Isolation of microparticles and biological cells on microfluidic chips has received considerable attention due to their applications in numerous areas such as medical and engineering fields. Microparticles separation is of great importance in bioassays due to the need for smaller sample and device size and lower manufacturing costs. In this study, we first explain the concepts of separation and microfluidic science along with their applications in the medical sciences, and then, a conceptual design of a novel inertial microfluidic system is proposed and analyzed. The PDMS spiral microfluidic device was fabricated, and its effects on the separation of particles with sizes similar to biological particles were experimentally analyzed. This separation technique can be used to separate cancer cells from the normal ones in the blood samples. These components required for testing were selected, assembled, and finally, a very affordable microfluidic kit was provided. Different experiments were designed, and the results were analyzed using appropriate software and methods. Separator system tests with polydisperse hollow glass particles (diameter 2–20 µm), and monodisperse Polystyrene particles (diameter 5 & 15 µm), and the results exhibit an acceptable chip performance with 86% of efficiency for both monodisperse particles and polydisperse particles. The microchannel collects particles with an average diameter of 15.8, 9.4, and 5.9 μm at the proposed reservoirs. This chip can be integrated into a more extensive point-of-care diagnostic system to test blood samples.
BhagatAASBowHHouHW, et al. Microfluidics for cell separation. Med Biol Eng Comput2010; 48(10): 999–1014.
2.
XiangNWangJLiQ, et al. Precise size-based cell separation via the coupling of inertial microfluidics and deterministic lateral displacement. Anal Chem2019; 91(15): 10328–10334.
3.
NguyenNVLe ManhTNguyenTS, et al. Applied electric field analysis and numerical investigations of the continuous cell separation in a dielectrophoresis-based microfluidic channel. J Sci Adv Mater Devices2021; 6(1): 11–18.
4.
Di CarloD. Inertial microfluidics. Lab Chip2009; 9(21): 3038–3046.
5.
ZhangJYanSYuanD, et al. Fundamentals and applications of inertial microfluidics: a review. Lab Chip2016; 16(1): 10–34.
6.
PrinceMMaXDockerP, et al. The development of a novel Bio-MEMS filtration chip for the separation of specific cells in fluid suspension. Proc IMechE, Part H: J Engineering in Medicine2007; 221(2): 113–128.
7.
VasilescuSAKhorsandiSDingL, et al. A microfluidic approach to rapid sperm recovery from heterogeneous cell suspensions. Sci Rep2021: 11(1): 7917.
8.
LinECaoTNagrathS, et al. Circulating tumor cells: diagnostic and therapeutic applications. Annu Rev Biomed Eng2018; 20(1): 329–352.
9.
AshworthT. A case of cancer in which cells similar to those in the tumours were seen in the blood after death. Aust Med J1869; 14: 146.
10.
ZhangXXuXRenY, et al. Numerical simulation of circulating tumor cell separation in a dielectrophoresis based Y-Y shaped microfluidic device. Sep Purif Technol2021; 255: 117343.
11.
GossettDRWeaverWMMachAJ, et al. Label-free cell separation and sorting in microfluidic systems. Anal Bioanal Chem2010; 397(8): 3249–3267.
12.
FarahiniaAZhangWJBadeaI. Novel microfluidic approaches to circulating tumor cell separation and sorting of blood cells: a review. J Sci Adv Mater Devices. Epub ahead of print 26March2021. DOI: 10.1016/j.jsamd.2021.03.005.
13.
HouHWWarkianiMEKhooBL, et al. Isolation and retrieval of circulating tumor cells using centrifugal forces. Sci Rep2013; 3: 1259.
14.
LeeMGShinJHBaeCY, et al. Label-free cancer cell separation from human whole blood using inertial microfluidics at low shear stress. Anal Chem2013; 85(13): 6213–6218.
15.
ChenQLinJ-M. Microfluidic cell isolation and recognition for biomedical applications. In: LinJM (ed.) Cell analysis on microfluidics. Integrated analytical systems. Singapore: Springer, 2018, pp.95–118.
16.
LeeWCBhagatAASHuangS, et al. High-throughput cell cycle synchronization using inertial forces in spiral microchannels. Lab Chip2011; 11(7): 1359.
17.
LiangWLiuJYangX, et al. Microfluidic-based cancer cell separation using active and passive mechanisms. Microfluid Nanofluidics2020; 24(4): 1–19.
18.
ZhangMZhengAZhengZC, et al. Multiphase flow experiment and simulation for cells-on-a-chip devices. Proc IMechE, Part H: J Engineering in Medicine2019; 233(4): 432–443.
19.
ZborowskiMChalmersJJ. Rare cell separation and analysis by magnetic sorting. Anal Chem2011; 83(21): 8050–8056.
20.
LenshofAMagnussonCLaurellT. Acoustofluidics 8: applications of acoustophoresis in continuous flow microsystems. Lab Chip2012; 12(7): 1210.
21.
PødenphantMAshleyNKoprowskaK, et al. Separation of cancer cells from white blood cells by pinched flow fractionation. Lab Chip2015; 15(24): 4598–4606.
22.
WuZWillingBBjerketorpJ, et al. Soft inertial microfluidics for high throughput separation of bacteria from human blood cells. Lab Chip2009; 9(9): 1193.
23.
HosokawaMHayataTFukudaY, et al. Size-selective microcavity array for rapid and efficient detection of circulating tumor cells. Anal Chem2010; 82(15): 6629–6635.
24.
NiveditaNPapautskyI. Continuous separation of blood cells in spiral microfluidic devices. Biomicrofluidics2013; 7(5): 054101.
