Several biomedical analyses are performed on particular types of cells present in body samples or using functionalized microparticles. Success in such analyses depends on the ability to separate or ...isolate the target cells or microparticles from the rest of the sample. In conventional procedures, multiple pieces of equipment, such as centrifuges, magnets, and macroscale filters, are used for such purposes, which are time-consuming, associated with human error, and require several operational steps. In the past two decades, there has been a tendency to develop microfluidic techniques, so-called lab-on-a-chip, to miniaturize and automate these procedures. The processes used for the separation and isolation of the cells and microparticles are scaled down into a small microfluidic chip, requiring very small amounts of sample. Differences in the physical and biological properties of the target cells from the other components present in the sample are the key to the development of such microfluidic techniques. These techniques are categorized as filtration-, hydrodynamic-, dielectrophoretic-, acoustic- and magnetic-based methods. Here we review the microfluidic techniques developed for sorting, separation, and isolation of cells and microparticles for biomedical applications. The mechanisms behind such techniques are thoroughly explained and the applications in which these techniques have been adopted are reviewed.
We have reviewed the microfluidic approaches for cell/particle isolation and sorting, and extensively explained the mechanism behind each method.
Abstract
Advances in lab-on-a-chip (LOC) devices have led to significant improvements in the on-chip manipulation, separation, sorting, and isolation of particles and cells. Among various LOC-based ...approaches such as inertia-based methods, acoustophoresis, and magnetophoresis, the planar-slanted-electrode dielectrophoresis (DEP) method has demonstrated great potential as a label-free, cost-effective, and user-friendly approach. However, the devices built based on this method suffer from low flow throughput compared to devices functioning based on other LOC-based manipulation approaches. In order to overcome this obstacle, the geometrical parameters of these types of DEP-based devices must be studied to increase the effectiveness of DEP manipulation. With the consideration of both numerical and experimental studies, this paper studies the geometrical factors of a LOC platform consisting of tilted planar electrodes with the goal of achieving higher throughput in continuous manipulation of polystyrene particles. COMSOL Multiphysics software was used to study the effect of the electrodes geometry on the induced electric field. The simulation results show that by increasing the electrode’s width and decreasing the electrode’s spacing, higher DEP force is generated. Furthermore, the experimental outcomes indicated that lower channel height, higher voltage, and larger particle size resulted in the most improvement to DEP manipulation. Additionally, the experimental results demonstrated that slanted electrodes with an angle of 8° with respect to the direction of flow provide a more effective configuration.
Traditional cell/particle isolation methods are time-consuming and expensive and can lead to morphology disruptions due to high induced shear stress. To address these problems, novel ...lab-on-a-chip-based purification methods have been employed. Among various methods introduced for the separation and purification of cells and synthetics particles, acoustofluidics has been one of the most effective methods. Unlike traditional separation techniques carried out in clinical laboratories based on chemical properties, the acoustofluidic process relies on the physical properties of the sample. Using acoustofluidics, manipulating cells and particles can be achieved in a label-free, contact-free, and highly biocompatible manner. To optimize the functionality of the platform, the numerical study should be taken into account before conducting experimental tests to save time and reduce fabrication expenses. Most current numerical studies have only considered one-dimensional harmonic standing waves to simulate the acoustic pressure distribution. However, one-dimensional simulations cannot calculate the actual acoustic pressure distribution inside the microchannel due to its limitation in considering longitudinal waves. To address this limitation, a two-dimensional numerical simulation was conducted in this study. Our numerical simulation investigates the effects of the platform geometrical and operational conditions on the separation efficiency. Next, the optimal values are tested in an experimental setting to validate these optimal parameters and conditions. This work provides a guideline for future acoustofluidic chip designs with a high degree of reproducibility and efficiency.
Lab‐on‐chip devices are widely being used for binary and ternary cell/particle separation applications. Among the lab‐on‐chip methods, dielectrophoresis (DEP) is a cost‐effective and label‐free ...method, with great capabilities for size‐based separation of cells and particles, which is mostly performed in sheath‐assisted forms. However, the elimination of the sheath flows offers advantages such as ease of operation and higher sample throughput. In this work, we present a comparison of sheath‐assisted and sheathless DEP separation of three sizes of microparticles using tilted electrodes. The sheath‐assisted design was capable of separating the 5, 10, and 15 μm particles with a separation efficiency as high as 98.0% for 15 μm particles. By adding a DEP focusing region, a sheathless DEP separator was proposed, which offered higher throughputs (up to 10 times) at the cost of lowering the separation efficiency (a reduction up to 10.3% for 15 μm) compared to the sheath‐assisted design. To enhance the separation efficiency, a combination of the DEP focusing accompanied by weak sheath flows from both sides was proposed. This design achieved the highest sample separation yield in the outlets (as high as 98.7% for 15 μm) with a sample throughput of more than 4.2 μL/min. This study provides insights into the choice of an appropriate platform for any application in which the yield, purity, throughput, and portability must be considered.
