Skip to main content
SpringerLink
Log in

Circulating Tumor Cell Enrichment Technologies

  • Chapter
  • First Online:
Tumor Liquid Biopsies

Part of the book series: Recent Results in Cancer Research ((RECENTCANCER,volume 215))

Abstract

Circulating tumor cells (CTCs) are responsible for the metastatic spread of cancer and therefore are extremely valuable not only for basic research on cancer metastasis but also as potential biomarkers in diagnosing and managing cancer in the clinic. While relatively non-invasive access to the blood tissue presents an opportunity, CTCs are mixed with approximately billion-times more-populated blood cells in circulation. Therefore, the accuracy of technologies for reliable enrichment of the rare CTC population from blood samples is critical to the success of downstream analyses. The focus of this chapter is to provide the reader an overview of significant advances made in the development of diverse CTC enrichment technologies by presenting the strengths of individual techniques in addition to specific challenges remaining to be addressed.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 49.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 64.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 89.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Aceto N, Bardia A, Miyamoto DT et al (2014) Circulating tumor cell clusters are oligoclonal precursors of breast cancer metastasis. Cell 158(5):1110–1122

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Adams AA, Okagbare PI, Feng J et al (2008) Highly efficient circulating tumor cell isolation from whole blood and label-free enumeration using polymer-based microfluidics with an integrated conductivity sensor. J Am Chem Soc 130(27):8633–8841

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Adams DL, Zhu P, Makarova OV et al (2014) The systematic study of circulating tumor cell isolation using lithographic microfilters. RSC Adv 4(9):4334–4342

    Article  CAS  Google Scholar 

  • Alix-Panabières C, Pantel K (2013) Circulating tumor cells: liquid biopsy of cancer. Clin Chem 59(1):110–118

    Article  PubMed  CAS  Google Scholar 

  • Alix-Panabières C, Pantel K (2014) Challenges in circulating tumour cell research. Nat Rev Cancer 14(9):623–631

    Article  PubMed  CAS  Google Scholar 

  • Allan AL, Keeney M (2009) Circulating tumor cell analysis: technical and statistical considerations for application to the clinic. J Oncol 2010:426218

    PubMed  PubMed Central  Google Scholar 

  • Al-Mehdi AB, Tozawa K, Fisher AB et al (2000) Intravascular origin of metastasis from the proliferation of endothelium-attached tumor cells: a new model for metastasis. Nat Med 6(1):100–102

    Article  CAS  PubMed  Google Scholar 

  • Antfolk M, Antfolk C, Lilja H et al (2015) A single inlet two-stage acoustophoresis chip enabling tumor cell enrichment from white blood cells. Lab Chip 15(9):2102–2109

    Article  CAS  PubMed  Google Scholar 

  • Au SH, Edd J, Stoddard AE et al (2017) Microfluidic isolation of circulating tumor cell clusters by size and asymmetry. Sci Rep 7:2433

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Au SH, Storey BD, Moore JC et al (2016) Clusters of circulating tumor cells traverse capillary-sized vessels. Proc Natl Acad Sci U S A 113(18):4947–4952

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Augustsson P, Magnusson C, Nordin M et al (2012) Microfluidic, label-free enrichment of prostate cancer cells in blood based on acoustophoresis. Anal Chem 84(18):7954–7962

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Besant JD, Mohamadi RM, Aldridge PM et al (2015) Velocity valleys enable efficient capture and spatial sorting of nanoparticle-bound cancer cells. Nanoscale 7(14):6278–6285

    Article  CAS  PubMed  Google Scholar 

  • Bruno JG (2015) Predicting the uncertain future of aptamer-based diagnostics and therapeutics. Molecules 20(4):6866–6887

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Budd GT, Cristofanilli M, Ellis MJ et al (2006) Circulating tumor cells versus imaging-predicting overall survival in metastatic breast cancer. Clin Cancer Res 12(21):6403–6409

    Article  CAS  PubMed  Google Scholar 

  • Bunka DH, Stockley PG (2006) Aptamers come of age-at last. Nat Rev Microbiol 4(8):588–596

