Rapid separation of white blood cells from whole blood sample is often required for their subsequent analyses of functions and phenotypes, and many advances have been made in this field. However, most current microfiltration-based cell separation microfluidic chips still suffer from low-throughput and membrane clogging. This paper reports on a high-throughput and clogging-free microfluidic filtration platform, which features with an integrated bidirectional micropump and commercially available polycarbonate microporous membranes. The integrated bidirectional micropump enables the fluid to flush micropores back and forth, effectively avoiding membrane clogging. The microporous membrane allows red blood cells passing through high-density pores in a cross-flow mixed with dead-end filtration mode. All the separation processes, including blood and buffer loading, separation, and sample collection, are automatically controlled for easy operation and high throughput. Both microbead mixture and undiluted whole blood sample are separated by the platform effectively. In particular, for white blood cell separation, the chip recovered 72.1% white blood cells with an over 232-fold enrichment ratio at a throughput as high as 37.5 μl/min. This high-throughput, clogging-free, and highly integrated platform holds great promise for point-of-care blood pretreatment, analysis, and diagnosis applications.

1.
M.
Toner
and
D.
Irimia
,
Annu. Rev. Biomed. Eng.
7
,
77
(
2005
).
2.
V.
Vandelinder
and
A.
Groisman
,
Anal. Chem.
79
,
2023
(
2007
).
3.
A. A. S.
Bhagat
,
H.
Bow
,
H. W.
Hou
,
S. J.
Tan
,
C. T.
Lim
, and
J.
Han
,
Med. Biol. Eng. Comput.
48
,
999
(
2010
).
4.
D. R.
Gossett
,
W. M.
Weaver
,
A. J.
Mach
,
S. C.
Hur
,
H.
Tat
,
K.
Tse
,
W.
Lee
,
H.
Amini
, and
D.
Di Carlo
,
Anal. Bioanal. Chem.
397
,
3249
(
2010
).
6.
Z. T. F.
Yu
,
K. M.
Aw Yong
, and
J.
Fu
,
Small
10
,
1687
(
2014
).
7.
M. M.
Wang
,
E.
Tu
,
D. E.
Raymond
,
J. M.
Yang
,
H.
Zhang
,
N.
Hagen
,
B.
Dees
,
E. M.
Mercer
,
A. H.
Forster
,
I.
Kariv
,
P. J.
Marchand
, and
W. F.
Butler
,
Nat. Biotechnol.
23
,
83
(
2005
).
8.
S.
Miltenyi
,
W.
Muller
,
W.
Weichel
, and
A.
Radbruch
,
Cytometry
11
,
231
(
1990
).
9.
I.
Doh
and
Y. H.
Cho
,
Sens. Actuators, A
121
,
59
(
2005
).
10.
R. S.
Pawell
,
D. W.
Inglis
,
T. J.
Barber
, and
R. A.
Taylor
,
Biomicrofluidics
7
,
056501
(
2013
).
11.
T.
Krüger
,
D.
Holmes
, and
P. V.
Coveney
,
Biomicrofluidics
8
,
054114
(
2014
).
12.
J. A.
Davis
,
D. W.
Inglis
,
K. J.
Morton
,
D. A.
Lawrence
,
L. R.
Huang
,
S. Y.
Chou
,
J. C.
Sturm
, and
R. H.
Austin
,
Proc. Natl. Acad. Sci. U.S.A.
103
,
14779
(
2006
).
13.
M.
Yamada
and
M.
Seki
,
Lab Chip
5
,
1233
(
2005
).
14.
S.
Sugaya
,
M.
Yamada
, and
M.
Seki
,
Biomicrofluidics
5
,
024103
(
2011
).
15.
S.
Torino
,
M.
Iodice
,
I.
Rendina
,
G.
Coppola
, and
E.
Schonbrun
,
Biomicrofluidics
9
,
064107
(
2015
).
16.
T.
Morijiri
,
S.
Sunahiro
,
M.
Senaha
,
M.
Yamada
, and
M.
Seki
,
Microfluid. Nanofluid.
11
,
105
(
2011
).
17.
J.
Takagi
,
M.
Yamada
, and
M.
Seki
,
Lab Chip
5
,
778
(
2005
).
18.
J.
Sun
,
C.
Liu
,
M.
Li
,
J.
Wang
,
Y.
Xianyu
,
G.
Hu
, and
X.
Jiang
,
Biomicrofluidics
7
,
11802
(
2013
).
19.
N.
Nivedita
and
I.
Papautsky
,
Biomicrofluidics
7
,
054101
(
2013
).
20.
S. S.
Kuntaegowdanahalli
,
A. S.
Bhagat
, and
I.