•We used dielectrophoresis for the manipulation of polystyrene particles.•The effect of several factors on the particle displacement were studied.•A model to predict the dielectrophoresis-induced ...displacement of particles was developed.•The DEP-based manipulation of NIH 3T3 mouse fibroblast cells were investigated.•Polystyrene particles were sorted with excellent separation purity (99 %).
Cell/particle separation enabled by lab-on-a-chip (LOC) devices has been a promising solution for separating target cells from the body fluids. Understanding the effects of fabrication and performance parameters on the separation efficiency can further advance applications of such devices in life sciences. This study presents a parametric study on the displacement of the cell-representative polystyrene particles in dielectrophoresis (DEP) based microseparators. The proposed device includes slanted planar interdigitated electrodes to apply a lateral DEP force on the particles. The effect of fabrication parameters (i.e., the channel length and width, and the deflection angle of the electrodes), as well as operational factors (i.e., the volumetric throughput and particle size) on the DEP-induced displacement, are studied. The results show that the volumetric throughput has the most contribution to the position of the particles. Among the geometrical parameters, the channel length is found to be the most effective factor in the particles position, while the effect of the channel width is shown to be negligible. The device was also tested with NIH 3T3 mouse fibroblast cells, which exhibited the same behavior. The results of this research render the desired separation performance to be attained via the design of low-angle slanted electrodes alongside with a balance between the volumetric throughput and the length of the DEP region. These findings lead to a successful size-selective sorting or focusing of 5 μm–15 μm particles, which can provide valuable insights into the design of microfluidic platforms to selectively separate different cell types in biofluids.
This study presents a low‐cost, tunable, and stretchable sensor fabricated based on spandex (SpX) yarns coated with graphene nanoplatelets (GnP) through a dip‐coating process. The SpX/GnP is wrapped ...into a stretchable silicone rubber (SR) sheath to protect the conductive layer against harsh conditions, which allows for fabricating washable wearable sensors. Dip‐coating parameters are optimized to obtain the maximum GnP coating rate. The covering sheath is tailored to achieve high stretchability beyond the sensing limit of 104% for SpX/GnP/SR sensors. Adjustable sensitivity is attained by manipulating SpX immersion times broadening its application for a wide range of strains: Gauge factors as high as two orders of magnitude are achieved at tensile strains greater than ≈40%. The fabricated sensors are tested for two applications: First, the SpX/GnP sensors are integrated into composite fabrics (with no negative impact on the structural integrity of the part) for screening the yarn displacements, resin flow, solidification during the hot press forming process, and structural health monitoring under mechanical loads with minimal cross‐sensitivity to temperature/humidity. Second, the capability of SpX/GnP/SP sensors in detection of a wide range of bodily motions (from the joint motion to arterial blood pressure) is demonstrated.
Low‐cost fabrication of stretchable yarn sensors based on graphene‐decorated spandex is demonstrated. Sensors are fabricated through dip coating, and the sensing layer is protected by a silicone rubber sheath for wash durability. The sensors exhibit tunable sensitivity and wide sensing range making them a promising candidate for applications ranging from wearable devices to composites manufacturing and health monitoring.
Lab‐on‐a‐chip (LOC) technologies can take advantage of sheath flows for particle/cell focusing before sensing or sorting. The integration of focusing with other microscale manipulation techniques ...(e.g., sorting) creates a trade‐off between the throughput of the device and its performance. Therefore, exploring the effective parameters for cells/particles focusing enables us to improve the desired output of LOC devices. A common configuration for sheath‐assisted focusing is Y junctions, which are parametrically studied in this paper. First, a computational model was developed and validated by comparing it with our experimental results. Using COMSOL Multiphysics modeling, the effects of multiple parameters were studied. These parameters include the sheath flow ratio (sheath flow over total flow), width ratio (width of the sheath inlet over the total width), junction angles, and particle size on the focusing width and the distribution of the particles within the focusing region. Then, the numerical data were used to develop two generalized linear models to predict the focusing width of the particles and the standard deviation of the position of the particles. The results showed that the focusing width is greatly impacted by the sheath flow rate ratio. Further, the standard deviation of the position of the particles, which represents the concentration of the particles, is mostly dependent on the flow rate ratio, width ratio, and particle size. Our results provide a better understanding of how the device geometrical and operational factors affect the position of the particles in the development of high‐performance on‐chip sensing and sorting of both cells and particles.
