Abstract

White blood cells (WBCs) are essential in resisting and removing infection-causing foreign factors, and isolating them is vital in diverse applications. Microfluidic devices offer an edge in isolating white blood cells since passive microfluidic devices offer cost-effective sample processing crucial for diagnosis. A single device to separate various components of blood, such as plasma, WBC, and platelet, could yield significant advantages. To achieve this goal, here, we thoroughly evaluated several passive devices experimentally to determine their suitability for white blood cell separation from human blood. This study considered one blood plasma separation (BPS) device and two platelet separation devices. We further delve into the physical phenomena responsible for plasma and cell separation, exploring their similarities and differences using numerical tool. The behavior of cells in the flow path for various hematocrit values has also been uncovered over a wide range of flow rates. We found that red blood cells (RBCs) aggregation at the center of the channel helps in enhancing margination of WBCs. The shear rate has to be low to support the smooth separation of WBCs from other cells. The addition of a secondary flow boosts the separation as it broadens the streamlines of WBCs further away from the center of the channel. The aspect ratio, flow resistance ratio of the channels, and width of the cell-free layer play a significant role in WBC separation. This study is significant because it shows that a single microfluidic device can be employed for multiple purposes—obtaining WBC and platelet-rich plasma (PRP).

References

1.
Mathew
,
J.
,
Sankar
,
P.
, and
Varacallo
,
M.
,
2024
, “
Physiology, Blood Plasma
,”
StatPearls
,
StatPearls Publishing
,
Treasure Island, FL
, accessed May 4, 2024, http://www.ncbi.nlm.nih.gov/books/NBK531504/
2.
Tigner
,
A.
,
Ibrahim
,
S. A.
, and
Murray
,
I. V.
,
2025
, “
Histology, White Blood Cell
,”
StatPearls
,
StatPearls Publishing
,
Treasure Island, FL
, accessed Feb. 26, 2025, http://www.ncbi.nlm.nih.gov/books/NBK563148/
3.
Hoffbrand
,
A. V.
, and
Moss
,
P. A. H.
,
2016
,
Hoffbrand's Essential Haematology
,
Wiley
,
Chichester, West Sussex, UK/Hoboken, NJ
.
4.
Lopez
,
J.
,
2015
, “
Carl A. Burtis and David E. Bruns: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics, 7th Ed.: Elsevier, Amsterdam, 1075 pp, ISBN 978-1-4557-4165-6
,”
Indian J. Clin. Biochem.
,
30
(
2
), p.
243
.10.1007/s12291-014-0474-9
5.
Chen
,
L.
,
Deng
,
H.
,
Cui
,
H.
,
Fang
,
J.
,
Zuo
,
Z.
,
Deng
,
J.
,
Li
,
Y.
,
Wang
,
X.
, and
Zhao
,
L.
,
2018
, “
Inflammatory Responses and Inflammation-Associated Diseases in Organs
,”
Oncotarget
,
9
(
6
), pp.
7204
7218
.10.18632/oncotarget.23208
6.
Mitchell
,
M. J.
, and
King
,
M. R.
,
2015
, “
Leukocytes as Carriers for Targeted Cancer Drug Delivery
,”
Expert Opin. Drug Delivery
,
12
(
3
), pp.
375
392
.10.1517/17425247.2015.966684
7.
Nguyen
,
V.-C.
,
Nguyen
,
T. H.
,
Phan
,
T. H.
,
Tran
,
T.-H. T.
,
Pham
,
T. T. T.
,
Ho
,
T. D.
, and
Nguyen
,
H. H. T.
, et al.,
2023
, “
Fragment Length Profiles of Cancer Mutations Enhance Detection of Circulating Tumor DNA in Patients With Early-Stage Hepatocellular Carcinoma
,”
BMC Cancer
,
23
(
1
), p.
233
.10.1186/s12885-023-10681-0
8.
Hassan
,
U.
,
Reddy
,
B.
,
Damhorst
,
G.
,
Sonoiki
,
O.
,
Ghonge
,
T.
,
Yang
,
C.
, and
Bashir
,
R.
,
2015
, “
A Microfluidic Biochip for Complete Blood Cell Counts at the Point-of-Care
,”
Technology
,
03
(
4
), pp.
201
213
.10.1142/S2339547815500090
9.
Schafer
,
D. N.
,
Gibson
,
E. A.
,
Salim
,
E. A.
,
Palmer
,
A. E.
,
Jimenez
,
R.
, and
Squier
,
J.
,
2009
, “
Microfluidic Cell Counter With Embedded Optical Fibers Fabricated by Femtosecond Laser Ablation and Anodic Bonding
,”
Opt. Express
,
17
(
8
), p.
6068
.10.1364/OE.17.006068
10.
Sun
,
T.
, and
Morgan
,
H.
,
2010
, “
Single-Cell Microfluidic Impedance Cytometry: A Review
,”
Microfluid. Nanofluid.
,
8
(
4
), pp.
423
443
.10.1007/s10404-010-0580-9
11.
Tripathi
,
S.
,
Kumar
,
Y. V. B.
,
Agrawal
,
A.
,
Prabhakar
,
A.
, and
Joshi
,
S. S.
,
2016
, “
Microdevice for Plasma Separation From Whole Human Blood Using Bio-Physical and Geometrical Effects
,”
Sci. Rep.
,
6
(
1
), p.
26749
.10.1038/srep26749
12.
Laxmi
,
V.
,
Joshi
,
S. S.
, and
Agrawal
,
A.
,
2020
, “
Design Evolution and Performance Study of a Reliable Platelet-Rich Plasma Microdevice
,”
Ind. Eng. Chem. Res.
,
59
(
46
), pp.
