Microfluidic Blood Cell Sorting: Now and Beyond

Yu, Zeta Tak For; Yong, Koh Meng Aw; Fu, Jianping

doi:10.1002/smll.201302907

Cited by 140 publications

(132 citation statements)

References 149 publications

(251 reference statements)

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“…The blood sample was diluted with a phosphate buffered saline (PBS) solution by a factor of 20 which led to the best performance for the current design. Similar dilution rates are reported by other groups using cell deviation mechanisms [41]. Generally, there is a trade-off between dilution rate and separation efficiency.…”

Section: Particle Suspension and Blood Preparationsupporting

confidence: 86%

“…Microscale blood fractionation is a research area of great interest. A variety of microfluidic devices with the aim of integrating blood plasma extraction have been investigated and reviewed [41,43,44], thereby harnessing the advantages of miniaturized systems. Although, in comparison the yield of the presented system is lower, there are several possibilities to improve the performance, e.g., with a symmetric geometry [45], parallelization [46] or installing units in series [23,47].…”

Section: Human Blood Plasma Separationmentioning

confidence: 99%

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Microfluidic Vortex Enhancement for on-Chip Sample Preparation

et al. 2015

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In the past decade a large amount of analysis techniques have been scaled down to the microfluidic level. However, in many cases the necessary sample preparation, such as separation, mixing and concentration, remains to be performed off-chip. This represents a major hurdle for the introduction of miniaturized sample-in/answer-out systems, preventing the exploitation of microfluidic's potential for small, rapid and accurate diagnostic products. New flow engineering methods are required to address this hitherto insufficiently studied aspect. One microfluidic tool that can be used to miniaturize and integrate sample preparation procedures are microvortices. They have been successfully applied as microcentrifuges, mixers, particle separators, to name but a few. In this work, we utilize a novel corner structure at a sudden channel expansion of a microfluidic chip to enhance the formation of a microvortex. For a maximum area of the microvortex, both chip geometry and corner structure were optimized with a computational fluid dynamic (CFD) model. Fluorescent particle trace measurements with the optimized design prove Micromachines 2015, 6 240 that the corner structure increases the size of the vortex. Furthermore, vortices are induced by the corner structure at low flow rates while no recirculation is observed without a corner structure. Finally, successful separation of plasma from human blood was accomplished, demonstrating a potential application for clinical sample preparation. The extracted plasma was characterized by a flow cytometer and compared to plasma obtained from a standard benchtop centrifuge and from chips without a corner structure.

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Section: Particle Suspension and Blood Preparationsupporting

confidence: 86%

Section: Human Blood Plasma Separationmentioning

confidence: 99%

Microfluidic Vortex Enhancement for on-Chip Sample Preparation

et al. 2015

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“…Rare cells in the circulatory system carry significance for improving cancer prognosis and monitoring treatment response 1 . The ultimate goal of liquid biopsy based detection of rare cells requires a multi-modal system that can process raw samples by separating, sorting and enriching for specific cell populations, and finally identifying the targeted cells via known biological markers 40 .…”

Section: Discussionmentioning

confidence: 99%

“…Efficient separation of cellular populations from whole blood is an essential preparatory step for many biological and clinical assays 1 . Conventional macro-scale cell sorting techniques include density gradient based centrifugation, immunolabeling-based separation such as fluorescence activated or, magnetic-activated cell sorting (FACS, MACS, respectively) and CellSearch.…”

Section: Introductionmentioning

confidence: 99%

Whole-blood sorting, enrichment and in situ immunolabeling of cellular subsets using acoustic microstreaming

et al. 2018

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Analyzing undiluted whole human blood is a challenge due to its complex composition of hematopoietic cellular populations, nucleic acids, metabolites, and proteins. We present a novel multi-functional microfluidic acoustic streaming platform that enables sorting, enrichment and in situ identification of cellular subsets from whole blood. This single device platform, based on lateral cavity acoustic transducers (LCAT), enables (1) the sorting of undiluted donor whole blood into its cellular subsets (platelets, RBCs, and WBCs), (2) the enrichment and retrieval of breast cancer cells (MCF-7) spiked in donor whole blood at rare cell relevant concentrations (10 mL − 1 ), and (3) on-chip immunofluorescent labeling for the detection of specific target cellular populations by their known marker expression patterns. Our approach thus demonstrates a compact system that integrates upstream sample processing with downstream separation/enrichment, to carry out multi-parametric cell analysis for blood-based diagnosis and liquid biopsy blood sampling.

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“…[1][2][3] For example, due to the current interest in the investigation of bacteria living in association with humans, it was important to separate bacterial cells from human cells. 4 Effective classification of blood cells can bring important information into the blood for diagnosis of diseases immune deficiency and genetic abnormalities.…”

Section: Introductionmentioning

confidence: 99%

Enhancement of microfluidic particle separation using cross-flow filters with hydrodynamic focusing

Chiu

Huang

2016

Biomicrofluidics

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A microfluidic chip is proposed to separate microparticles using cross-flow filtration enhanced with hydrodynamic focusing. By exploiting a buffer flow from the side, the microparticles in the sample flow are pushed on one side of the microchannels, lining up to pass through the filters. Meanwhile a larger pressure gradient in the filters is obtained to enhance separation efficiency. Compared with the traditional cross-flow filtration, our proposed mechanism has the buffer flow to create a moving virtual boundary for the sample flow to actively push all the particles to reach the filters for separation. It further allows higher flow rates. The device only requires soft lithograph fabrication to create microchannels and a novel pressurized bonding technique to make high-aspect-ratio filtration structures. A mixture of polystyrene microparticles with 2.7 lm and 10.6 lm diameters are successfully separated. 96.2 6 2.8% of the large particle are recovered with a purity of 97.9 6 0.5%, while 97.5 6 0.4% of the small particle are depleted with a purity of 99.2 6 0.4% at a sample throughput of 10 ll/min. The experiment is also conducted to show the feasibility of this mechanism to separate biological cells with the sample solutions of spiked PC3 cells in whole blood. By virtue of its high separation efficiency, our device offers a label-free separation technique and potential integration with other components, thereby serving as a promising tool for continuous cell filtration and analysis applications. V C 2016 AIP Publishing LLC.

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Microfluidic Blood Cell Sorting: Now and Beyond

Cited by 140 publications

References 149 publications

Microfluidic Vortex Enhancement for on-Chip Sample Preparation

Microfluidic Vortex Enhancement for on-Chip Sample Preparation

Whole-blood sorting, enrichment and in situ immunolabeling of cellular subsets using acoustic microstreaming

Enhancement of microfluidic particle separation using cross-flow filters with hydrodynamic focusing

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