Microfluidic Hydrodynamic Cell Separation: A Review
TL;DR: In this article, the basic ideas and fluid mechanics for the hydrodynamic interaction of a particle in a microfluidic system are presented. And different kinds of devices are introduced with detailed descriptions of their mechanisms, designs and performances.
Abstract: Microfluidic continuous cell separation based on hydrodynamic interaction in a microfluidic channel has attracted attention because of its robustness, high throughput and cell viability This paper systematically gives an overview on recent advances in hydrodynamic particle and cell separation in microfluidic devices It presents the basic ideas and fluid mechanics for the hydrodynamic interaction of a particle in a microfluidic system Secondly, different kinds of devices are introduced with detailed descriptions of their mechanisms, designs and performances Finally, the review addresses some practical issues of microfluidic sorting devices for use in biological or medical studies
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TL;DR: In this article, the authors present an extensive review of relevant biophysical laws, along with experimental details of various passive separation techniques and devices exploiting these physical effects, and compare the relative performances, and the advantages and disadvantages of microdevices discussed in the literature.
Abstract: Blood plasma separation is vital in the field of diagnostics and health care. Due to the inherent advantages obtained in the transition to microscale, the recent trend in these fields is a rapid shift towards the miniaturization of complex macro processes. Plasma separation in microdevices is one such process which has received extensive attention from researchers globally. Blood plasma separation techniques based on microfluidic platforms can be broadly classified into two categories. While active techniques utilize external force fields for separation, the passive techniques are dependent on biophysical effects, cell behavior, hydrodynamic forces and channel geometry for blood plasma separation. In general, passive separation methods are favored in comparison to active methods because they tend to avoid design complexities and are relatively easy to integrate with biosensors; additionally they are cost effective. Here we review passive separation techniques demonstrating separation and blood behavior at microscale. We present an extensive review of relevant biophysical laws, along with experimental details of various passive separation techniques and devices exploiting these physical effects. The relative performances, and the advantages and disadvantages of microdevices discussed in the literature, are compared and future challenges are brought about.
181 citations
TL;DR: This article critically review the most promising hydrodynamic, dielectrophoretic and magnetic force-based microfluidic CTC-capture devices utilizing the physical and biochemical properties of CTCs.
Abstract: Circulating tumor cells (CTCs) in the bloodstream are considered good indicators of the presence of a primary tumor or even metastases. CTC capture has great importance in early detection of cancer, especially in identifying novel therapeutic routes for cancer patients by finding personalized druggable targets for the pharmaceutical industry. Recent developments in microfluidics and nanotechnology improved the capabilities of CTC detection and capture, including purity, selectivity and throughput. This article covers the recent technological improvements in microfluidics-based CTC-capture methods utilizing the physical and biochemical properties of CTCs. We critically review the most promising hydrodynamic, dielectrophoretic and magnetic force-based microfluidic CTC-capture devices.
106 citations
Cites background from "Microfluidic Hydrodynamic Cell Sepa..."
...Based on the dominant forces, hydrodynamic separation can be further classified into laminar-based, inertia-based and biomimeticsbased flows [23]....
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...The cell-wall interaction can be further divided into continuous wall (channels) and discrete wall (obstacles) [23]....
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TL;DR: In this paper, a review of different techniques and the recent applications regarding the micro-fluidic bio-particle manipulation for different biotechnology applications are presented, and challenges and the future research directions for micro-particles manipulation are addressed.
65 citations
Cites background from "Microfluidic Hydrodynamic Cell Sepa..."
...Introducing obstacles and posts with a critical spacing can be utilized as filter structure to capture (trap) or isolate specific bio-particle of interest with a size larger than the critical size [6]....
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TL;DR: A review of devices that detect and capture CTCs using different cell properties (surface markers, size, deformability, electrical properties, etc.) and discusses the process of tumor cell dissemination, the biology of C TCs, epithelial-mesenchymal transition (EMT), and several challenges and clinical applications of CTC detection.