20515
20526
.10.1021/acs.iecr.0c03590
13.
Quirynen
,
M.
,
Siawasch
,
S. A. M.
,
Yu
,
J.
, and
Miron
,
R. J.
,
2025
, “
Essential Principles for Blood Centrifugation
,”
Periodontol. 2000
,
97
(
1
), pp.
43
51
.10.1111/prd.12555
14.
Cha
,
H.
,
Kang
,
X.
,
Yuan
,
D.
,
De Villiers
,
B.
,
Mak
,
J.
,
Nguyen
,
N.-T.
, and
Zhang
,
J.
,
2025
, “
High-Efficient White Blood Cell Separation From Whole Blood Using Cascaded Inertial Microfluidics
,”
Talanta
,
284
, p.
127200
.10.1016/j.talanta.2024.127200
15.
Leverett
,
L. B.
,
Hellums
,
J. D.
,
Alfrey
,
C. P.
, and
Lynch
,
E. C.
,
1972
, “
Red Blood Cell Damage by Shear Stress
,”
Biophys. J.
,
12
(
3
), pp.
257
273
.10.1016/S0006-3495(72)86085-5
16.
Krzek
,
M.
,
Stroobants
,
S.
,
Gelin
,
P.
,
De Malsche
,
W.
, and
Maes
,
D.
,
2022
, “
Influence of Centrifugation and Shaking on the Self-Assembly of Lysozyme Fibrils
,”
Biomolecules
,
12
(
12
), p.
1746
.10.3390/biom12121746
17.
Harper
,
G. J.
,
1981
, “
Contamination of the Environment by Special Purpose Centrifuges Used in Clinical Laboratories
,”
J. Clin. Pathol.
,
34
(
10
), pp.
1114
1123
.10.1136/jcp.34.10.1114
18.
Hayhurst
,
A.
, and
Georgiou
,
G.
,
2001
, “
High-Throughput Antibody Isolation
,”
Curr. Opin. Chem. Biol.
,
5
(
6
), pp.
683
689
.10.1016/S1367-5931(01)00266-6
19.
Vuorte
,
J.
,
Jansson
,
S.-E.
, and
Repo
,
H.
,
2001
, “
Evaluation of Red Blood Cell Lysing Solutions in the Study of Neutrophil Oxidative Burst by the DCFH Assay
,”
Cytometry
,
43
(
4
), pp.
290
296
.10.1002/1097-0320(20010401)43:4<290::AID-CYTO1061>3.0.CO;2-X
20.
Hirano
,
R.
,
Namazuda
,
K.
,
Suemitsu
,
J.
,
Harashima
,
T.
, and
Hirata
,
N.
,
2017
, “
Plasma Separation Using a Membrane
,”
Transfus. Apheresis Sci.
,
56
(
5
), pp.
649
653
.10.1016/j.transci.2017.08.008
21.
Laxmi
,
V.
,
Joshi
,
S. S.
, and
Agrawal
,
A.
,
2022
, “
Extracting White Blood Cells From Blood on Microfluidics Platform: A Review of Isolation Techniques and Working Mechanisms
,”
J. Micromech. Microeng.
,
32
(
5
), p.
053001
.10.1088/1361-6439/ac586e
22.
Lu
,
N.
,
Tay
,
H. M.
,
Petchakup
,
C.
,
He
,
L.
,
Gong
,
L.
,
Maw
,
K. K.
, and
Leong
,
S. Y.
, et al.,
2023
, “
Label-Free Microfluidic Cell Sorting and Detection for Rapid Blood Analysis
,”
Lab Chip
,
23
(
5
), pp.
1226
1257
.10.1039/D2LC00904H
23.
Farahinia
,
A.
,
Khani
,
M.
,
Morhart
,
T. A.
,
Wells
,
G.
,
Badea
,
I.
,
Wilson
,
L. D.
, and
Zhang
,
W.
,
2024
, “
A Novel Size-Based Centrifugal Microfluidic Design to Enrich and Magnetically Isolate Circulating Tumor Cells From Blood Cells Through Biocompatible Magnetite–Arginine Nanoparticles
,”
Sensors
,
24
(
18
), p.
6031
.10.3390/s24186031
24.
Sethu
,
P.
,
Sin
,
A.
, and
Toner
,
M.
,
2006
, “
Microfluidic Diffusive Filter for Apheresis (Leukapheresis)
,”
Lab Chip
,
6
(
1
), pp.
83
89
.10.1039/B512049G
25.
Hui
,
W. C.
,
Yobas
,
L.
,
Samper
,
V. D.
,
Heng
,
C.-K.
,
Liw
,
S.
,
Ji
,
H.
,
Chen
,
Y.
,
Cong
,
L.
,
Li
,
J.
, and
Lim
,
T. M.
,
2007
, “
Microfluidic Systems for Extracting Nucleic Acids for DNA and RNA Analysis
,”
Sens. Actuators Phys.
,
133
(
2
), pp.
335
339
.10.1016/j.sna.2006.06.031
26.
Ji
,
H. M.
,
Samper
,
V.
,
Chen
,
Y.
,
Heng
,
C. K.
,
Lim
,
T. M.
, and
Yobas
,
L.
,
2008
, “
Silicon-Based Microfilters for Whole Blood Cell Separation
,”
Biomed. Microdevices
,
10
(
2
), pp.
251
257
.10.1007/s10544-007-9131-x
27.
Alvankarian
,
J.
,
Bahadorimehr
,
A.
, and
Yeop Majlis
,
B.
,
2013
, “
A Pillar-Based Microfilter for Isolation of White Blood Cells on Elastomeric Substrate
,”
Biomicrofluidics
,
7
(
1
), p.