    Article  CAS  PubMed  Google Scholar 

  • Chandran K, Yoganathan A, Rittgers S (2007) Biofluid mechanics: the human circulation. CRC Press, Boca Raton

    Google Scholar 

  • Chen GD, Fachin F, Fernandez-Suarez M et al (2011) Nanoporous elements in microfluidics for multiscale manipulation of bioparticles. Small 7(8):1061–1067

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cheng IF, Chang HC, Hou D et al (2007) An integrated dielectrophoretic chip for continuous bioparticle filtering, focusing, sorting, trapping, and detecting. Biomicrofluidics 1(2):021503

    Article  PubMed Central  CAS  Google Scholar 

  • Cheng IF, Huang WL, Chen TY et al (2015) Antibody-free isolation of rare cancer cells from blood based on 3D lateral dielectrophoresis. Lab Chip 15(14):2950–2959

    Article  CAS  PubMed  Google Scholar 

  • Cheng SB, Xie M, Xu JQ et al (2016) High-efficiency capture of individual and cluster of circulating tumor cells by a microchip embedded with three-dimensional poly (dimethylsiloxane) scaffold. Anal Chem 88(13):6773–6780

    Article  CAS  PubMed  Google Scholar 

  • Cherdron W, Durst F, Whitelaw JH (1978) Asymmetric flows and instabilities in symmetric ducts with sudden expansions. J Fluid Mech 84(1):13–31

    Article  CAS  Google Scholar 

  • Chinen LT, de Carvalho FM, Rocha BM et al (2013) Cytokeratin-based CTC counting unrelated to clinical follow up. J Thorac Dis 5(5):593

    PubMed  PubMed Central  Google Scholar 

  • Choi H, Kim KB, Jeon CS et al (2013) A label-free DC impedance-based microcytometer for circulating rare cancer cell counting. Lab Chip 13(5):970–977

    Article  CAS  PubMed  Google Scholar 

  • Coumans FAW, van Dalum G, Beck M et al (2013) Filtration parameters influencing circulating tumor cell enrichment from whole blood. PLoS ONE 8(4):e61774

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cristofanilli M, Budd GT, Ellis MJ et al (2004) Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med 351:781–791

    Article  CAS  PubMed  Google Scholar 

  • Davies J, Dawkes AC, Haymes AG et al (1994) A scanning tunneling microscopy comparison of passive antibody adsorption and biotinylated antibody linkage to streptavidin on microtiter wells. J Immunolog Meth 167(1–2):263–269

    Article  CAS  Google Scholar 

  • Davis JA, Inglis DW, Morton KJ et al (2006) Deterministic hydrodynamics: taking blood apart. Proc Natl Acad Sci U S A 103(40):14779–14784

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • De Bono JS, Scher HI, Montgomery RB et al (2008) Circulating tumor cells predict survival benefit from treatment in metastatic castration-resistant prostate cancer. Clin Cancer Res 14(19):6302–6309

    Article  PubMed  CAS  Google Scholar 

  • Desitter I, Guerrouahen BS, Benali-Furet N et al (2011) A new device for rapid isolation by size and characterization of rare circulating tumor cells. Anticancer Res 31(2):427–441

    PubMed  Google Scholar 

  • Dharmasiri U, Balamurugan S, Adams AA et al (2009) Highly efficient capture and enumeration of low abundance prostate cancer cells using prostate‐specific membrane antigen aptamers immobilized to a polymeric microfluidic device. Electrophoresis 30(18):3289–3300

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Di Carlo D (2009) Inertial microfluidics. Lab Chip 9(21):3038–3046

    Article  PubMed  CAS  Google Scholar 

  • Di Carlo D, Irimia D, Tompkins RG et al (2007) Continuous inertial focusing, ordering, and separation of particles in microchannels. Proc Natl Acad Sci U S A 104(48):18892–18897

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Dickey DD, Giangrande PH (2016) Oligonucleotide aptamers: a next-generation technology for the capture and detection of circulating tumor cells. Methods 97:94–103