In this paper, an impedance-transduced sensor is developed based on a nanostructured graphene (GN) and poly (methyl methacrylate) (PMMA) sensing film for the detection of individual volatile organic ...compounds (VOCs) in aqueous media. Benefiting from a porous and high surface area, the nanostructured nanofiber is characterized by scanning electron microscopy (SEM) and optimized by the electrochemical impedance spectroscopy (EIS) technique. The recorded EIS data indicate the selective recognition of four VOCs of interest at a constant pH while there is no redox probe. The non-faradaic responses to each analyte at different concentrations are correlated with a three-element equivalent circuit (resistances of the solution and the film, and a pseudo-capacitance). To analyze the ability of the sensing film in distinguishing between VOCs with similar average boiling points, the values of the individual equivalent circuit elements are used as features and clustered in three-dimensional (3D) plots. Among the features, the two representing the maximum differences between the VOCs are represented in a two-dimensional (2D) plot to show the selectivity of the sensor. The feature extraction analysis demonstrates that the constant phase element (CPE) of the equivalent circuit is a more accurate predictor of VOCs than the interfacial capacitance. These results show high selectivity of the sensorial platform due to the synergistic pairing of nanostructured GN and PMMA.
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•Detection of VOCs in aqueous media without the use of redox probe is developed.•PMMA has a high impact on the robustness of the sensing layer.•Equivalent circuit elements values are used as features to show sensor selectivity.
Cryptosporidium is a critical waterborne protozoan pathogen found in water resources that have been a major cause of death and serious illnesses worldwide, costing millions of dollars annually for ...its detection and treatment. Over the past several decades, substantial efforts have been made towards developing techniques for the detection of Cryptosporidium. Early diagnostic techniques were established based on the existing tools in laboratories, such as microscopes. Advancements in fluorescence microscopy, immunological, and molecular techniques have led to the development of several kits for the detection of Cryptosporidium spp. However, these methods have several limitations, such as long processing times, large sample volumes, the requirement for bulky and expensive laboratory tools, and the high cost of reagents. There is an urgent need to improve these existing techniques and develop low-cost, portable and rapid detection tools for applications in the water quality industry. In this review, we compare recent advances in nanotechnology, biosensing and microfluidics that have facilitated the development of sophisticated tools for the detection of Cryptosporidium spp.Finally, we highlight the advantages and disadvantages, of these state-of-the-art detection methods compared to current analytical methodologies and discuss the need for future developments to improve such methods for detecting Cryptosporidium in the water supply chain to enable real-time and on-site monitoring in water resources and remote areas.
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•Conventional and lab-on-chip methods for detection of Cryptosporidium are reviewed.•Immunological, molecular, and nanotechnology detection techniques are discussed.•Lab-on-chip methods reduce processing time from days to as low as hours.•Novel detection methods offer a detection limit as low as a single oocyst.
Emerging sutureless wound-closure techniques have led to paradigm shifts in wound management. State-of-the-art biomaterials offer biocompatible and biodegradable platforms enabling high cohesion ...(toughness) and adhesion for rapid bleeding control as well as robust attachment of implantable devices. Tough bioadhesion stems from the synergistic contributions of cohesive and adhesive interactions. This Review provides a biomacromolecular design roadmap for the development of tough adhesive surgical sealants. We discuss a library of materials and methods to introduce toughness and adhesion to biomaterials. Intrinsically tough and elastic polymers are leveraged primarily by introducing strong but dynamic inter- and intramolecular interactions either through polymer chain design or using crosslink regulating additives. In addition, many efforts have been made to promote underwater adhesion
via
covalent/noncovalent bonds, or through micro/macro-interlock mechanisms at the tissue interfaces. The materials settings and functional additives for this purpose and the related characterization methods are reviewed. Measurements and reporting needs for fair comparisons of different materials and their properties are discussed. Finally, future directions and further research opportunities for developing tough bioadhesive surgical sealants are highlighted.
Bioadhesive materials are promising candidates for sealing wounds as replacements for suturing and stapling techniques. Design of biomaterials involves introducing adhesive functionality into tough polymer networks.
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