014102
.10.1063/1.4774068
28.
Li
,
X.
,
Chen
,
W.
,
Liu
,
G.
,
Lu
,
W.
, and
Fu
,
J.
,
2014
, “
Continuous-Flow Microfluidic Blood Cell Sorting for Unprocessed Whole Blood Using Surface-Micromachined Microfiltration Membranes
,”
Lab Chip
,
14
(
14
), pp.
2565
2575
.10.1039/C4LC00350K
29.
Guo
,
Q.
,
Duffy
,
S. P.
,
Matthews
,
K.
,
Islamzada
,
E.
, and
Ma
,
H.
,
2017
, “
Deformability Based Cell Sorting Using Microfluidic Ratchets Enabling Phenotypic Separation of Leukocytes Directly From Whole Blood
,”
Sci. Rep.
,
7
(
1
), p.
6627
.10.1038/s41598-017-06865-x
30.
Zheng
,
S.
,
Liu
,
J.-Q.
, and
Tai
,
Y.-C.
,
2008
, “
Streamline-Based Microfluidic Devices for Erythrocytes and Leukocytes Separation
,”
J. Microelectromech. Syst.
,
17
(
4
), pp.
1029
1038
.10.1109/JMEMS.2008.924274
31.
Huang
,
Y.
,
Chen
,
P.
,
Niu
,
M.
, and
Peng
,
W. K.
,
2025
, “
Robust and Efficient Separation of White Blood Cells From Blood Using a Microfluidic Chip With a Pair of Linearly Tapered Crossflow Filter Arrays
,”
Microchim. Acta
,
192
(
1
), p. 1
41
.10.1007/s00604-024-06913-0
32.
Shevkoplyas
,
S. S.
,
Yoshida
,
T.
,
Munn
,
L. L.
, and
Bitensky
,
M. W.
,
2005
, “
Biomimetic Autoseparation of Leukocytes From Whole Blood in a Microfluidic Device
,”
Anal. Chem.
,
77
(
3
), pp.
933
937
.10.1021/ac049037i
33.
Jain
,
A.
, and
Munn
,
L. L.
,
2011
, “
Biomimetic Postcapillary Expansions for Enhancing Rare Blood Cell Separation on a Microfluidic Chip
,”
Lab Chip
,
11
(
17
), p.
2941
.10.1039/c1lc20401g
34.
Lombodorj
,
B.
,
Tseng
,
H. C.
,
Chang
,
H.-Y.
,
Lu
,
Y.-W.
,
Tumurpurev
,
N.
,
Lee
,
C.-W.
,
Ganbat
,
B.
,
Wu
,
R.-G.
, and
Tseng
,
F.-G.
,
2020
, “
High-Throughput White Blood Cell (Leukocyte) Enrichment From Whole Blood Using Hydrodynamic and Inertial Forces
,”
Micromachines
,
11
(
3
), p.
275
.10.3390/mi11030275
35.
Zhang
,
J.
,
Yuan
,
D.
,
Sluyter
,
R.
,
Yan
,
S.
,
Zhao
,
Q.
,
Xia
,
H.
,
Tan
,
S. H.
,
Nguyen
,
N.-T.
, and
Li
,
W.
,
2017
, “
High-Throughput Separation of White Blood Cells From Whole Blood Using Inertial Microfluidics
,”
IEEE Trans. Biomed. Circuits Syst.
,
11
(
6
), pp.
1422
1430
.10.1109/TBCAS.2017.2735440
36.
Ramachandraiah
,
H.
,
Svahn
,
H. A.
, and
Russom
,
A.
,
2017
, “
Inertial Microfluidics Combined With Selective Cell Lysis for High Throughput Separation of Nucleated Cells From Whole Blood
,”
RSC Adv.
,
7
(
47
), pp.
29505
29514
.10.1039/C7RA02992F
37.
Zhu
,
S.
,
Wu
,
D.
,
Han
,
Y.
,
Wang
,
C.
,
Xiang
,
N.
, and
Ni
,
Z.
,
2020
, “
Inertial Microfluidic Cube for Automatic and Fast Extraction of White Blood Cells From Whole Blood
,”
Lab Chip
,
20
(
2
), pp.
244
252
.10.1039/C9LC00942F
38.
Tan
,
J. K. S.
,
Park
,
S.-Y.
,
Leo
,
H. L.
, and
Kim
,
S.
,
2017
, “
Continuous Separation of White Blood Cells From Whole Blood Using Viscoelastic Effects
,”
IEEE Trans. Biomed. Circuits Syst.
,
11
(
6
), pp.
1431
1437
.10.1109/TBCAS.2017.2748232
39.
Nam
,
J.
,
Yoon
,
J.
,
Kim
,
J.
,
Jang
,
W. S.
, and
Lim
,
C. S.
,
2019
, “
Continuous Erythrocyte Removal and Leukocyte Separation From Whole Blood Based on Viscoelastic Cell Focusing and the Margination Phenomenon
,”
J. Chromatogr. A
,
1595
, pp.
230
239
.10.1016/j.chroma.2019.02.019
40.
Zheng
,
S.
,
Yung
,
R.
,
Tai
,
Y.-C.
, and
Kasdan
,
H.
,
2005
, “
Deterministic Lateral Displacement MEMS Device for Continuous Blood Cell Separation
,” 18th IEEE International Conference on Micro Electro Mechanical Systems (
MEMS 2005
),
Miami Beach, FL
, Jan. 30—Feb. 3, pp.
851
854
.10.1109/MEMSYS.2005.1454063
41.
Li
,
N.
,
Kamei
,
D. T.
, and
Ho
,
C.-M.
