Skip to main content
Log in

A rapid and simple method for efficient capture and accurate discrimination of circulating tumor cells using aptamer conjugated magnetic beads and surface-enhanced Raman scattering imaging

  • Research Paper
  • Published:
Analytical and Bioanalytical Chemistry Aims and scope Submit manuscript

Abstract

The efficient isolation and the accurate phenotype discrimination of circulating tumor cells (CTCs) are expected to provide much valuable information for the understanding of tumor metastasis and to play an important role in personalized treatment of cancer patients in the future. In this study, we developed a novel, rapid, and simple method for efficient capture and accurate identification of CTCs using aptamer conjugated magnetic beads and surface-enhanced Raman scattering (SERS) imaging technique. Using aptamer conjugated magnetic beads, rare target cancer cells can be captured efficiently from buffer and whole blood sample with capture efficiency of 73 % and 55 %, respectively. Meanwhile, captured cancer cells were labeled by specific SERS probes and can be identified readily and accurately by SERS imaging technique. Results of our experiment demonstrate the potential feasibility of aptamer conjugated magnetic beads coupled with SERS imaging technique for the efficient capture and accurate discrimination of CTCs in clinical whole blood sample.

Schematic Representation of CTCs Capture and Identification Using Apt-MBs and SERS Imaging

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Scheme 1
Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Maheswaran S, Haber DA (2010) Circulating tumor cells: a window into cancer biology and metastasis. Curr Opin Genet Dev 20(1):96–99

    Article  CAS  Google Scholar 

  2. Paterlini-Brechot P, Benali NL (2007) Circulating tumor cells (CTC) detection: clinical impact and future directions. Cancer Lett 253(2):180–204

    Article  CAS  Google Scholar 

  3. Ring A, Smith IE, Dowsett M (2004) Circulating tumor cells in breast cancer. Lancet Oncol 5(2):79–88

    Article  Google Scholar 

  4. den Toonder J (2011) Circulating tumor cells: the grand challenge. Lab Chip 11(3):375–377

    Article  Google Scholar 

  5. Pantel K, Alix-Panabie C (2010) Circulating tumor cells in cancer patients: challenges and perspectives. Trends Mol Med 16(9):398–406

    Article  Google Scholar 

  6. Racila E, Euhus D, Weiss AJ, Rao C, McConnell J, Terstappen LW, Uhr JW (1998) Detection and characterization of carcinoma cells in the blood. Proc Natl Acad Sci U S A 95(8):4589–4594

    Article  CAS  Google Scholar 

  7. Talasaz AH, Powell AA, Huber DE, Berbee JG, Roh KH, Yu W, Xiao W, Davis MM, Pease RF, Mindrinos MN, Jeffrey SS, Davis RW (2009) Isolating highly enriched populations of circulating epithelial cells and other rare cells from blood using a magnetic sweeper device. Proc Natl Acad Sci U S A 106(10):3970–3975

    Article  CAS  Google Scholar 

  8. Flatmark K, Bjørnland K, Johannessen HO, Hegstad E, Rosales R, Hårklau L, Solhaug JH, Faye RS, Søreide O, Fodstad Ø (2002) Immunomagnetic detection of micrometastatic cells in bone marrow of colorectal cancer patients. Clin Cancer Res 8(2):444–449

    Google Scholar 

  9. Zigeuner RE, Riesenberg R, Pohla H, Hofstetter A, Oberneder R (2003) Isolation of circulating cancer cells from whole blood by immunomagnetic cell enrichment and unenriched immunocytochemistry in vitro. J Urol 169(2):701–705

    Article  CAS  Google Scholar 

  10. Wang X, Qian XM, Beitler JJ, Chen ZG, Khuri FR, Lewis MM, Shin HJC, Nie SM, Shin DM (2011) Detection of circulating tumor cells in human peripheral blood using surface-enhanced Raman scattering nanoparticles. Cancer Res 71(5):1526–1532

    Article  CAS  Google Scholar 

  11. Zheng S, Lin H, Liu JQ, Balic M, Datar R, Cote RJ, Tai YC (2007) Membrane microfilter device for selective capture electrolysis and genomic analysis of human circulating tumor cells. J Chromatogr A 1162(2):154–161

    Article  CAS  Google Scholar 

  12. Wang Y, Zhou F, Liu X, Yuan L, Li D, Wang Y, Chen H (2013) Aptamer-modified micro/nanostructured surfaces: efficient capture of Ramos cells in serum environment. ACS Appl Mater Interfaces 5(9):3816–3823

