Search Results (24)

The manipulation of cells and bioparticles has garnered significant interest in the field of viscoelastic microfluidics, particularly regarding its capacity for single-stream focusing within a three-dimensional and simple microchannel structure. The inherent simplicity of this method enables the effective manipulation of particles, facilitating the separation and focusing of various cell types, including blood cells, circulating tumor cells (CTCs), and microalgae. However, the viscoelastic nature of the particles imposes limitations in the handling of submicron-sized particles, due to a significant decrease in the viscoelastic force acting on the particle. In this study, we propose a microfluidic device featuring a cruciform cross-sectional microchannel with 45 µm and 45 µm of its vertical and horizontal size, respectively. The cruciform microchannel, which has a 270° reflex angle on four corners, can increase the viscoelastic force on the particles, allowing the device to focus submicron-sized particles down to 180 nm in a single-stream manner. It is important to note that the single-stream formation was maintained, while the channel width at the outlet region was drastically increased, allowing for the enrichment of submicron-sized particles. For biological feasibility, the proposed device also demonstrates the single-stream focusing on biological particles such as bacteria. The presented microfluidic device would have great potential for the focusing and enrichment of nanoparticles including bacteria in a highly robust manner, expecting its use in the various fields such as diverse biological analysis and biomedical research. Full article

Dielectrophoresis (DEP) has been widely employed in microfluidic platforms for particle or cell manipulation in biomedical science applications due to its accurate, fast, label-free, and low-cost diagnostic technique. However, the application of the DEP technique towards protein manipulation has yet to be extensively explored due to the challenges of the complexity of protein itself, such as its complex morphologies, extremely minuscule particle size, inherent electrical properties, and temperature sensitivity, which make it relatively more challenging. Furthermore, given that protein DEP investigation requires entering the micro- to nano-scale level of DEP configuration, various challenging factors such as electrohydrodynamic effects, electrolysis, joule heating, and electrothermal force that emerge will make it more difficult in realizing protein DEP investigation. This review study has discussed the fundamental theory of DEP and considerations toward protein DEP manipulation. In particular, it focused on the DEP theoretical principle towards protein, protein DEP application challenges, microfluidic platform considerations, medium considerations, and a critically reviewed list of protein bioparticles that have been investigated were all highlighted. Full article

Analyte migration order is a major aspect in all migration-based analytical separations methods. Presented here is the manipulation of the migration order of microparticles in an insulator-based electrokinetic separation. Three distinct particle mixtures were studied: a binary mixture of particles with similar electrical charge and different sizes, and two tertiary mixtures of particles of distinct sizes. Each one of the particle mixtures was separated twice, the first separation was performed under low voltage (linear electrokinetic regime) and the second separation was performed under high voltage (nonlinear electrokinetic regime). Linear electrophoresis, which discriminates particles by charge, is the dominant electrokinetic effect in the linear regime; while nonlinear electrophoresis, which discriminates particles by size and shape, is the dominant electrokinetic effect in the nonlinear regime. The separation results obtained with the three particle mixtures illustrated that particle elution order can be changed by switching from the linear electrokinetic regime to the nonlinear electrokinetic regime. Also, in all cases, better separation performances in terms of separation resolution (Rs) were obtained by employing the nonlinear electrokinetic regime allowing nonlinear electrophoresis to be the discriminatory electrokinetic mechanism. These findings could be applied to analyze complex samples containing bioparticles of interest within the micron size range. This is the first report where particle elution order is altered in an iEK system. Full article

Acoustofluidics is an emerging research field wherein either mixing or (bio)-particle separation is conducted. High-power acoustic streaming can produce more intense and rapid flow patterns, leading to faster and more efficient liquid mixing. However, without cooling, the temperature of the piezoelectric element that is used to supply acoustic power to the fluid could rise above 50% of the Curie point of the piezomaterial, thereby accelerating its aging degradation. In addition, the supply of excessive heat to a liquid may lead to irreproducible streaming effects and gas bubble formation. To control these phenomena, in this paper, we present a feedback temperature control system integrated into an acoustofluidic setup using bulk acoustic waves (BAWs) to elevate mass transfer and manipulation of particles. The system performance was tested by measuring mixing efficiency and determining the average velocity magnitude of acoustic streaming. The results show that the integrated temperature control system keeps the temperature at the set point even at high acoustic powers and improves the reproducibility of the acoustofluidic setup performance when the applied voltage is as high as 200 V. Full article

