Recent Advances in Microfluidic Platform for Physical and Immunological Detection and Capture of Circulating Tumor Cells
Abstract
:1. Introduction
2. Fabrication of Microfluidic Devices for the Isolation of CTCs
2.1. Additive Manufacturing
2.2. Etching Technique
2.3. Mold Punching Technique
2.4. Photolithography Technique
2.5. Printing Technique
2.6. Overall Summary of the Fabrication Process
3. Isolation of Circulating Tumor Cells (CTCs) by Microfluidic Devices
3.1. Size-Based Isolation
3.2. Inertial Focusing Microchannel-Based Isolation
3.3. Dielectrophoresis-Based Isolation
3.4. Magnetic Field-Based Isolation
3.4.1. Immunomagnetic (Label)-Based Isolation
3.4.2. Label-Free-Based Magnetic Isolation
3.5. Acoustic-Based Isolation
3.6. Combined Method-Based Isolation
3.7. Electrochemical-Based Isolation
3.8. Biological Interaction-Based Isolation
3.9. Overview of Microfluidic Device Performance for the Isolation of Circulating Tumor Cells
4. Conclusions and Prospects
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Isolation Method | Device Fabrication | Device Dimension | Flow Rate | Efficiency | Cancer Cell Lines | Ref. |
---|---|---|---|---|---|---|
Size-based isolation | ||||||
Size and deformability | Double-layer photolithography | L = 500 μm T = 23 μm | 2.5 mL/h | ~97% | LM2 MDA-MB-231 | [93] |
Size | Wet etching technique and thermal bonding technique | L = 22 mm H = 40 μm | 200 μL/min | 85% | BGC823, H1975, PC-3, SKBR3 | [82] |
Size-based PDMS microflitration membrane | Photolithography | T = 60 μm | 10 mL/h | >90% | A549, SK-MES-1, H446 | [90] |
Size | Photolithography | Main channel L = 80 µm; Main channel L = 50 µm H = 50 µm | 10 mL/h | 82% | SKBR3, MCF-7, MDAMB231 | [105] |
Inertial focusing microchannel-based isolation | ||||||
Label-free, inertial migration of cells | Photolithography | L = 20 mm W = 150 µm H = 50 µm | 300 µL/min | >99% | H460, HCC827 | [62] |
Rotation-induced inertial lift force | photolithography | W = 100, 200, 400 µm D = 30 µm | 9 µL/min | 90% | U87 | [126] |
Dean vortex flow, inertial lift force | Photolithography | - | 1.7 mL/min | 54% | FaDu, CAL27, RPMI2650, UD-SCC9 HNC cells, MDA-MB-468 | [120] |
Inertial and Dean drag forces | Photolithography | W = 500 μm H = 170 μm | 100 μL/min | ≥85% | MDA-MB-231, MCF-7, T24 | [127] |
Inertial microfluidics and Dean flow physics | Photolithography | L = 9.75 mm W = 350 µm | 400–2700 μL/min | >94% | MDA-MB-231, Jurkat, K562, HeLa | [128] |
Size-dependent lateral migration | Photolithography | Capillary inner and outer diameter = 50 and 360 μm; H = 200 μm L = 5 and 1 cm | 200 μL/min | 94% | MCF-7 | [129] |
Self-amplified inertial-focused (SAIF) separation | Photolithography | Zigzag channel W = 40 μm; First expansion region W = 0.84 mm; Second expansion region W = 1.64 mm; H = 50 μm | 0.4 mL/min | ~80% | A549, MCF-7, HeLa | [121] |
Vortex and inertial cell focusing lift force | Photolithography | L = 1000 μm W = 40 μm H = 70 μm; Trapping zone L, W = 720, 230 μm | 8 mL/min | 83% | MCF-7 | [130] |