,
2007
, “
On-Chip Continuous Blood Cell Subtype Separation by Deterministic Lateral Displacement
,”
2007 Second IEEE International Conference on Nano/Micro Engineered and Molecular Systems
, Bangkok, Thailand, Jan. 16–19, pp.
932
936
.10.1109/NEMS.2007.352171
42.
Davis
,
J. A.
,
Inglis
,
D. W.
,
Morton
,
K. J.
,
Lawrence
,
D. A.
,
Huang
,
L. R.
,
Chou
,
S. Y.
,
Sturm
,
J. C.
, and
Austin
,
R. H.
,
2006
, “
Deterministic Hydrodynamics: Taking Blood Apart
,”
Proc. Natl. Acad. Sci.
,
103
(
40
), pp.
14779
14784
.10.1073/pnas.0605967103
43.
Inglis
,
D. W.
,
Davis
,
J. A.
,
Austin
,
R. H.
, and
Sturm
,
J. C.
,
2006
, “
Critical Particle Size for Fractionation by Deterministic Lateral Displacement
,”
Lab Chip
,
6
(
5
), p.
655
.10.1039/b515371a
44.
Kim
,
B.
,
Choi
,
Y. J.
,
Seo
,
H.
,
Shin
,
E.
, and
Choi
,
S.
,
2016
, “
Deterministic Migration‐Based Separation of White Blood Cells
,”
Small
,
12
(
37
), pp.
5159
5168
.10.1002/smll.201601652
45.
Han
,
K.-H.
, and
Frazier
,
A. B.
,
2008
, “
Lateral-Driven Continuous Dielectrophoretic Microseparators for Blood Cells Suspended in a Highly Conductive Medium
,”
Lab Chip
,
8
(
7
), p.
1079
.10.1039/b802321b
46.
Wang
,
X.-B.
,
Yang
,
J.
,
Huang
,
Y.
,
Vykoukal
,
J.
,
Becker
,
F. F.
, and
Gascoyne
,
P. R. C.
,
2000
, “
Cell Separation by Dielectrophoretic Field-Flow-Fractionation
,”
Anal. Chem.
,
72
(
4
), pp.
832
839
.10.1021/ac990922o
47.
Grenvall
,
C.
,
Magnusson
,
C.
,
Lilja
,
H.
, and
Laurell
,
T.
,
2015
, “
Concurrent Isolation of Lymphocytes and Granulocytes Using Prefocused Free Flow Acoustophoresis
,”
Anal. Chem.
,
87
(
11
), pp.
5596
5604
.10.1021/acs.analchem.5b00370
48.
Urbansky
,
A.
,
Olm
,
F.
,
Scheding
,
S.
,
Laurell
,
T.
, and
Lenshof
,
A.
,
2019
, “
Label-Free Separation of Leukocyte Subpopulations Using High Throughput Multiplex Acoustophoresis
,”
Lab Chip
,
19
(
8
), pp.
1406
1416
.10.1039/C9LC00181F
49.
Mohapatra
,
D.
,
Purwar
,
R.
, and
Agrawal
,
A.
,
2024
, “
Parametric Study on the Margination of White Blood Cells (WBCs) in a Passive Microfluidic Device
,”
Int. J. Thermofluids
,
23
, p.
100751
.10.1016/j.ijft.2024.100751
50.
Prabhakar
,
A.
,
Kumar
,
Y. V. B. V.
,
Tripathi
,
S.
, and
Agrawal
,
A.
,
2015
, “
A Novel, Compact and Efficient Microchannel Arrangement With Multiple Hydrodynamic Effects for Blood Plasma Separation
,”
Microfluid. Nanofluid.
,
18
(
5–6
), pp.
995
1006
.10.1007/s10404-014-1488-6
51.
Tripathi
,
S.
,
Varun Kumar
,
Y. V. B.
,
Prabhakar
,
A.
,
Joshi
,
S. S.
, and
Agrawal
,
A.
,
2015
, “
Performance Study of Microfluidic Devices for Blood Plasma Separation—A Designer's Perspective
,”
J. Micromech. Microeng.
,
25
(
8
), p.
084004
.10.1088/0960-1317/25/8/084004
52.
Shibeshi
,
S. S.
, and
Collins
,
W. E.
,
2005
, “
The Rheology of Blood Flow in a Branched Arterial System
,”
Appl. Rheol.
,
15
(
6
), pp.
398
405
.10.1515/arh-2005-0020
53.
Sousa
,
P. C.
,
Pinho
,
F. T.
,
Oliveira
,
M. S. N.
, and
Alves
,
M. A.
,
2011
, “
Extensional Flow of Blood Analog Solutions in Microfluidic Devices
,”
Biomicrofluidics
,
5
(
1
), p.
014108
.10.1063/1.3567888
54.
Ho
,
B. P.
, and
Leal
,
L. G.
,
1974
, “
Inertial Migration of Rigid Spheres in Two-Dimensional Unidirectional Flows
,”
J. Fluid Mech.
,
65
(
2
), pp.
365
400
.10.1017/S0022112074001431
55.
Zhou
,
J.
,
Tu
,
C.
,
Liang
,
Y.
,
Huang
,
B.
,
Fang
,
Y.
,
Liang
,
X.
,
Papautsky
,
I.
, and
Ye
,
X.
,
2018
, “
Isolation of Cells From Whole Blood Using Shear-Induced Diffusion
,”
Sci. Rep.
,
8
(
1
), p.
9411
.10.1038/s41598-018-27779-2
56.
Yang
,
X.
,
Forouzan
,
O.
,
Brown
,
T. P.
, and
Shevkoplyas
,
S. S.
,
2012
, “
Integrated Separation of Blood Plasma From Whole Blood for Microfluidic Paper-Based Analytical Devices
,”
Lab Chip
,
12
(
2
), pp.
