To study an environmental or biological solution, it is essential to separate its constituents. In this study, a 3D-deformable dynamic microfilter was developed to selectively separate the target substance from a solution. This microfilter is a fine metallic nickel structure fabricated using photolithography and electroplating techniques. It is gold-coated across its entire surface with multiple slits of 10–20 μm in width. Its two-dimensional shape is deformed into a three-dimensional shape when used for fluid separation due to hydrodynamic forces. By adjusting the pressure applied to the microfilter, the size of the gap created by deformation can be changed. To effectively isolate the target substance, the relationship between the solution flow rate and the extent of microfilter deformation was investigated. The filtration experiments demonstrated the microfilter’s ability to isolate the target substance with elastic deformation without undergoing plastic deformation. Additionally, modification of the microfilter surface with nucleic acid aptamers resulted in the selective isolation of the target cell, which further demonstrates the potential application of microfilters in the isolation of specific components of heterogeneous solutions.

1
Baeuerle
,
P. A.
and
Gires
,
O.
, “
EpCAM (CD326) finding its role in cancer
,”
Br. J. Cancer
96
,
417
423
(
2007
).
2
Bouab
,
E.
,
Jiménez-Zenteno
,
A. K.
,
Estève
,
A.
,
Bourrier
,
D.
,
Vieu
,
C.
, and
Cerf
,
A.
, “
Fabrication of 3D microdevices from planar electroplating for the isolation of cancer associated cells in blood
,”
Microelectron. Eng.
213
,
69
73
(
2019
).
3
Chan
,
J.
,
Kayani
,
A.
,
Ali
,
M.
,
Kok
,
C.
,
Majlis
,
B.
,
Hoe
,
S.
,
Marzuki
,
M.
,
Khoo
,
A.
,
Ostrikov
,
K.
,
Rahman
,
M.
, and
Sriram
,
S.
, “
Dielectrophoresis-based microfluidic platforms for cancer diagnostics
,”
Biomicrofluidics
12
,
011503
(
2018
).
4
Cristofanilli
,
M.
,
Budd
,
G. T.
,
Ellis
,
M. J.
,
Stopeck
,
A.
,
Matera
,
J.
,
Miller
,
M. C.
,
Reuben
,
J. M.
,
Doyle
,
G. V.
,
Allard
,
W. J.
,
Terstappen
,
L. W. M. M.
, and
Hayes
,
D. F.
, “
Circulating tumor cells, disease progression, and survival in metastatic breast cancer
,”
N. Engl. J. Med.
351
,
781
791
(
2004
).
5
Fabbri
,
F.
,
Carloni
,
S.
,
Zoli
,
W.
,
Ulivi
,
P.
,
Gallerani
,
G.
,
Fici
,
G.
,
Chiadini
,
E.
,
Passardi
,
A.
,
Frassineti
,
G.
,
Ragazzini
,
A.
, and
Amadori
,
D.
, “
Detection and recovery of circulating colon cancer cells using a dielectrophoresis-based device: KRAS mutation status in pure CTCs
,”
Cancer Lett.
335
,
225
231
(
2013
).
6
Gascoyne
,
P.
and
Shim
,
S.
, “
Isolation of circulating tumor cells by dielectrophoresis
,”
Cancers
6
,
545
579
(
2014
).
7
Hammami
,
M. B.
,
Chhaparia
,
A.
,
Piao
,
J.
,
Zhou
,
Y.
,
Hachem
,
C.
, and
Lai
,
J.
, “
Mixed adenocarcinoma and squamous cell carcinoma of duodenum: A case report and review of the literature
,”
Case Rep. Gastroenterol.
11
,
402
410
(
2017
).
8
Hou
,
J. M.
,
Krebs
,
M. G.
,
Lancashire
,
L.
,
Sloane
,
R.
,
Backen
,
A.
,
Swain
,
R. K.
,
Priest
,
L. J. C.
,
Greystoke
,
A.
,
Zhou
,
C.
,
Morris
,
K.
,
Ward
,
T.
,
Blackhall
,
F. H.
, and
Dive
,
C.
, “
Clinical significance and molecular characteristics of circulating tumor cells and circulating tumor microemboli in patients with small-cell lung cancer
,”
J. Clin. Oncol.
30
,
525
532
(
2012
).
9
Huang
,
T.
,
Jia
,
C.
,
Jun-Yang
,
S. W.
,
Zhang H
,
W.
,
Cong
,
H.
,
Jing
,
F.
,
Mao
,
H.-J.
