Label-Free Cancer Cell Separation from Human Whole Blood Using Inertial Microfluidics at Low Shear Stress

Lee, Myung Gwon; Shin, Joong Ho; Bae, Chae Yun; Choi, Sungyoung; Park, Je‐Kyun

doi:10.1021/ac4006149

Cited by 186 publications

(127 citation statements)

References 27 publications

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“…red blood cells and white blood cells) are dominated by Dean drag, shifting towards opposite side. Finally, it enables a sizebased particle/cell separation and enrichment 81 .…”

Section: Straight Channel With Pillar Arrays or Expansion-contractionmentioning

confidence: 99%

Fundamentals and applications of inertial microfluidics: a review

et al. 2016

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In the last decade, inertial microfluidics has attracted significant attention and a wide variety of channel designs that focus, concentrate and separate particles and fluids have been demonstrated. In contrast to conventional microfluidic technologies, where fluid inertia is negligible and flow remains almost within the Stokes flow region with very low Reynolds number (Re < 1), inertial microfluidics works in the intermediate Reynolds number range (~1 < Re < ~100) between Stokes and turbulent regimes. In this intermediate range, both inertia and fluid viscosity are finite and bring about several intriguing effects that form the basis of inertial microfluidics including (i) inertial migration and (ii) secondary flow. Due to the superior features of high-throughput, simplicity, precise manipulation and low cost, inertial microfluidics is a very promising candidate for cellular sample processing, especially for samples with low abundant targets. In this review, we first discuss the fundamental kinematics of particles in microchannels to familiarise readers with the mechanisms and underlying physics in inertial microfluidic systems. We then present a comprehensive review of recent developments and key applications of inertial microfluidic systems according to their microchannel structures. Finally, we discuss the perspective of employing fluid inertia in microfluidics for particle manipulation. Due to the superior benefits of inertial microfluidics, this promising technology will still be an attractive topic in the near future, with more novel designs and further applications in biology, medicine and industry on the horizon. ABSTRACT:In the last decade, inertial microfluidics has attracted significant attention and a wide variety of channel designs that focus, concentrate and separate particles and fluids have been demonstrated. In contrast to conventional microfluidic technologies, where fluid inertia is negligible and flow remains almost within Stokes flow region with very low Reynolds number Re <<1, inertial microfluidics works in the intermediate Reynolds number range (~1 < Re < ~100) between Stokes and turbulent regimes. In this intermediate range, both inertia and fluid viscosity are finite, and bring about several intriguing effects that form the basis of inertial microfluidics including: (i) inertial migration and (ii) secondary flow. Due to the superior features of high-throughput, simplicity, precise manipulation and low cost, inertial microfluidics is a very promising candidate for cellular sample processing, especially for sample with low abundant targets. In this review, we first discuss the fundamental kinematics of particles in microchannels to familiarise readers with mechanisms and underlying physics in inertial microfluidic systems. We then present a comprehensive review of recent developments and key applications of inertial microfluidic systems according to their microchannel structures. Finally, we discuss the perspective of employing fluid inertia in microfluidics for particle manipu...

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“…red blood cells and white blood cells) are dominated by Dean drag, shifting towards opposite side. Finally, it enables a sizebased particle/cell separation and enrichment 81 .…”

Section: Straight Channel With Pillar Arrays or Expansion-contractionmentioning

confidence: 99%

Fundamentals and applications of inertial microfluidics: a review

et al. 2016

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“…50,51 In a sheath-based channel, however, such a low flow rate (and thus throughput) was critical to permit a high 99% efficiency. 52 Thus, in most of the systems reported to date, there is a clear tradeoff between throughput and efficiency, i.e., high filtration efficiency requires low throughput and vice versa. Our device presented herein, however, offers high efficiency while maintaining a relatively high throughput, leading to a more efficient way in processing large sample volumes.…”

