Circulating tumor cells (CTCs), which are thought to be the main candidate for metastasis, are gaining importance owing to their potential impact on human health and public welfare. For capturing CTCs, antigen-antibody interaction has been used in which specific antigens expressed on cell surface of CTCs can be bound to antibodies immobilized on substrates. Conventional detection methods for CTCs have often suffered not only from relatively low antigen-antibody coupling efficiency but also from cumbersome fabrication processes of micro/nano-structures for CTCs capture. Herein, we report a facile, robust antibody-based CTCs detection technique using centrifugal force, which can enhance the capturing efficacy of CTCs. We validate chemical functionalization process of antibodies on a silica substrate by using atomic force microscopy. Furthermore, it turned out that the centrifugal force from a benchtop centrifuge is enough to produce a ~2.3-fold increase in capture yield of CTCs through enhancement of binding avidity between CTCs and the antibodies. Our result points out the great potential of our method for practical application in CTCs diagnostics and opens a new avenue for biological and chemical sensing.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
Steeg, P.S. Tumor metastasis: mechanistic insights and clinical challenges. Nat. Med. 12, 895–904 (2006).
Allard, W.J. et al. Tumor Cells Circulate in the Peripheral Blood of All Major Carcinomas but not in Healthy Subjects or Patients With Nonmalignant Diseases. Clin. Cancer Res. 10, 6897–6904 (2004).
Zieglschmid, V., Hollmann, C. & Bocher, O. Detection of disseminated tumor cells in peripheral blood. Crit. Rev. Clin. Lab. Sci. 42, 155–196 (2005).
Racila, E. et al. Detection and characterization of carcinoma cells in the blood. Proc. Natl. Acad. Sci. U. S. A. 95, 4589–4594 (1998).
Krivacic, R.T. et al. A rare-cell detector for cancer. Proc. Natl. Acad. Sci. U. S. A. 101, 10501–10504 (2004).
Kwon, T. et al. Carbon Nanotube-Patterned Surface-Based Recognition of Carcinoembryonic Antigens in Tumor Cells for Cancer Diagnosis. J. Phys. Chem. Lett. 4, 1126–1130 (2013).
Vardakis, N. et al. Prognostic Significance of the Detection of Peripheral Blood CEACAM5mRNA-Positive Cells by Real-Time Polymerase Chain Reaction in Operable Colorectal Cancer. Clin. Cancer Res. 17, 165–173 (2011).
Miller, M.C., Doyle, G.V. & Terstappen, L.W.M.M. Significance of Circulating Tumor Cells Detected by the CellSearch System in Patients with Metastatic Breast Colorectal and Prostate Cancer. J. Oncol. 2010, 2010 (2010).
Aggarwal, C. et al. Relationship among circulating tumor cells, CEA and overall survival in patients with metastatic colorectal cancer. Ann. Oncol. 24, 420–428 (2013).
Hou, S. et al. Capture and Stimulated Release of Circulating Tumor Cells on Polymer-Grafted Silicon Nano structures. Adv. Mater. 25, 1547–1551 (2013).
Hyun, K.A. & Jung, H.I. Microfluidic devices for the isolation of circulating rare cells: A focus on affinitybased, dielectrophoresis, and hydrophoresis. Electrophoresis 34, 1028–1041 (2013).
Hyun, K.A. & Jung, H.I. Advances and critical concerns with the microfluidic enrichments of circulating tumor cells. Lab Chip 14, 45–56 (2014).
Chiu, W.J. et al. Monitoring Cluster Ions Derived from Aptamer-Modified Gold Nanofilms under Laser Desorption/ Ionization for the Detection of Circulating Tumor Cells. Acs Appl. Mater. Inter. 7, 8622–8630 (2015).
Gu, Y.J. et al. Detection of circulating tumor cells in prostate cancer based on carboxylated graphene oxide modified light addressable potentiometric sensor. Biosens. Bioelectron. 66, 24–31 (2015).
Wang, C. et al. Simultaneous isolation and detection of circulating tumor cells with a microfluidic siliconnanowire-array integrated with magnetic upconversion nanoprobes. Biomaterials 54, 55–62 (2015).
Arlett, J.L., Myers, E.B. & Roukes, M.L. Comparative advantages of mechanical biosensors. Nat. Nano. 6, 203–215 (2011).
Roberts, M.A. & Kelley, S.O. Ultrasensitive Detection of Enzymatic Activity with Nanowire Electrodes. J. Am. Chem. Soc. 129, 11356–11357 (2007).
Busse, S., Scheumann, V., Menges, B. & Mittler, S. Sensitivity studies for specific binding reactions using the biotin/streptavidin system by evanescent optical methods. Biosens. Bioelectron. 17, 704–710 (2002).
Hou, H.W. et al. Isolation and retrieval of circulating tumor cells using centrifugal forces. Sci. Rep. 3, 1259 (2013).
Waggoner, P.S. & Craighead, H.G. Micro-and nanomechanical sensors for environmental, chemical, and biological detection. Lab Chip 7, 1238–1255 (2007).
Wang, S. et al. Three-Dimensional Nanostructured Substrates toward Efficient Capture of Circulating Tumor Cells. Angew. Chem.-Int. Edit. 48, 8970–8973 (2009).
Stern, E. et al. Label-free biomarker detection from whole blood. Nat. Nano. 5, 138–142 (2010).
Wang, S.T. et al. Three-Dimensional Nanostructured Substrates toward Efficient Capture of Circulating Tumor Cells. Angew. Chem. Int. Edit. 48, 8970–8973 (2009).
Kuespert, K., Pils, S. & Hauck, C.R. CEACAMs: their role in physiology and pathophysiology. Curr. Opin. Cell Biol. 18, 565–571 (2006).
Hanley, W.D., Burdick, M.M., Konstantopoulos, K. & Sackstein, R. CD44 on LS174T Colon Carcinoma Cells Possesses E-Selectin Ligand Activity. Cancer Res. 65, 5812–5817 (2005).
Yang, J. et al. In Situ Detection of Live Cancer Cells by Using Bioprobes Based on Au Nanoparticles. Langmuir 24, 12112–12115 (2008).
Park, J., Choi, W., Jang, K. & Na, S. High-sensitivity detection of silver ions using oligonucleotide-immobilized oscillator. Biosens. Bioelectron. 41, 471–476 (2013).
Ido, S. et al. Immunoactive two-dimensional selfassembly of monoclonal antibodies in aqueous solution revealed by atomic force microscopy. Nat. Mater. 13, 264–270 (2014).
Nicoletti, I. et al. A rapid and simple method for measuring thymocyte apoptosis by propidium iodide staining and flow cytometry. J. Immund. Methods. 139, 271–279 (1991).
Martin, S.J., Bradley, J.G. & Cotter, T.G. HL-60 cells induced to differentiate towards neutrophils subsequently die via apoptosis. Clin. Exp. Immunol. 79, 448–453 (2008).
Zangle, T.A. & Teitell, M.A. Live-cell mass profiling: an emerging approach in quantitative biophysics. Nat. Methods. 11, 1221–1228 (2014).
About this article
Cite this article
Bang, D., Lee, T., Park, J. et al. Enhancement of Capturing Efficacy for Circulating Tumor Cells by Centrifugation. BioChip J 12, 38–45 (2018). https://doi.org/10.1007/s13206-017-2105-z
- Circulating tumor cell
- Antigen-antibody interaction
- Capturing efficacy
- Atomic force microscope