,
Jin
,
Q.-H.
,
Zhang
,
Z.
,
Chen
,
Y.
,
Li
,
G.
,
Mao
,
G.
, and
Zhao
,
J.
, “
Highly sensitive enumeration of circulating tumor cells in lung cancer patients using a size-based filtration microfluidic chip
,”
Biosens. Bioelectron.
51
,
213
218
(
2014
).
10
Iliescu
,
F.
,
Poenar
,
D.
,
Yu
,
F.
,
Ni
,
M.
,
Chan
,
K.
,
Cima
,
I.
,
Taylor
,
H.
,
Cima
,
I.
, and
Iliescu
,
C.
, “
Recent advances in microfluidic methods in cancer liquid biopsy
,”
Biomicrofluidics
13
,
041503
(
2019
).
11
Jen
,
C.
,
Chang
,
H.
,
Huang
,
C.
, and
Chen
,
K.
, “
A microfabricated module for isolating cervical carcinoma cells from peripheral blood utilizing dielectrophoresis in stepping electric fields
,”
Microsyst. Technol.
18
,
1887
1896
(
2012
).
12
Kanaoka
,
C.
, “
Fine particle filtration technology using fiber as dust collection medium
,”
KONA Powder Part. J.
36
,
88
113
(
2019
).
13
Kunugi
,
M.
, “
A review of current methods for the determination of particulate
,”
J. Jpn. Soc. Air Pollution
25
,
355
370
(
1990
).
14
Lee
,
M.
,
Choi
,
H.
,
Kumita
,
M.
, and
Otani
,
Y.
, “
Present status of air filters and exploration of their new applications
,”
KONA Powder Part. J.
37
,
19
27
(
2020
).
15
Liu
,
H.-Y.
,
Koch
,
C.
,
Haller
,
A.
,
Joosse
,
S. A.
,
Kumar
,
R.
,
Vellekoop
,
M. J.
,
Horst
,
L. J.
,
Keller
,
L.
,
Babayan
,
A.
,
Failla
,
A. V.
,
Jensen
,
J.
,
Peine
,
S.
,
Keplinger
,
F.
,
Fuchs
,
H.
,
Pantel
,
K.
, and
Hirtz
,
M.
, “
Evaluation of microfluidic ceiling designs for the capture of circulating tumor cells on a microarray platform
,”
Adv. Biosyst.
4
,
1900162
(
2020
).
16
Muhanna
,
N.
,
Mepham
,
A.
,
Mohamadi
,
R. M.
,
Chan
,
H.
,
Khan
,
T.
,
Akens
,
M.
,
Besant
,
J. D.
,
Irish
,
J.
, and
Kelley
,
S. O.
, “
Nanoparticle-based sorting of circulating tumor cells by epithelial antigen expression during disease progression in an animal model
,”
Nanomedicine
11
,
1613
1620
(
2015
).
17
Nagrath
,
S.
,
Sequist
,
L. V.
,
Maheswaran
,
S.
,
Bell
,
D. W.
,
Irimia
,
D.
,
Ulkus
,
L.
,
Smith
,
M. R.
,
Kwak
,
E. L.
,
Digumarthy
,
S.
,
Muzikansky
,
A.
,
Ryan
,
P.
,
Balis
,
U. J.
,
Tompkins
,
R. G.
,
Haber
,
D. A.
, and
Toner
,
M.
, “
Isolation of rare circulating tumour cells in cancer patients by microchip technology
,”
Nature
450
,
1235
1239
(
2007
).
18
Ollier
,
E.
,
Go
,
D. E.
,
Che
,
J.
,
Gossett
,
D. R.
,
O’Byrne
,
S.
,
Weaver
,
W. M.
,
Kummer
,
N.
,
Rettig
,
M.
,
Goldman
,
J.
,
Nickols
,
N.
,
McCloskey
,
S.
,
Kulkarni
,
R. P.
, and
Carlo
,
D. D.
, “
Size-selective collection of circulating tumor cells using vortex technology
,”
Lab Chip
14
,
63
77
(
2014
).
19
Patriarca
,
C.
,
Macchi
,
R. M.
,
Marschner
,
A. K.
, and
Mellstedt
,
H.
, “
Epithelial cell adhesion molecule expression (CD326) in cancer: A short review
,”
Cancer Treat Rev.
38
,
68
75
(
2012
).
20
Plaks
,
V.
,
Koopman
,
C.
, and
Werb
,
Z.
, “
Circulating tumor cells
,”
Science
341
,
1186
1188
(
2013
).
