A numbering-up strategy of hydrodynamic microfluidic filters for continuous-flow high-throughput cell sorting.

Even though a number of microfluidic systems for particle/cell sorting have been proposed, facile and versatile platforms that provide sufficient sorting throughput and good operability are still under development. Here we present a simple but effective numbering-up strategy to dramatically increase the throughput of a continuous-flow particle/cell sorting scheme based on hydrodynamic filtration (HDF). A microfluidic channel equipped with multiple branches has been employed as a unit structure for size-based filtration, which realizes precise sorting without necessitating sheath flows. According to the concept of resistive circuit models, we designed and fabricated microdevices incorporating 64 or 128 closely assembled, multiplied units with a separation size of 5.0/7.0 μm. In proof-of-concept experiments, we successfully separated single micrometer-sized model particles and directly separated blood cells (erythrocytes and leukocytes) from blood samples. Additionally, we further increased the unit numbers by laminating multiple layers at a processing speed of up to 15 mL min-1. The presented numbering-up strategy would provide a valuable insight that is universally applicable to general microfluidic particle/cell sorters and may facilitate the actual use of microfluidic systems in biological studies and clinical diagnosis.

[1]  Zhonghua Ni,et al.  Concentration‐controlled particle focusing in spiral elasto‐inertial microfluidic devices , 2018, Electrophoresis.

[2]  Chulhee Choi,et al.  Microfluidic self-sorting of mammalian cells to achieve cell cycle synchrony by hydrophoresis. , 2009, Analytical chemistry.

[3]  Aram J. Chung,et al.  Continuous inertial microparticle and blood cell separation in straight channels with local microstructures. , 2016, Lab on a chip.

[4]  J. Sturm,et al.  Continuous Particle Separation Through Deterministic Lateral Displacement , 2004, Science.

[5]  Xian-Bo Zhang,et al.  Gravitational sedimentation induced blood delamination for continuous plasma separation on a microfluidics chip. , 2012, Analytical chemistry.

[6]  Robert E. Nordon,et al.  Scaling deterministic lateral displacement arrays for high throughput and dilution-free enrichment of leukocytes , 2011 .

[7]  Wei Wang,et al.  A microfluidic device based on gravity and electric force driving for flow cytometry and fluorescence activated cell sorting. , 2004, Lab on a chip.

[8]  C. Lim,et al.  Isolation and retrieval of circulating tumor cells using centrifugal forces , 2013, Scientific Reports.

[9]  Paul H. Bessette,et al.  Marker-specific sorting of rare cells using dielectrophoresis. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[10]  Han Wei Hou,et al.  Broad spectrum immunomodulation using biomimetic blood cell margination for sepsis therapy. , 2016, Lab on a chip.

[11]  Pier Luca Maffettone,et al.  Particle Migration due to Viscoelasticity of the Suspending Liquid and Its Relevance in Microfluidic Devices , 2017 .

[12]  Am Allison Schaap,et al.  Sorting algal cells by morphology in spiral microchannels using inertial microfluidics , 2016 .

[13]  Ian Papautsky,et al.  A high throughput microfluidic platform for size-selective enrichment of cell populations in tissue and blood samples. , 2017, The Analyst.

[14]  Majid Ebrahimi Warkiani,et al.  Multiplexing slanted spiral microchannels for ultra-fast blood plasma separation. , 2016, Lab on a chip.

[15]  Sergey S. Shevkoplyas,et al.  A high-throughput microfluidic approach for 1000-fold leukocyte reduction of platelet-rich plasma , 2016, Scientific Reports.

[16]  G. Whitesides,et al.  Components for integrated poly(dimethylsiloxane) microfluidic systems , 2002, Electrophoresis.

[17]  M. Yamada,et al.  Pinched flow fractionation: continuous size separation of particles utilizing a laminar flow profile in a pinched microchannel. , 2004, Analytical chemistry.

[18]  Nanjing Hao,et al.  Microfluidic Screening of Circulating Tumor Biomarkers toward Liquid Biopsy , 2018 .

[19]  T. Huang,et al.  Acoustic separation of circulating tumor cells , 2015, Proceedings of the National Academy of Sciences.

[20]  Weihua Li,et al.  High throughput extraction of plasma using a secondary flow-aided inertial microfluidic device , 2014 .

[21]  Gabriel P López,et al.  Microfluidic cell sorting: a review of the advances in the separation of cells from debulking to rare cell isolation. , 2015, Lab on a chip.

[22]  Wei Lu,et al.  Continuous-flow microfluidic blood cell sorting for unprocessed whole blood using surface-micromachined microfiltration membranes. , 2014, Lab on a chip.

