Review Article

Benchtop Technologies for Circulating Tumor Cells Separation Based on Biophysical Properties

Table 1

Performance specification of physical based CTCs separation methods.

MethodTarget of cancer cell lineCTCs separation efficiency Cell viabilityPurityFlow rate (whole blood/time)References

Centrifugation (Ficoll-Hypaque)Human breast cancer cells (MCF-7)~46%90%Lara et al. [26]

Centrifugation (OncoQuick)MCF-7, ZR-75-1, and Hs578TMCF-7: 57.89%
ZR-75-1: 59.80%
Hs578T: 57.14%
Königsberg et al. [27]

Microfiltration (pore type)Human breast cancer cells (MCF-7, MDA-MB-453, and SK-BR-3) and human prostate adenocarcinoma cancer cells (LNCAP, PC3)7 μm pore filter:
(i) 98 ± 2% (fixed MCF-7 cells)
(ii) 85 ± 3% (unfixed MCF-7 cells)
8 μm pore filter:
(i) 73 ± 13% (fixed MCF-7 cells)
(ii) 50 ± 14% (unfixed MCF-7 cells)
~10 mL/min (concentration: 104 cells/mL)Adams et al. [10]
Human prostate cancer PC-3 cells>90%>90% Lu et al. [28]

Microfiltration (3D membrane)Human prostate adenocarcinoma cell line (LNCaP) and human breast adenocarcinoma cell line (MCF-7)>86%85%~3.75 mL/min (concentration: 106 cells/mL)Zheng et al. [11]
Human gastric carcinoma cell line (NCI N-87)>85%2.5 mL/min (concentration: 2.5 × 105 cells/mL)Yusa et al. [12]
Breast cancer cell lines: MCF-7, MDA-MB-23178%–83%71%–74%— 
(1 μ/cancer cells spiked into 1 mL of undiluted blood)
Zhou et al. [13]

Microfiltration (weir-type)Human A431 cancer cells>95%>98%~5 mL/hr (10 tumors cells/mL of whole blood)Chung et al. [15]

Microfiltration (pillar type)MCF-7, SK-BR-3, J82, T24, RT4, and LNCaP>90%≥93%>90%Lin et al. [29]

Microfiltration (hetero-packed bead type)Human breast cancer cells (MCF-7)21%–40%0.2 mL/hr (concentration: 106/mL)Arya et al. [30]

Dielectrophoresis (planar configuration)Human breast cancer cells (MCF-7)(i) MCF-7: 75.18%
(ii) RBC: 99.24%
(iii) WBC: 94.23%
(i) MCF-7: 16.24%
(ii) RBC: —
(iii) WBC: —
~250 μL/sMoon et al. [31]

Dielectrophoresis (contactless mode)Human cervical carcinoma cell (HeLa cells)64.5%— 
(concentration in diluted solution: 2.5 × 105 HeLa cells/mL, 3.25 × 106 RBC cells/mL, 3.25 × 103 WBC cells/mL)
Huang et al. [19]

AcoustophoresisProstate cancer cell line:
 DU145, PC3, and LNCAPPFA-fixed cell sample 
(i) DU145 and PC3:
85.4% at  J/m3, 96.6% at  J/m3
(ii) LNCaP:
55.5% at  J/m3, 78.8% at  J/m3
Non-PFA-fixed cell sample 
(i) DU145:
36.1% at  J/m3, 83.7% at  J/m3
No significant changes were observed for acoustophoresis treated and untreated samplesPFA-fixed cell sample 
(i) DU145 and PC3:
99.3% at  J/m3, 97.9% at  J/m3
Non-PFA-fixed cell sample 
(i) DU145:
99.5% at  J/m3, 93% at  J/m3
~450 μL/min (2.5 × 105 tumor cells/mL spiked with 10-fold diluted whole blood) Augustsson et al. [32]
 DU145, PC3, LNCAP, and VCaPThe average cell dead is <1% for DU145 and PC3, while ≤3% for LNCAP and VCaP ~100 μL/minBurguillos et al. [33]

Hydrodynamic sorting (pinched flow fractionation)MV3-melanoma cells100%~100%(i) 0.4% hematocrit: 66.6%
(ii) 4% hematocrit: 15.4%
(iii) 9% hematocrit: 5.5%
600 μL/h (concentration in diluted solution: 8 × 105 tumor cells/mL, 6 × 108 RBC cells/mL)Geislinger and Franke [34]

Hydrodynamic sorting (deterministic lateral displacement)Human breast cancer cell line: MDAMB231, MCF10A, and PC3≥85%≥95%10 mL/min (concentration:
107 cancer cells in 1 mL of blood diluted with buffer)
Loutherback et al. [22]

Hydrodynamic sorting (inertial lift force)MCF-7>85%>98%50%3 mL/hr (concentration: 10–100 CTCs/mL of diluted whole blood samples)Hou et al. [23]

Hydrodynamic sorting (inertia force)MCF-7, T24, and MDA-MB-231>80%>80%~4 log depletion of WBCs2.0 mL/min (500 tumour cells per 7.5 mL of whole blood)Warkiani et al. [35]

Hydrodynamic sorting (inertia force)MCF-7 cancer cells99.5%3 to 12 mL/h (processing 4.2 × 107 cells/min to 2 × 107 cells/min) Lee et al. [24]