21
Revzin
,
A.
,
Maverakis
,
E.
, and
Chang
,
H.
, “
Biosensors for immune cell analysis—A perspective
,”
Biomicrofluidics
6
,
021301
(
2012
).
22
Riethdorf
,
S.
,
Fritsche
,
H.
,
Müller
,
V.
,
Rau
,
T.
,
Schindlbeck
,
C.
,
Rack
,
B.
,
Janni
,
W.
,
Coith
,
C.
,
Beck
,
K.
,
Jänicke
,
F.
,
Jackson
,
S.
,
Gornet
,
T.
,
Cristofanilli
,
M.
, and
Pantel
,
K.
, “
Detection of circulating tumor cells in peripheral blood of patients with metastatic breast cancer: A validation study of the cell search system
,”
Clin. Cancer Res.
13
,
920
928
(
2007
).
23
Sarioglu
,
A. F.
,
Aceto
,
N.
,
Kojic
,
N.
,
Donaldson
,
M. C.
,
Zeinali
,
M.
,
Hamza
,
B.
,
Engstrom
,
A.
,
Zhu
,
H.
,
Sundaresan
,
T. K.
,
Miyamoto
,
D. T.
,
Luo
,
X.
,
Bardia
,
A.
,
Wittner
,
B. S.
,
Ramaswamy
,
S.
,
Shioda
,
T.
,
Ting
,
D. T.
,
Stott
,
S. L.
,
Kapur
,
R.
,
Maheswaran
,
S.
,
Haber
,
D. A.
, and
Toner
,
M.
, “
A microfluidic device for label-free, physical capture of circulating tumor cell clusters
,”
Nat. Methods
12
,
685
(
2015
).
24
Scher
,
H. I.
,
Heller
,
G.
,
Molina
,
A.
,
Attard
,
G.
,
Danila
,
D. C.
,
Jia
,
X.
,
Peng
,
W.
,
Sandhu
,
S. K.
,
Olmos
,
D.
,
Riisnaes
,
R.
,
McCormack
,
R.
,
Burzykowski
,
T.
,
Kheoh
,
T.
,
Fleisher
,
M.
,
Buyse
,
M.
, and
Bono
,
J. S.
, “
Circulating tumor cell biomarker panel as an individual level surrogate for survival in metastatic castration-resistant prostate cancer
,”
J. Clin. Oncol.
33
,
1348
1355
(
2015
).
25
Song
,
Y.
,
Zhu
,
Z.
,
An
,
Y.
,
Zhang
,
W.
,
Zhang
,
H.
,
Liu
,
D.
,
Yu
,
C.
,
Duan
,
W.
, and
Yang
,
C. J.
, “
Selection of DNA aptamers against epithelial cell adhesion molecule for cancer cell imaging and circulating tumor cell capture
,”
Anal. Chem.
85
(
8
),
4141
4149
(
2013
).
26
Umezawa
,
K.
and
Nuri
,
Y.
, “
Progress of filtration technologies for inclusion removal
,”
Tetsu To Hagane
75
,
1829
1838
(
1989
).
27
Wasniewski
,
M.
,
Guiot
,
A. L.
,
Schereffer
,
J. L.
,
Tribout
,
L.
,
Mähar
,
K.
, and
Cliquet
,
F.
, “
Evaluation of an ELISA to detect rabies antibodies in orally vaccinated foxes and raccoon dogs sampled in the field
,”
J. Virol. Methods
187
,
264
270
(
2013
).
28
Went
,
P. T.
,
Lugli
,
A.
,
Meier
,
S.
,
Bundi
,
M.
,
Mirlacher
,
M.
,
Sauter
,
G.
, and
Dirnhofer
,
S.
, “
Frequent EpCam protein expression in human carcinomas
,”
Hum. Pathol.
35
,
122
128
(
2004
).
29
Wu
,
L.
,
Zamay
,
G. S.
,
Kolovskaya
,
O. S.
,
Zamay
,
T. N.
, and
Berezovski
,
M. V.
, “
Aptamer-based microfluidics for isolation, release and analysis of circulating tumor cells
,”
Trends Anal. Chem.
117
,
69
77
(
2019
).
30
Zhou
,
J.
,
Mukherjee
,
P.
,
Gao
,
H.
,
Luan
,
Q.
, and
Papautsky
,
I.
, “
Label-free microfluidic sorting of microparticles
,”
Appl. Phys. Lett. Bioeng.
3
,
041504
(
2019
).

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