Size sorting, line focusing, and isolation of microparticles or cells are fundamental ingredients in the improvement of disease diagnostic tools adopted in biology and biomedicine. Microfluidic devices are exploited as a solution to transport and manipulate (bio)particles via a liquid flow. Use of acoustic waves traveling through the fluid provides non-contact solutions to the handling goal, by exploiting the acoustophoretic phenomenon. In this paper, a finite element model of a microfluidic surface acoustic wave-based device for the manipulation of microparticles is reported. Counter-propagating waves are designed to interfere inside a PDMS microchannel and generate a standing surface acoustic wave which is transmitted to the fluid as a standing pressure field. A model of the cross-section of the device is considered to perform a sensitivity analysis of such a standing pressure field to uncertainties related to the geometry of the microchannel, especially in terms of thickness and width of the fluid domain. To also assess the effects caused by possible secondary waves traveling in the microchannel, the PDMS is modeled as an elastic solid material. Remarkable effects and possible issues in microparticle actuation, as related to the size of the microchannel, are discussed by way of exemplary results. Full article

Optical tweezers (OTs) can transfer light momentum to particles, achieving the precise manipulation of particles through optical forces. Due to the properties of non-contact and precise control, OTs have provided a gateway for exploring the mysteries behind nonlinear optics, soft-condensed-matter physics, molecular biology, and analytical chemistry. In recent years, OTs have been combined with microfluidic chips to overcome their limitations in, for instance, speed and efficiency, creating a technology known as “optofluidic tweezers.” This paper describes static OTs briefly first. Next, we overview recent developments in optofluidic tweezers, summarizing advancements in capture, manipulation, sorting, and measurement based on different technologies. The focus is on various kinds of optofluidic tweezers, such as holographic optical tweezers, photonic-crystal optical tweezers, and waveguide optical tweezers. Moreover, there is a continuing trend of combining optofluidic tweezers with other techniques to achieve greater functionality, such as antigen–antibody interactions and Raman tweezers. We conclude by summarizing the main challenges and future directions in this research field. Full article

The manipulation of biomedical particles, such as separating circulating tumor cells from blood, based on standing surface acoustic wave (SSAW) has been widely used due to its advantages of label-free approaches and good biocompatibility. However, most of the existing SSAW-based separation technologies are dedicated to isolate bioparticles in only two different sizes. It is still challenging to fractionate various particles in more than two different sizes with high efficiency and accuracy. In this work, to tackle the problems of low efficiency for multiple cell particle separation, integrated multi-stage SSAW devices with different wavelengths driven by modulated signals were designed and studied. A three-dimensional microfluidic device model was proposed and analyzed using the finite element method (FEM). In addition, the effect of the slanted angle, acoustic pressure, and the resonant frequency of the SAW device on the particle separation were systemically studied. From the theoretical results, the separation efficiency of three different size particles based on the multi-stage SSAW devices reached 99%, which was significantly improved compared with conventional single-stage SSAW devices. Full article

Microfluidic devices can provide innovative means to handle and control the transport of (bio)particles within a fluid flow. The advantage of microscale devices is that different components can be integrated in a single chip at low cost, with a negligible power consumption, compared to alternative solutions. In this work, a numerical investigation is developed on the use of standing surface acoustic waves (SAWs) generated within a microfluidic channel in order to manipulate microparticles. Far-field waves are generated via inter-digital transducers (IDTs), travel on the surface of a piezoelectric substrate and finally interfere in the channel, giving rise to a standing wave solution in terms of acoustic pressure. Results are reported for different geometries of the channel, to define the sensitivity of the acoustic pressure field to the relevant geometric features of the channel. This investigation shows how the acoustic radiation and drag forces interact with each other to move and focus the particles, possibly leading to a separation of heterogeneous ones, and generally provide a way to manipulate them at a small scale. Full article

Non-spherical shape is a general appearance feature for bioparticles. Therefore, a mechanical mechanism study of non-spherical particle migration in a microfluidic chip is essential for more precise isolation of target particles. With the manipulation of non-spherical particles, refined disease detection or medical intervention for human beings will be achievable in the future. In this review, fabrication and manipulation of non-spherical particles are discussed. Firstly, various fabrication methods for non-spherical microparticle are introduced. Then, the active and passive manipulation techniques for non-spherical particles are briefly reviewed, including straight inertial microchannels, secondary flow inertial microchannels and deterministic lateral displacement microchannels with extremely high resolution. Finally, applications of viscoelastic flow are presented which obviously increase the precision of non-spherical particle separation. Although various techniques have been employed to improve the performance of non-spherical particle manipulation, the universal mechanism behind this has not been fully discussed. The aim of this review is to provide a reference for non-spherical particle manipulation study researchers in every detail and inspire thoughts for non-spherical particle focused device design. Full article

