A simple pyramid-shaped microchamber towards highly efficient isolation of circulating tumor cells from breast cancer patients
- 194 Downloads
Isolation and detection of circulating tumor cells (CTCs) has showed a great clinical impact for tumor diagnosis and treatment monitoring. Despite significant progresses of the existing technologies, feasible and cost-effective CTC isolation techniques are more desirable. In this study, a novel method was developed for highly efficient isolation of CTCs from breast cancer patients based on biophysical properties using a pyramid-shaped microchamber. Through optimization tests, the outlet height of 6 μm and the flow rate of 200 μL/min were chosen as the optimal conditions. The capture efficiencies of more than 85% were achieved for cancer cell lines (SKBR3, BGC823, PC3, and H1975) spiked in DMEM and healthy blood samples without clogging issue. In clinic assay, the platform identified CTCs in 13 of 20 breast cancer patients (65%) with an average of 4.25 ± 4.96 CTCs/2 mL, whereas only one cell was recognized as CTC in 1 of 15 healthy blood samples. The statistical analyses results demonstrated that both CTC positive rate and CTC counts were positive correlated with TNM stage (p < 0.001; p = 0.02, respectively). This microfluidic platform successfully demonstrated the clinical feasibility of CTC isolation and would hold great potential of clinical application in predicting and monitoring the prognosis of cancer patients.
KeywordsCirculating tumor cells (CTCs) Cell isolation Pyramid-shaped microchamber Microfluidic chip Breast cancer
This work was supported in part by following foundations: (1) National Natural Science Foundation of China (81372358, 81527801 and 51303140); (2) Natural Science Foundation of Hubei Province, China (2014CFA029); (3) Colleges of Hubei Province Outstanding Youth Science and Technology Innovation Team (T201305); (4) Applied Foundational Research Program of Wuhan Municipal Science and Technology Bureau (2015060101010056).
- Q.Q. Huang, B. Cai, B.L. Chen, L. Rao, Z.B. He, R.X. He, F. Guo, L.B. Zhao, K.K. Kondamareddy, W. Liu, S.S. Guo, X.Z. Zhao, Adv. Healthcare Mater. 5(1554) (2016)Google Scholar
- S.Z. Li, Y.F. Gao, X.R. Chen, L.M. Qin, B.R. Cheng, S.B. Wang, S.X. Wang, G.X. Zhao, K. Liu, N.G. Zhang, Biomed. Microdevices 19(93) (2017)Google Scholar
- B.Y. Shew, H.C. Chu, C.K. Chen, Y.C. Su, Y.H. Hsieh, L.J. Lai, S.J. Liu, C.H. Leng, Sensor. Actuat. A: Phys. 163(128) (2010)Google Scholar
- S.L. Stott, C.H. Hsu, D.I. Tsukrov, M. Yu, D.T. Miyamoto, B.A. Waltman, S.M. Rothenberg, A.M. Shah, M.E. Smas, G.K. Korir, F.P. Floyd, A.J. Gilman, J.B. Lord, D. Winokur, S. Springer, D. Irimia, S. Nagrath, L.V. Sequist, R.J. Lee, K.J. Isselbacher, S. Maheswaran, D.A. Haber, M. Toner, Proc. Natl. Acad. Sci. U. S. A. 107, 18392 (2010)CrossRefGoogle Scholar
- M. Tang, C.Y. Wen, L.L. Wu, S.L. Hong, J. Hu, C.M. Xu, D.W. Pang, Z.L. Zhang, Lab Chip 16, 1214 (2016)Google Scholar
- X.L. Yu, R.X. He, S.S. Li, B. Cai, L.B. Zhao, L. Liao, W. Liu, Q. Zeng, H. Wang, S.S. Guo, X.Z. Zhao, Small 9, (3895) 2013Google Scholar