Please confirm you are human (Sign Up for free to never see this)
← Back to Search
Pinched Flow Coupled Shear-modulated Inertial Microfluidics For High-throughput Rare Blood Cell Separation.
A. Bhagat, H. Hou, L. Li, C. T. Lim, J. Han
Published 2011 · Chemistry, Medicine
Save to my Library
Download PDFAnalyze on Scholarcy
Blood is a highly complex bio-fluid with cellular components making up >40% of the total volume, thus making its analysis challenging and time-consuming. In this work, we introduce a high-throughput size-based separation method for processing diluted blood using inertial microfluidics. The technique takes advantage of the preferential cell focusing in high aspect-ratio microchannels coupled with pinched flow dynamics for isolating low abundance cells from blood. As an application of the developed technique, we demonstrate the isolation of cancer cells (circulating tumor cells (CTCs)) spiked in blood by exploiting the difference in size between CTCs and hematologic cells. The microchannel dimensions and processing parameters were optimized to enable high throughput and high resolution separation, comparable to existing CTC isolation technologies. Results from experiments conducted with MCF-7 cells spiked into whole blood indicate >80% cell recovery with an impressive 3.25 × 10(5) fold enrichment over red blood cells (RBCs) and 1.2 × 10(4) fold enrichment over peripheral blood leukocytes (PBL). In spite of a 20× sample dilution, the fast operating flow rate allows the processing of ∼10(8) cells min(-1) through a single microfluidic device. The device design can be easily customized for isolating other rare cells from blood including peripheral blood leukocytes and fetal nucleated red blood cells by simply varying the 'pinching' width. The advantage of simple label-free separation, combined with the ability to retrieve viable cells post enrichment and minimal sample pre-processing presents numerous applications for use in clinical diagnosis and conducting fundamental studies.
This paper references
Shear stress effects on human embryonic kidney cells in Vitro
N. Stathopoulos (1985)
Carcinoma invasion and metastasis: a role for epithelial-mesenchymal transition?
E. Thompson (2005)
Membrane microfilter device for selective capture, electrolysis and genomic analysis of human circulating tumor cells.
Siyang Zheng (2007)
Wall-induced forces on a rigid sphere at finite Reynolds number
Lanying Zeng (2005)
Biochip for separating fetal cells from maternal circulation.
H. Mohamed (2007)
Estimation of disruption of animal cells by laminar shear stress
C. Born (1992)
Altered expression of CD11b/CD18 and CD62L on human monocytes after cell preparation procedures.
J. Lundahl (1995)
Pinched flow fractionation: continuous size separation of particles utilizing a laminar flow profile in a pinched microchannel.
Masumi Yamada (2004)
Morphometry of human leukocytes.
G. W. Schmid-Schönbein (1980)
Stability of molded polydimethylsiloxane microstructures
E. Delamarche (1997)
Isolation of tumor cells using size and deformation.
H. Mohamed (2009)
Microdevice for the isolation and enumeration of cancer cells from blood
S. J. Tan (2009)
Capture of circulating tumor cells from whole blood of prostate cancer patients using geometrically enhanced differential immunocapture (GEDI) and a prostate-specific antibody.
J. Gleghorn (2010)
Case study of the morphologic variation of circulating tumor cells.
D. Marrinucci (2007)
Enrichment of rare cancer cells through depletion of normal cells using density and flow-through, immunomagnetic cell separation.
Oscar R. Lara (2004)
Microfluidics for cell separation
A. Bhagat (2010)
The measurement and therapeutic implications of circulating tumour cells in breast cancer
J. Smerage (2006)
New technologies for the detection of circulating tumour cells.
N. Gerges (2010)
Direct measurement of the impact of impaired erythrocyte deformability on microvascular network perfusion in a microfluidic device.
S. Shevkoplyas (2006)
Perfusion in microfluidic cross-flow: separation of white blood cells from whole blood and exchange of medium in a continuous flow.
V. Vandelinder (2007)
Highly efficient circulating tumor cell isolation from whole blood and label-free enumeration using polymer-based microfluidics with an integrated conductivity sensor.
André A. Adams (2008)
M. Toner (2005)
Microfluidic diffusive filter for apheresis (leukapheresis).