274
280
.10.1039/C1LC20803A
57.
Qiu
,
X.
,
Jiang
,
H.
,
Zhang
,
X.
,
Li
,
K.
,
Ge
,
S.
,
Xia
,
N.
, and
Mauk
,
M. G.
,
2020
, “
A Plasma Separator With a Multifunctional Deformable Chamber Equipped With a Porous Membrane for Point-of-Care Diagnostics
,”
Analyst
,
145
(
18
), pp.
6138
6147
.10.1039/D0AN01014F
58.
Su
,
X.
,
Zhang
,
J.
,
Zhang
,
D.
,
Wang
,
Y.
,
Chen
,
M.
,
Weng
,
Z.
, and
Wang
,
J.
, et al.,
2020
, “
High-Efficiency Plasma Separator Based on Immunocapture and Filtration
,”
Micromachines
,
11
(
4
), p.
352
.10.3390/mi11040352
59.
Xu
,
B.
,
Zhang
,
J.
,
Pan
,
D.
,
Ni
,
J.
,
Yin
,
K.
,
Zhang
,
Q.
,
Ding
,
Y.
,
Li
,
A.
,
Wu
,
D.
, and
Shen
,
Z.
,
2022
, “
High-Performance Blood Plasma Separation Based on a Janus Membrane Technique and RBC Agglutination Reaction
,”
Lab Chip
,
22
(
22
), pp.
4382
4392
.10.1039/D2LC00508E
60.
Shimizu
,
H.
,
Kumagai
,
M.
,
Mori
,
E.
,
Mawatari
,
K.
, and
Kitamori
,
T.
,
2016
, “
Whole Blood Analysis Using Microfluidic Plasma Separation and Enzyme-Linked Immunosorbent Assay Devices
,”
Anal. Methods
,
8
(
42
), pp.
7597
7602
.10.1039/C6AY01779G
61.
Xie
,
Y.
,
Chen
,
D.
,
Lin
,
S.
,
Wang
,
Z.
, and
Cui
,
D.
,
2016
, “
A Robust and Easily Integrated Plasma Separation Chip Using Gravitational Sedimentation of Blood Cells Filling-in High-Aspect-Ratio Weir Structure
,”
RSC Adv.
,
6
(
36
), pp.
30722
30727
.10.1039/C6RA01447J
62.
Sun
,
M.
,
Khan
,
Z. S.
, and
Vanapalli
,
S. A.
,
2012
, “
Blood Plasma Separation in a Long Two-Phase Plug Flowing Through Disposable Tubing
,”
Lab Chip
,
12
(
24
), p.
5225
.10.1039/c2lc40544j
63.
Maria
,
M. S.
,
Rakesh
,
P. E.
,
Chandra
,
T. S.
, and
Sen
,
A. K.
,
2016
, “
Capillary Flow of Blood in a Microchannel With Differential Wetting for Blood Plasma Separation and On-Chip Glucose Detection
,”
Biomicrofluidics
,
10
(
5
), p.
054108
.10.1063/1.4962874
64.
Sakamoto
,
H.
,
Hatsuda
,
R.
,
Miyamura
,
K.
, and
Sugiyama
,
S.
,
2012
, “
Plasma Separation PMMA Device Driven by Capillary Force Controlling Surface Wettability
,”
Micro Nano Lett.
,
7
(
1
), pp.
64
67
.10.1049/mnl.2011.0627
65.
Baillargeon
,
K. R.
,
Murray
,
L. P.
,
Deraney
,
R. N.
, and
Mace
,
C. R.
,
2020
, “
High-Yielding Separation and Collection of Plasma From Whole Blood Using Passive Filtration
,”
Anal. Chem.
,
92
(
24
), pp.
16245
16252
.10.1021/acs.analchem.0c04127
66.
Kuan
,
D.-H.
,
Wu
,
C.-C.
,
Su
,
W.-Y.
, and
Huang
,
N.-T.
,
2018
, “
A Microfluidic Device for Simultaneous Extraction of Plasma, Red Blood Cells, and On-Chip White Blood Cell Trapping
,”
Sci. Rep.
,
8
(
1
), p.
15345
.10.1038/s41598-018-33738-8
67.
Kim
,
H.
,
Park
,
H.
,
Chung
,
D. R.
,
Kim
,
T.
,
Park
,
E.
, and
Kang
,
M.
,
2022
, “
A Self-Pressure-Driven Blood Plasma-Separation Device for Point-of-Care Diagnostics
,”
Talanta
,
247
, p.
123562
.10.1016/j.talanta.2022.123562
68.
Son
,
J. H.
,
Lee
,
S. H.
,
Hong
,
S.
,
Park
,
S.
,
Lee
,
J.
,
Dickey
,
A. M.
, and
Lee
,
L. P.
,
2014
, “
Hemolysis-Free Blood Plasma Separation
,”
Lab Chip
,
14
(
13
), pp.
2287
2292
.10.1039/C4LC00149D
69.
Kuo
,
J.-N.
, and
Lin
,
B.-Y.
,
2018
, “
Microfluidic Blood-Plasma Separation Chip Using Channel Size Filtration Effect
,”
Microsyst. Technol.
,
24
(
4
), pp.
2063
2070
.10.1007/s00542-017-3607-2
70.
Geng
,
Z.
,
Ju
,
Y.
,
Wang
,
Q.
,
Wang
,
W.
, and
Li
,
Z.
,
2013
, “
Multi-Component Continuous Separation Chip Composed of Micropillar Arrays in a Split-Level Spiral Channel
,”
RSC Adv.
,
3
(
34
), p.
14798
.10.1039/c3ra41906a
71.
Park
,
S.
