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Biocompatible TiO2 nanoparticle-based cell immunoassay for circulating tumor cells capture and identification from cancer patients

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Abstract

We demonstrate the isolation of circulating tumor cells (CTCs) with a biocompatible nano-film composed of TiO2 nanoparticles. Due to the enhanced topographic interaction between nano-film and cancer cell surface, cancer cells (HCT116) spiked into PBS and healthy blood can be recovered from the suspension, whose efficiencies were respectively 80 % and 50 %. Benifit from the biocompatibility of this nano-film, in-situ culture of the captured cancer cells is also available, which provides an alternative selection when the capture cell number was inadequate or the sample cannot be analyzed immediately. For the proof-of-concept study, we use this nano-film to separate the circulating tumor cells from the colorectal and gastric cancer patient peripheral blood samples and the captured CTCs are identified by a three-colored immunocytochemistry method. We investigated the cancer cells capture strength at the nano-bio interface through exposing the cells to fluid shear stress in microfluidic device, which can be utilized to increase the purity of CTCs. The result indicated that 50 % of the captured cells can be detached from the substrate when the fluid shear stress was 180 dyn cm−2. By integration of this CTCs capture nano-film with other single cell analysis device, we expected to further explore their applications in genome sequencing based on the captured CTCs.

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References

  • A.A. Adams, P.I. Okagbare, J. Feng, M.L. Hupert, D. Patterson, J. Gottert, R.L. McCarley, D. Nikitopoulos, M.C. Murphy, S.A. Soper, J. Am. Chem. Soc. 130, 8633–8641 (2008)

    Article  Google Scholar 

  • C.A. Bichsel, S. Gobaa, S. Kobel, C. Secondini, G.N. Thalmann, M.G. Cecchini, M.P. Lutolf, Lab Chip 12, 2313–2316 (2012)

    Article  Google Scholar 

  • D. Chen, L. Cao, F. Huang, P. Imperia, Y.-B. Cheng, R.A. Caruso, J. Am. Chem. Soc. 132, 4438–4444 (2010)

    Article  Google Scholar 

  • D. Chen, F. Huang, Y.-B. Cheng, R.A. Caruso, Adv. Mater. 21, 2206–2210 (2009)

    Article  Google Scholar 

  • W. Chen, S. Weng, F. Zhang, S. Allen, X. Li, L. Bao, R.H.W. Lam, J.A. Macoska, S.D. Merajver, J. Fu, ACS Nano 7, 566–575 (2013)

    Article  Google Scholar 

  • Y.K. Chung, J. Reboud, K.C. Lee, H.M. Lim, P.Y. Lim, K.Y. Wang, K.C. Tang, H.M. Ji, Y. Chen, Biosens. Bioelectron. 26, 2520–2526 (2011)

    Article  Google Scholar 

  • S.J. Cohen, C.J.A. Punt, N. Iannotti, B.H. Saidman, K.D. Sabbath, N.Y. Gabrail, J. Picus, M.A. Morse, E. Mitchell, M.C. Miller, G.V. Doyle, H. Tissing, L. Terstappen, N.J. Meropol, Ann. Oncol. 20, 1223–1229 (2009)

    Article  Google Scholar 

  • M. Cristofanilli, G.T. Budd, M.J. Ellis, A. Stopeck, J. Matera, M.C. Miller, J.M. Reuben, G.V. Doyle, W.J. Allard, L.W.M.M. Terstappen, D.F. Hayes, N. Engl, J. Med. 351, 781–791 (2004)

    Google Scholar 

  • D.C. Danila, K. Pantel, M. Fleisher, H.I. Scher, Cancer J. 17, 438–450 (2011)

    Article  Google Scholar 

  • K.E. Fischer, B.J. Alemán, S.L. Tao, R.H. Daniels, E.M. Li, M.D. Bunger, G. Nagaraj, P. Singh, A. Zettl, T.A. Desai, Nano Lett. 9, 716–720 (2009)

    Article  Google Scholar 

  • E.M.V. Hoek, G.K. Agarwal, J. Colloid Interf Sci. 298, 50–58 (2006)

    Article  Google Scholar 

  • K. Hoshino, Y.Y. Huang, N. Lane, M. Huebschman, J.W. Uhr, E.P. Frenkel, X.J. Zhang, Lab Chip 11, 3449–3457 (2011)

    Article  Google Scholar 

  • M. Hosokawa, T. Hayata, Y. Fukuda, A. Arakaki, T. Yoshino, T. Tanaka, T. Matsunaga, Anal. Chem. 82, 6629–6635 (2010)

    Article  Google Scholar 

  • S. Hou, H. Zhao, L. Zhao, Q. Shen, K.S. Wei, D.Y. Suh, A. Nakao, M.A. Garcia, M. Song, T. Lee, B. Xiong, S.-C. Luo, H.-R. Tseng, H.-h. Yu, Adv. Mater. 25, 1547–1551 (2013)

    Article  Google Scholar 

  • K.-A. Hyun, K. Kwon, H. Han, S.-I. Kim, H.-I. Jung, Biosens. Bioelectron. 40, 206–212 (2013)

    Article  Google Scholar 

  • J.H. Kang, S. Krause, H. Tobin, A. Mammoto, M. Kanapathipillai, D.E. Ingber, Lab Chip 12, 2175–2181 (2012)