P. Sethu (2006)
Retention of leukocytes in capillaries: role of cell size and deformability.
G. Downey (1990)
Centrifugation attenuates the fluid shear response of circulating leukocytes
Shunichi Fukuda (2002)
Size-selective microcavity array for rapid and efficient detection of circulating tumor cells.
M. Hosokawa (2010)
Isolating highly enriched populations of circulating epithelial cells and other rare cells from blood using a magnetic sweeper device
Amirali H. Talasaz (2009)
Biomimetic autoseparation of leukocytes from whole blood in a microfluidic device.
S. Shevkoplyas (2005)
Cell filtration‐laser scanning cytometry for the characterisation of circulating breast cancer cells
L. Zabaglo (2003)
Lateral Forces on a Sphere
Jean-Philippe Matas (2004)
Continuous inertial focusing, ordering, and separation of particles in microchannels
D. Di Carlo (2007)
Enrichment, immunomorphological, and genetic characterization of fetal cells circulating in maternal blood.
G. Vona (2002)
Application of a filtration- and isolation-by-size technique for the detection of circulating tumor cells in cutaneous melanoma.
V. De Giorgi (2010)
Enhanced particle filtration in straight microchannels using shear-modulated inertial migration
A. Bhagat (2008)
Isolation of lymphocytes, granulocytes and macrophages.
A. Bøyum (1976)
Multiorifice flow fractionation: continuous size-based separation of microspheres using a series of contraction/expansion microchannels.
Jaesung Park (2009)
Cancer Invasion and Metastasis
C. Wittekind (2005)
Continuous focusing of microparticles using inertial lift force and vorticity via multi-orifice microfluidic channels.
J. Park (2009)
Circulating tumor cells, disease progression, and survival in metastatic breast cancer.
M. Cristofanilli (2004)
Migration of particles undergoing pressure-driven flow in a circular conduit
R. Hampton (1997)
Deformability based cell margination--a simple microfluidic design for malaria-infected erythrocyte separation.
H. Hou (2010)
Deformability study of breast cancer cells using microfluidics
H. Hou (2009)
High Ep-CAM Expression is Associated with Poor Prognosis in Node-positive Breast Cancer
G. Spizzo (2004)
Behaviour of macroscopic rigid spheres in Poiseuille flow Part 1. Determination of local concentration by statistical analysis of particle passages through crossed light beams
G. Segré (1962)
Flow-induced deformation of shallow microfluidic channels.
T. Gervais (2006)
Deformability‐based flow cytometry
Bryan Lincoln (2004)
Inertial microfluidics for continuous particle filtration and extraction
A. Bhagat (2009)
Isolation of plasma from whole blood using planar microfilters for lab-on-a-chip applications.
T. A. Crowley (2005)
Separation of plasma from whole human blood in a continuous cross-flow in a molded microfluidic device.
V. Vandelinder (2006)
A microfluidic device for practical label-free CD4(+) T cell counting of HIV-infected subjects.
X. Cheng (2007)
Isolation of rare circulating tumour cells in cancer patients by microchip technology
S. Nagrath (2007)
Circulating tumor cells (CTC) detection: clinical impact and future directions.
P. Paterlini-Bréchot (2007)
Radial Particle Displacements in Poiseuille Flow of Suspensions
G. Segré (1961)
The inertial lift on a spherical particle in a plane Poiseuille flow at large channel Reynolds number
E. S. Asmolov (1999)
Continuous particle separation in spiral microchannels using Dean flows and differential migration.
A. Bhagat (2008)
Inertial migration of rigid spherical particles in Poiseuille flow
Jean-Philippe Matas (2004)
Microsystems for the capture of low-abundance cells.
Udara Dharmasiri (2010)
Deterministic hydrodynamics: Taking blood apart
J. A. Davis (2006)
Circulating Tumor Cells at Each Follow-up Time Point during Therapy of Metastatic Breast Cancer Patients Predict Progression-Free and Overall Survival
D. Hayes (2006)
Isolation by size of epithelial tumor cells : a new method for the immunomorphological and molecular characterization of circulatingtumor cells.
