is abolished by oxygen plasma and HF-Dip.     

Large scale fractal aggregates using the tunable dimension cluster-cluster aggregation

The tunable dimension cluster-cluster aggregation (tdCCA) [R. Thouy, R. Jullien, J. Phys. A: Math. Gen. 27 (1994) 2953] provides a computational model for creating fractal aggregates with a tunable fractal dimension. A straightforward implementation of this model requires a computational effort scaling with O(N_total⁴) of the number of particles N_total. By applying two minor changes to the algorithm the computational effort can be reduced to O(N_total²) and allows an efficient parallel implementation of the tdCCA. On a modern parallel computer a fractal aggregate of one million particles has been built in less than 24 h.     

Prediction of the durability of limestone aggregates using computational techniques

Neural Computing and Applications - The durability of aggregates is an important factor that is used as an input parameter in desirable engineering properties along with resistance to exposure...     

Bioparticle separation and manipulation using dielectrophoresis

Manipulation and separation of micro-sized particles, particularly biological particles, using the dielectrophoretic (DEP) force is an emerging technique in MEMS technology. This paper presents a DEP-based microsystem for the selective manipulation and separation of bioparticles using dielectrophoretic effects. The microfabricated DEP device consists of a sandwich structure, in which a microchannel with electrode array lining on its bottom is sandwiched between the substrate and the glass lid. Dielectrophoretic behavior of polystyrene particles with diameter of 4.3 μm was studied. Both positive DEP and negative DEP were observed. Particles under positive DEP were attracted to the edges of the electrodes, while those under negative DEP were repelled away from the electrodes and levitated at certain height above the electrodes (within a proper range of frequencies of the electric field). Levitation height of the particles was measured. It was demonstrated that the levitation height of a specific particle strongly depends on the combined contributions of a number of parameters, such as the frequency of the electric field, dielectric properties of the particles and the surrounding medium. Different particles can be separated and manipulated on the basis of their difference in these parameters.     

Nonlinear blind source separation using kernels

We derive a new method for solving nonlinear blind source separation (BSS) problems by exploiting second-order statistics in a kernel induced feature space. This paper extends a new and efficient closed-form linear algorithm to the nonlinear domain using the kernel trick originally applied in support vector machines (SVMs). This technique could likewise be applied to other linear covariance-based source separation algorithms. Experiments on realistic nonlinear mixtures of speech signals, gas multisensor data, and visual disparity data illustrate the applicability of our approach.     

Real-time hand detection using continuous skeletons

In this paper, a fast and reliable method for hand detection based on continuous skeletons approach is presented. It demonstrates real-time working speed and high detection accuracy (3–5% both FAR and FRR) on a large dataset (50 persons, 80 videos, 2322 frames). These make it suitable for use as a part of modern hand identification systems including mobile ones. Overall, the study shows that continuous skeletons approach can be used as prior for object and background color models in segmentation methods with supervised learning (e.g., interactive segmentation with seeds or abounding box).