    Article  CAS  PubMed  Google Scholar 

  • Ding X, Peng Z, Lin SC et al (2014) Cell separation using tilted-angle standing surface acoustic waves. Proc Natl Acad Sci U S A 111(36):12992–12997

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fan X, Jia C, Yang J et al (2015) A microfluidic chip integrated with a high-density PDMS-based microfiltration membrane for rapid isolation and detection of circulating tumor cells. Biosens Bioelectron 71:380–386

    Article  CAS  PubMed  Google Scholar 

  • Fan ZH, Vitha MF (2016) Circulating tumor cells: isolation and analysis. Wiley, Hoboken

    Book  Google Scholar 

  • Farokhzad OC, Jon S, Khademhosseini A et al (2004) Nanoparticle-aptamer bioconjugates. Cancer Res 64(21):7668–7672

    Article  CAS  PubMed  Google Scholar 

  • Fawcett DW, Vallee BL, Soule MH (1950) A method for concentration and segregation of malignant cells from bloody, pleural and peritoneal fluids. Science 3:34–36

    Article  Google Scholar 

  • Ferreira MM, Ramani VC, Jeffrey SS (2016) Circulating tumor cell technologies. Mol Oncol 10(3):374–394

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fidler IJ (2003) The pathogenesis of cancer metastasis: the ‘seed and soil’ hypothesis revisited. Nat Rev Cancer 3(6):453–459

    Article  CAS  PubMed  Google Scholar 

  • Freidin MB, Tay A, Freydina DV et al (2014) An assessment of diagnostic performance of a filter-based antibody-independent peripheral blood circulating tumour cell capture paired with cytomorphologic criteria for the diagnosis of cancer. Lung Cancer 85(2):182–185

    Article  PubMed  Google Scholar 

  • Fujii T (2002) PDMS-based microfluidic devices for biomedical applications. Microelectron Eng 61:907–914

    Article  Google Scholar 

  • Giordano A, Gao H, Anfossi S et al (2012) Epithelial-mesenchymal transition and stem cell markers in patients with HER2-positive metastatic breast cancer. Mol Cancer Ther 11(11):2526–2534

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Goto W, Kashiwagi S, Asano Y et al (2017) Circulating tumor cell clusters-associated gene plakoglobin is a significant prognostic predictor in patients with breast cancer. Biomark Res 5(1):19

    Article  PubMed  PubMed Central  Google Scholar 

  • Gupta V, Jafferji I, Garza M et al (2012) ApoStream™, a new dielectrophoretic device for antibody independent isolation and recovery of viable cancer cells from blood. Biomicrofluidics 6(2):024133

    Article  PubMed Central  Google Scholar 

  • Harb W, Fan A, Tran T et al (2013) Mutational analysis of circulating tumor cells using a novel microfluidic collection device and qPCR assay. Transl Oncol 6(5):528IN1-538

    Article  PubMed  PubMed Central  Google Scholar 

  • Hayes DF, Cristofanilli M, Budd GT et al (2006) Circulating tumor cells at each follow-up time point during therapy of metastatic breast cancer patients predict progression-free and overall survival. Clin Cancer Res 12(14):4218–4224

    Article  CAS  PubMed  Google Scholar 

  • Holm SH, Beech JP, Barrett MP et al (2011) Separation of parasites from human blood using deterministic lateral displacement. Lab Chip 11(7):1326–1332

    Article  CAS  PubMed  Google Scholar 

  • Hong Y, Fang F, Zhang Q (2016) Circulating tumor cell clusters: what we know and what we expect. Int J Oncol 49(6):2206–2216

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hoshino K, Huang YY, Lane N et al (2011) Microchip-based immunomagnetic detection of circulating tumor cells. Lab Chip 11(20):3449–3457

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hosic S, Murthy SK, Koppes AN (2015) Microfluidic sample preparation for single cell analysis. Anal Chem 88(1):354–380

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Hou HW, Warkiani ME, Khoo BL et al (2013a) Isolation and retrieval of circulating tumor cells using centrifugal forces. Sci Rep 3:1259

