Search Results (37)

Simulative and experimental studies were carried out to address multi-dimensional particle fractionation of non-biological particles according to size, shape, and density inside a high-throughput DLD array. Density sensitive separation was achieved for melamine and polystyrene particles at a diameter of 5 µm at a Reynolds number (Re) of 82, corresponding to an overall flow rate of 11.3 mL/min. This process is very sensitive, as no fractionation occurred for Re = 85 (11.7 mL/min). For the first time, the fractionation of elliptical polystyrene particles (5 × 10 µm) at Re > 1 was investigated up to Re = 80 (11 mL/min). A separation of elliptical particles from spherical melamine particles (5 µm) was observed in single experiments at all investigated Reynolds numbers. However, the separation is not reliably repeatable due to partial clogging of ellipsoidal particles along the posts. In addition, higher concentrations of polydisperse silica suspensions were experimentally investigated by using polydisperse silica particles at concentrations up to 0.4% (m/V) up to Re = 80 (20 mL/min). The separation size generally decreased with increasing Reynolds number and increased with increasing concentration. Separation efficiency decreased with increasing concentration, independent of the Reynolds number. In order to investigate the material-dependent separation in a contactless dielectrophoresis system (cDEP), the resolved CFD-DEM software was extended to calculate dielectrophoretic forces on particles. With this, the second stage of a serial-combined DLD-DEP system was simulated, showing good separation at lower flow rates. For these systems, different fabrication methods to minimize the distance between the electrodes and the fluid as well as the requirement to withstand high-throughput applications, were investigated. Full article

The precise preparation and application of nanomicrospheres is currently an emerging research hotspot in the cutting-edge cross-disciplines. As an important functional material, nanosized microspheres show a broad application prospect in biomedicine, chemical engineering, materials science, and other fields. However, microspheres with good monodispersity are still facing technical bottlenecks, such as complicated preparation process and high cost. In this study, a multistage cyclic dielectrophoresis (MC-DEP) technique is innovatively proposed to successfully realize the high-resolution sorting of submicron microspheres. A dielectrophoresis chip adopts a unique electrode design, in which the electrodes are arranged at the top and bottom of the microchannel at the same time. This symmetric electrode structure effectively eliminates the difference in the distribution of dielectrophoretic force in the perpendicular direction and ensures the homogeneity of the initial state of particle sorting. Three pairs of focusing electrodes are in the front section of the microchannel for preaggregation of the microspheres, and the deflection electrodes in the back section are to realize particle size sorting. After this, the upper and lower limits of particle size are limited by multiple cycles of sorting. The multistage cyclic sorting increases the stability of particle deflection under dielectrophoretic forces and reduces the error perturbation caused by the fluid environment. The experimental results show that the multistage cycling sorting scheme significantly improves the monodispersity of the microspheres, and the coefficient of variation of the particle size is significantly reduced from the initial 12.3% to 5.4% after three cycles of sorting, which fully verifies the superior performance of this technology. Full article

Bacterial membrane vesicle (BMV) nanoparticles are secreted naturally by bacteria throughout their lifecycle and are a rich source of biomarkers from the parent bacteria, but they are currently underutilized for clinical diagnostic applications, such as pathogen identification, due to the time-consuming and low-yield nature of traditional recovery methods required for analysis. The recovery of BMVs is particularly difficult from complex biological fluids. Here, we demonstrate a recovery method that uses dielectrophoretic (DEP) forces generated on electrokinetic microfluidic chips to isolate and analyze BMVs from human plasma. DEP takes advantage of the natural difference in dielectric properties between the BMVs and the surrounding plasma fluid to quickly and consistently collect these particles from as little as 25 µL of plasma. Using DEP and immunofluorescence staining of the LPS biomarker carried on BMVs, we have demonstrated a lower limit of detection of 4.31 × 10⁹ BMVs/mL. The successful isolation of BMVs from human plasma using DEP, and subsequent on-chip immunostaining for biomarkers, enables the development of future assays to identify the presence of specific bacterial species by analyzing BMVs from small amounts of complex body fluid. Full article

The controlled contact between two micro-sized objects, such as beads and cells, and the assessment of their adhesion status is demonstrated in this research. The controlled contact is carried out in a microfluidic channel under flow conditions and makes use of a combination of hydrodynamic traps, flow drag force and dielectrophoretic (DEP) force to maintain the two objects in contact for the desired duration in a first step. Then, the pair objects are separated in the second step in order to explore their adhesion status. Adhesion events are mediated by the bond formed between a receptor and its ligand, and their binding kinetic parameters can be extracted from the measurements using the proposed device. Full article

