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Advances in isolation and detection of circulating tumor cells based on microfluidics

Dan Zou, Daxiang Cui()
Institute of Nano Biomedicine and Engineering, Shanghai Engineering Research Center for Intelligent Instrument for Diagnosis and Therapy, Department of Instrument Science & Engineering, School of Electronic Information and Electrical Engineering, National Center for Translational Medicine, Collaborative Innovational Center for System Biology, Shanghai Jiao Tong University, Shanghai 200240, China
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Abstract

Circulating tumor cells (CTCs) are the cancer cells that circulate in the peripheral blood after escaping from the original or metastatic tumors. CTCs could be used as non-invasive source of clinical information in early diagnosis of cancer and evaluation of cancer development. In recent years, CTC research has become a hotspot field wherein many novel CTC detection technologies based on microfluidics have been developed. Great advances have been made that exhibit obvious technical advantages, but cannot yet satisfy the current clinical requirements. In this study, we review the main advances in isolation and detection methods of CTC based on microfluidics research over several years, propose five technical indicators for evaluating these methods, and explore the application prospects. We also discuss the concepts, issues, approaches, advantages, limitations, and challenges with an aim of stimulating a broader interest in developing microfluidics-based CTC detection technology.

Keywords

Circulating tumor cellsisolation and detectionmicrofluidics

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Cancer Biology & Medicine
Volume 15 Issue 4,
November 2018
Pages 335-353
DOI: 10.20892/j.issn.2095-3941.2018.0256
Cite this article:
Zou D, Cui D. Advances in isolation and detection of circulating tumor cells based on microfluidics. Cancer Biology & Medicine, 2018, 15(4): 335-353. https://doi.org/10.20892/j.issn.2095-3941.2018.0256
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Five key parameters of summarized methods

Capture ratePurity (leukocytes elimination)ThroughputBiocompatibilityClinical studiesReferece
Cell line/mediumEfficiencyCancer typeLOD
YFP+ cells/whole blood77%(97.3 ± 1.2)%0.5 mL/h-Spiked tumor cells1 cell/million WBCs 53
H209 lung cancer cells/whole blood(70.5 ± 5.2)%(91.5 ± 5.6)%0.5 μL/min--- 2
MCF-7 cells/whole blood(87 ± 13)%~(93 ± 3)%-50 μL/min(58 ± 3)%~(74 ± 20)%EDTA anticoagulated whole blood samples4–168 CTCs/20 patients1–7 CTC clusters/10 patients 14
ECTCs/PBSECTCs/whole blood(71.9 ± 4.2)%(67.4 ± 0.7)%(2.7 ± 1.3)%1 mL/12 min(82.1 ± 2.1)% (viability reduction)Colorectal tumor cells3 CTCs at all six samples 56
MCTCs/PBSMCTCs/whole blood(71.3 ± 4.5)%(66.6 ± 6.4)%(80.5 ± 2.5)% (viability reduction)Healthy donorsNone
MCF-7(96.3 ± 1.5)%85.9%150 μL/min--- 60
MDA-MB-231(81.2 ± 3.5)%82.8%
SKOV3 cells/HL-60 or K562 cells66.84% or 66.81%--92.7%SKOV3 cells/human whole blood37.35%–61.3% 66
A549 cells/diluted human blood(58.0 ± 19.7)%-1 μL/min--- 73
CEM, Ramons and DAPI cells80%80%---- 75
MCF7 cells/10ⅹ diluted blood25%–35%(35.1 ± 7.3)%>10 mL/h56%Stage IV NSCLC- 21
BGC823, HCT116, PC3/DMEM medium(93.7 ± 3.2)%---BGC823/human blood7.30 ± 7.29 CTCs/2 mL 77
BGC823, HCT116, PC3/blood(91.0 ± 3.0)%
OECM-1 cells/PBMCs-(34.8 ± 14.0)%(in clinical tests)--Head-and-neck cancer- 78
A549/PBS-(97.07 ± 2.79)%1 mL/h-Pancreatic, lung, breast and colon cancer283.3 CTC-like cells/11 patients 79
HCC cells3%–93%99.9%Within 30 min/mL92.3%HCC3 CTC subtypes/one sample80
MCF-7 cells(98.1 ± 0.8)%59.5%-(93.8 ± 0.1)%MCF-7 cells/healthy blood5 cells/mL81
ATCC, Manassas, VA92.9%11.7%6 mL/h(80.8 ± 2.4)%NSCLC1165 CTCs/6.5 mL369 CTCs/5.5 mL48
HeLa cells92.7%43.4%Within 30 min/mL97.7%Ovarian, cervical, breast cancer1–16 CTCs/mL82
HCT116 cells(93.92 ± 3.92)%>75%->90%--83
MCF-7 cells(93.49 ± 3.03)%80%
MCF-7 cells/ whole blood50%–70%--(95 ± 3)% in the release group--84
H358/blood(83.6 ± 7.6)%-5 mL/h(89.8 ± 6.4)%Lung cancer8.6 CTCs/mL85
SW620/blood(81.3 ± 5.3)%(85.2 ± 7.0)%Colorectal cancer19.4 CTCs/mL
PC3, MCF-7 and NCI-H1650 cells85%–100%-1–3 mL/hhighLung cancer-86
HeLa, MCF-7, K562>85.8%>86.1%1.89×109 cells/min---31
MCF-7, MDA-MB231, MDA-MB-436, HCC78, AGS(95.9 ± 3.1)%->3 mL/mingoodBreast cancer patients stomach cancer patients0–540 CTCs/7.5 mL2–485 CTCs/7.5 mL87
Melanoma CTCs, LM-MEL-33 cells(70.2 ± 6)%-Within 50 min-LM-MEL-33cells79 cells/7.5 mL88
PANC-1 cells(91.99 ± 4.94)%>80%N*50 μL/min---89
A549 cell line-(85.6 ± 4.5)%100 μL/h---90
LNCaP89%>92%200 μL/min---57