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Hou S, Zhao L, Shen Q et al (2013b) Polymer nanofiber-embedded microchips for detection, isolation, and molecular analysis of single circulating melanoma cells. Angew Chem Int Ed 52(12):3379–3383

    Article  CAS  Google Scholar 

  • Huang LR, Cox EC, Austin RH et al (2004) Continuous particle separation through deterministic lateral displacement. Science 304(5673):987–990

    Article  CAS  PubMed  Google Scholar 

  • Hughes AD, King MR (2010) Use of naturally occurring halloysite nanotubes for enhanced capture of flowing cells. Langmuir 26(14):12155–12164

    Article  CAS  PubMed  Google Scholar 

  • Hur SC, Mach AJ, Di Carlo D (2011) High-throughput size-based rare cell enrichment using microscale vortices. Biomicrofluidics 5(2):022206

    Article  PubMed Central  CAS  Google Scholar 

  • Hur SC, Tse HT, Di Carlo D (2010) Sheathless inertial cell ordering for extreme throughput flow cytometry. Lab Chip 10(3):274–280

    Article  CAS  PubMed  Google Scholar 

  • Hyun KA, Lee TY, Jung HI (2013) Negative enrichment of circulating tumor cells using a geometrically activated surface interaction chip. Anal Chem 85(9):4439–4445

    Article  CAS  PubMed  Google Scholar 

  • Inglis DW, Davis JA, Austin RH et al (2006) Critical particle size for fractionation by deterministic lateral displacement. Lab Chip 6(5):655–658

    Article  CAS  PubMed  Google Scholar 

  • Jackson JM, Witek MA, Kamande JW et al (2017) Materials and microfluidics: enabling the efficient isolation and analysis of circulating tumour cells. Chem Soc Rev 46(14):4245–4280

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jahr S, Hentze H, Englisch S et al (2001) DNA fragments in the blood plasma of cancer patients: quantitations and evidence for their origin from apoptotic and necrotic cells. Cancer Res 61(4):1659–1665

    CAS  PubMed  Google Scholar 

  • Ji HM, Samper V, Chen Y et al (2008) Silicon-based microfilters for whole blood cell separation. Biomed Microdevices 10(2):251–257

    Article  PubMed  Google Scholar 

  • Karabacak NM, Spuhler PS, Fachin F et al (2014) Microfluidic, marker-free isolation of circulating tumor cells from blood samples. Nat Protoc 9(3):694

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Karnis A, Goldsmith HL, Mason SG (1966) The flow of suspensions through tubes: V. Inertial effects. Can J Chem Eng 44(4):181–193

    Article  CAS  Google Scholar 

  • Katkov II, Mazur P (1999) Factors affecting yield and survival of cells when suspensions are subjected to centrifugation. Cell Biochem Biophys 31(3):231–245

    Article  CAS  PubMed  Google Scholar 

  • Kim YJ, Koo GB, Lee JY et al (2014) A microchip filter device incorporating slit arrays and 3-D flow for detection of circulating tumor cells using CAV1-EpCAM conjugated microbeads. Biomaterials 35(26):7501–7510

    Article  CAS  PubMed  Google Scholar 

  • Krishnamurthy S, Bischoff F, Ann Mayer J et al (2013) Discordance in HER2 gene amplification in circulating and disseminated tumor cells in patients with operable breast cancer. Cancer Med 2(2):226–233

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kuczenski RS, Chang HC, Revzin A (2011) Dielectrophoretic microfluidic device for the continuous sorting of Escherichia coli from blood cells. Biomicrofluidics 5(3):032005

    Article  PubMed Central  CAS  Google Scholar 

  • Labib M, Green B, Mohamadi RM et al (2016) Aptamer and antisense-mediated two-dimensional isolation of specific cancer cell subpopulations. J Am Chem Soc 138(8):2476–2479

    Article  CAS  PubMed  Google Scholar 

  • Lara O, Tong X, Zborowski M et al (2004) Enrichment of rare cancer cells through depletion of normal cells using density and flow-through, immunomagnetic cell separation. Exp Hematol 32(10):891–904