Papautsky
,
Lab Chip
9
,
2973
(
2009
).
21.
K.
Aran
,
A.
Fok
,
L. A.
Sasso
,
N.
Kamdar
,
Y.
Guan
,
Q.
Sun
,
A.
Ündar
, and
J. D.
Zahn
,
Lab Chip
11
,
2858
(
2011
).
22.
S.
Zheng
,
H.
Lin
,
J.-Q.
Liu
,
M.
Balic
,
R.
Datar
,
R. J.
Cote
, and
Y.-C.
Tai
,
J. Chromatogr. A
1162
,
154
(
2007
).
23.
V.
Vandelinder
and
A.
Groisman
,
Anal. Chem.
78
,
3765
(
2006
).
24.
P.
Wilding
,
L. J.
Kricka
,
J.
Cheng
,
G.
Hvichia
,
M. A.
Shoffner
, and
P.
Fortina
,
Anal. Biochem.
257
,
95
(
1998
).
25.
Y.
Nam
,
M.
Kim
, and
T.
Kim
,
Sens. Actuators, B
190
,
86
(
2014
).
26.
T. G.
Kang
,
Y.-J.
Yoon
,
H.
Ji
,
P. Y.
Lim
, and
Y.
Chen
,
J. Micromech. Microeng.
24
,
087001
(
2014
).
27.
J.
Alvankarian
,
A.
Bahadorimehr
, and
B.
Yeop Majlis
,
Biomicrofluidics
7
,
014102
(
2013
).
28.
T. F.
Didar
,
K.
Li
,
M.
Tabrizian
, and
T.
Veres
,
Lab Chip
13
,
2615
(
2013
).
29.
T. F.
Didar
,
K.
Li
,
T.
Veres
, and
M.
Tabrizian
,
Biomaterials
34
,
5588
(
2013
).
30.
M.
Hosokawa
,
T.
Yoshikawa
,
R.
Negishi
,
T.
Yoshino
,
Y.
Koh
,
H.
Kenmotsu
,
T.
Naito
,
T.
Takahashi
,
N.
Yamamoto
,
Y.
Kikuhara
,
H.
Kanbara
,
T.
Tanaka
,
K.
Yamaguchi
, and
T.
Matsunaga
,
Anal. Chem.
85
,
5692
(
2013
).
31.
M.
Hosokawa
,
M.
Asami
,
S.
Nakamura
,
T.
Yoshino
,
N.
Tsujimura
,
M.
Takahashi
,
S.
Nakasono
,
T.
Tanaka
, and
T.
Matsunaga
,
Biotechnol. Bioeng.
109
,
2017
(
2012
).
32.
H.
Wei
,
B. H.
Chueh
,
H.
Wu
,
E. W.
Hall
,
C. W.
Li
,
R.
Schirhagl
,
J. M.
Lin
, and
R. N.
Zare
,
Lab Chip
11
,
238
(
2011
).
33.
R.
Schirhagl
,
I.
Fuereder
,
E. W.
Hall
,
B. C.
Medeiros
, and
R. N.
Zare
,
Lab Chip
11
,
3130
(
2011
).
34.
X.
Li
,
W.
Chen
,
G.
Liu
,
W.
Lu
, and
J.
Fu
,
Lab Chip
14
,
2565
(
2014
).
35.
H. M.
Ji
,
V.
Samper
,
Y.
Chen
,
C. K.
Heng
,
T. M.
Lim
, and
L.
Yobas
,
Biomed. Microdevices
10
,
251
(
2008
).
36.
X.
Chen
,
D. F.
Cui
,
C. C.
Liu
, and
H.
Li
,
Sens. Actuators, B
130
,
216
(
2008
).
37.
J. S.
Shim
,
A. W.
Browne
, and
C. H.
Ahn
,
Biomed. Microdevices
12
,
949
(
2010
).
38.
M. A.
Unger
,
H. P.
Chou
,
T.
Thorsen
,
A.
Scherer
, and
S. R.
Quake
,
Science
288
,
113
(
2000
).
39.
M.
Du
,
X.
Ye
,
K.
Wu
, and
Z.
Zhou
,
Sensors (Basel)
9
,
2611
(
2009
).
40.
M.
Du
,
Z.
Ma
,
X.
Ye
, and
Z.
Zhou
,
Sci. China Technol. Sci.
56
,
1047
(
2013
).
41.
M.
Gironès
,
R. G. H.
Lammertink
, and
M.
Wessling
,
J. Memb. Sci.
273
,
68
(
2006
).
42.
K.
Aran
,
L. A.
Sasso
,
N.
Kamdar
, and
J. D.
Zahn
,
Lab Chip
10
,
548
(
2010
).
You do not currently have access to this content.