[23]  Saeid Nahavandi,et al.  Dielectrophoretic platforms for bio-microfluidic systems. , 2011, Biosensors & bioelectronics.

[24]  H. Amini,et al.  Label-free cell separation and sorting in microfluidic systems , 2010, Analytical and bioanalytical chemistry.

[25]  Thomas Laurell,et al.  Acoustofluidics 8: applications of acoustophoresis in continuous flow microsystems. , 2012, Lab on a chip.

[26]  M. Yamada,et al.  Microfluidic particle sorter employing flow splitting and recombining. , 2006, Analytical chemistry.

[27]  Minoru Seki,et al.  Microfluidic System Enabling Multistep Tuning of Extraction Time Periods for Kinetic Analysis of Droplet-Based Liquid-Liquid Extraction. , 2016, Analytical chemistry.

[28]  A. Bhagat,et al.  Inertial microfluidics for continuous particle separation in spiral microchannels. , 2009, Lab on a chip.

[29]  Sheng Yan,et al.  Recent progress of particle migration in viscoelastic fluids. , 2018, Lab on a chip.

[30]  Han Wei Hou,et al.  Rapid and label-free microfluidic neutrophil purification and phenotyping in diabetes mellitus , 2016, Scientific Reports.

[31]  D. Di Carlo,et al.  Continuous scalable blood filtration device using inertial microfluidics , 2010, Biotechnology and bioengineering.

[32]  M. Yamada,et al.  Hydrodynamic filtration for on-chip particle concentration and classification utilizing microfluidics. , 2005, Lab on a chip.

[33]  Tony Jun Huang,et al.  A high-throughput acoustic cell sorter. , 2015, Lab on a chip.

[34]  David Issadore,et al.  Kilo-scale droplet generation in three-dimensional monolithic elastomer device (3D MED). , 2015, Lab on a chip.

[35]  Nicole Pamme,et al.  On-chip bioanalysis with magnetic particles. , 2012, Current opinion in chemical biology.

[36]  Peter C. Y. Chen,et al.  Slanted spiral microfluidics for the ultra-fast, label-free isolation of circulating tumor cells. , 2014, Lab on a chip.

[37]  Minoru Seki,et al.  Blood cell classification utilizing hydrodynamic filtration , 2008 .

[38]  Murat Karabacak,et al.  Continuous Flow Microfluidic Bioparticle Concentrator , 2015, Scientific Reports.

[39]  Han Wei Hou,et al.  Rapid purification of sub-micrometer particles for enhanced drug release and microvesicles isolation , 2017 .

[40]  Li Zhang,et al.  Factory-on-chip: Modularised microfluidic reactors for continuous mass production of functional materials , 2017 .

[41]  Michael P Barrett,et al.  Separation of parasites from human blood using deterministic lateral displacement. , 2011, Lab on a chip.

[42]  R. Tompkins,et al.  Continuous inertial focusing, ordering, and separation of particles in microchannels , 2007, Proceedings of the National Academy of Sciences.

[43]  Nam-Trung Nguyen,et al.  High-Throughput Separation of White Blood Cells From Whole Blood Using Inertial Microfluidics , 2017, IEEE Transactions on Biomedical Circuits and Systems.

[44]  Minoru Seki,et al.  Magnetophoresis-integrated hydrodynamic filtration system for size- and surface marker-based two-dimensional cell sorting. , 2013, Analytical chemistry.

[45]  Da-Han Kuan,et al.  A Microfluidic Device for Simultaneous Extraction of Plasma, Red Blood Cells, and On-Chip White Blood Cell Trapping , 2018, Scientific Reports.

[46]  M. Yamada,et al.  Continuous particle separation in a microchannel having asymmetrically arranged multiple branches. , 2005, Lab on a chip.

[47]  Chulhee Choi,et al.  Continuous blood cell separation by hydrophoretic filtration. , 2007, Lab on a chip.

[48]  T. Laurell,et al.  Continuous flow microfluidic separation and processing of rare cells and bioparticles found in blood - A review. , 2017, Analytica chimica acta.

[49]  G M Whitesides,et al.  Fabrication of topologically complex three-dimensional microfluidic systems in PDMS by rapid prototyping. , 2000, Analytical chemistry.

[50]  Jin-Ming Lin,et al.  Microfluidic technologies in cell isolation and analysis for biomedical applications. , 2017, The Analyst.

[51]  Minoru Seki,et al.  Slanted, asymmetric microfluidic lattices as size-selective sieves for continuous particle/cell sorting. , 2017, Lab on a chip.