Biomedical Microdevices

, 20:83 | Cite as

A simple pyramid-shaped microchamber towards highly efficient isolation of circulating tumor cells from breast cancer patients

  • Feng Liu
  • Shuibing Wang
  • Zhigang Lu
  • Yumei Sun
  • Chaogang Yang
  • Qiongwei Zhou
  • Shaoli Hong
  • Shengxiang Wang
  • Bin Xiong
  • Kan LiuEmail author
  • Nangang ZhangEmail author


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.


Circulating 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).

Supplementary material

10544_2018_326_MOESM1_ESM.docx (133 kb)
ESM 1 (DOCX 133 kb)


  1. A.F. Chambers, A.C. Groom, I.C. MacDonald, Nat. Rev. Cancer 2, 563 (2002)CrossRefGoogle Scholar
  2. W.P. Chou, H.M. Wang, J.H. Chang, T.K. Chiu, C.H. Hsieh, C.J. Liao, M.H. Wu, Sensor. Actuat. B: Chem. 241, 245 (2017)CrossRefGoogle Scholar
  3. H. Esmaeilsabzali, T.V. Beischlag, M.E. Cox, N. Dechev, A.M. Parameswaran, E.J. Park, Biomed. Microdevices 18(22), 22 (2016)CrossRefGoogle Scholar
  4. I.J. Fidler, Nat. Rev. Cancer 3, 453 (2003)CrossRefGoogle Scholar
  5. T.M. Geislinger, M.E.M. Stamp, A. Wixforth, T. Franke, Appl. Phys. Lett. 107, 203702 (2015)CrossRefGoogle Scholar
  6. F. Guo, X.H. Ji, K. Liu, R.X. He, L.B. Zhao, Z.X. Guo, W. Liu, S.S. Guo, X.Z. Zhao, Appl. Phys. Lett. 96, 193701 (2010)CrossRefGoogle Scholar
  7. V. Gupta, I. Jafferji, M. Garza, V.O. Melnikova, D.K. Hasegawa, R. Pethig, D.W. Davis, Biomicrofluidics 6, 024133 (2012)CrossRefGoogle Scholar
  8. M. Hosokawa, T. Hayata, Y. Fukuda, A. Arakaki, T. Yoshino, T. Tanaka, T. Matsunaga, Anal. Chem. 82, 6629 (2010)CrossRefGoogle Scholar
  9. M. Hosokawa, H. Kenmotsu, Y. Koh, T. Yoshino, T. Yoshikawa, T. Naito, T. Takahashi, H. Hurakami, Y. Nakamura, A. Tsuya, T. Shukuya, A. Ono, H. Akamatsu, R. Watanabe, S. Ono, K. Mori, H. Kanbara, K. Yamaguchi, T. Tanaka, T. Matsunaga, N. Yamanoto, PLoS One 8, e67466 (2013)CrossRefGoogle Scholar
  10. S. Hou, L. Zhao, Q. Shen, J. Yu, C. Ng, X. Kong, D. Wu, M. Song, X. Shi, X. Xu, Angew. Chem. Int. Ed. 52, 3379 (2013)CrossRefGoogle Scholar
  11. C. Huang, H. Liu, N.H. Bander, B.J. Kirby, Biomed. Microdevices 15, 941 (2013)CrossRefGoogle Scholar
  12. Q.Q. Huang, B.L. Chen, R.X. He, Z.B. He, B. Cai, J.H. Xu, W. Qian, H.L. Chan, W. Liu, S.S. Guo, X.Z. Zhao, J.K. Yuan, Adv. Healthcare Mater. 3, 1420 (2014a)CrossRefGoogle Scholar
  13. C. Huang, C. Liu, J. Loo, T. Stakenborg, L. Lagae, Appl. Phys. Lett. 104, 013703 (2014b)CrossRefGoogle Scholar
  14. C. Huang, G. Yang, Q. Ha, J.X. Meng, S.T. Wang, Adv. Mater. 27, 310 (2015)CrossRefGoogle Scholar
  15. 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
  16. S.M. Jo, S.H. Noh, Z. Jin, Y. Lim, J. Cheon, H.S. Kim, Sensor. Actuat. B: Chem. 201, 144 (2014)CrossRefGoogle Scholar
  17. J. Jung, S.K. Seo, Y.D. Joo, K.H. Han, Sensor. Actuat. B: Chem. 157, 314 (2011)CrossRefGoogle Scholar
  18. Y.T. Kang, I. Doh, Y.H. Cho, Biomed. Microdevices 17, 45 (2015)CrossRefGoogle Scholar
  19. B.J. Kirby, M. Jodari, M.S. Loftus, G. Gakhar, E.D. Pratt, C. Chanel-Vos, J.P. Gleghorn, S.M. Santana, H. Liu, J.P. Smith, V.N. Navarro, S.T. Tagawa, N.H. Bander, D.M. Nanus, P. Giannakakou, PLoS One 7, e35976 (2012)CrossRefGoogle Scholar
  20. C.A. Klein, Science 321, 1785 (2008)CrossRefGoogle Scholar
  21. T.Y. Lee, K.A. Hyun, S.I. Kim, H.I. Jung, Sensor. Actuat. B: Chem. 238, 1144 (2017)CrossRefGoogle Scholar