Inertial lift force and Dean drag force | Photolithography | L = 5.5 mm W = 130 μm H = 500 μm | 1 mL/min | 90% | MCTC | [131] |
Dielectrophoresis-based isolation | ||||||
Optically induced dielectrophoretic (ODEP) force | Metal mould-punching | Main channel, L = 25 mm, W = 1000 μm, H = 100 μm; Side channel, L = 15 mm, W = 400 μm, H = 100 μm | 2.5 μL/min | 41.5% | PC-3 | [135] |
Dielectrophoresis at wireless bipolar electrode (BPE) array | Photolithography | L = 2.95 mm W = 200 µm H = 25 µm | 20 μm/s | 96% | MDA-MB-231, Jurkat E6-1 T | [136] |
Dielectrophoresis (DEP) force | Photolithography and wet etching | L = 7 mm H = 50 µm | 100 µL/min | 92 ± 9% | NCI-H1975 | [137] |
Optically induced dielectrophoresis (ODEP) | Metal mould-punching | Main channel, L = 2500 µm, W = 1000 μm, H = 60 μm; Side channel, L = 2500 μm, W = 400 μm, H = 60 μm | - | 81.0 ± 0.7% | PC-3, SW620 | [85] |
Magnetic field-based isolation | ||||||
Immunomagnetics and size-based filtration | Photolithography | T = 50 μm | 2 mL/min | ~89% | MCF-7 | [96] |
EpCAM-specific conjugation of MNPs | Photolithography | Microchannel W = 250 μm; Trapping site H = 400 μm, W = 100 μm | 150 µL/min | ~81.2–96.3% | MDA-MB-231, MCF-7 | [89] |
EpCAM-based positive method and CD45/CD66b-based negative method by lateral magnetophoresis | Photolithography | Free-bead capture microchannel, L = 42.5 mm, W = 1 mm, H = 50 µm; Lateral magnetophoretic microchannel, L = 42.5 mm, W = 2.8 mm, H = 100 µm | 2 mL/h and 3.2 mL/h | 83.1% | MDA-MB-231, PC-3, SKBR3, MCF-7 | [140] |
Magnet deformability | Photolithography | L = 49,000 µm W = 10,000 µm | 3 mL/h | 90% | HCT116, SW480, MCF-7 | [97] |
Immunomagnetic technique | Photolithography | L = 9 mm W = 1 mm | - | 97–107% | SKBR3, PC-3, Colo205 | [99] |
Magnetic-ranking cytometry and phenotypic profiling of CTCs | Photolithography | L = 8.75 cm H = 50 µm | 500 µL/h | >90% | SKBR3, PC-3, MDA-MB-231 | [141] |
MNP-labeled aptamers | Photolithography | - | 25 mL/h | ~79% | PC-3, SKBR3 | [142] |
Magnetic-bead-mediated dual-antibody functionalised microfluidics | Photolithography | - | 0.8 mL/h | >85% | LnCAP and LnCAP-EMP | [143] |
Cell size difference in ferrofluids under permanent magnetic influence | Photolithography | L = 2.54 mm W, H = 635 µm | 8 µL/min | >99% | HeLa | [144] |
Ferrodynamic cell separation | Photolithography | L = 4.94 cm W = 900 µm | 6 mL/h | ~92.9% | H1299, A549, H3122, PC-3, MCF-7, HCC1806 | [145] |
Acoustic-based isolation | ||||||
Cell size difference in ferrofluids | Photolithography | L = 5.81 cm W = 900 µm | 20 µL/min | 82.2% | A549, H1299, MCF-7, MDA-MB-231 | [146] |
Lateral cavity acoustic transducers | Photolithography | W = 750 µm H = 100 µm | 25 µL/min | 94% | Breast, bone, lung cancer cells | [103] |
Hydrodynamic and SAW focusing separation | Photolithography | - | 7.5 mL/h | >86% | MCF-7, HeLa, PC-3, LNCaP | [150] |