Section: -8mentioning

confidence: 99%

Modulation of rotation-induced lift force for cell filtration in a low aspect ratio microchannel

et al. 2014

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Cell filtration is a critical step in sample preparation in many bioapplications. Herein, we report on a simple, filter-free, microfluidic platform based on hydrodynamic inertial migration. Our approach builds on the concept of two-stage inertial migration which permits precise prediction of microparticle position within the microchannel. Our design manipulates equilibrium positions of larger microparticles by modulating rotation-induced lift force in a low aspect ratio microchannel. Here, we demonstrate filtration of microparticles with extreme efficiency (>99%). Using multiple prostate cell lines (LNCaP and human prostate epithelial tumor cells), we show filtration from spiked blood, with 3-fold concentration and >83% viability. Results of a proliferation assay show normal cell division and suggest no negative effects on intrinsic properties. Considering the planar low-aspect-ratio structure and predictable focusing, we envision promising applications and easy integration with existing lab-on-a-chip systems. V C 2014 AIP Publishing LLC.

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“…It has recently found application in the separation of nucleated cells (14), cancerous cells (15), and stem cells (16) from whole blood. It has also been used in the separation of Escherichia coli from erythrocytes (17).…”

mentioning

confidence: 99%

Enhancing the Detection of Giardia duodenalis Cysts in Foods by Inertial Microfluidic Separation

Ganz

Clime

Farber

et al. 2015

Appl Environ Microbiol

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The sensitivity and specificity of current Giardia cyst detection methods for foods are largely determined by the effectiveness of the elution, separation, and concentration methods used. The aim of these methods is to produce a final suspension with an adequate concentration of Giardia cysts for detection and a low concentration of interfering food debris. In the present study, a microfluidic device, which makes use of inertial separation, was designed and fabricated for the separation of Giardia cysts. A cyclical pumping platform and protocol was developed to concentrate 10-ml suspensions down to less than 1 ml. Tests involving Giardia duodenalis cysts and 1.90-m microbeads in pure suspensions demonstrated the specificity of the microfluidic chip for cysts over smaller nonspecific particles. As the suspension cycled through the chip, a large number of beads were removed (70%) and the majority of the cysts were concentrated (82%). Subsequently, the microfluidic inertial separation chip was integrated into a method for the detection of G. duodenalis cysts from lettuce samples. The method greatly reduced the concentration of background debris in the final suspensions (10-fold reduction) in comparison to that obtained by a conventional method. The method also recovered an average of 68.4% of cysts from 25-g lettuce samples and had a limit of detection (LOD) of 38 cysts. While the recovery of cysts by inertial separation was slightly lower, and the LOD slightly higher, than with the conventional method, the sample analysis time was greatly reduced, as there were far fewer background food particles interfering with the detection of cysts by immunofluorescence microscopy. Giardia duodenalis is an enteric protozoan parasite which infects a wide range of hosts, including humans and a variety of domestic and wild mammals. It is the most commonly identified intestinal parasite worldwide (1), with an estimated 2.8 ϫ 10 8 human cases of giardiasis annually (2). G. duodenalis prevalence is much higher in children than adults and in developing than developed countries (3). Transmission of giardiasis involves the ingestion of the environmentally robust cyst life stage, either by direct contact or indirectly through cyst-contaminated water or food. It is currently estimated that 7% of giardiasis cases in the United States are foodborne (4). Foods that have previously been reported to be contaminated with G. duodenalis cysts include fresh fruits and vegetables, shellfish, and, more recently, meats (5). Fresh fruits and vegetables contaminated with G. duodenalis cysts are of particular public health concern, as they are generally consumed raw and often originate in developing countries with lower standards of water quality and hygiene. An overview by Robertson (6) of the foodborne outbreaks which occurred between the years 1984 and 2012 identified a total of nine giardiasis outbreaks worldwide. A summary of the reported incidence of Giardia spp. in fresh produce was tabulated by Dixon (7) and included 38 studies, with prevalence...

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Label-Free Cancer Cell Separation from Human Whole Blood Using Inertial Microfluidics at Low Shear Stress

Cited by 186 publications

References 27 publications

Fundamentals and applications of inertial microfluidics: a review

Fundamentals and applications of inertial microfluidics: a review

Modulation of rotation-induced lift force for cell filtration in a low aspect ratio microchannel

Enhancing the Detection of Giardia duodenalis Cysts in Foods by Inertial Microfluidic Separation

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