    Article  PubMed  Google Scholar 

  • Lara O, Tong X, Zborowski M et al (2006) Comparison of two immunomagnetic separation technologies to deplete T cells from human blood samples. Biotechnol Bioeng 94(1):66–80

    Article  CAS  PubMed  Google Scholar 

  • Lee HJ, Cho HY, Oh JH et al (2013a) Simultaneous capture and in situ analysis of circulating tumor cells using multiple hybrid nanoparticles. Biosens Bioelectron 47:508–514

    Article  CAS  PubMed  Google Scholar 

  • Lee MG, Choi S, Park JK (2010) Rapid multivortex mixing in an alternately formed contraction-expansion array microchannel. Biomed Microdevices 12(6):1019–1026

    Article  CAS  PubMed  Google Scholar 

  • Lee MG, Shin JH, Bae CY et al (2013b) Label-free cancer cell separation from human whole blood using inertial microfluidics at low shear stress. Anal Chem 85(13):6213–6218

    Article  CAS  PubMed  Google Scholar 

  • Li H, Meng QH, Noh H et al (2017) Detection of circulating tumor cells from cryopreserved human sarcoma peripheral blood mononuclear cells. Cancer Lett 403:216–223

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li P, Mao Z, Peng Z et al (2015) Acoustic separation of circulating tumor cells. Proc Natl Acad Sci U S A 112(16):4970–4975

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lin H, Balic M, Zheng S et al (2011) Disseminated and circulating tumor cells: role in effective cancer management. Crit Rev Oncol Hematol 77(1):1–11

    Article  PubMed  Google Scholar 

  • Lin HK, Zheng S, Williams AJ et al (2010) Portable filter-based microdevice for detection and characterization of circulating tumor cells. Clin Cancer Res 16(20):5011–5018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu G, Mao X, Phillips JA et al (2009) Aptamer−nanoparticle strip biosensor for sensitive detection of cancer cells. Anal Chem 81(24):10013–10018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Loutherback K, Chou KS, Newman J et al (2010) Improved performance of deterministic lateral displacement arrays with triangular posts. Microfluid Nanofluid 9(6):1143–1149

    Article  Google Scholar 

  • Loutherback K, D’Silva J, Liu L et al (2012) Deterministic separation of cancer cells from blood at 10 mL/min. AIP Adv 2(4):042107

    Article  PubMed Central  CAS  Google Scholar 

  • Lu B, Zheng S, Quach BQ et al (2010a) A study of the autofluorescence of parylene materials for μTAS applications. Lab Chip 10(14):1826–1834

    Article  CAS  PubMed  Google Scholar 

  • Lu J, Fan T, Zhao Q et al (2010b) Isolation of circulating epithelial and tumor progenitor cells with an invasive phenotype from breast cancer patients. Int J Cancer 126(3):669–683

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lu YT, Zhao L, Shen Q et al (2013) NanoVelcro Chip for CTC enumeration in prostate cancer patients. Nat Methods 64(2):144–152

    CAS  Google Scholar 

  • Lu Y, Liang H, Yu T et al (2015) Isolation and characterization of living circulating tumor cells in patients by immunomagnetic negative enrichment coupled with flow cytometry. Cancer 121(17):3036–3045

    Article  CAS  PubMed  Google Scholar 

  • Lucci A, Hall CS, Lodhi AK et al (2012) Circulating tumour cells in non-metastatic breast cancer: a prospective study. Lancet Oncol 13(7):688–695

    Article  PubMed  Google Scholar 

  • Lustberg M, Jatana KR, Zborowski M et al (2012) Emerging technologies for CTC detection based on depletion of normal cells. In: Ignatiadis M, Sotiriou C, Pantel K (eds) Minimal residual disease and circulating tumor cells in breast cancer. Springer, Heidelberg, pp 97–110

    Chapter  Google Scholar 

  • Ma H, Liu J, Ali MM et al (2015) Nucleic acid aptamers in cancer research, diagnosis and therapy. Chem Soc Rev 44(5):1240–1256