Abstract: Metastasis is the main cause of death in cancer patients worldwide. During metastasis, cancer cells detach from the primary tumor and invade distant tissue. The cells that undergo this process are called circulating tumor cells (CTCs). Studies show that the number of CTCs in the peripheral blood can predict progression-free survival and overall survival and can be informative concerning the efficacy of treatment. Research is now concentrated on developing devices that can detect CTCs in the blood of cancer patients with improved sensitivity and specificity that can lead to improved clinical evaluation. This review focuses on devices that detect and capture CTCs using different cell properties (surface markers, size, deformability, electrical properties, etc.). We also discuss the process of tumor cell dissemination, the biology of CTCs, epithelial–mesenchymal transition (EMT), and several challenges and clinical applications of CTC detection.
40 citations
TL;DR: The proposed particle separation device offers high‐throughput operation with purity >97% and recovery rate >99%.
Abstract: A particle suspended in a fluid within a microfluidic channel experiences a direct acoustic radiation force (ARF) when traveling surface acoustic waves (TSAWs) couple with the fluid at the Rayleigh angle, thus producing two components of the ARF. Most SAW-based microfluidic devices rely on the horizontal component of the ARF to migrate prefocused particles laterally across a microchannel width. Although the magnitude of the vertical component of the ARF is more than twice the magnitude of the horizontal component, it is long ignored due to polydimethylsiloxane (PDMS) microchannel fabrication limitations and difficulties in particle focusing along the vertical direction. In the present work, a single-layered PDMS microfluidic chip is devised for hydrodynamically focusing particles in the vertical plane while explicitly taking advantage of the horizontal ARF component to slow down the selected particles and the stronger vertical ARF component to push the particles in the upward direction to realize continuous particle separation. The proposed particle separation device offers high-throughput operation with purity >97% and recovery rate >99%. It is simple in its fabrication and versatile due to the single-layered microchannel design, combined with vertical hydrodynamic focusing and the use of both the horizontal and vertical components of the ARF.
36 citations
References
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TL;DR: The manipulation of fluids in channels with dimensions of tens of micrometres — microfluidics — has emerged as a distinct new field that has the potential to influence subject areas from chemical synthesis and biological analysis to optics and information technology.
Abstract: The manipulation of fluids in channels with dimensions of tens of micrometres--microfluidics--has emerged as a distinct new field. Microfluidics has the potential to influence subject areas from chemical synthesis and biological analysis to optics and information technology. But the field is still at an early stage of development. Even as the basic science and technological demonstrations develop, other problems must be addressed: choosing and focusing on initial applications, and developing strategies to complete the cycle of development, including commercialization. The solutions to these problems will require imagination and ingenuity.
8,260 citations
"Microfluidic Hydrodynamic Cell Sepa..." refers background in this paper
...During the last twenty years, microfluidics has witnessed rapid advancements in different kinds of areas [3-4]....
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...The robust, simple and continuous format indicates its high possibility for practical applications, production and further for commercialization [3, 77]....
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TL;DR: A review of the physics of small volumes (nanoliters) of fluids is presented, as parametrized by a series of dimensionless numbers expressing the relative importance of various physical phenomena as mentioned in this paper.
Abstract: Microfabricated integrated circuits revolutionized computation by vastly reducing the space, labor, and time required for calculations. Microfluidic systems hold similar promise for the large-scale automation of chemistry and biology, suggesting the possibility of numerous experiments performed rapidly and in parallel, while consuming little reagent. While it is too early to tell whether such a vision will be realized, significant progress has been achieved, and various applications of significant scientific and practical interest have been developed. Here a review of the physics of small volumes (nanoliters) of fluids is presented, as parametrized by a series of dimensionless numbers expressing the relative importance of various physical phenomena. Specifically, this review explores the Reynolds number Re, addressing inertial effects; the Peclet number Pe, which concerns convective and diffusive transport; the capillary number Ca expressing the importance of interfacial tension; the Deborah, Weissenberg, and elasticity numbers De, Wi, and El, describing elastic effects due to deformable microstructural elements like polymers; the Grashof and Rayleigh numbers Gr and Ra, describing density-driven flows; and the Knudsen number, describing the importance of noncontinuum molecular effects. Furthermore, the long-range nature of viscous flows and the small device dimensions inherent in microfluidics mean that the influence of boundaries is typically significant. A variety of strategies have been developed to manipulate fluids by exploiting boundary effects; among these are electrokinetic effects, acoustic streaming, and fluid-structure interactions. The goal is to describe the physics behind the rich variety of fluid phenomena occurring on the nanoliter scale using simple scaling arguments, with the hopes of developing an intuitive sense for this occasionally counterintuitive world.
