Table 2.
Summary of analytical performance of microfluidic devices applied to real samples screening from lung cancer
| Tumor type | Microfluidic device | Number of samples | Detection rate of CTCs | CTCs/ml (SD) | Additional tests | Refs. |
|---|---|---|---|---|---|---|
| NSCLC | CTC-Chip (affinity-based) | 55 (human) | – | Mean: 155/ml (236) | EGFR mutation test | [176] |
| Lung cancer early stage patients | Immunoaffinity-based microfluidic device | 19 (human) | 68% | 1–11/ml (3) | mRNA expression level determination | [177] |
| Cancer and non-cancer lung diseases | Microfluidic SiNW with MUNPs conjugated with anti-EpCAM | 21 (human) | ~ 90% | – | Immuno-fluorescence staining and imaging under the confocal fluorescence microscope | [109] |
| 344SQ and 393P | Nanoroughened adhesion-based capture of CTCs | 9 (mice) | Capture yields of > 80% | 0–1148/ml (−) | Positive staining of anti-cytokeratin and DAPI; negative staining of anti-CD45; and appropriate morphometric characteristics including cell size, shape, and nuclear size | [173] |
| Lung cancer | Ultra-high throughput microfluidic Vortex technology | 15 (human) | ~ 80% | 0.5–24.2/ml | Staining with DAPI, anti-CD45-PE, and FITC-conjugated CK cocktail against Pan-CK AE1/AE3, CK3-6H5, and CK CAM5.2 before imaging. Following CK staining, some samples were stained for granulocytes with CD66b-AlexaFluor647 (CD66b-AF647), or for EMT markers with anti EpCAM-FITC, anti-vimentin-AlexaFluor647 (VIM-AF647, Abcam), and anti N-Cadherin (NCAD-AF67, Abcam) | [175] |
| Advanced-stage metastatic non-small cell lung cancer |
Ultra-high-throughput spiral microfluidic Biochip |
5 (human) | 100% | 33–135/ml |
Immunofluorescence staining and Fluorescent Automated Cytometry System (FACS) Analysis |
[148] |
| Advanced stage metastatic lung cancers, patients with non-small cell lung cancer | Ultra High-Throughput Spiral Microfluidics | 35 (human) | 100% | 10–1535/ml | Immunophenotyping (Pan-cytokeratin/CD45, CD44/CD24, EpCAM), FISH (EML4-ALK) or targeted somatic mutation analysis. Ultra-sensitive mass spectrometry based system to highlight the presence of an EGFR-activating mutation in both isolated | [158] |
| Metastatic lung cancer | Inertial-based microfluidic cell sorter | 34 (human) | 90% | – | Immunostaining and CK-19 mRNA detection | [110] |
| Lung cancer | FAST disc | 35 (human) | 68.6% | 0–62/7.5 ml | Real-time polymerized chain reaction (PCR) | [150] |
| Lung cancer | Size-based microfluidic chip | 77 (human) | – | 1.85–68.45/ml | Immune-fluorescent staining combining an epithelial marker and a mesenchymal marker | [154] |
| Non-small cell lung cancer (NSCLC) patients | Label-free high-throughput microfluidic approach | 16 stage IV NSCLC (human) | 93.8% | – | Fluorescent staining (CK+/CD45-/DAPI+) and cytomorphological characteristics (large nuclear size > 9 μm and nuclear-to-cytoplasmic ratio > 0.8) to classify cells as CTCs | [178] |
| Lung cancer | Size-based microfluidic chip with contained array and filter channel array | 200 (human) |
Stage I (42.86%) Stage II (72.92%) Stage III (96.88%) Stage IV (96.49%) |
Stage I (5.0 ± 5.121/ml) Stage II (8.731 ± 6.36/ml) Stage III (16.81 ± 9.556/ml) Stage IV (28.72 ± 17.39/ml) |
Immunofluorescence staining, using epithelial marker (CK-FITC), DAPI and CD45-PE | [179] |
| NSCLC patients | Vortex HT chip | 22 (human) | – | 0.1 to 9.67 CTCs/ml | Immunostaining | [180] |
SiNW silicon nanowire array, MUNPs multifunctional magnetic upconversion nanoparticles, FAST fluid assisted separation technology