The high-precision and high-purity isolation of circulating tumor cells (CTCs) from whole blood is vital to early cancer detection. Cascaded microfluidic separation is highly efficient because it connects multiple-stage separations in series. Here, we numerically investigated sheathless tumor cell separation with size-dependent cascaded inertial and deterministic lateral displacement (DLD) microfluidic device. The inertial microfluidic is arranged in the first-stage unit for particle focusing and rough sorting, and the cascaded DLD microfluidic is arranged in the second stage for realizing further sorting and purification. A parametric study with flow rate range from 100–600 μl/min and aspect ratio range from 60:100 to 60:300 of the first stage was carried out to optimize channel structure for realizing high-efficiency separation. Then, the pre-separation mechanism within the spiral microchannel was analyzed. The purity of the obtained CTCs and the separation efficiency were further improved using a droplet-type microcolumn DLD microfluidic device as the second unit. The cascade eliminates the need for additional force fields and reduces device complexity while simplifying operation and reducing the chance of sample contamination.
REFERENCES
1.
T.
Zhou
,
J.
He
,
Z.
Wu
,
Q.
Bian
,
X.
He
,
S.
Zhou
,
J.
Zhao
,
T.
Wu
,
L.
Shi
, and
H.
Yan
, “
Dielectrophoretic–inertial microfluidics for Symbiodinium separation and enrichment
,” Phys. Fluids
36
(3
), 032018
(2024
).2.
A. T.
Aldemir
,
S.
Cadirci
, and
L.
Trabzon
, “
Investigation of inertial focusing of micro- and nanoparticles in spiral microchannels using computational fluid dynamics
,” Phys. Fluids
35
(11
), 112012
(2023
).3.
A. A. S.
Bhagat
,
H.
Bow
,
H. W.
Hou
,
S. J.
Tan
,
J.
Han
, and
C. T.
Lim
, “
Microfluidics for cell separation
,” Med. Biol. Eng. Comput.
48
(10
), 999
–1014
(2010
).4.
C.
Macaraniag
,
Q.
Luan
,
J.
Zhou
, and
I.
Papautsky
, “
Microfluidic techniques for isolation, formation, and characterization of circulating tumor cells and clusters
,” APL Bioeng.
6
(3
), 031501
(2022
).5.
H.
Cho
,
J.
Kim
,
H.
Song
,
K. Y.
Sohn
,
M.
Jeon
, and
K.-H.
Han
, “
Microfluidic technologies for circulating tumor cell isolation
,” Analyst
143
(13
), 2936
–2970
(2018
).6.
J. P.
Gurung
,
M.
Gel
, and
M. A. B.
Baker
, “
Microfluidic techniques for separation of bacterial cells via taxis
,” Microb. Cell
7
(3
), 66
–79
(2020
).7.
Y.
Wu
,
Y.
Wang
,
Y.
Lu
,
X.
Luo
,
Y.
Huang
,
T.
Xie
,
C.
Pilarsky
,
Y.
Dang
, and
J.
Zhang
, “
Microfluidic technology for the isolation and analysis of exosomes
,” Micromachines
13
(10
), 1571
(2022
).8.
M.
Bayareh
, “
An updated review on particle separation in passive microfluidic devices
,” Chem. Eng. Process.-Process Intensif.
153
, 107984
(2020
).9.
M. G.
Lee
,
J. H.
Shin
,
C. Y.
Bae
,
S.
Choi
, and
J.-K.
Park
, “
Label-free cancer cell separation from human whole blood using inertial microfluidics at low shear stress
,” Anal. Chem.
85
(13
), 6213
–6218
(2013
).10.
R.
Nasiri
,
A.
Shamloo
,
S.
Ahadian
,
L.
Amirifar
,
J.
Akbari
,
M. J.
Goudie
,
K.
Lee
,
N.
Ashammakhi
,
M. R.
Dokmeci
,
D.
Di Carlo
, and
A.
Khademhosseini
, “
Microfluidic‐based approaches in targeted cell/particle separation based on physical properties: Fundamentals and applications
,” Small
16
(29
), 2000171
(2020
).11.
A.
Hochstetter
,
R.
Vernekar
,
R. H.
Austin
,
H.
Becker
,
J. P.
Beech
,
D. A.
Fedosov
,
G.
Gompper
,
S.-C.
Kim
,
J. T.
Smith
,
G.
Stolovitzky
,
J. O.
Tegenfeldt
,
B. H.
Wunsch
,
K. K.
Zeming
,
T.
Krüger
, and
D. W.
Inglis
, “
Deterministic lateral displacement: Challenges and perspectives
,” ACS Nano
14
(9
), 10784
–10795
(2020
).12.
T.
Peng
,
J.
Qiang
, and
S.
Yuan
, “
Sheathless inertial particle focusing methods within microfluidic devices: A review
,” Front. Bioeng. Biotechnol.
11
, 1331968
(2024
).13.
G.
Esposito
,
S.
Romano
,
M. A.
Hulsen
,
G.
D'Avino
, and
M. M.
Villone
, “
Numerical simulations of cell sorting through inertial microfluidics
,” Phys. Fluids
34
(7
), 072009
(2022
).14.