  22. 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
  23. L.Y. Luk, C.M.L. Chan, A.H.K. Cheung, V.H.M. Lee, P.B.S. Lai, B.B.Y. Ma, E.P. Hui, M.Y.Y. Lam, T.C.C. Au, A.T.C. Chan, Br. J. Cancer 104, 1000 (2011)CrossRefGoogle Scholar
  24. H. Min, S.M. Jo, H.S. Kim, Small 11, 2536 (2015)CrossRefGoogle Scholar
  25. S. Nagrath, L.V. Sequist, S. Maheswaran, D.W. Bell, D. Irimia, L. Ulkus, M.R. Smith, E.L. Kwak, S. Digumarthy, A. Muzikansky, P. Ryan, U.J. Balis, R.G. Tompkins, D.A. Haber, M. Toner, Nature 450, 1235 (2007)CrossRefGoogle Scholar
  26. T. Ohnaga, Y. Shimada, M. Moriyama, H. Kishi, T. Obata, K. Takata, T. Okumura, T. Nagata, A. Muraguchi, K. Tsukada, Biomed. Microdevices 15, 611 (2013)CrossRefGoogle Scholar
  27. A. Qin, S.Y. Park, S.P. Duffy, K. Matthews, R.R. Ang, T. Todenhöer, H. Abdi, A. Azad, J. Bazov, K.N. Chi, P.C. Black, H.S. Ma, Lab Chip 15, 2278 (2015)CrossRefGoogle Scholar
  28. A.E. Saliba, L. Saias, E. Psychari, N. Minc, D. Simon, F.C. Bidard, C. Mathiot, J.Y. Pierga, V. Fraisier, J. Salamero, V. Saada, F. Farace, P. Vielh, L. Malaquin, J.L. Viovy, Proc. Natl. Acad. Sci. U. S. A. 107, 14524 (2010)CrossRefGoogle Scholar
  29. S.M. Santana, H. Liu, N.H. Bander, J.P. Gleghorn, B.J. Kirby, Biomed. Microdevices 14, 401 (2012)CrossRefGoogle Scholar
  30. 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
  31. 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
  32. S.J. Tan, L. Yobas, G.Y.H. Lee, C.N. Ong, C.T. Lim, Biomed. Microdevices 11, 883 (2009)CrossRefGoogle Scholar
  33. Y. Tang, J. Shi, S. Li, L. Wang, Y.E. Cayre, Y. Chen, Sci. Rep. 4, 6052 (2014)CrossRefGoogle Scholar
  34. 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
  35. S.T. Wang, H. Wang, J. Jiao, K.J. Chen, G.E. Owens, K.I. Kamei, J. Sun, D.J. Sherman, C.P. Behrenbruch, H. Wu, H.R. Tseng, Angew. Chem. Int. Ed. 48, 8970 (2009)CrossRefGoogle Scholar
  36. M.E. Warkiani, B.L. Khoo, L. Wu, A.K.P. Tay, A.A.S. Bhagat, J. Han, C.T. Lim, Nat. Protoc. 11, 134 (2016)CrossRefGoogle Scholar
  37. P. Xue, Y.F. Wu, J.H. Guo, Y.J. Kang, Biomed. Microdevices 17, 39 (2015)CrossRefGoogle Scholar
  38. C.G. Yang, N.G. Zhang, S.Y. Wang, D.D. Shi, C.X. Zhang, K. Liu, B. Xiong, J. Transl. Med. 16, 139 (2018)CrossRefGoogle Scholar
  39. 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
  40. X.L. Yu, B.R. Wang, N.G. Zhang, C.Q. Yin, H. Chen, L.L. Zhang, B. Cai, Z.B. He, L. Rao, W. Liu, F.B. Wang, S.S. Guo, X.Z. Zhao, ACS Appl. Mater. Interfaces 7, 24001 (2015)CrossRefGoogle Scholar
  41. N.G. Zhang, Y.L. Deng, Q.D. Tai, B.R. Cheng, L.B. Zhao, Q.L. Shen, R.X. He, L.Y. Hong, W. Liu, S.S. Guo, K. Liu, H.R. Tseng, B. Xiong, X.Z. Zhao, Adv. Mater. 24, 2756 (2012)CrossRefGoogle Scholar
  42. M.D. Zhou, S. Hao, A.J. Williams, R.A. Harouaka, B. Schrand, S. Rawal, Z. Ao, R. Brennaman, E. Gilboa, B. Lu, S.W. Wang, J.Y. Zhu, R. Datar, R. Cote, Y.C. Tai, S.Y. Zheng, Sci. Rep. 4, 7392 (2014)CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.College of Electronic and Electrical EngineeringWuhan Textile UniversityWuhanPeople’s Republic of China
  2. 2.Hubei Cancer Clinical Study CenterZhongnan Hospital of Wuhan UniversityWuhanPeople’s Republic of China
  3. 3.School of Life Science and TechnologyUniversity of Electronic Science and Technology of ChinaChengduPeople’s Republic of China

Personalised recommendations