Table 1.
Microfluidic rare cell separation applications based on positive and negative magnetophoresis.
| Cell type | Method | Surface marker | Magnetic element | Purity | Cell concentration | Capture rate | Throughput | Viability | References |
|---|---|---|---|---|---|---|---|---|---|
| STEM AND PROGENITOR CELLS | |||||||||
| Endothelial progenitor cells (EPCs) | PM -MNP internalization (positive enrichment) | NU | NdFeB permanent magnet | NR | NR | 40% | 0.3 mL h−1 | No difference between treated and untreated cells after 24 h in viability and tube formation function was reported | Kim et al., 2009 |
| Hematopoietic stem cells (HSCs) | PM -MNP labeling (positive enrichment) |
CD34 | Permanent magnet | NR | 5 × 107 cells mL−1 | 88% | 0.15 mL h−1 | NR | Wu et al., 2010 |
| Hematopoietic stem cells (HSCs) and endothelial progenitor cells (EPCs) | PM -MNP labeling(positive enrichment) |
CD133 | Electromagnetic wire | NR | HSC: ~6750 cells mL−1 EPC: ~1190 cells mL−1 | HSC: > 96% EPC: > 95% |
>14 mL h−1 | No adverse effect on cell viability | Plouffe et al., 2012 |
| Mouse lung multipotent stem cells (MLSCs) | PM -MNP labeling (negative and positive enrichment) |
CD45 (-) CD31 (-) FITC (+) |
Magnet | 96–99% | NR | NR | 1.2 mL h−1 | Good self-renewal and proliferation capacity was obtained | Zeng et al., 2015 |
| TUMOR CELLS | |||||||||
| Human colon adenocarcinoma cells (COLO205) and human breast cancer cells (SKBR3) |
PM - MNP labeling (positive enrichment) |
EpCAM | NdFeB permanent magnet | NR | 5–1,000 cells mL−1 (TC: RBC = ~1: 107- 109) |
COLO205: 90% SKBR3: 86% |
10 mL h−1 | NR | Hoshino et al., 2011 |
| Mouse metastatic breast cancer cells (M6C) | PM - MNP labeling (positive enrichment) |
EpCAM | NdFeB permanent magnet | <0.4% WBC capture | 2–80 cells mL−1 | ~90% | 1.2 mL h−1 | > 90% | Kang et al., 2012 |
| Breast cancer cells (MCF-7) and lung cancer cells (HCC827) |
PM -MNP labeling (positive enrichment) |
EpCAM | Permanent magnet | NR | ~10 cells mL−1 | ~80% | NR | NR | Yoo et al., 2016 |
| Human breast cancer cells (MCF-7 and MDA-MB-23) | PM -MNP labeling (positive enrichment) |
EpCAM | Permanent magnet | NR | 103- 105 cells mL−1 (MCF-7: MDA-MB-231 = 1:1) |
MCF-7: 95.7% MDA-MB-23: 79.3% |
3 mL h−1 | NR | Kwak et al., 2017 |
| Human acute monocytic leukemia cells (THP-1) | PM -MNP labeling (positive enrichment) |
CD45 | NdFeB permanent magnet | NR | 106 cells mL−1 | NR | 4.2 mL h−1 | NR | Huang et al., 2018 |
| Human colon cancer cells (COLO205) | PM -MNP labeling (positive enrichment) |
EpCAM | Permanent magnet + nickel micromagnets | NR | ~60 cells mL−1 | Increased by 19% compared to no-micromagnet condition | 2.5 mL h−1 | NR | Chen et al., 2015 |
| Breast cancer cells (SKBR-3) | PM -MNP labeling (positive enrichment) |
EpCAM | NdFeB permanent magnet + ferromagnetic nickel-iron wires | 97% | 7 × 101-6 × 104 cells mL−1 | 90% | 2–5 mL h−1 | 100% of the isolated cells were intact | Kim et al., 2013b |
