Plasma is a host of numerous analytes such as proteins, metabolites, circulating nucleic acids (CNAs), and pathogens, and it contains massive information about the functioning of the whole body, which is of great importance for the clinical diagnosis. Plasma needs to be completely cell-free for effective detection of these analytes. The key process of plasma extraction is to eliminate the contamination from blood cells. Centrifugation, a golden standard method for blood separation, is generally lab-intensive, time consuming, and even dangerous to some extent, and needs to be operated by well-trained staffs. Membrane filtration can filter cells very effectively according to its pore size, but it is prone to clogging by dense particle concentration and suffers from limited capacity of filtration. Frequent rinse is lab-intensive and undesirable. In this work, we proposed and fabricated an integrated microfluidic device that combined particle inertial focusing and membrane filter for high efficient blood plasma separation. The integrated microfluidic device was evaluated by the diluted (×1/10, ×1/20) whole blood, and the quality of the extracted blood plasma was measured and compared with that from the standard centrifugation. We found that the quality of the extracted blood plasma from the proposed device can be equivalent to that from the standard centrifugation. This study demonstrates a significant progress toward the practical application of inertial microfluidics with membrane filter for high-throughput and highly efficient blood plasma extraction.

References

References
1.
Toner
,
M.
, and
Irimia
,
D.
,
2005
, “
Blood-on-a-Chip
,”
Annu. Rev. Biomed. Eng.
,
7
(
1
), pp.
77
103
.
2.
Aran
,
K.
,
Fok
,
A.
,
Sasso
,
L. A.
,
Kamdar
,
N.
,
Guan
,
Y.
,
Sun
,
Q.
,
Ündar
,
A.
, and
Zahn
,
J. D.
,
2011
, “
Microfiltration Platform for Continuous Blood Plasma Protein Extraction From Whole Blood During Cardiac Surgery
,”
Lab Chip
,
11
(
17
), pp.
2858
2868
.
3.
Petersson
,
F.
,
Åberg
,
L.
,
Swärd-Nilsson
,
A.-M.
, and
Laurell
,
T.
,
2007
, “
Free Flow Acoustophoresis: Microfluidic-Based Mode of Particle and Cell Separation
,”
Anal. Chem.
,
79
(
14
), pp.
5117
5123
.
4.
Kersaudy-Kerhoas
,
M.
, and
Sollier
,
E.
,
2013
, “
Micro-Scale Blood Plasma Separation: From Acoustophoresis to Egg-Beaters
,”
Lab Chip
,
13
(
17
), pp.
3323
3346
.
5.
Li
,
M.
,
Li
,
S.
,
Li
,
W.
,
Wen
,
W.
, and
Alici
,
G.
,
2013
, “
Continuous Manipulation and Separation of Particles Using Combined Obstacle-and Curvature-Induced Direct Current Dielectrophoresis
,”
Electrophoresis
,
34
(
7
), pp.
952
960
.
6.
Çetin
,
B.
, and
Li
,
D.
,
2011
, “
Dielectrophoresis in Microfluidics Technology
,”
Electrophoresis
,
32
(
18
), pp.
2410
2427
.
7.
Pamme
,
N.
, and
Wilhelm
,
C.
,
2006
, “
Continuous Sorting of Magnetic Cells Via On-Chip Free-Flow Magnetophoresis
,”
Lab Chip
,
6
(
8
), pp.
974
980
.
8.
Gao
,
Y.
,
Jian
,
Y.
,
Zhang
,
L.
, and
Huang
,
J.
,
2007
, “
Magnetophoresis of Nonmagnetic Particles in Ferrofluids
,”
J. Phys. Chem. C
,
111
(
29
), pp.
10785
10791
.
9.
Huang
,
L. R.
,
Cox
,
E. C.
,
Austin
,
R. H.
, and
Sturm
,
J. C.
,
2004
, “
Continuous Particle Separation Through Deterministic Lateral Displacement
,”
Science
,
304
(
5673
), pp.
987
990
.
10.
Liu
,
Z.
,
Huang
,
F.
,
Du
,
J.
,
Shu
,
W.
,
Feng
,
H.
,
Xu
,
X.
, and
Chen
,
Y.
,
2013
, “
Rapid Isolation of Cancer Cells Using Microfluidic Deterministic Lateral Displacement Structure
,”
Biomicrofluid
,
7
(
1
), p.
011801
.
11.
Green
,
J. V.
,
Radisic
,
M.
, and
Murthy
,
S. K.
,
2009
, “
Deterministic Lateral Displacement as a Means to Enrich Large Cells for Tissue Engineering
,”
Anal. Chem.
,
81
(
21
), pp.
9178
9182
.
12.
Choi
,
S.
,
Song
,
S.
,
Choi
,
C.
, and
Park
,
J. K.
,
2008
, “
Sheathless Focusing of Microbeads and Blood Cells Based on Hydrophoresis
,”
Small
,
4
(
5
), pp.
634
641
.
13.
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
), pp.
2993
3003
.
14.
Di Carlo
,
D.
,
2009
, “
Inertial Microfluidics
,”
Lab Chip
,
9
(
21
), pp.
3038
3046
.
15.
Zhang
,
J.
,
Yan
,
S.
,
Sluyter
,
R.
,
Li
,
W.
,
Alici
,
G.
, and
Nguyen
,
N.-T.
,
2014
, “
Inertial Particle Separation by Differential Equilibrium Positions in a Symmetrical Serpentine Micro-Channel
,”
Sci. Rep.
,
4
(
3
), p.
4527
.
16.