25.
SegréGSilberbergA. Radial particle displacements in poiseuille flow of suspensions. Nature1961; 189(4760): 209–210.
26.
Razavi BazazSMashhadianAEhsaniA, et al. Computational inertial microfluidics: a review. Lab Chip 202; 20(6): 1023–1048.
27.
NasiriRShamlooAAhadianS, et al. Microfluidic-based approaches in targeted cell/particle separation based on physical properties: fundamentals and applications. Small2020; 16(29): 2000171.
28.
KarabacakNMSpuhlerPSFachinF, et al. Microfluidic, marker-free isolation of circulating tumor cells from blood samples. Nat Protoc2014; 9(3): 694–710.
29.
AbdullaALiuWGholamipour-ShiraziA, et al. High-throughput isolation of circulating tumor cells using cascaded inertial focusing microfluidic channel. Anal Chem2018; 90(7): 4397–4405.
30.
LeeMGShinJHChoiS, et al. Enhanced blood plasma separation by modulation of inertial lift force. Sens Actuators B Chem2014; 190: 311–317.
31.
CatarinoSORodriguesROPinhoD, et al. Blood cells separation and sorting techniques of passive microfluidic devices: from fabrication to applications. Micromachines2019; 10(9): 593.
32.
GrassilliE. A microfluidic device for label-free sorting of circulating tumor cells. Chicago, IL: University of Illinois at Chicago, 2018.
33.
ZhouYMaZAiY. Sheathless inertial cell focusing and sorting with serial reverse wavy channel structures. Microsyst Nanoeng2018; 4(1): 1–4.
34.
BayarehMMortazaviS. Binary collision of drops in simple shear flow at finite Reynolds numbers: geometry and viscosity ratio effects. Adv Eng Softw2011; 42(8): 604–611.
35.
BayarehMMortazaviS. Three-dimensional numerical simulation of drops suspended in simple shear flow at finite Reynolds numbers. Int J Multiph Flow2011; 37(10): 1315–1330.
36.
LiuNPetchakupCTayHM, et al. Spiral inertial microfluidics for cell separation and biomedical applications. In: TokeshiM (ed.) Aplications of microfluidic systems in biology and medicine. bioanalysis (advanced materials, methods, and devices). Singapore: Springer, 2019, pp.99–150.
37.
YoonDHHaJBBahkYK, et al. Size-selective separation of micro beads by utilizing secondary flow in a curved rectangular microchannel. Lab Chip2009; 9(1): 87–90.
38.
DeanWR. LXXII. The stream-line motion of fluid in a curved pipe (second paper). London Edinburgh Dublin Philos Mag J Sci1928; 5(30): 673–695.
39.
NiveditaNLigraniPPapautskyI. Dean flow dynamics in low-aspect ratio spiral microchannels. Sci Rep2017; 7: 1–10.
40.
KuntaegowdanahalliSSBhagatAASKumarG, et al. Inertial microfluidics for continuous particle separation in spiral microchannels. Lab Chip2009; 9(20): 2973–2980.
41.
WarkianiMEKhooBLWuL, et al. Ultra-fast, label-free isolation of circulating tumor cells from blood using spiral microfluidics. Nat Protoc2016; 11(1): 134–148.
42.
SajeeshPSenAK. Particle separation and sorting in microfluidic devices: a review. Microfluid Nanofluidics2014; 17(1): 1–52.
43.
HejazianMLiWNguyenNT. Lab on a chip for continuous-flow magnetic cell separation. Lab Chip2015; 15(4): 959–970.
44.
PappasD. Microfluidics and cancer analysis: cell separation, cell/tissue culture, cell mechanics, and integrated analysis systems. Analyst2016; 141(2): 525–535.
45.
ChenKangfuFanZ. Hugh. “Introduction to Microfluidics.” Circulating Tumor Cells: Isolation and Analysis; FanZH, Ed.; John Wiley & Sons, Inc.: Hoboken, NJ, USA (2016): 33–50.
46.
MihandoustARazavi BazazSMaleki-JirsaraeiN, et al. High-throughput particle concentration using complex cross-section microchannels. Micromachines2020; 11(4): 440.
47.
NgoILLaiTKChoiHJ, et al. A study on mixing performance of dean flows through spiral micro-channel under various effects. Phys Fluids2020; 32(2): 022004.
48.
WarkianiMEGuanGLuanKB, et al. Slanted spiral microfluidics for the ultra-fast, label-free isolation of circulating tumor cells. Lab Chip2014; 14(1): 128–137.
49.
RafeieMZhangJAsadniaM, et al. Multiplexing slanted spiral microchannels for ultra-fast blood plasma separation. Lab Chip2016; 16(15): 2791–2802.
50.
ShirinyABayarehM. Inertial focusing of CTCs in a novel spiral microchannel. Chem Eng Sci2021; 229: 116102.
51.
BayarehMAshaniMNUsefianA. Active and passive micromixers: a comprehensive review. Chem Eng Process2020; 147: 107771.
52.
ZabetianMSaidiMSShafiiMB, et al. Separation of microparticles suspended in a minichannel using laser radiation pressure. Appl Opt2013; 52(20): 4950.
53.
JackRM. The study of pancreatic circulating tumor cells via isolation with an integrated microfluidic immunomagnetic (IMI) device, http://deepblue.lib.umich.edu/handle/2027.42/135916 (2016, accessed 16 May 2021).
54.
ShiJWuBLiS, et al. Shear stress analysis and its effects on cell viability and cell proliferation in drop-on-demand bioprinting. Biomed Phys Eng Express2018; 4(4): 045028.