| Breast cancer cells (MCF-7) | PM -MNP labeling (positive enrichment) |
EpCAM | NdFeB permanent magnet + ferromagnetic nickel-cobalt wires | NR | 1.25−2.5 × 105 cells mL−1 | 93% | 2.4–6 mL h−1 | NR | Park et al., 2015 |
| Breast cancer cells (MCF-7) | PM -MNP labeling (positive enrichment) |
EpCAM | NdFeB permanent magnet + ferromagnetic nickel-iron wires | 6.9–67.9% | 1–10 cells mL−1 | 99.08% | 4 mL h−1 | NR | Cho et al., 2016 |
| Human lung cancer cells (A549) | PM -MUNP labeling (positive enrichment) |
EpCAM | Permanent magnet + silicon wires | NR | 5 × 103 cells mL−1 | ~90% | ~1 mL h−1 | Re-collected cells showed almost the same morphology compared to control cells | Wang et al., 2015 |
| (i) Lung cancer cells (H-1650) (ii) Lung cancer cells (HCC827 and H-1650), breast cancer cells (MCF-7), human prostate cancer cells (LNCaP and PC-3) and human bladder cancer cells (T24) (EpCAM epxression levels: ~2000/cell to ~500,000/cell) |
PM -MNP labeling (positive enrichment) |
EpCAM |
NdFeB permanent magnet + nickel-iron coated magnetic sifter |
NR |
(i) 4–470 cells mL−1 (ii) 50-100 cells mL−1 (>90% for >100 k EpCAM/cell) |
H-1650: 95.7% HCC827, H-1650, MCF-7, LNCaP: 90% PC-3: 48%, T24: 17.7% |
10 mL h−1 |
Unchanged cell viability was obtained |
Earhart et al., 2014 |
| Human ovarian cancer cells (HeLa) | PM -MNP labeling (positive enrichment) |
EpCAM | Nickel-iron -based microstripline | NR | 106 cells mL−1 | 79% | 0.06 mL h−1 | 100% cell viability was obtained with cooling | Wong et al., 2016 |
| B lymphoid cells (Raji cell line) (target) T lymphoid cells (Jurkat cell line) (non-target) |
PM -in situ magnetic labeling (positive enrichment) |
CD19 | Cooled electromagnet coil + microcontact printed ferrofluidic dots | 96% | 2 × 106 cells mL−1 (Raji cells to total = 33%) |
94% | 3.6 × 104 – 3.6 × 105 total cells h−1 |
Viable cells with ability to move and divide were reported | Saliba et al., 2010 |
| Human lung cancer cells (A549) | PM - in situ magnetic labeling (positive enrichment) |
WGA modification | Magnetic solenoid coil + nickel micropillars | ~93% | 1.5 × 105 cells mL−1 | 62–74% | NR | NR | Liu et al., 2007 |
| Human T-lymphocytic leukemic cells (JM) and human ovarian cancer cell (HeLa) |
PM -MNP labeling (positive enrichment) |
CD4 | NdFeB permanent magnet | >90% | ~2 × 106 mL−1 | NR | ~3.6 × 105 cells h−1 | NR | Mizuno et al., 2013 |
| Breast cancer cells (MCF-7) | PM -MNP labeling (positive enrichment) |
EpCAM | NdFeB permanent magnets + | NR | 103−3.3 × 104 cells mL−1 | up to 88% | ~0.1 mL h−1 | NR | Kirby et al., 2015 |
| Lung carcinoma cells (H1299-GFP) | PM -MNP labeling (negative enrichment) |
CD45 | Permanent magnet | ~50% | 101-105 cells mL−1 | ~90% | 60 mL h−1 | >90% | Jiang et al., 2017 |
| Human ovarian cancer cells (HeLa) | PM -MNP internalization (positive enrichment) |
NU | NdFeB permanent magnet | NR | 5 × 105 cells mL−1 | NR | NR | NR | Pamme and Wilhelm, 2006 |
| Breast cancer cells (MDA-MB-231) |
PM -magnetic susceptibility difference (negative enrichment) |