,
Shabani
,
R.
,
Schumacher
,
M.
,
Kim
,
Y.-S.
,
Bae
,
Y. M.
,
Lee
,
K.-H.
, and
Cho
,
H. J.
,
2016
, “
On-Chip Whole Blood Plasma Separator Based on Microfiltration, Sedimentation and Wetting Contrast
,”
Microsyst. Technol.
,
22
(
8
), pp.
2077
2085
.10.1007/s00542-015-2656-7
72.
Gao
,
Q.
,
Chang
,
Y.
,
Deng
,
Q.
, and
You
,
H.
,
2020
, “
A Simple and Rapid Method for Blood Plasma Separation Driven by Capillary Force With an Application in Protein Detection
,”
Anal. Methods
,
12
(
20
), pp.
2560
2570
.10.1039/D0AY00240B
73.
Xiao
,
Z.
,
Sun
,
L.
,
Yang
,
Y.
,
Feng
,
Z.
,
Dai
,
S.
,
Yang
,
H.
,
Zhang
,
X.
,
Sheu
,
C.-L.
, and
Guo
,
W.
,
2021
, “
High-Performance Passive Plasma Separation on OSTE Pillar Forest
,”
Biosensors
,
11
(
10
), p.
355
.10.3390/bios11100355
74.
Madadi
,
H.
,
Casals-Terré
,
J.
, and
Mohammadi
,
M.
,
2015
, “
Self-Driven Filter-Based Blood Plasma Separator Microfluidic Chip for Point-of-Care Testing
,”
Biofabrication
,
7
(
2
), p.
025007
.10.1088/1758-5090/7/2/025007
75.
Karimi
,
S.
,
Mojaddam
,
M.
,
Majidi
,
S.
,
Mehrdel
,
P.
,
Farré-Lladós
,
J.
, and
Casals-Terré
,
J.
,
2021
, “
Numerical and Experimental Analysis of a High-Throughput Blood Plasma Separator for Point-of-Care Applications
,”
Anal. Bioanal. Chem.
,
413
(
11
), pp.
2867
2878
.10.1007/s00216-021-03190-1
76.
Zhang
,
H.
,
Anoop
,
K.
,
Huang
,
C.
,
Sadr
,
R.
,
Gupte
,
R.
,
Dai
,
J.
, and
Han
,
A.
,
2022
, “
A Circular Gradient-Width Crossflow Microfluidic Platform for High-Efficiency Blood Plasma Separation
,”
Sens. Actuators B: Chem.
,
354
, p.
131180
.10.1016/j.snb.2021.131180
77.
Yang
,
S.
,
Ündar
,
A.
, and
Zahn
,
J. D.
,
2006
, “
A Microfluidic Device for Continuous, Real Time Blood Plasma Separation
,”
Lab Chip
,
6
(
7
), pp.
871
880
.10.1039/B516401J
78.
Kersaudy-Kerhoas
,
M.
,
Kavanagh
,
D. M.
,
Dhariwal
,
R. S.
,
Campbell
,
C. J.
, and
Desmulliez
,
M. P. Y.
,
2010
, “
Validation of a Blood Plasma Separation System by Biomarker Detection
,”
Lab Chip
,
10
(
12
), p.
1587
.10.1039/b926834k
79.
Marchalot
,
J.
,
Fouillet
,
Y.
, and
Achard
,
J.-L.
,
2014
, “
Multi-Step Microfluidic System for Blood Plasma Separation: Architecture and Separation Efficiency
,”
Microfluid. Nanofluid.
,
17
(
1
), pp.
167
180
.10.1007/s10404-013-1296-4
80.
Maria
,
M. S.
,
Kumar
,
B. S.
,
Chandra
,
T. S.
, and
Sen
,
A. K.
,
2015
, “
Development of a Microfluidic Device for Cell Concentration and Blood Cell-Plasma Separation
,”
Biomed. Microdevices
,
17
(
6
), p.
115
.10.1007/s10544-015-0017-z
81.
Rafeie
,
M.
,
Zhang
,
J.
,
Asadnia
,
M.
,
Li
,
W.
, and
Warkiani
,
M. E.
,
2016
, “
Multiplexing Slanted Spiral Microchannels for Ultra-Fast Blood Plasma Separation
,”
Lab Chip
,
16
(
15
), pp.
2791
2802
.10.1039/C6LC00713A
82.
Yuan
,
D.
,
Zhang
,
J.
,
Sluyter
,
R.
,
Zhao
,
Q.
,
Yan
,
S.
,
Alici
,
G.
, and
Li
,
W.
,
2016
, “
Continuous Plasma Extraction Under Viscoelastic Fluid in a Straight Channel With Asymmetrical Expansion–Contraction Cavity Arrays
,”
Lab Chip
,
16
(
20
), pp.
3919
3928
.10.1039/C6LC00843G
83.
Lee
,
L. M.
,
Bhatt
,
K. H.
,
Haithcock
,
D. W.
, and
Prabhakarpandian
,
B.
,
2023
, “
Blood Component Separation in Straight Microfluidic Channels
,”
Biomicrofluidics
,
17
(
5
), p.
054106
.10.1063/5.0176457
84.
Leong
,
S. Y.
,
Lok
,
W. W.
,
Goh
,
K. Y.
,
Ong
,
H. B.
,
Tay
,
H. M.
,
Su
,
C.
, and
Kong
,
F.
, et al.,
2024
, “
High-Throughput Microfluidic Extraction of Platelet-Free Plasma for MicroRNA and Extracellular Vesicle Analysis
,”
ACS Nano
,
18
(
8
), pp.
6623
6637
.10.1021/acsnano.3c12862
85.
Mohammadi
,
M.
