Advertisement

Biomedical Microdevices

, 20:99 | Cite as

Combined immunomagnetic capture coupled with ultrasensitive plasmonic detection of circulating tumor cells in blood

  • Weiyu Shen
  • Yi Song
  • Alison Burklund
  • Biao Le
  • Ru Zhang
  • Lijie Wang
  • Yong Xi
  • Kun Qian
  • Ting Shen
  • John X. J. ZhangEmail author
Article
  • 159 Downloads

Abstract

We demonstrate enhanced on-chip circulating tumor cell (CTC) detection through the incorporation of plasmonic-enhanced near-infrared (NIR) fluorescence screening. Specifically, the performance of plasmonic gold coated chips was evaluated on our previously reported immunomagnetic CTC capture system and compared to the performance of a regular chip. Three main performance metrics were evaluated: capture efficiency, capture reproducibility, and clinical efficacy. Use of the plasmonic chip to capture SK-BR-3 cells in PBS, resulted in a capture efficiency of 82%, compared to 76% with a regular chip. Both chips showed excellent capture reproducibility for all three cells lines evaluated (MCF-7, SK-BR-3, Colo 205) in both PBS and peripheral blood, with R2 values ranging from 0.983 to 0.996. Finally, performance of the plasmonic chip was evaluated on thirteen peripheral blood samples in patients with both breast and prostate cancer. The regular chip detected 2–8 cells per 5 mL of blood, while the plasmonic chip detected 8–85 cells per 5 mL of blood in parallel samples. In summary, we successfully demonstrate improved CTC capture and detection capabilities through use of plasmonic-enhanced near-infrared (NIR) fluorescence screening in both in vitro and ex vivo experiments. This work not only has the potential to improve clinical outcomes though improved CTC analysis, but also demonstrates successful interface design between plasmonic materials and cell capture for bioanalytical applications.

Keywords

Circulating tumor cells Microfluidics Immunomagnetic capture Plasmonic detection Hematology 

Notes

Acknowledgements

The authors are grateful for the financial support from the National Institute of Health (NIH) Director’s Transformative Research Award (R01HL137157), NSF ECCS-1509369, and Norris Cotton Cancer Center Developmental Funds (Pilot Projects). We would also like to acknowledge Professor Hongjie Dai and his team from Stanford University for providing the expertise and resources on plasmonic detection.

Author’s contributions

K.Q, T.S. and J.X.Z. conceived and designed the experiments; Y.S., YW.S., B.L. and R.Z. performed the experiment; WY.S.,LJ. W. and Y. X. collected healthy donors and patients; WY. S., A.B. and Y.S. wrote the paper; K.Q., T.S. and J X.Z. revised the paper.

Compliance with ethical standards

Conflicts of interest

NanoLite Systems has a technology licensing agreement with the corresponding author (John X. J. Zhang) for the CellRich™ system, but we have no other personal or financial conflicts of interests to disclose.