Interdigital transducers (IDTs) and focused interdigital transducers (FIDTs) generating standing SAWs and travelling pulsed SAWs | Photolithography | W = 65 µm H = 50 µm | 0.3 µL/min | ~90% | U87 | [151] |
Acoustic impedance contrast | Photolithography and deep reactive ion etching (DRIE) | L = 20 mm W = 380 µm H = 200 µm | 20–60 µL/min | >86% | HeLa, MDA-MA-231 | [152] |
Microvortices generated by acoustic vibration | Photolithography | L = 50 mm W = 40 mm H = 200 µm | 10 µL/min | >90% | DU145 | [153] |
Continuous flow acoustophoretic negative selection | Photolithography | Maun channel, L = 20 mm, W = 375 µm, H = 150 µm; Sub channel, L = 10 mm, W = 300 µm, H = 150 µm | 100, 400 µL/min | >98% | MCF-7, DU145 | [154] |
Combined method-based isolation | ||||||
Inertial and magnetic method | Photolithography | W = 400 µm H = 80 µm | 1000 µL/min | ~95% | MCF-7 | [107] |
Vortex trapping and impedance cytometry | - | L = 1 cm H = 70 µm | 100 µL/min | ~ 98% | MCF-7, LoVo, HT-29 human colon cells, | [95] |
Inertial hydrodynamic forces and bifurcation law | CNC micromachining | W = 0.26 mm H = 0.2 mm | - | 85% | MCF-7 | [155] |
Inertial and deformability-based principle | Photolithography | L = 1–1.5 cm W = 400, 300, 200 µm | 80 mL/h | >90% | MCF-7 | [156] |
Integrated device with acoustofluidic label-free separation and direct dielectrophoretic cell trapping | Photolithography | L = 2.3 cm W = 375 µm H = 150 µm | 80, 160 µL/min | ~76% | DU145 | [157] |
Inertial-ferrohydrodynamic cell separation | Photolithography | H = 60 µm | ~60 mL/h | 94.8% | H1299, MDA-MB-231, MCF-7, H3122 | [158] |
Micropore-arrayed filtration and magnetic bead-functionalised antibody-mediated detection | Molding technique | Micropore L, W = 20 mm, diameter = 10 µm | - | ~85% | PC-9 | [115] |
Lateral cavity acoustic transducers (LCAT) and biomarker-based immuno-labelling | Photolithography | Main, side channel W = 500, 100 µm H = 100 µm | 25 µL/min | ~100% | MCF-7, SKBR3 | [159] |
Electrochemical isolation | ||||||
Antibody-mediated electrochemical release and lysis | Photolithography | L = 40 mm W = 20 mm | 1 mL/h | 85–100% | PC-3, MCF-7, NCl-H1650 | [91] |
Electrochemical detection and electric-filed influenced hydrodynamic flow | Screen printing | W = 95 ± 2.5 µm H = 15 ± 1.5 µm | 5 µL/min | 92 ± 0.5% | HEK-293, HeLa | [116] |
Biological interaction-based isolation | ||||||
EpCAM-expressing cells using antibody-coated microposts | Photolithography | L = 20 mm H = 50–100 µm | 1.5–2.5 mL/h | 93% | PC-3 | [162] |
Aptamer-functionalized micropillars | Photolithography | - | 1 mL/h | 80% | W480 colorectal, LNCap prostate, KATO III gastric cancer cells, K-562 chronic myelogenous leukemia cells | [161] |
Anti-EpCAM-coated channel surface with herringbone grooves | Photolithography | L = 50 mm W = 2.1 mm H = 50 µm | 1 µL/s | >90% | L3.6pl, BxPC-3, MIAPaCa-2 | [163] |
EpCAM antibody-functionalised pillars | Laser direct-write technique | Micropost diameter = 420 µm; Pitch = 245 µm | 90 µL/min | ~76% | HEC-1A | [25] |