NU | Permanent magnet +ferromagnetic nickel wire | NR | NR | 94.8% | 0.0025–0.0200 mL h−1 | NR | Han et al., 2006 |
| Breast cancer cells (SKBR3, MDA-MB-231) Prostate cancer cells (PC3-9) |
PM -MNP labeling (positive enrichment) |
EpCAM | Quadrupole magnetic circuit | >3.5-log purification resulted in 1,500 WBCs mL−1 | 200–1,000 cells mL−1 | SKBR3: 98.6 ± 4.3% MDA-MB-231: 77.8 ± 7.8% PC3-9: 89.7 ± 4.5% |
8 mL h−1 (3.6 × 1010 cells h−1) |
Viable cells were obtained | Ozkumur et al., 2013 |
| Human breast cancer cells (MCF10A and MCF10A-LBX1) | PM -MNP labeling (negative enrichment) |
CD45 CD15 |
2.5-log purification resulted in 32,000 WBCs mL−1 | MCF10A: 96.7 ± 1.9% MCF10A: 97.0 ± 1.7% |
|||||
| Human melanoma cells (WM164), breast cancer cells (MB231, SKBR3), human lung cancer cells (PC9) and prostate cancer cells (PC3-9) | PM -MNP labeling (negative enrichment) |
CD66b CD45 |
Permanent magnet | 3.8-log purification | ~103 cells mL−1 | 97% | 8 mL h−1 (3.6 × 1010 cells h−1) |
NR | Karabacak et al., 2014 |
| Human melanoma cells (SkMel28), lung cancer cells (H1650, H1975, H3122), prostate cancer cells (NCAP, PC3, PC3-9, VCAP) and breast cancer cells (MB231, MCF-7, SkBR) | PM -MNP labeling (negative enrichment) |
CD66b CD45 CD16 |
Magnetic circuit | Purification resulted in 445 WBC mL−1 | 19–5,000 cells mL−1 | 99.5% | 5.4−7.2 × 1010 cells h−1 | NR | Fachin et al., 2017 |
| Human colon cancer cells (HCT8) | PM -MNP labeling (negative enrichment) |
CD45 | Permanent magnet | Purification resulted in 83.99± 1.00% WBC depletion |
104 cells mL−1 | 70 ± 5% (for single round of depletion) |
NR | Unchanged cell viability when a pulsation frequency of 0.05 Hz was used | Luo et al., 2015 |
| Colorectal adenocarcinoma cells (HT29) | PM -MNP labeling (negative enrichment) |
CD45 | Magnet + layer of NdFeB magnetic grains | NR | 50- 250 cells mL−1 | 87–96% | 5 mL h−1 | NR | Chung et al., 2013 |
| Oncogenic human monocyte cells (U937) | NM | NU | NdFeB permanent magnet + nickel microstructure | >90% | 8 × 107 cells mL−1 (U937: RBC = 1:400) | NR | 105 cells h−1 | NR | Shen et al., 2012 |
| Breast cancer cells (MDA-MB-231), colorectal cancer cells (HCT116 and HT29), lung cancer cells (HCC827) and esophageal cancer cells (JHEsoAD1) | NM | NU | NdFeB permanent magnet | NR | NR | NR | No flow | Unchanged cell viability for long term cultivation in paramagnetic medium was reported | Durmus et al., 2015 |
| Breast cancer cells (MDAMB-231), lung cancer cells (A549), ovarian cancer cells (HEYA8) and prostate cancer cells (PC-3) |
NM | NU | NdFeB permanent magnet | NR | NR | NR | 0.36 mL h−1 | NR | Amin et al., 2017 |
PM, positive magnetophoresis; NM, negative magnetophoresis.
NR, not reported; NU, not used.
Capture rate, the ratio of the number of cells collected after separation to the total number of cells loaded to the chip.
Purity, the ratio of the number of target cells collected after separation to the total number of collected cells.