Table 2 Summary of analytical performance of microfluidic devices applied to real samples screening from lung cancer

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]