    Article  CAS  Google Scholar 

  13. Sheng W, Chen T, Kamath R, Xiong X, Tan W, Fan ZH (2012) Aptamer-enabled efficient isolation of cancer cells from whole blood using a microfluidic device. Anal Chem 84(9):4199–4206

    Article  CAS  Google Scholar 

  14. Ozkumur E, Shah AM, Ciciliano JC, Emmink BL, Miyamoto DT, Brachtel E, Yu M, Chen PI, Morgan B, Trautwein J, Kimura A, Sengupta S, Stott SL, Karabacak NM, Barber TA, Walsh JR, Smith K, Spuhler PS, Sullivan JP, Lee RJ, Ting DT, Luo X, Shaw AT, Bardia A, Sequist LV, Louis DN, Maheswaran S, Kapur R, Haber DA, Toner M (2013) Inertial focusing for tumor antigen-dependent and -independent sorting of rare circulating tumor cells. Sci Transl Med 5(179), 179ra47

  15. Riethdorf S, Fritsche H, Müller V, Rau T, Schindlbeck C, Rack B, Janni W, Coith C, Beck K, Jänicke F, Jackson S, Gornet T, Cristofanilli M, Pantel K (2007) Detection of circulating tumor cells in peripheral blood of patients with metastatic breast cancer: a validation study of the Cell Search system. Clin Cancer Res 13(3):920–928

    Article  CAS  Google Scholar 

  16. Sefah K, Tang ZW, Shangguan DH, Chen H, Lopez-Colon D, Li Y, Parekh P, Martin J, Meng L, Phillips JA, Kim YM, Tan WH (2009) Molecular recognition of acute myeloid leukemia using aptamers. Leukemia 23(2):235–244

    Article  CAS  Google Scholar 

  17. Patel DJ, Suri AK, Jiang L, Fan P, Kumar RA, Nonin S (1997) Structure recognition and adaptive binding in RNA aptamer complexes. J Mol Biol 272(5):645–664

    Article  CAS  Google Scholar 

  18. Mairal T, Özalp VC, Sánchez PL, Mir M, Katakis I, O'Sullivan CK (2008) Aptamers: molecular tools for analytical applications. Anal Bioanal Chem 390(4):989–1007

    Article  CAS  Google Scholar 

  19. Hu M, Zhang K (2013) The Application of aptamers in cancer research: an up-to-date review. Future Oncol 9(3):369–376

    Article  CAS  Google Scholar 

  20. Daniels DA, Chen H, Hicke BJ, Swiderek KM, Gold L (2003) A tenascin-C aptamer identified by tumor cell SELEX: systematic evolution of ligands by exponential enrichment. Proc Natl Acad Sci U S A 100(26):15416–15421

    Article  CAS  Google Scholar 

  21. Shangguan D, Li Y, Tang Z, Cao ZC, Chen HW, Mallikaratchy P, Sefah K, Yang CJ, Tan W (2006) Aptamers evolved from live cells as effective molecular probes for cancer study. Proc Natl Acad Sci U S A 103(32):11838–11843

    Article  CAS  Google Scholar 

  22. Shangguan D, Cao ZC, Li Y, Tan W (2007) Aptamers evolved from cultured cancer cells reveal molecular differences of cancer cells in patient samples. Clin Chem 53(6):1153–1155

    Article  CAS  Google Scholar 

  23. Sefah K, Meng L, Lopez-Colon D, Jimenez E, Liu C, Tan W (2010) DNA aptamers as molecular probes for colorectal cancer study. PLoS One 5(12), e14269

    Article  Google Scholar 

  24. Zhang R, Zhang Y, Dong ZC, Jiang S, Zhang C, Chen LG, Zhang L, Liao Y, Aizpurua J, Luo Y, Yang JL, Hou JG (2013) Chemical mapping of a single molecule by plasmon-enhanced Raman scattering. Nature 498(7452):82–86

    Article  CAS  Google Scholar 

  25. Vendrell M, Maiti KK, Dhaliwal K, Chang YT (2013) Surface-enhanced Raman scattering in cancer detection and imaging. Trends Biotechnol 31(4):249–257

    Article  CAS  Google Scholar 

  26. Li MQ, Xu J, Romero-Gonzalez M, Banwart SA, Huang WE (2012) Single cell Raman spectroscopy for cell sorting and imaging. Curr Opin Biotechnol 23(1):56–63

    Article  CAS  Google Scholar 

  27. Bantz KC, Meyer AF, Wittenberg NJ, Im H, Kurtulus O, Lee SH, Lindquist NC, Oh SH, Haynes CL (2011) Recent progress in SERS biosensing. Phys Chem Chem Phys 13(24):11551–11567