R. N.
Valani
,
B.
Harding
, and
Y. M.
Stokes
, “
Utilizing bifurcations to separate particles in spiral inertial microfluidics
,” Phys. Fluids
35
(1
), 011703
(2023
).15.
Z.
Zhu
,
H.
Ren
,
D.
Wu
,
Z.
Ni
, and
N.
Xiang
, “
High-throughput and simultaneous inertial separation of tumor cells and clusters from malignant effusions using spiral-contraction-expansion channels
,” Microsyst. Nanoeng.
10
(1
), 36
(2024
).16.
H.
Cha
,
H.
Fallahi
,
Y.
Dai
,
D.
Yuan
,
H.
An
,
N. T.
Nguyen
, and
J.
Zhang
, “
Multiphysics microfluidics for cell manipulation and separation: A review
,” Lab Chip
22
(3
), 423
–444
(2022
).17.
N.
Xiang
,
J.
Wang
,
Q.
Li
,
Y.
Han
,
D.
Huang
, and
Z.
Ni
, “
Precise size-based cell separation via the coupling of inertial microfluidics and deterministic lateral displacement
,” Anal. Chem.
91
(15
), 10328
–10334
(2019
).18.
Y.
Lu
,
J.
Ying
,
S.
Mu
,
W.
Tan
, and
G.
Zhu
, “
Sheathless and high-throughput separation of multi-target particles combining inertia and deterministic lateral displacement (DLD) in a microchannel
,” Sep. Purif. Technol.
345
, 127369
(2024
).19.
M.
Wu
,
K.
Chen
,
S.
Yang
,
Z.
Wang
,
P.-H.
Huang
,
J.
Mai
,
Z.-Y.
Li
, and
T. J.
Huang
, “
High-throughput cell focusing and separation via acoustofluidic tweezers
,” Lab Chip
18
(19
), 3003
–3010
(2018
).20.
K.
Mutafopulos
,
P.
Spink
,
C. D.
Lofstrom
,
P. J.
Lu
,
H.
Lu
,
J. C.
Sharpe
,
T.
Franke
, and
D. A.
Weitz
, “
Traveling surface acoustic wave (TSAW) microfluidic fluorescence activated cell sorter (μFACS)
,” Lab Chip
19
(14
), 2435
–2443
(2019
).21.
A.
Abdulla
,
W.
Liu
,
A.
Gholamipour-Shirazi
,
J.
Sun
, and
X.
Ding
, “
High-throughput isolation of circulating tumor cells using cascaded inertial focusing microfluidic channel
,” Anal. Chem.
90
(7
), 4397
–4405
(2018
).22.
Z.
Sheidaei
,
P.
Akbarzadeh
, and
N.
Kashaninejad
, “
Advances in numerical approaches for microfluidic cell analysis platforms
,” J. Sci. Adv. Mater. Devices
5
(3
), 295
–307
(2020
).23.
A.
Shamloo
,
S.
Ahmad
, and
M.
Momeni
, “
Design and parameter study of integrated microfluidic platform for CTC isolation and enquiry; A numerical approach
,” Biosensors
8
(2
), 56
(2018
).24.
X.
Chen
,
H.
Lv
, and
Y.
Zhang
, “
A novel study on separation of particles driven in two steps based on standing surface acoustic waves
,” Chaos, Solitons Fractals
162
, 112419
(2022
).25.
Q.
Zhao
,
D.
Yuan
,
J.
Zhang
, and
W.
Li
, “
A review of secondary flow in inertial microfluidics
,” Micromachines
11
(5
), 461
(2020
).26.
J. M.
Martel
and
M.
Toner
, “
Inertial focusing in microfluidics
,” Annu. Rev. Biomed. Eng.
16
(1
), 371
–396
(2014
).27.
N.
Liu
,
C.
Petchakup
,
H. M.
Tay
,
K. H. H.
Li
, and
H. W.
Hou
, in Applications of Microfluidic Systems in Biology and Medicine
(
Springer
, 2019
), pp. 99
–150
.28.
H.
Amini
,
W.
Lee
, and
D.
Di Carlo
, “
Inertial microfluidic physics
,” Lab Chip
14
(15
), 2739
–2761
(2014
).29.
D.
Di Carlo
, “
Inertial microfluidics
,” Lab Chip
9
(21
), 3038
(2009
).30.
S.
Ookawara
,
R.
Higashi
,
D.
Street
, and
K.
Ogawa
, “
Feasibility study on concentration of slurry and classification of contained particles by microchannel
,” Chem. Eng. J.
101
(1–3
), 171
–178
(2004
).31.
J.
Zhang
,
D.
Yuan
,
Q.
Zhao
,
A. J. T.
Teo
,
S.
Yan
,
C. H.
Ooi
,
W.
Li
, and
N.-T.
Nguyen
, “
Fundamentals of differential particle inertial focusing in symmetric sinusoidal microchannels
,” Anal. Chem.
91
(6
), 4077
–4084
(2019
).32.
