Table 2.
Overall methods for isolating CTCs
| Isolation principle | Example technology | CTC/cancer type | Advantages | Disadvantages | Ref |
|---|---|---|---|---|---|
| Size-based methods | |||||
| Membrane microfilters | ISET |
Non-small cell lung, colorectal cancers, melanoma |
+ High sensitivity + Isolation of CTC clusters |
-High loss of small cells | [71] |
| FAST | Colorectal, breast, stomach, lung cancers | KRAS mutation analysis | + High sensitivity | -High loss of small cells | [72] |
| Microfluidic technologies | ieSCI-chip | Breast cancer |
+ High capture efficiency + Fast isolation and processing |
-Limited sample volume -Slow flow rate |
[73] |
| Microfluidic technologies | Labyrinth | Non-small cell lung, liver cancers |
+ Isolation of clusters + Depletion of more than 95% of leukocytes + High cell viability |
-High loss of small cells | [74] |
| Immuno-affinity strategy (cell biological properties) | |||||
| Negative selection | RosetteSep | Liver, breast cancers |
+ Isolation of CTC clusters + Fast isolation (40 min) + CTC marker-free isolation |
-High number of untargeted cells | [75] |
| Positive selection | CELLSEARCH® (Janssen Diagnostics) | Metastatic breast cancer, Colorectal, Prostate |
+ FDA-approved + marker's dependence + Most clinically validated capture technique + high Specificity |
-Low purity of captured CTC -low Sensitivity -cannot Identify EMT |
[76] |
| Positive selection | MACS system (Miltenyi Biotec) |
Non-small-cell lung cancer (NSCLC) Breast (HER2 +) |
+ Identifies EpCAM negative CTCs + Can combined with leukocytes depletion |
-Expensive -Low cell viability -Dependence on expressed proteins -Hard to automate |
[77] |
| Functional Assays | |||||
| Secretory Protein | EPISPOT | Breast cancer |
+ High sensitivity / specificity + Independent Ag phenotype + Allows CTC quantifying |
-Just allows CTC detection based on protein secretion | [78] |
| Adhesive CTC | Vita-Assay (Vitatex) | Prostate | + Allows detection of invasive n CTC | -Low purity | [79] |
| Dielectrophoresis | |||||
| Dielectrophoretic cage | DEPArray™ (Silicon Biosystems) | Breast | Isolation of single CTCs for downstream gene analysis | -High loss of small cells | [80] |
| DEP-FFF | ApoStream® (ApoCell) | Breast | + Independent of EpCAM + useful for viability analysis and culture | Processes more than 10 mL/h | [81] |
| Combined methods | |||||
| Positive selection and microfluidic approaches | RBC-chip | Colorectal cancer |
+ High sensitivity and specificity + High viability |
-Isolation of only EpCAM-positive CTCs | [82] |
| Positive selection and microfluidic approaches | Herringbone-Chip | Lung cancer |
+ One step method + High capture efficiency + Isolation of clusters |
-Isolation of only EpCAM- and EGFR-positive CTCs | [83] |
| Non-microfluidic approaches and cell biological properties | AccuCyte-RareCyte/PIC & RUN | Prostate, breast, lung cancers |
+ High viability + High capture efficiency + provide CTC culturing |
-The presence of false-positive CTCs | [84] |