    Article  Google Scholar 

  28. Pallaoro A, Hoonejani MR, Braun GB, Meinhart CD, Moskovits M (2015) Rapid identification by surface-enhanced Raman spectroscopy of cancer cells at low concentrations flowing in a microfluidic channel. ACS Nano 9(4):4328–4336

    Article  CAS  Google Scholar 

  29. Nolan JP, Duggan E, Liu E, Condello D, Dave I, Stoner SA (2012) Single cell analysis using surface enhanced Raman scattering (SERS) tags. Methods 57(3):272–279

    Article  CAS  Google Scholar 

  30. MacLaughlin CM, Mullaithilaga N, Yang GS, Ip SY, Wang C, Walker GC (2013) Surface-enhanced Raman scattering dye-labeled Au nanoparticles for triplexed detection of leukemia and lymphoma cells and SERS flow cytometry. Langmuir 29(6):1908–1919

    Article  CAS  Google Scholar 

  31. Lee S, Chon H, Lee M, Choo J, Shin SY, Lee YH, Rhyu IJ, Son SW, Oh CH (2009) Surface-enhanced Raman scattering imaging of HER2 cancer markers overexpressed in single MCF7 cells using antibody conjugated hollow gold nanospheres. Biosens Bioelectron 24(7):2260–2263

    Article  CAS  Google Scholar 

  32. Park H, Lee S, Chen L, Lee EK, Shin SY, Lee YH, Son SW, Oh CH, Song JM, Kang SH, Choo J (2009) SERS imaging of HER2-overexpressed MCF7 cells using antibody-conjugated gold nanorods. Phys Chem Chem Phys 11(34):7444–7449

    Article  CAS  Google Scholar 

  33. Lee S, Kim S, Choo J, Shin SY, Lee YH, Choi HY, Ha S, Kang K, Oh CH (2007) Biological imaging of HEK293 cells expressing PLC gamma 1 using surface-enhanced Raman microscopy. Anal Chem 79(3):916–922

    Article  CAS  Google Scholar 

  34. Freitag I, Matthaus C, Csaki A, Clement JH, Cialla-May D, Weber K, Krafft C, Popp J (2015) Differentiation of MCF-7 tumor cells from leukocytes and fibroblast cells using epithelial cell adhesion molecule targeted multicore surface-enhanced Raman spectroscopy labels. J Biomed Opt 20(5):055002. doi:10.1117/1.JBO.20.5.055002

  35. Pallaoro A, Braun GB, Moskovits M (2011) Quantitative ratiometric discrimination between noncancerous and cancerous prostate cells based on neuropilin-1 overexpression. Proc Natl Acad Sci U S A 108(40):16559–16564

    Article  CAS  Google Scholar 

  36. Maiti KK, Samanta A, Vendrell M, Soh KS, Olivo M, Chang YT (2011) Multiplex cancer cell detection by SERS nanotags with cyanine and triphenylmethine Raman reporters. Chem Commun 47(12):3514–3516

    Article  CAS  Google Scholar 

  37. Yang J, Wang Z, Zong S, Song C, Zhang R, Cui Y (2012) Distinguishing breast cancer cells using surface-enhanced Raman scattering. Anal Bioanal Chem 402(3):1093–1100

    Article  CAS  Google Scholar 

  38. Zhang P, Zhang R, Gao M, Zhang X (2014) Novel nitrocellulose membrane substrate for efficient analysis of circulating tumor cells coupled with surface-enhanced Raman scattering imaging. ACS Appl Mater Interfaces 6(1):370–376

    Article  CAS  Google Scholar 

  39. Frens G (1973) Controlled nucleation for regulation of particle size in monodisperse gold suspensions. Nat Phys Sci 241(105):20–22

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by National Basic Research Program of China (Project 2012CB910604), the National High-Tech R&D Program (Project 2012AA020202), and the National Natural Science Foundation of China (Project: 21275034 and 21475027).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Mingxia Gao.

Ethics declarations

Compliance with Ethical Standards

Conflict of interest

The authors declare no competing financial interest.

Electronic supplementary material

Below is the link to the electronic supplementary material.

ESM 1

(PDF 1.76 MB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sun, C., Zhang, R., Gao, M. et al. A rapid and simple method for efficient capture and accurate discrimination of circulating tumor cells using aptamer conjugated magnetic beads and surface-enhanced Raman scattering imaging. Anal Bioanal Chem 407, 8883–8892 (2015). https://doi.org/10.1007/s00216-015-9049-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00216-015-9049-8

Keywords

Navigation