Microfluidic‐Based Approaches in Targeted Cell/Particle Separation Based on Physical Properties: Fundamentals and Applications

Nasiri, Rohollah; Shamloo, Amir; Ahadian, Samad; Amirifar, Leyla; Âkbari, Jafar; Goudie, Marcus J.; Lee, KangJu; Ashammakhi, Nureddin; Dokmeci, Mehmet R.; Carlo, Dino Di; Khademhosseini, Ali

doi:10.1002/smll.202000171

Cited by 162 publications

(105 citation statements)

References 258 publications

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“…The standing acoustic wave in the microfluidic channel has nodes and antinodes, cells flowing through these periodic pressure nodes and antinodes are subjected to different acoustic radiation forces, the force is proportional to the cell size, resulting in the difference in lateral displacement, and then realizes the separation of CTC [87,88]. Acoustophoresis-based CTC separation has the following advantages: it separates cells in a label-free, contact-free, and biocompatible manner, and retains cells' original state, integrity, and function [21]. However, the problem is that the flow rate is low (1.2 mL h −1 ) [89], and the blood needs to be lysed or diluted in a large proportion.…”

Section: Methods Based On Physical Propertiesmentioning

confidence: 99%

Electrochemical Detection and Point-of-Care Testing for Circulating Tumor Cells: Current Techniques and Future Potentials

Han

Sun

et al. 2020

Sensors

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Circulating tumor cells (CTCs) are tumor cells that escaped from the primary tumor or the metastasis into the blood and they play a major role in the initiation of metastasis and tumor recurrence. Thus, it is widely accepted that CTC is the main target of liquid biopsy. In the past few decades, the separation of CTC based on the electrochemical method has attracted widespread attention due to its convenience, rapidness, low cost, high sensitivity, and no need for complex instruments and equipment. At present, CTC detection is not widely used in the clinic due to various reasons. Point-of-care CTC detection provides us with a possibility, which is sensitive, fast, cheap, and easy to operate. More importantly, the testing instrument is small and portable, and the testing does not require specialized laboratories and specialized clinical examiners. In this review, we summarized the latest developments in the electrochemical-based CTC detection and point-of-care CTC detection, and discussed the challenges and possible trends.

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Section: Methods Based On Physical Propertiesmentioning

confidence: 99%

Electrochemical Detection and Point-of-Care Testing for Circulating Tumor Cells: Current Techniques and Future Potentials

Han

Sun

et al. 2020

Sensors

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“…Cell manipulation, as a preliminary step for cell-based analysis, is a rapidly growing area of interdisciplinary research for the development of single-cell technologies. Over the past two decades, single-cell manipulation and analysis methods have improved significantly due to advances in microfluidic cell manipulation methods 1 , 2 . These methods can be broadly categorized as either passive or active.…”

Section: Introductionmentioning

confidence: 99%

Parametric study on the geometrical parameters of a lab-on-a-chip platform with tilted planar electrodes for continuous dielectrophoretic manipulation of microparticles

Dalili

Taatizadeh

Tahmooressi

et al. 2020

Sci Rep

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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 planarslanted-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. Cell manipulation, as a preliminary step for cell-based analysis, is a rapidly growing area of interdisciplinary research for the development of single-cell technologies. Over the past two decades, single-cell manipulation and analysis methods have improved significantly due to advances in microfluidic cell manipulation methods 1,2. These methods can be broadly categorized as either passive or active. The passive methods, including microfiltration 3 , inertia-based 4 , contraction-expansion channels 5 , deterministic lateral displacement 6 , and pinched flow fractionation 7 , do not rely on any external forces. On the other hand, the active methods, such as dielectrophoresis (DEP) 8 , magnetophoresis 9 , acoustophoresis 10 , and optical-based manipulation 11 , require an external force to manipulate the cells/particles. Although passive methods can handle higher flow rates, active methods offer more control over cells/particles, real-time tuning, reliability, and higher manipulation efficiency 12-14 .

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“…Microfluidic cell separation devices benefit from portability, low cost, small size, and blood compatibility [ 24 ]. In particular, label-free cell separation techniques decrease cell damage and eliminate the costly steps of cell labeling [ 25 ].…”

Section: Introductionmentioning

confidence: 99%

“…The simulation and modeling of microfluidic devices is a useful method for predicting device performance and finding optimal properties and flow rates prior to fabrication and trial and error experimentation. Additionally, it improves the understanding of the mechanisms behind microfluidic flow and phenomena while providing insight into flow and particle/cell behavior inside microfluidic devices [ 25 ]. In this work, the numerical simulation of a centrifugal microfluidic platform for CTCs separation from blood in a size-based and label-free manner was carried out by using an inertial focusing approach on a CD.…”

Section: Introductionmentioning

confidence: 99%

Design and Simulation of an Integrated Centrifugal Microfluidic Device for CTCs Separation and Cell Lysis

et al. 2020

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Separation of circulating tumor cells (CTCs) from blood samples and subsequent DNA extraction from these cells play a crucial role in cancer research and drug discovery. Microfluidics is a versatile technology that has been applied to create niche solutions to biomedical applications, such as cell separation and mixing, droplet generation, bioprinting, and organs on a chip. Centrifugal microfluidic biochips created on compact disks show great potential in processing biological samples for point of care diagnostics. This study investigates the design and numerical simulation of an integrated microfluidic device, including a cell separation unit for isolating CTCs from a blood sample and a micromixer unit for cell lysis on a rotating disk platform. For this purpose, an inertial microfluidic device was designed for the separation of target cells by using contraction–expansion microchannel arrays. Additionally, a micromixer was incorporated to mix separated target cells with the cell lysis chemical reagent to dissolve their membranes to facilitate further assays. Our numerical simulation approach was validated for both cell separation and micromixer units and corroborates existing experimental results. In the first compartment of the proposed device (cell separation unit), several simulations were performed at different angular velocities from 500 rpm to 3000 rpm to find the optimum angular velocity for maximum separation efficiency. By using the proposed inertial separation approach, CTCs, were successfully separated from white blood cells (WBCs) with high efficiency (~90%) at an angular velocity of 2000 rpm. Furthermore, a serpentine channel with rectangular obstacles was designed to achieve a highly efficient micromixer unit with high mixing quality (~98%) for isolated CTCs lysis at 2000 rpm.

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Microfluidic‐Based Approaches in Targeted Cell/Particle Separation Based on Physical Properties: Fundamentals and Applications

Cited by 162 publications

References 258 publications

Electrochemical Detection and Point-of-Care Testing for Circulating Tumor Cells: Current Techniques and Future Potentials

Electrochemical Detection and Point-of-Care Testing for Circulating Tumor Cells: Current Techniques and Future Potentials

Parametric study on the geometrical parameters of a lab-on-a-chip platform with tilted planar electrodes for continuous dielectrophoretic manipulation of microparticles

Design and Simulation of an Integrated Centrifugal Microfluidic Device for CTCs Separation and Cell Lysis

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