Table 3.
Commercially available platforms for CTC detections based on their biophysical properties (label-free technologies).
| Device | Technology | Tumor Type | Clinical Value | Remarks | Ref. |
|---|---|---|---|---|---|
| Filtration | |||||
| ISET® (Rarecells Diagnostics) | Filter based isolation and enrichment (PCL based filters) | -Lung (NSCLC) -Breast -Melanoma -Hepatocellular carcinoma |
-Prognosis -Treatment regiment |
-High efficiency capture compared to CellSearch -Label-free (no need to use antibodies) -Detection limit: 1 CTC/mL -Sensitivity: 76.37% a -Specificity: 82.39% a |
[47,48] |
| MetaCell® system (MetaCell Ltd.) | size-based enrichment and separation | -Esophageal -Lung -Pancreatic |
-Diagnosis -Prognosis |
-Allows post-capture analysis and cell culture | [46] |
| Parylene filter (Circulogix) | Filter based isolation and enrichment | -Breast | -Diagnosis -Prognosis |
-Post-capture downstream analysis for enumeration and immunophenotypic characterization -Fixation prior to capture eliminates post capture functional assays (cell culture and protein extraction and analysis) -Studies have been assessed in preclinical setups -Detection limit: 25 CTCs/7.5 mL -Capture efficiency: ~90% |
[49] |
| ScreenCell® Cyto | Filter based size-exclusion separation and enrichment of CTC | -Melanoma | -Diagnostics -Treatment regimen (personalized medicine) |
-Post-capture analysis and cell culture -Allows microscopic examinations of collected CTC -Minimal studies have been assessed and all are preclinical |
[50] |
| CellSieve (Creatv MicroTech) | micofilter based isolation and enrichment | -Breast -Prostate |
-Prognosis -Diagnosis |
-High efficiency isolation compared to CellSearch technology -Post capture histo- and immune-phenotypic characterization of CTC |
[51] |
| Microfluidics | |||||
| Parsortix™ technology (Angle plc) | Microfluidic separation of CTC based on their size and deformability. Viable cells are released by reversing the flow. | -Ovarian | -Diagnosis | -Antigen-independent capture with subsequent molecular analysis -Minimal studies have been assessed and all are preclinical -Sensitivity: 92% b (in primary and relapse ovarian cancer) -Specificity: 100% b |
[52] |
| Density gradient separation | |||||
| RosetteSep™ CTC Enrichment Cocktail/EasyStep CD45 Depletion (STEMCELL Technologies) | Immunodensity negative selection for CTC using tetrameric antibody complexes that recognizes CD45, CD66b and glycophorin on WBC and RBC | -Pancreatic -Breast |
-Prognosis | Unwanted cells are targeted for removal with Tetrameric Antibody Complexes that pellets with RBCs | [53] |
| OncoQuick(Greiner BioOne, Frickenhausen, Germany) | Separation of erythrocytes and some leukocytes from CTC by porous membrane filtration followed by density-grade centrifugation for CTC enrichment | -Gastrointestinal cancer -Advanced breast cancer |
-prognosis | -Dual technology for separation of CTC based on size and buoyant density -High tumor cell rate recovery compared to other density-gradient techniques -Post-CTC capture processing is possible |
[54,55] |
| Cyttel | Negative immune-magnetic selection of WBC (CD45 antibody) followed by gradient centrifugation and slide smearing of isolated CTC | -Lung (NSCLC) | -Prognosis -Treatment regimen |
-High detection rate (bimodal identification of CTC: negative selection followed by in situ hybridization) |
[56] |
| AccuCyte–CyteFinder (RareCyte) | Automated rapid imaging of single rare cells, CTC in this case, preceded by density-based cell separation | -adenocarcinoma | -prognosis | -Dual technology platform for single-cell analysis -high sensitivity detection of CD positive CTC -ability to analyze RNA post capture and enrichment -minimal studies have been assessed and all are preclinical |
[57] |
| Functional Assays | |||||
| EPISPOT | Negative enrichment using CD45 depletion and short-term culture | -Breast | -Prognosis | -Allows CTC detection based on protein secretion -High sensitivity and specificity -Independent of tumor antigen phenotype capture -Allows quantification of CTC |
[58] |
| Vita-Assay (Vitatex) | Functional cell separation using density gradient centrifugation followed by preferential adhesion of CTC to collagen adhesion matrix (CAM-enrichment). | -Prostate | -N.A. | -Allows CTC detection based on invasion properties -Low purity (0.5–35%) |
[59] |
| Imaging | |||||
| CytoTrack | The blood sample is speed on a glass disc that is rotated at high speed. Fluorescently labelled cells against EpCAM are scanned with laser beam | -Breast | -Diagnosis | -Analyzes 100M cells/min -Low recovery rates of CTC |
[60] |
| FASTcell (SRI) | Fiber optic array scanning technology (FAST) | -Breast | -Prognosis -Guided therapy (personalized treatments) |
-High sensitivity of CTC detection based on biomarkers expression -Allows simultaneous detection of multiple tumor specific biomarkers -Analyzes 25M cells/min |
[61] |
| Epic (Epic Sciences) | RBC lysis and IF for CK, CD45, and DAPI and other markers followed by high-definition imaging | -Prostate | -prognosis -treatment regimen |
-Unbiased screen of all blood nucleated cells for detection of individual CTCs and clusters | [62] |
| ImageStream® (Amnis) | Immunogenetic sorting of blood followed by flow cytometery and fluorescent microscopy for CTC enumeration. | -Hepatocellular carcinoma | -Diagnosis | -Low precision when CTC count is low -Analyzes 5000 cells/s -Sensitivity: 68.75% c -Specificity: 72.97% c with likelihood ratio of 2.544 |
[63] |
| Dielectrophoresis | |||||
| DEPArray™ (Silicon Biosystems) | Moving dielectrophoretic cages for cell capture coupled with sanger sequencing | -Breast | -Tumor and treatment monitoring -Prognosis |
Isolation of single CTCs for dowstream gene analysis | [64] |
| ApoStream® (ApoCell) | Detection of CTC based on dielectrophoric Field-flow Fractionation (DEP-FFF) in a microfluidic chamber | Breast | -N.A. | -Detection independent of EpCAM expression; useful for viability analysis and culture -processes more than 10 mL/h -Studies have been assessed in preclinical setups |
[65] |
| Inertial focusing | |||||
| Vortex | CTC extraction using microscale vortices and inertial focusing | -Breast -Lung |
-Prognosis -Diagnosis -Treatment regimen |
-Fast processing time of samples (20 min per 7.5 mL of blood) -High CTC integrity and purity post-detection (>50% up to 94%) |
[66] |
| ClearCell® FX (Clearbridge BioMedics) | Separation of CTC based on size using Dean Flow Fractionation (DFF) (inertial focusing) | -Lung | -Molecular diagnostics | -Captured CTC can be analyzed post-capture and enrichment in culture -Low recovery rates -Label free (no need for antibody use) -Single step isolation and retrieval process from any type of body fluids -Processes 1–1.5 mL/min -Sensitivity: 80.4% c -Specificity: 85.7% c |
[67] |
N.A.: not available; a Agreement with presence of tumor biomarkers (i.e., CEA, NSE, Cyfra21-1) using ELISA; b Utilizing a cut-off threshold value for the expression of 30 genes to retain 100% specificity; c Obtained by ROC curve analysis (cut-off = 3.5 CTCs).