Amini
,
H.
,
Lee
,
W.
, and
Di Carlo
,
D.
,
2014
, “
Inertial Microfluidic Physics
,”
Lab Chip
,
14
(
15
), pp.
2739
2761
.
17.
Zhang
,
J.
,
Yan
,
S.
,
Yuan
,
D.
,
Alici
,
G.
,
Nguyen
,
N.-T.
,
Warkiani
,
M. E.
, and
Li
,
W.
,
2016
, “
Fundamentals and Applications of Inertial Microfluidics: A Review
,”
Lab Chip
,
16
(
1
), pp.
10
34
.
18.
Service
,
A. R. C. B.
,
2016
, “
Blood Donation
,” Australian Red Cross, Adelaide, Australia, accessed Mar. 10,
2016
, http://www.donateblood.com.au/learn#how-donation-works
19.
Mach
,
A. J.
, and
Di Carlo
,
D.
,
2010
, “
Continuous Scalable Blood Filtration Device Using Inertial Microfluidics
,”
Biotechnol. Bioeng.
,
107
(
2
), pp.
302
311
.
20.
Xiang
,
N.
, and
Ni
,
Z.
,
2015
, “
High-Throughput Blood Cell Focusing and Plasma Isolation Using Spiral Inertial Microfluidic Devices
,”
Biomed. Microdevices
,
17
(
6
), pp.
1
11
.
21.
Lee
,
M. G.
,
Choi
,
S.
,
Kim
,
H. J.
,
Lim
,
H. K.
,
Kim
,
J. H.
,
Huh
,
N.
, and
Park
,
J. K.
,
2011
, “
Inertial Blood Plasma Separation in a Contraction–Expansion Array Microchannel
,”
Appl. Phys. Lett.
,
98
(
25
), p.
253702
.
22.
Lee
,
M. G.
,
Shin
,
J. H.
,
Choi
,
S.
, and
Park
,
J.-K.
,
2014
, “
Enhanced Blood Plasma Separation by Modulation of Inertial Lift Force
,”
Sens. Actuators, B
,
190
(
1
), pp.
311
317
.
23.
Zhang
,
J.
,
Yan
,
S.
,
Li
,
W.
,
Alici
,
G.
, and
Nguyen
,
N.-T.
,
2014
, “
High Throughput Extraction of Plasma Using a Secondary Flow-Aided Inertial Microfluidic Device
,”
RSC Adv.
,
4
(
63
), pp.
33149
33159
.
24.
Moorthy
,
J.
, and
Beebe
,
D. J.
,
2003
, “
In Situ Fabricated Porous Filters for Microsystems
,”
Lab Chip
,
3
(
2
), pp.
62
66
.
25.
Gan
,
W.
,
Zhuang
,
B.
,
Zhang
,
P.
,
Han
,
J.
,
Li
,
C.-X.
, and
Liu
,
P.
,
2014
, “
A Filter Paper-Based Microdevice for Low-Cost, Rapid, and Automated DNA Extraction and Amplification From Diverse Sample Types
,”
Lab Chip
,
14
(
19
), pp.
3719
3728
.
26.
Wang
,
S.
,
Sarenac
,
D.
,
Chen
,
M.
,
Huang
,
S.-H.
,
Giguel
,
F. F.
,
Kuritzkes
,
D. R.
, and
Demirci
,
U.
,
2012
, “
Simple Filter Microchip for Rapid Separation of Plasma and Viruses From Whole Blood
,”
Int. J. Nanomed.
,
7
(
9
), pp.
5019
5028
.
27.
Son
,
J. H.
,
Lee
,
S. H.
,
Hong
,
S.
,
Park
,
S.-M.
,
Lee
,
J.
,
Dickey
,
A. M.
, and
Lee
,
L. P.
,
2014
, “
Hemolysis-Free Blood Plasma Separation
,”
Lab Chip
,
14
(
13
), pp.
2287
2292
.
28.
Liu
,
C.
,
Mauk
,
M.
,
Gross
,
R.
,
Bushman
,
F. D.
,
Edelstein
,
P. H.
,
Collman
,
R. G.
, and
Bau
,
H. H.
,
2013
, “
Membrane-Based, Sedimentation-Assisted Plasma Separator for Point-of-Care Applications
,”
Anal. Chem.
,
85
(
21
), pp.
10463
10470
.
29.
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
.
30.
Késmárky
,
G.
,
Kenyeres
,
P.
,
Rábai
,
M.
, and
Tóth
,
K.
,
2008
, “
Plasma Viscosity: A Forgotten Variable
,”
Clin. Hemorheol. Microcirc.
,
39
(
1–4
), pp.
243
246
.
31.
Kim
,
J.
,
Surapaneni
,
R.
, and
Gale
,
B. K.
,
2009
, “
Rapid Prototyping of Microfluidic Systems Using a PDMS/Polymer Tape Composite
,”
Lab Chip
,
9
(
9
), pp.
1290
1293
.
32.
Tan
,
H. Y.
,
Loke
,
W. K.
, and
Nguyen
,
N.-T.
,
2010
, “
A Reliable Method for Bonding Polydimethylsiloxane (PDMS) to Polymethylmethacrylate (PMMA) and Its Application in Micropumps
,”
Sens. Actuators, B
,
151
(
1
), pp.
133
139
.
33.
Syringe-filters.com
,
2013
, “
Membrane Selection Guide
,” Altmann Analytik GmbH & Co. KG., Munich, Germany, accessed Mar. 10, 2016, http://www.syringe-filters.com/membrane-selection-guide.php
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