,
Madadi
,
H.
,
Casals-Terré
,
J.
, and
Sellarès
,
J.
,
2015
, “
Hydrodynamic and Direct-Current Insulator-Based Dielectrophoresis (H-DC-iDEP) Microfluidic Blood Plasma Separation
,”
Anal. Bioanal. Chem.
,
407
(
16
), pp.
4733
4744
.10.1007/s00216-015-8678-2
86.
Kang
,
D.-H.
,
Kim
,
K.
, and
Kim
,
Y.-J.
,
2018
, “
An Anti-Clogging Method for Improving the Performance and Lifespan of Blood Plasma Separation Devices in Real-Time and Continuous Microfluidic Systems
,”
Sci. Rep.
,
8
(
1
), p.
17015
.10.1038/s41598-018-35235-4
87.
Bakhtiaridoost
,
S.
,
Habibiyan
,
H.
, and
Ghafoorifard
,
H.
,
2023
, “
A Microfluidic Device to Separate High-Quality Plasma From Undiluted Whole Blood Sample Using an Enhanced Gravitational Sedimentation Mechanism
,”
Anal. Chim. Acta
,
1239
, p.
340641
.10.1016/j.aca.2022.340641
88.
Pommer
,
M. S.
,
Zhang
,
Y.
,
Keerthi
,
N.
,
Chen
,
D.
,
Thomson
,
J. A.
,
Meinhart
,
C. D.
, and
Soh
,
H. T.
,
2008
, “
Dielectrophoretic Separation of Platelets From Diluted Whole Blood in Microfluidic Channels
,”
Electrophoresis
,
29
(
6
), pp.
1213
1218
.10.1002/elps.200700607
89.
Piacentini
,
N.
,
Mernier
,
G.
,
Tornay
,
R.
, and
Renaud
,
P.
,
2011
, “
Separation of Platelets From Other Blood Cells in Continuous-Flow by Dielectrophoresis Field-Flow-Fractionation
,”
Biomicrofluidics
,
5
(
3
), p.
034122
.10.1063/1.3640045
90.
Nam
,
J.
,
Lim
,
H.
,
Kim
,
D.
, and
Shin
,
S.
,
2011
, “
Separation of Platelets From Whole Blood Using Standing Surface Acoustic Waves in a Microchannel
,”
Lab Chip
,
11
(
19
), p.
3361
.10.1039/c1lc20346k
91.
Chen
,
Y.
,
Wu
,
M.
,
Ren
,
L.
,
Liu
,
J.
,
Whitley
,
P. H.
,
Wang
,
L.
, and
Huang
,
T. J.
,
2016
, “
High-Throughput Acoustic Separation of Platelets From Whole Blood
,”
Lab Chip
,
16
(
18
), pp.
3466
3472
.10.1039/C6LC00682E
92.
Dickson
,
M. N.
,
Amar
,
L.
,
Hill
,
M.
,
Schwartz
,
J.
, and
Leonard
,
E. F.
,
2012
, “
A Scalable, Micropore, Platelet Rich Plasma Separation Device
,”
Biomed. Microdevices
,
14
(
6
), pp.
1095
1102
.10.1007/s10544-012-9675-2
93.
Mehendale
,
N.
,
Sharma
,
O.
,
Pandey
,
S.
, and
Paul
,
D.
,
2018
, “
Clogging-Free Continuous Operation With Whole Blood in a Radial Pillar Device (RAPID)
,”
Biomed. Microdevices
,
20
(
3
), p.
75
.10.1007/s10544-018-0319-z
94.
Nho
,
H. W.
,
Yang
,
N.
,
Song
,
J.
,
Park
,
J. S.
, and
Yoon
,
T. H.
,
2017
, “
Separations of Spherical and Disc-Shaped Polystyrene Particles and Blood Components (Red Blood Cells and Platelets) Using Pinched Flow Fractionation Device With a Tilted Sidewall and Vertical Focusing Channels (t-PFF-v)
,”
Sens. Actuators B: Chem.
,
249
, pp.
131
141
.10.1016/j.snb.2017.04.081
95.
Geislinger
,
T. M.
,
Eggart
,
B.
,
Braunmüller
,
S.
,
Schmid
,
L.
, and
Franke
,
T.
,
2012
, “
Separation of Blood Cells Using Hydrodynamic Lift
,”
Appl. Phys. Lett.
,
100
(
18
), p.
183701
.10.1063/1.4709614
96.
Di Carlo
,
D.
,
Edd
,
J. F.
,
Irimia
,
D.
,
Tompkins
,
R. G.
, and
Toner
,
M.
,
2008
, “
Equilibrium Separation and Filtration of Particles Using Differential Inertial Focusing
,”
Anal. Chem.
,
80
(
6
), pp.
2204
2211
.10.1021/ac702283m
97.
Lam
,
F. W.
,
Phillips
,
J.
,
Landry
,
P.
,
Magadi
,
S.
,
Smith
,
C. W.
,
Rumbaut
,
R. E.
, and
Burns
,
A. R.
,
2015
, “
Platelet Recruitment Promotes Keratocyte Repopulation Following Corneal Epithelial Abrasion in the Mouse
,”
PLoS One
,
10
(
3
), p.
e0118950
.10.1371/journal.pone.0118950
98.
Clark
,
S. R.
,
Ma
,
A. C.
,
Tavener
,
S. A.
,
McDonald
,
B.
,
Goodarzi
,
Z.
,
Kelly
,
M. M.
, and
Patel
,
K. D.
, et al.,
2007
, “
Platelet TLR4 Activates Neutrophil Extracellular Traps to Ensnare Bacteria in Septic Blood
,”
Nat. Med.
,
13
(
4
), pp.