References

  1. W.J. Allard, J. Matera, M.C. Miller, M. Repollet, M.C. Connelly, C. Rao, A.G. Tibbe, J.W. Uhr, L.W. Terstappen, Clin. Cancer Res. 10, 2 (2004)CrossRefGoogle Scholar
  2. M.C. Chang, Y.T. Chang, J.Y. Chen, Y.M. Jeng, C.Y. Yang, Y.W. Tien, S.H. Yang, H.L. Chen, T.Y. Liang, C.F. Wang, E.Y. Lee, Y.C. Chang, W.H. Lee, Clin. Chem. 62, 3 (2016)CrossRefGoogle Scholar
  3. J.Y. Chen, W.S. Tsai, H.J. Shao, J.C. Wu, J.M. Lai, S.H. Lu, T.F. Hung, C.T. Yang, L.C. Wu, J.S. Chen, W.H. Lee, Y.C. Chang, PLoS One 11, 3 (2016)Google Scholar
  4. M. Erkan, M. Kurtoglu, J. Kleeff, Expert Rev Gastroenterol Hepatol 10, 3 (2016)CrossRefGoogle Scholar
  5. D.L. Holliday, V. Speirs, Breast Cancer Res. 13, 4 (2011)CrossRefGoogle Scholar
  6. G. Hong, S.M. Tabakman, K. Welsher, Z. Chen, J.T. Robinson, H. Wang, B. Zhang, H. Dai, Angew. Chem. 50, 4644 (2011).  https://doi.org/10.1002/anie.201100934 CrossRefGoogle Scholar
  7. K. Hoshino, Y. Huang, N. Lane, M. Huebschman, J.W. Uhr, E.P. Frenkel, J.X. Zhang, Lab Chip 11, 20 (2011)CrossRefGoogle Scholar
  8. K. Hoshino, H. Chung, C. Wu, K. Rajendran, Y. Huang, P. Chen, K. Sokolov, J. Kim, X.J. Zhang, J. Circ. Biomark. 4, 11 (2015)CrossRefGoogle Scholar
  9. H.M. Kang, G.H. Kim, H.K. Jeon, D.H. Kim, T.Y. Jeon, D.Y. Park, H. Jeong, W.J. Chun, M.H. Kim, J. Park, M. Lim, T.H. Kim, Y.K. Cho, PLoS One 12, 6 (2017)Google Scholar
  10. X. Li, T. Kuznetsova, N. Cauwenberghs, M. Wheeler, H. Maecker, J.C. Wu, F. Haddad, H. Dai, Proc. Natl. Acad. Sci. U. S. A. 114, 27 (2017)CrossRefGoogle Scholar
  11. T. Matsui, T. Onouchi, K. Shiogama, Y. Mizutani, K. Inada, F. Yu, D. Hayasaka, K. Morita, H. Ogawa, F. Mahara, Y. Tsutsumi, Acta Histochem. Cytochem. 48, 5 (2015)CrossRefGoogle Scholar
  12. P. Paterlini-Brechot, N.L. Benali, Cancer Lett. 253, 2 (2007)CrossRefGoogle Scholar
  13. V.H. Perez-Gonzalez, R.C. Gallo-Villanueva, S. Camacho-Leon, J.I. Gomez-Quiñones, J.M. Rodriguez-Delgado, S.O. Martinez-Chapa, IET Nanobiotechnol. 10, 5 (2016)CrossRefGoogle Scholar
  14. C. Printz, Cancer 123, 6 (2017)Google Scholar
  15. M. Sahmani, M. Vatanmakanian, M. Goudarzi, N. Mobarra, M. Azad, Asian Pac. J. Cancer Prev. 17, 3 (2016)CrossRefGoogle Scholar
  16. T. Sawada, J. Araki, T. Yamashita, M. Masubuchi, T. Chiyoda, M. Yunokawa, K. Hoshi, S. Tao, S. Yamamura, S. Yatsushiro, K. Abe, M. Kataoka, T. Shimoyama, Y. Maeda, K. Kuroi, K. Tamura, T. Sawazumi, H. Minami, Y. Suda, F. Koizumi, EBioMedicine 11, 173 (2016).  https://doi.org/10.1016/j.ebiom.2016.07.027 CrossRefGoogle Scholar
  17. T.N. Seyfried, L.C. Huysentruyt, Crit. Rev. Oncog. 18, 1–2 (2013)CrossRefGoogle Scholar
  18. S.M. Tabakman, L. Lau, J.T. Robinson, J. Price, S.P. Sherlock, H. Wang, B. Zhang, Z. Chen, S. Tangsombatvisit, J.A. Jarrell, P.J. Utz, H. Dai, Nat. Commun. 2, 9 (2011)CrossRefGoogle Scholar
  19. A. Tadimety, A. Syed, Y. Nie, C.R. Long, K.M. Kreadya, J.X. Zhang, Integr. Biol. 9, 22 (2017)CrossRefGoogle Scholar
  20. A. Tadimety, A. Closson, C. Li, Y. Song, T. Shen, J.X. Zhang, Crit. Rev. Clin. Lab. Sci. 55, 3 (2018)CrossRefGoogle Scholar
  21. X. Wang, L. Shi, Q. Tao, H. Bao, J. Wu, D. Cai, F. Wang, Y. Zhao, G. Tian, Y. Li, C. Qao, H. Chen, J. Virol. Methods 167, 2 (2010)Google Scholar
  22. C.H. Wu, Y.Y. Huang, K. Hoshino, P. Chen, H. Liu, E.P. Frenkel, J.X. Zhang, K.V. Sokolov, ACS Nano 7, 10 (2013)Google Scholar
  23. J. Wu, X. Wei, J. Gan, J. Lou, T. Shen, B. Liu, J.X. Zhang, K. Qian, Adv. Funct. Mater. 26, 4016 (2016).  https://doi.org/10.1002/adfm.201504184 CrossRefGoogle Scholar
  24. B. Zhang, J.A. Jarrell, J.V. Price, S.M. Tabakman, Y. Li, M. Gong, G. Hong, J. Feng, P.J. Utz, H. Dai, PLoS One 8, 7 (2013)Google Scholar
  25. Y. Zhang, X. Zhang, J. Zhang, B. Sun, L. Zheng, J. Li, S. Liu, G. Sui, Z. Yin, Cancer Biol Ther 17, 11 (2016)CrossRefGoogle Scholar
  26. R. Zhang, B. Le, W. Xu, K. Guo, X. Sun, H. Su, L. Huang, J. Huang, T. Shen, T. Liao, Y. Liang, J.X. Zhang, H. Dai, K. Qian. “Magnetic ‘squashing’ of circulating tumor cells on plasmonic substrates for ultrasensitive NIR fluorescence detection”. 2018Google Scholar
  27. Y. Zhu, K. Kekalo, C. NDong, Y. Huang, F. Shubitidze, K.E. Krisword, I. Baker, J.X. Zhang, Adv. Funct. Mater. 26, 3953 (2016).  https://doi.org/10.1002/adfm.201504176 CrossRefGoogle Scholar

Copyright information

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

Authors and Affiliations

  • Weiyu Shen
    • 1
    • 2
  • Yi Song
    • 3
  • Alison Burklund
    • 4
  • Biao Le
    • 3
  • Ru Zhang
    • 5
  • Lijie Wang
    • 1
    • 2
  • Yong Xi
    • 1
    • 2
  • Kun Qian
    • 5
  • Ting Shen
    • 3
    • 6
  • John X. J. Zhang
    • 4
    • 7
    Email author
  1. 1.Department of Thoracic Surgery, Ningbo Medical CenterLihuili Eastern HospitalNingboChina
  2. 2.Department of Thoracic Surgery, Ningbo Medical CenterTaipei Medical UniversityNingboChina
  3. 3.Ningbo M&J Medical Technologies Co. LtdNingboChina
  4. 4.Thayer School of EngineeringDartmouth CollegeHanoverUSA
  5. 5.School of Biomedical Engineering, Med-X Research InstituteShanghai Jiao Tong UniversityShanghaiPeople’s Republic of China
  6. 6.NanoLite SystemsAustinUSA
  7. 7.Norris Cotton Cancer CenterDartmouth Hitchcock Medical CenterHanoverUSA

Personalised recommendations