Dielectrophoresis (DEP) is one of the microfluid-based techniques that can manipulate the red blood cells (RBC) for blood plasma separation, which is used in many medical screening/diagnosis applications. The tapered aluminium microelectrode array (TAMA) is fabricated for potential sensitivity enhancement of RBC manipulation in lateral and vertical directions. In this paper, the migration properties of dielectrophoretically manipulated RBC in TAMA platform are studied at different peak-to-peak voltage (Vpp) and duration supplied onto the microelectrodes. Positive DEP manipulation is conducted at 440 kHz with the RBC of 4.00 ± 0.2 µm average radius attracted to the higher electric field intensity regions, which are the microelectrodes. High percentage of RBC migration occurred at longer manipulation time and high electrode voltage. During DEP manipulation, the RBC are postulated to levitate upwards, experience the electro-orientation mechanism and form the pearl chains before migrating to the electrodes. The presence of external forces other than the dielectrophoretic force may also affect the migration response of RBC. The safe operating limit of 10 Vpp and manipulation duration of ≤50 s prevent RBC rupture while providing high migration percentage. It is crucial to define the safe working region for TAMA devices that manipulate small RBC volume (~10 µL). Full article

Electrostatic traveling wave (ETW) methods have shown promising performance in dust mitigation of solar panels, particle transport and separation in in situ space resource utilization, cell manipulation, and separation in biology. The ETW field distribution is required to analyze the forces applied to particles and to evaluate ETW design parameters. This study presents the numerical results of the ETW field distribution generated by a parallel electrode array using both the charge simulation method (CSM) and the boundary element method (BEM). A low accumulated error of the CSM is achieved by properly arranging the positions and numbers of contour points and fictitious charges. The BEM can avoid the inconvenience of the charge position required in the CSM. The numerical results show extremely close agreement between the CSM and BEM. For simplification, the method of images is introduced in the implementation of the CSM and BEM. Moreover, analytical formulas are obtained for the integral of Green’s function along boundary elements. For further validation, the results are cross-checked using the finite element method (FEM). It is found that discrepancies occur at the ends of the electrode array. Finally, analyses are provided of the electric field and dielectrophoretic (DEP) components. Emphasis is given to the regions close to the electrode surfaces. These results provide guidance for the fabrication of ETW systems for various applications. Full article

Cell counting and sorting is a vital step in the purification process within the area of biomedical research. It has been widely reported and accepted that the use of hydrodynamic focusing in conjunction with the application of a dielectrophoretic (DEP) force allows efficient separation of biological entities such as platelets from red blood cell (RBC) samples due to their size difference. This paper presents computational results of a multiphysics simulation modelling study on evaluating continuous separation of RBCs and platelets in a microfluidic device design with saw-tooth profile electrodes via DEP. The theoretical cell particle trajectory, particle cell counting, and particle separation distance study results reported in this work were predicted using COMSOL v6.0 Multiphysics simulation software. To validate the numerical model used in this work for the reported device design, we first developed a simple y-channel microfluidic device with square “in fluid” electrodes similar to the design reported previously in other works. We then compared the obtained simulation results for the simple y-channel device with the square in fluid electrodes to the reported experimental work done on this simple design which resulted in 98% agreement. The design reported in this work is an improvement over existing designs in that it can perform rapid separation of RBCs (estimated 99% purification) and platelets in a total time of 6–7 s at a minimum voltage setting of 1 V and at a minimum frequency of 1 Hz. The threshold for efficient separation of cells ends at 1000 kHz for a 1 V setting. The saw-tooth electrode profile appears to be an improvement over existing designs in that the sharp corners reduced the required horizontal distance needed for separation to occur and contributed to a non-uniform DEP electric field. The results of this simulation study further suggest that this DEP separation technique may potentially be applied to improve the efficiency of separation processes of biological sample scenarios and simultaneously increase the accuracy of diagnostic processes via cell counting and sorting. Full article