E. S.
Asmolov
, “
The inertial lift on a spherical particle in a plane Poiseuille flow at large channel Reynolds number
,” J. Fluid Mech.
381
, 63
–87
(1999
).33.
J.
McGrath
,
M.
Jimenez
, and
H.
Bridle
, “
Deterministic lateral displacement for particle separation: A review
,” Lab Chip
14
(21
), 4139
–4158
(2014
).34.
X.
Xu
,
Z.
Li
, and
A.
Nehorai
, “
Finite element simulations of hydrodynamic trapping in microfluidic particle-trap array systems
,” Biomicrofluidics
7
(5
), 054108
(2013
).35.
T.
Salafi
,
Y.
Zhang
, and
Y.
Zhang
, “
A review on deterministic lateral displacement for particle separation and detection
,” Nano-Micro Lett.
11
, 77
(2019
).36.
A. A. S.
Bhagat
,
S. S.
Kuntaegowdanahalli
, and
I.
Papautsky
, “
Enhanced particle filtration in straight microchannels using shear-modulated inertial migration
,” Phys. Fluids
20
(10
), 101702
(2008
).37.
S. S.
Kuntaegowdanahalli
,
A. A. S.
Bhagat
,
G.
Kumar
, and
I.
Papautsky
, “
Inertial microfluidics for continuous particle separation in spiral microchannels
,” Lab Chip
9
(20
), 2973
(2009
).38.
Z.
Akbari
,
M. A.
Raoufi
,
S.
Mirjalali
, and
B.
Aghajanloo
, “
A review on inertial microfluidic fabrication methods
,” Biomicrofluidics
17
(5
), 051504
(2023
).39.
G.
Li
,
Y.
Ji
,
Y.
Wu
,
Y.
Liu
,
H.
Li
,
Y.
Wang
,
M.
Chi
,
H.
Sun
, and
H.
Zhu
, “
Multistage microfluidic cell sorting method and chip based on size and stiffness
,” Biosens. Bioelectron.
237
, 115451
(2023
).40.
W.
Pakhira
,
R.
Kumar
, and
K. M.
Ibrahimi
, “
Distinct separation of multiple CTCs using inertial focusing phenomena utilizing single-looped spiral microfluidic lab-on-chip
,” Chem. Eng. Sci.
275
, 118724
(2023
).41.
A.-D.
Van
and
V.-S.
Pham
, “
A numerical modeling study on the impact of particle concentration on the particle sorting in spiral channels
,” Phys. Fluids
36
(5
), 052002
(2024
).42.
J.
Su
,
X.
Chen
,
Y.
Zhu
, and
G.
Hu
, “
Machine learning assisted fast prediction of inertial lift in microchannels
,” Lab Chip
21
(13
), 2544
–2556
(2021
).43.
T.
Peng
,
M.
Zhou
,
S.
Yuan
, and
B.
Jiang
, “
Trapping stable bubbles in hydrophobic microchannel for continuous ultrasonic microparticle manipulation
,” Sens. Actuators, A
331
, 113045
(2021
).44.
T.
Peng
,
X.
Lin
,
S.
Yuan
,
M.
Zhou
,
B.
Jiang
, and
Y.
Jia
, “
Mixing enhancement in a straight microchannel with ultrasonically activated attached bubbles
,” Int. J. Heat Mass Transfer
217
, 124635
(2023
).45.
T.
Peng
,
J.
Qiang
, and
S.
Yuan
, “
Investigation on a cascaded inertial and acoustic microfluidic device for sheathless and label-free separation of circulating tumor cells
,” Phys. Fluids
35
(8
), 082009
(2023
).46.
A. J.
Chung
, “
A minireview on inertial microfluidics fundamentals: Inertial particle focusing and secondary flow
,” BioChip J.
13
(1
), 53
–63
(2019
).47.
D.
Di Carlo
,
J. F.
Edd
,
K. J.
Humphry
,
H. A.
Stone
, and
M.
Toner
, “
Particle segregation and dynamics in confined flows
,” Phys. Rev. Lett.
102
(9
), 094503
(2009
).48.
Z.
Shen
,
A.
Wu
, and
X.
Chen
, “
Current detection technologies for circulating tumor cells
,” Chem. Soc. Rev.
46
(8
), 2038
–2056
(2017
).49.
M.
Ilie
,
V.
Hofman
,
E.
Long-Mira
,
E.
Selva
,
J.-M.
Vignaud
,
B.
Padovani
,
J.
Mouroux
,
C.-H.
Marquette
, and
P.
Hofman
, “
‘Sentinel’ circulating tumor cells allow early diagnosis of lung cancer in patients with chronic obstructive pulmonary disease
,” PLoS One
9
(10
), e111597
(2014
).50.
B. M.
Dincau
,
A.
Aghilinejad
,
T.
Hammersley
,
X.
Chen
, and
J. H.
Kim
, “
Deterministic lateral displacement (DLD) in the high Reynolds number regime: High-throughput and dynamic separation characteristics
,” Microfluid. Nanofluid.
22
(6
), 59
(2018
).© 2024 Author(s). Published under an exclusive license by AIP Publishing.
2024
Author(s)
You do not currently have access to this content.