4,044 citations
"Microfluidic Hydrodynamic Cell Sepa..." refers background in this paper
...For a further study, the readers can refer to the review by Squires and Quake [4] or the recent text book on theoretical microfluidics by Bruus [17]....
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...During the last twenty years, microfluidics has witnessed rapid advancements in different kinds of areas [3-4]....
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TL;DR: The CTC-chip successfully identified CTCs in the peripheral blood of patients with metastatic lung, prostate, pancreatic, breast and colon cancer in 115 of 116 samples, with a range of 5–1,281CTCs per ml and approximately 50% purity.
Abstract: Viable tumour-derived epithelial cells (circulating tumour cells or CTCs) have been identified in peripheral blood from cancer patients and are probably the origin of intractable metastatic disease. Although extremely rare, CTCs represent a potential alternative to invasive biopsies as a source of tumour tissue for the detection, characterization and monitoring of non-haematologic cancers. The ability to identify, isolate, propagate and molecularly characterize CTC subpopulations could further the discovery of cancer stem cell biomarkers and expand the understanding of the biology of metastasis. Current strategies for isolating CTCs are limited to complex analytic approaches that generate very low yield and purity. Here we describe the development of a unique microfluidic platform (the 'CTC-chip') capable of efficient and selective separation of viable CTCs from peripheral whole blood samples, mediated by the interaction of target CTCs with antibody (EpCAM)-coated microposts under precisely controlled laminar flow conditions, and without requisite pre-labelling or processing of samples. The CTC-chip successfully identified CTCs in the peripheral blood of patients with metastatic lung, prostate, pancreatic, breast and colon cancer in 115 of 116 (99%) samples, with a range of 5-1,281 CTCs per ml and approximately 50% purity. In addition, CTCs were isolated in 7/7 patients with early-stage prostate cancer. Given the high sensitivity and specificity of the CTC-chip, we tested its potential utility in monitoring response to anti-cancer therapy. In a small cohort of patients with metastatic cancer undergoing systemic treatment, temporal changes in CTC numbers correlated reasonably well with the clinical course of disease as measured by standard radiographic methods. Thus, the CTC-chip provides a new and effective tool for accurate identification and measurement of CTCs in patients with cancer. It has broad implications in advancing both cancer biology research and clinical cancer management, including the detection, diagnosis and monitoring of cancer.
3,450 citations
TL;DR: This work presents a passive method for mixing streams of steady pressure-driven flows in microchannels at low Reynolds number, and uses bas-relief structures on the floor of the channel that are easily fabricated with commonly used methods of planar lithography.
Abstract: It is difficult to mix solutions in microchannels. Under typical operating conditions, flows in these channels are laminar—the spontaneous fluctuations of velocity that tend to homogenize fluids in turbulent flows are absent, and molecular diffusion across the channels is slow. We present a passive method for mixing streams of steady pressure-driven flows in microchannels at low Reynolds number. Using this method, the length of the channel required for mixing grows only logarithmically with the Pe «clet number, and hydrodynamic dispersion along the channel is reduced relative to that in a simple, smooth channel. This method uses bas-relief structures on the floor of the channel that are easily fabricated with commonly used methods of planar lithography.
3,269 citations
TL;DR: In this paper, a modular construction of a miniaturized "total chemical analysis system" is proposed, and theoretical performances of such systems based on flow injection analysis, chromatography and electrophoresis are compared with those of existing chemical sensors and analysis systems.
Abstract: Following the trend towards smaller channel inner diameter for better separation performance and shorter channel length for shorter transport time, a modular construction of a miniaturized 'total chemical analysis system' is proposed. The theoretical performances of such systems based on flow injection analysis, chromatography and electrophoresis, are compared with those of existing chemical sensors and analysis systems.
3,017 citations
"Microfluidic Hydrodynamic Cell Sepa..." refers background in this paper
...In the late 20th century, with the development of micro engineering, a new interdisciplinary field – microfluidics – appeared [1-2]....
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