Glioblastoma multiforme is one of the most aggressive malignant primary brain tumors. To design effective treatment strategies, we need to better understand the behavior of glioma cells while maintaining their genetic and phenotypic stability. Here, we investigated the deformation and migration profile of U87 Glioma cells under the influence of dielectrophoretic forces. We fabricated a gold microelectrode array within a microfluidic channel and applied sinusoidal wave AC potential at 3 V_pp, ranging from 30 kHz to 10 MHz frequencies, to generate DEP forces. We followed the dielectrophoretic movement and deformation changes of 100 glioma cells at each frequency. We observed that the mean dielectrophoretic displacements of glioma cells were significantly different at varying frequencies with the maximum and minimum traveling distances of 13.22 µm and 1.37 µm, respectively. The dielectrophoretic deformation indexes of U87 glioma cells altered between 0.027–0.040. It was 0.036 in the absence of dielectrophoretic forces. This approach presents a rapid, robust, and sensitive characterization method for quantifying membrane deformation of glioma cells to determine the state of the cells or efficacy of administrated drugs. Full article

Identification of circulating tumor cells (CTCs) from a majority of various cell pools has been an appealing topic for diagnostic purposes. This study numerically demonstrates the isolation of CTCs from blood cells by the combination of dielectrophoresis and magnetophoresis in a microfluidic chip. Taking advantage of the label-free property, the separation of red blood cells, platelets, T cells, HT-29, and MDA-231 was conducted in the microchannel. By using the ferromagnet structure with double segments and a relatively shorter distance in between, a strong gradient of the magnetic field, i.e., sufficiently large MAP forces acting on the cells, can be generated, leading to a high separation resolution. In order to generate strong DEP forces, the non-uniform electric field gradient is induced by applying the electric voltage through the microchannel across a pair of asymmetric orifices, i.e., a small orifice and a large orifice on the opposite wall of the channel sides. The distribution of the gradient of the magnetic field near the edge of ferromagnet segments, the gradient of the non-uniform electric field in the vicinity of the asymmetric orifices, and the flow field were investigated. In this numerical simulation, the effects of the ferromagnet structure on the magnetic field, the flow rate, as well as the strength of the electric field on their combined magnetophoretic and dielectrophoretic behaviors and trajectories are systemically studied. The simulation results demonstrate the potential of both property- and size-based cell isolation in the microfluidic device by implementing magnetophoresis and dielectrophoresis. Full article

Noninvasive manipulation of nanoscopic species in liquids has attracted considerable attention due to its potential applications in diverse fields. Many sophisticated methodologies have been developed to control and study nanoscopic entities, but the low-power, cost-effective, and versatile manipulation of nanometer-sized objects in liquids remains challenging. Here, we present a dielectrophoretic (DEP) manipulation technique based on nanogap electrodes, with which the on-demand capturing, enriching, and sorting of nano-objects in microfluidic systems can be achieved. The dielectrophoretic control unit consists of a pair of swelling-induced nanogap electrodes crossing a microchannel, generating a steep electric field gradient and thus strong DEP force for the effective manipulation of nano-objects microfluidics. The trapping, enriching, and sorting of nanoparticles and DNAs were performed with this device to demonstrate its potential applications in micro/nanofluidics, which opens an alternative avenue for the non-invasive manipulation and characterization of nanoparticles such as DNA, proteins, and viruses. Full article

Piezoelectric ZnO-based composites have been explored as a flexible and compact sensor for the implantable biomedical systems used in cardio surgery. In this work, a progressive development route was investigated to enhance the performance of piezoelectric composites incorporated with different shape, concentration and connectivity of ZnO fillers. ZnO microrods (MRs) have been successfully synthesized homogeneously in aqueous solution using a novel process-based on chemical bath deposition (CBD) method. The morphological analysis along with Raman scattering and cathodoluminescence spectroscopy of ZnO MRs confirm their high crystalline quality, their orientation along the polar c-axis and the presence of hydrogen-related defects acting as shallow donors in their center. The experimental characterizations highlight that ZnO MR-based composites, with a higher aspect ratio (AR), lead to a significant improvement in the mechanical, dielectric and piezoelectric properties as opposed to the ZnO microparticles (MP) counterparts. The dielectrophoretic (DEP) process is then subjected to both ZnO MP- and MR-based composites, whose performance is expected to be improved as compared to the randomly dispersed composites, thanks to the creation of chain-like structures along the electric field direction. Furthermore, a numerical simulation using COMSOL software is developed to evaluate the influence of the material structuration as well as the filler’s shape on the electric field distribution within different phases (filler, matrix and interface) of the composites. Finally, the aligned MR piezoelectric composites are revealed to be high potential in the development of innovative compact and biocompatible force-sensing devices. Such a technological breakthrough allows the achievement of a real-time precise characterization of mitral valve (MV) coaptation to assist surgeons during MV repair surgery. Full article