463
469
.10.1038/nm1565
99.
Etulain
,
J.
,
2018
, “
Platelets in Wound Healing and Regenerative Medicine
,”
Platelets
,
29
(
6
), pp.
556
568
.10.1080/09537104.2018.1430357
100.
Burnouf
,
T.
,
2007
, “
Modern Plasma Fractionation
,”
Transfus. Med. Rev.
,
21
(
2
), pp.
101
117
.10.1016/j.tmrv.2006.11.001
101.
Yan
,
S.
,
Zhang
,
J.
,
Alici
,
G.
,
Du
,
H.
,
Zhu
,
Y.
, and
Li
,
W.
,
2014
, “
Isolating Plasma From Blood Using a Dielectrophoresis-Active Hydrophoretic Device
,”
Lab Chip
,
14
(
16
), p.
2993
.10.1039/C4LC00343H
102.
Chang
,
S.
, and
Cho
,
Y.-H.
,
2008
, “
A Continuous Size-Dependent Particle Separator Using a Negative Dielectrophoretic Virtual Pillar Array
,”
Lab Chip
,
8
(
11
), p.
1930
.10.1039/b806614k
103.
Moon
,
H.-S.
,
Kwon
,
K.
,
Kim
,
S.-I.
,
Han
,
H.
,
Sohn
,
J.
,
Lee
,
S.
, and
Jung
,
H.-I.
,
2011
, “
Continuous Separation of Breast Cancer Cells From Blood Samples Using Multi-Orifice Flow Fractionation (MOFF) and Dielectrophoresis (DEP)
,”
Lab Chip
,
11
(
6
), p.
1118
.10.1039/c0lc00345j
104.
Shirai
,
K.
,
Guan
,
G.
,
Meihui
,
T.
,
Xiaoling
,
P.
,
Oka
,
Y.
,
Takahashi
,
Y.
, and
Bhagat
,
A. A. S.
, et al.,
2022
, “
Hybrid Double-Spiral Microfluidic Chip for RBC-Lysis-Free Enrichment of Rare Cells From Whole Blood
,”
Lab Chip
,
22
(
22
), pp.
4418
4429
.10.1039/D2LC00713D
105.
Huang
,
D.
, and
Xiang
,
N.
,
2021
, “
Rapid and Precise Tumor Cell Separation Using the Combination of Size-Dependent Inertial and Size-Independent Magnetic Methods
,”
Lab Chip
,
21
(
7
), pp.
1409
1417
.10.1039/D0LC01223H
106.
Liu
,
Y.
,
Zhao
,
W.
,
Cheng
,
R.
,
Puig
,
A.
,
Hodgson
,
J.
,
Egan
,
M.
,
Cooper Pope
,
C. N.
,
Nikolinakos
,
P. G.
, and
Mao
,
L.
,
2021
, “
Label-Free Inertial-Ferrohydrodynamic Cell Separation With High Throughput and Resolution
,”
Lab Chip
,
21
(
14
), pp.
2738
2750
.10.1039/D1LC00282A
107.
Mizuno
,
M.
,
Yamada
,
M.
,
Mitamura
,
R.
,
Ike
,
K.
,
Toyama
,
K.
, and
Seki
,
M.
,
2013
, “
Magnetophoresis-Integrated Hydrodynamic Filtration System for Size- and Surface Marker-Based Two-Dimensional Cell Sorting
,”
Anal. Chem.
,
85
(
16
), pp.
7666
7673
.10.1021/ac303336f
108.
Beech
,
J. P.
,
Keim
,
K.
,
Ho
,
B. D.
,
Guiducci
,
C.
, and
Tegenfeldt
,
J. O.
,
2019
, “
Active Posts in Deterministic Lateral Displacement Devices
,”
Adv. Mater. Technol.
,
4
(
9
), p.
1900339
.10.1002/admt.201900339
109.
Beech
,
J. P.
,
Jönsson
,
P.
, and
Tegenfeldt
,
J. O.
,
2009
, “
Tipping the Balance of Deterministic Lateral Displacement Devices Using Dielectrophoresis
,”
Lab Chip
,
9
(
18
), p.
2698
.10.1039/b823275j
110.
Kim
,
D.
,
Luo
,
J.
,
Arriaga
,
E. A.
, and
Ros
,
A.
,
2018
, “
Deterministic Ratchet for Sub-Micrometer (Bio)Particle Separation
,”
Anal. Chem.
,
90
(
7
), pp.
4370
4379
.10.1021/acs.analchem.7b03774
111.
Mohapatra
,
D.
,
Purwar
,
R.
, and
Agrawal
,
A.
,
2024
, “
Effect of Viscosity on the Margination of White Blood Cells in an Inertial Flow Microfluidic Channel
,”
Fluid Mechanics and Fluid Power
, Volume
4
,
K. M.
Singh
,
S.
Dutta
,
S.
Subudhi
, and
N. K.
Singh
, eds.,
Springer Nature Singapore
,
Singapore
, pp.
543
551
.
112.
Yadav
,
S. P.
,
Sharma
,
A.
, and
Agrawal
,
A.
,
2023
, “
Accurate Modeling of Blood Flow in a Micro-Channel as a Non-Homogeneous Mixture Using Continuum Approach-Based Diffusive Flux Model
,”
Phys. Fluids
,
35
(
4
), p.
041905
.10.1063/5.0144794
113.
Yadav
,
S. P.
,
Sharma
,
A.
, and
Agrawal
,
A.
,
2024
, “
Modeling of Three-Dimensional Blood Flow in Microchannels Using a Two-Fluid Method
,”
Phys. Fluids
,
36
(
2
), p.
021904
.10.1063/5.0189178
You do not currently have access to this content.