    Article  Google Scholar 

  • Y.J. Kim, M.H. Lee, H.J. Kim, G. Lim, Y.S. Choi, N.-G. Park, K. Kim, W.I. Lee, Adv. Mater. 21, 3668–3673 (2009)

    Article  Google Scholar 

  • J. Kling, Nature Biotechnol. 30, 578–580 (2012)

    Article  Google Scholar 

  • S. Lankiewicz, S. Zimmermann, C. Hollmann, T. Hillemann, T.F. Greten, Mol. Oncol. 2, 349–355 (2008)

    Article  Google Scholar 

  • E.S. Lianidou, A. Markou, Clin. Chem. Lab. Med. 49, 1579–1590 (2011)

    Article  Google Scholar 

  • L.S. Lim, M. Hu, M.C. Huang, W.C. Cheong, A.T.L. Gan, X.L. Looi, S.M. Leong, E.S.-C. Koay, M.-H. Li, Lab Chip 12, 4388–4396 (2012)

    Article  Google Scholar 

  • S. Maheswaran, L.V. Sequist, S. Nagrath, L. Ulkus, B. Brannigan, C.V. Collura, E. Inserra, S. Diederichs, A.J. Iafrate, D.W. Bell, S. Digumarthy, A. Muzikansky, D. Irimia, J. Settleman, R.G. Tompkins, T.J. Lynch, M. Toner, D.A. Haber, N. Engl, J. Med. 359, 366–377 (2008)

    Google Scholar 

  • 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, 1235–1239 (2007)

    Article  Google Scholar 

  • A.E. Nel, L. Madler, D. Velegol, T. Xia, E.M.V. Hoek, P. Somasundaran, F. Klaessig, V. Castranova, M. Thompson, Nature Mater. 8, 543–557 (2009)

    Article  Google Scholar 

  • T. Okegawa, K. Nutahara, E. Higashihara, J. Urology 180, 1342–1347 (2008)

    Article  Google Scholar 

  • G.-S. Park, H. Kwon, D.W. Kwak, S.Y. Park, M. Kim, J.-H. Lee, H. Han, S. Heo, X.S. Li, J.H. Lee, Y.H. Kim, J.-G. Lee, W. Yang, H.Y. Cho, S.K. Kim, K. Kim, Nano Letters 12, 1638–1642 (2012)

    Article  Google Scholar 

  • A.A. Powell, A.H. Talasaz, H. Zhang, M.A. Coram, A. Reddy, G. Deng, M.L. Telli, R.H. Advani, R.W. Carlson, J.A. Mollick, S. Sheth, A.W. Kurian, J.M. Ford, F.E. Stockdale, S.R. Quake, R.F. Pease, M.N. Mindrinos, G. Bhanot, S.H. Dairkee, R.W. Davis, S.S. Jeffrey, PLoS ONE 7, e33788 (2012)

    Article  Google Scholar 

  • E.A. Punnoose, S.K. Atwal, J.M. Spoerke, H. Savage, A. Pandita, R.-F. Yeh, A. Pirzkall, B.M. Fine, L.C. Amler, D.S. Chen, M.R. Lackner, PLoS ONE 5, e12517 (2010)

    Article  Google Scholar 

  • J. Sekine, S.-C. Luo, S. Wang, B. Zhu, H.-R. Tseng, H.-h. Yu, Adv. Mater. 23, 4788–4792 (2011)

    Article  Google Scholar 

  • W. Sheng, T. Chen, R. Kamath, X. Xiong, W. Tan, Z.H. Fan, Anal. Chem. 84, 4199–4206 (2012)

    Article  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, 18392–18397 (2010)

    Article  Google Scholar 

  • Y. Wan, J. Tan, W. Asghar, Y.-T. Kim, Y. Liu, S.M. Iqbal, J. Phys, Chem. B 115, 13891–13896 (2011)

    Article  Google Scholar 

  • S.T. Wang, K. Liu, J.A. Liu, Z.T.F. Yu, X.W. Xu, L.B. Zhao, T. Lee, E.K. Lee, J. Reiss, Y.K. Lee, L.W.K. Chung, J.T. Huang, M. Rettig, D. Seligson, K.N. Duraiswamy, C.K.F. Shen, H.R. Tseng, Angew. Chem. Int. Ed. 50, 3084–3088 (2011)

    Article  Google Scholar 

  • 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, 8970–8973 (2009)

    Article  Google Scholar 

  • N. Zhang, Y. Deng, Q. Tai, B. Cheng, L. Zhao, Q. Shen, R. He, L. Hong, W. Liu, S. Guo, K. Liu, H.-R. Tseng, B. Xiong, X.-Z. Zhao, Adv. Mater. 24, 2756–2760 (2012)

    Article  Google Scholar 

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Acknowledgement

This research was partially supported by The National Basic Research Program (Grant No. 2011CB933300) and the National Natural Science Foundation of China (Grant Nos. 81272443, 51132001, J1210061 and 51272184). We thank Prof. Bin Xiong from the Oncology department of the Zhongnan Hospital of Wuhan University for providing the cancer patient blood samples and the normal blood samples

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Correspondence to Bin Xiong or Xing-Zhong Zhao.

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He, R., Zhao, L., Liu, Y. et al. Biocompatible TiO2 nanoparticle-based cell immunoassay for circulating tumor cells capture and identification from cancer patients. Biomed Microdevices 15, 617–626 (2013). https://doi.org/10.1007/s10544-013-9781-9

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