Silicon-on-insulator (SOI) nanowire or nanoribbon field-effect transistor (FET) biosensors are versatile platforms of electronic detectors for the real-time, label-free, and highly sensitive detection of a wide range of bioparticles. At a low analyte concentration in samples, the target particle diffusion transport to sensor elements is one of the main limitations in their detection. The dielectrophoretic (DEP) manipulation of bioparticles is one of the most successful techniques to overcome this limitation. In this study, TCAD modeling was used to analyze the distribution of the gradient of the electric fields E for the SOI-FET sensors with embedded DEP electrodes to optimize the conditions of the dielectrophoretic delivery of the analyte. Cases with asymmetrical and symmetrical rectangular electrodes with different heights, widths, and distances to the sensor, and with different sensor operation modes were considered. The results showed that the grad E² factor, which determines the DEP force and affects the bioparticle movement, strongly depended on the position of the DEP electrodes and the sensor operation point. The sensor operation point allows one to change the bioparticle movement direction and, as a result, change the efficiency of the delivery of the target particles to the sensor. Full article

The ability to accurately quantify dielectrophoretic (DEP) force is critical in the development of high-efficiency microfluidic systems. This is the first reported work that combines a textile electrode-based DEP sensing system with deep learning in order to estimate the DEP forces invoked on microparticles. We demonstrate how our deep learning model can process micrographs of pearl chains of polystyrene (PS) microbeads to estimate the DEP forces experienced. Numerous images obtained from our experiments at varying input voltages were preprocessed and used to train three deep convolutional neural networks, namely AlexNet, MobileNetV2, and VGG19. The performances of all the models was tested for their validation accuracies. Models were also tested with adversarial images to evaluate performance in terms of classification accuracy and resilience as a result of noise, image blur, and contrast changes. The results indicated that our method is robust under unfavorable real-world settings, demonstrating that it can be used for the direct estimation of dielectrophoretic force in point-of-care settings. Full article

This study aims at developing a miniaturized CMOS integrated silicon-based microfluidic system, compatible with a standard CMOS process, to enable the characterization, and separation of live and dead yeast cells (as model bio-particle organisms) in a cell mixture using the DEP technique. DEP offers excellent benefits in terms of cost, operational power, and especially easy electrode integration with the CMOS architecture, and requiring label-free sample preparation. This can increase the likeliness of using DEP in practical settings. In this work the DEP force was generated using an interdigitated electrode arrays (IDEs) placed on the bottom of a CMOS-based silicon microfluidic channel. This system was primarily used for the immobilization of yeast cells using DEP. This study validated the system for cell separation applications based on the distinct responses of live and dead cells and their surrounding media. The findings confirmed the device’s capability for efficient, rapid and selective cell separation. The viability of this CMOS embedded microfluidic for dielectrophoretic cell manipulation applications and compatibility of the dielectrophoretic structure with CMOS production line and electronics, enabling its future commercially mass production. Full article

Tendons are collagenous musculoskeletal tissues that connect muscles to bones and transfer the forces necessary for movement. Tendons are susceptible to injury and heal poorly, with long-term loss of function. Mesenchymal stem cell (MSC)-based therapies are a promising approach for treating tendon injuries but are challenged by the difficulties of controlling stem cell fate and of generating homogenous populations of stem cells optimized for tenogenesis (differentiation toward tendon). To address this issue, we aim to explore methods that can be used to identify and ultimately separate tenogenically differentiated MSCs from non-tenogenically differentiated MSCs. In this study, baseline and tenogenically differentiating murine MSCs were characterized for dielectric properties (conductivity and permittivity) of their outer membrane and cytoplasm using a dielectrophoretic (DEP) crossover technique. Experimental results showed that unique dielectric properties distinguished tenogenically differentiating MSCs from controls after three days of tenogenic induction. A single shell model was used to quantify the dielectric properties and determine membrane and cytoplasm conductivity and permittivity. Together, cell responses at the crossover frequency, cell morphology, and shell models showed that changes potentially indicative of early tenogenesis could be detected in the dielectric properties of MSCs as early as three days into differentiation. Differences in dielectric properties with tenogenesis indicate that the DEP-based label-free separation of tenogenically differentiating cells is possible and avoids the complications of current label-dependent flow cytometry-based separation techniques. Overall, this work illustrates the potential of DEP to generate homogeneous populations of differentiated stem cells for applications in tissue engineering and regenerative medicine. Full article