Combination of anti-EpCAM antibody and anti-N-cadherin antibody | Photolithography | L = 32 mm W = 34 mm H = 0.7 mm | 0.6 mL/h | 89.6% | SKOV-3 ovarian tumor cells | [104] |
Dual aptamer (EpCAM-5-1 and NC3S)-modified poly(lactic-co-glycolic acid) (PLGA) nanofiber | Electrospinning | L = 2 cm W = 1 cm H = 1 mm | 300 µL/min | 89–91% | A2780, OVCAR-3 | [164] |
Aptamer-immobilized microchannel | Photolithography | Cell channel W = 1 mm; DNA channel W = 0.5–1 mm H = ~25 µm | 5 µL/min | - | HeLa, CAOV-3 | [106] |
AlGaN/GaN HEMT biosensor array | Photolithography | L = 22 mm W = 13 mm | - | - | HCT-8 | [165] |
Size-based and multiplex SERS nanovectors | - | Filter gap = 12 µm, H = 40 µm | 1 µL/min | ~87–93% | SKBR3, MCF7, and MDA-MB-231 | [166] |
Microchannel functionalised with anti-EpCAM | 3D printing | L = 2 cm | 1 mL/h | ~87–92% | MCF-7, SW480, PC-3, 293T | [81] |
Gelatin-coated Ni foam functionalised with anti-WpCAM | Ni foam surface modification | L = 20 mm W = 4 mm H = 1 mm | 50 µL/min | ~88% | MCF-7 | [167] |
Lateral displacement (DLD) and herringbone CTC chip functionalised with EpCAM and CD41 antibodies | Deep reactive ion etching | H = 150 µm | 1.14 ± 0.24 mL/h | 60–83% | Lung, breast, melanoma cancer cells | [168] |
EpCAM and CD133 antibodies functionalised hexagonal array of posts | Photolithography | L = 44.6 mm W = 16.9 mm H = 100 µm | 1 mL/h | 13.6–97.5% | HT-29, Panc-1, PC-3, Hs-578T, Capan-1 | [169] |
Microcavity array functionalised with anti-EpCAM | Photolithography | H = 200 ± 10 µm Microcavity L, W = 30, 8 µm | 0.1 mL/min | ~76–83% | MCF-7, SW620 | [170] |
Magnetic ranking cytometry and CTC surface marker expression | Photolithography | L = 5.4 cm W = 4.3 cm H = 50 µm, Radii of Ni magnet = 145–235 µm | 400 µL/h | >90% | LNCaP, PC-3, PC-3M | [171] |
Isolation by size of epithelial tumor cell (ISET) and microbeads assisting ISET | - | L = 4 mm W = 17 mm H = 300 µm | 1 mL/min | ~72–93% | MCF-7, KATO III, PC-3 | [172] |
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Bhat, M.P.; Thendral, V.; Uthappa, U.T.; Lee, K.-H.; Kigga, M.; Altalhi, T.; Kurkuri, M.D.; Kant, K. Recent Advances in Microfluidic Platform for Physical and Immunological Detection and Capture of Circulating Tumor Cells. Biosensors 2022, 12, 220. https://doi.org/10.3390/bios12040220
Bhat MP, Thendral V, Uthappa UT, Lee K-H, Kigga M, Altalhi T, Kurkuri MD, Kant K. Recent Advances in Microfluidic Platform for Physical and Immunological Detection and Capture of Circulating Tumor Cells. Biosensors. 2022; 12(4):220. https://doi.org/10.3390/bios12040220
Chicago/Turabian StyleBhat, Mahesh Padmalaya, Venkatachalam Thendral, Uluvangada Thammaiah Uthappa, Kyeong-Hwan Lee, Madhuprasad Kigga, Tariq Altalhi, Mahaveer D. Kurkuri, and Krishna Kant. 2022. "Recent Advances in Microfluidic Platform for Physical and Immunological Detection and Capture of Circulating Tumor Cells" Biosensors 12, no. 4: 220. https://doi.org/10.3390/bios12040220