G. Vona (2000)
The epithelial–mesenchymal transition: new insights in signaling, development, and disease
J. Lee (2006)
Inertial migration of neutrally buoyant particles in a square duct: An investigation of multiple equilibrium positions
B. Chun (2006)
Continuous blood cell separation by hydrophoretic filtration.
Sungyoung Choi (2007)
Detection, clinical relevance and specific biological properties of disseminating tumour cells
K. Pantel (2008)
Circulating Tumor Cells versus Imaging—Predicting Overall Survival in Metastatic Breast Cancer
G. Budd (2006)
This paper is referenced by
Fabrication of Low-Cost Paper-Based Microfluidic Devices by Embossing or Cut-and-Stack Methods
M. Thuo (2014)
Emerging microfluidic devices for cancer cells/biomarkers manipulation and detection.
V. H. Perez-Gonzalez (2016)
Microfluidic Nanoparticles Focusing and Separation
Chao Zhao (2015)
VTX‐1 Liquid Biopsy System for Fully‐Automated and Label‐Free Isolation of Circulating Tumor Cells with Automated Enumeration by BioView Platform
Elodie Sollier-Christen (2018)
Accelerating Simulation of Particle Trajectories in Microfluidic Devices by Constructing a Cloud Database
Junchao Wang (2018)
A 3D printed three-dimensional centrifugal fluidic system for blood separation
Qin Xian-ming (2020)
Separation of extracellular nanovesicles and apoptotic bodies from cancer cell culture broth using tunable microfluidic systems
Soojeong Shin (2017)
Detecting Circulating Tumor Cells: Current Challenges and New Trends
Bin Hong (2013)
Biophysical Tools for Cellular and Subcellular Mechanical Actuation of Cell Signaling.
A. Liu (2016)
A review of sorting, separation and isolation of cells and microbeads for biomedical applications: microfluidic approaches.
A. Dalili (2018)
Isolation of cells from whole blood using shear-induced diffusion
J. Zhou (2018)
Enhancement of isolation sensitivity for the viable heterogeneous circulating tumor cells swelled by hypo-osmotic pressure
J. Bu (2017)
Rapid separation of human breast cancer cells from blood using a simple spiral channel device
D. Huang (2016)
Tunnel dielectrophoresis for ultra-high precision size-based cell separation.
Y. Kung (2020)
Microfluidic device for continuous deformability based separation of circulating tumor cells
Chao Jin (2014)
High throughput-per-footprint inertial focusing.
A. T. Çiftlik (2013)
Staged Inertial Microfluidic Focusing for Complex Fluid Enrichment.
Amy E. Reece (2015)
Hydrodynamic lift of vesicles and red blood cells in flow--from Fåhræus & Lindqvist to microfluidic cell sorting.
T. M. Geislinger (2014)
Multi-size spheroid formation using microfluidic funnels.
M. Marimuthu (2018)
Microfluidic Devices in the Fast-Growing Domain of Single-Cell Analysis.
Mashooq Khan (2018)
Rapid liquid biopsy for Mohs surgery: rare target cell separation from surgical margin lavage fluid with a high recovery rate and selectivity.
W. Zhou (2019)
Hybrid microfluidics combined with active and passive approaches for continuous cell separation
S. Yan (2017)
Detection and isolation of circulating tumor cells: principles and methods.
H. Esmaeilsabzali (2013)
Enabling systems biology approaches through microfabricated systems.
Mei Zhan (2013)
Paper membrane-based SERS platform for the determination of glucose in blood samples
H. Torul (2015)
Advances of lab-on-a-chip in isolation, detection and post-processing of circulating tumour cells.
L. Yu (2013)
MICROFLUIDIC DEVICE FOR CONTINUOUS DEFORMABILITY BASED SEPARATION OF CIRCULATING TUMOR CELLS by
S. M. McFaul (2014)
Shape-based separation of micro-/nanoparticles in liquid phases.
B. Behdani (2018)
High‐Speed Microfluidic Manipulation of Cells
A. Chung (2015)
A transfer function approach for predicting rare cell capture microdevice performance
J. Smith (2015)
Microluidic Sorting of Blood Cells by Negative Selection
Hua Gao (2016)
Microfluidics for manipulating cells.
Xuan Mu (2013)See more