Various conditions cause dispersions of particulate matter to circulate inside the anterior chamber of a human eye. These dispersed particles might reduce visual acuity or promote elevation of intraocular pressure (IOP), causing secondary complications such as particle related glaucoma, which is a major cause of blindness. Medical and surgical treatment options are available to manage these complications, yet preventive measures are not currently available. Conceptually, manipulating these dispersed particles in a way that reduces their negative impact could prevent these complications. However, as the eye is a closed system, manipulating dispersed particles in it is challenging. Standing acoustic waves have been previously shown to be a versatile tool for manipulation of bioparticles from nano-sized extracellular vesicles up to millimeter-sized organisms. Here we introduce for the first time a novel method utilizing standing acoustic waves to noninvasively manipulate intraocular particles inside the anterior chamber. Using a cylindrical acoustic resonator, we show ex vivo manipulation of pigmentary particles inside porcine eyes. We study the effect of wave intensity over time and rule out temperature changes that could damage tissues. Optical coherence tomography and histologic evaluations show no signs of damage or any other side effect that could be attributed to acoustic manipulation. Finally, we lay out a clear pathway to how this technique can be used as a non-invasive tool for preventing secondary glaucoma. This concept has the potential to control and arrange intraocular particles in specific locations without causing any damage to ocular tissue and allow aqueous humor normal outflow which is crucial for maintaining proper IOP levels. Full article

Separation and detection of cells and particles in a suspension are essential for various applications, including biomedical investigations and clinical diagnostics. Microfluidics realizes the miniaturization of analytical devices by controlling the motion of a small volume of fluids in microchannels and microchambers. Accordingly, microfluidic devices have been widely used in particle/cell manipulation processes. Different microfluidic methods for particle separation include dielectrophoretic, magnetic, optical, acoustic, hydrodynamic, and chemical techniques. Dielectrophoresis (DEP) is a method for manipulating polarizable particles’ trajectories in non-uniform electric fields using unique dielectric characteristics. It provides several advantages for dealing with neutral bioparticles owing to its sensitivity, selectivity, and noninvasive nature. This review provides a detailed study on the signal-based DEP methods that use the applied signal parameters, including frequency, amplitude, phase, and shape for cell/particle separation and manipulation. Rather than employing complex channels or time-consuming fabrication procedures, these methods realize sorting and detecting the cells/particles by modifying the signal parameters while using a relatively simple device. In addition, these methods can significantly impact clinical diagnostics by making low-cost and rapid separation possible. We conclude the review by discussing the technical and biological challenges of DEP techniques and providing future perspectives in this field. 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

Magnetic nanoparticles have attracted significant attention in various disciplines, including engineering and medicine. Microfluidic chips and lab-on-a-chip devices, with precise control over small volumes of fluids and tiny particles, are appropriate tools for the synthesis, manipulation, and evaluation of nanoparticles. Moreover, the controllability and automation offered by the microfluidic chips in combination with the unique capabilities of the magnetic nanoparticles and their ability to be remotely controlled and detected, have recently provided tremendous advances in biotechnology. In particular, microfluidic chips with magnetic nanoparticles serve as sensitive, high throughput, and portable devices for contactless detecting and manipulating DNAs, RNAs, living cells, and viruses. In this work, we review recent fundamental advances in the field with a focus on biomedical applications. First, we study novel microfluidic-based methods in synthesizing magnetic nanoparticles as well as microparticles encapsulating them. We review both continues-flow and droplet-based microreactors, including the ones based on the cross-flow, co-flow, and flow-focusing methods. Then, we investigate the microfluidic-based methods for manipulating tiny magnetic particles. These manipulation techniques include the ones based on external magnets, embedded micro-coils, and magnetic thin films. Finally, we review techniques invented for the detection and magnetic measurement of magnetic nanoparticles and magnetically labeled bioparticles. We include the advances in anisotropic magnetoresistive, giant magnetoresistive, tunneling magnetoresistive, and magnetorelaxometry sensors. Overall, this review covers a wide range of the field uniquely and provides essential information for designing “lab-on-a-chip” systems for synthesizing magnetic nanoparticles, labeling bioparticles with them, and sorting and detecting them on a single chip. Full article

Non-contact manipulation technology has a wide range of applications in the manipulation and fabrication of micro/nanomaterials. However, the manipulation devices are often complex, operated only by professionals, and limited by a single manipulation function. Here, we propose a simple versatile optoelectronic tweezer (OET) system that can be easily controlled for manipulating microparticles with different sizes. In this work, we designed and established an optoelectronic tweezer manipulation system. The OET system could be used to manipulate particles with a wide range of sizes from 2 μm to 150 μm. The system could also manipulate micro-objects of different dimensions like 1D spherical polystyrene microspheres, 2D rod-shaped euglena gracilis, and 3D spiral microspirulina. Optical microscopic patterns for trapping, storing, parallel transporting, and patterning microparticles were designed for versatile manipulation. The sorting, rotation, and assembly of single particles in a given region were experimentally demonstrated. In addition, temperatures measured under different objective lenses indicate that the system does not generate excessive heat to damage bioparticles. The non-contact versatile manipulation reduces operating process and contamination. In future work, the simple optoelectronic tweezers system can be used to control non-contaminated cell interaction and micro-nano manipulation. 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