    Article  CAS  PubMed  Google Scholar 

  • McDonald JC, Whitesides GM (2002) Poly(dimethylsiloxane) as a material for fabricating microfluidic devices. Acc Chem Res 35(7):491–499

    Article  CAS  PubMed  Google Scholar 

  • Meng S, Tripathy D, Frenkel EP et al (2004) Circulating tumor cells in patients with breast cancer dormancy. Clin Cancer Res 10(24):8152–8162

    Article  PubMed  Google Scholar 

  • Miltenyi S, Müller W, Weichel W et al (1990) High gradient magnetic cell separation with MACS. Cytometry Part A 11(2):231–238

    Article  CAS  Google Scholar 

  • Mittal S, Wong IY, Deen WM et al (2012) Antibody-functionalized fluid-permeable surfaces for rolling cell capture at high flow rates. Biophys J 102(4):721–730

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Moffatt HK (1964) Viscous and resistive eddies near a sharp corner. J Fluid Mech 18(1):1–8

    Article  Google Scholar 

  • Myung JH, Hong S (2015) Microfluidic devices to enrich and isolate circulating tumor cells. Lab Chip 15(24):4500–4511

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nagrath S, Sequist LV, Maheswaran S et al (2007) Isolation of rare circulating tumour cells in cancer patients by microchip technology. Nature 450(7173):1235–1239

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Neurauter AA, Bonyhadi M, Lien E et al (2007) Cell isolation and expansion using Dynabeads®. In: Scheper T, Belkin S, Bley T et al (eds) Advances in biochemical engineering/biotechnology. Springer, Heidelberg, pp 41–73

    Google Scholar 

  • Ozkumur E, Shah AM, Ciciliano JC et al (2013) Inertial focusing for tumor antigen–dependent and–independent sorting of rare circulating tumor cells. Sci Transl Med 5(179):179ra47

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

  • Pantel K, Brakenhoff RH, Brandt B (2008) Detection, clinical relevance and specific biological properties of disseminating tumour cells. Nat Rev Cancer 8(5):329–340

    Article  CAS  PubMed  Google Scholar 

  • Park JM, Lee JY, Lee JG et al (2012) Highly efficient assay of circulating tumor cells by selective sedimentation with a density gradient medium and microfiltration from whole blood. Anal Chem 84(17):7400–7407

    Article  CAS  PubMed  Google Scholar 

  • Phillips JA, Xu Y, Xia Z et al (2008) Enrichment of cancer cells using aptamers immobilized on a microfluidic channel. Anal Chem 81(3):1033–1039

    Article  CAS  Google Scholar 

  • Poudineh M, Aldridge PM, Ahmed S et al (2017a) Tracking the dynamics of circulating tumour cell phenotypes using nanoparticle-mediated magnetic ranking. Nat Nanotechnol 12(3):274–281

    Article  CAS  PubMed  Google Scholar 

  • Poudineh M, Labib M, Ahmed S et al (2017b) Profiling functional and biochemical phenotypes of circulating tumor cells using a two-dimensional sorting device. Angew Chem Int Ed 56(1):163–168

    Article  CAS  Google Scholar 

  • Powell AA, Talasaz AH, Zhang H et al (2012) Single cell profiling of circulating tumor cells: transcriptional heterogeneity and diversity from breast cancer cell lines. PLoS ONE 7(5):e33788

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Qian W, Zhang Y, Chen W (2015) Capturing cancer: emerging microfluidic technologies for the capture and characterization of circulating tumor cells. Small 11(32):3850–3872

    Article  CAS  PubMed  Google Scholar 

  • Riethdorf S, Fritsche H, Müller V et al (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  PubMed  Google Scholar 

  • Saliba AE, Saias L, Psychari E et al (2010) Microfluidic sorting and multimodal typing of cancer cells in self-assembled magnetic arrays. Proc Natl Acad Sci U S A 107(33):14524–14529

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sarioglu AF, Aceto N, Kojic N et al (2015) A microfluidic device for label-free, physical capture of circulating tumor cell clusters. Nat Methods 12(7):685–691

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sawyers CL (2008) The cancer biomarker problem. Nature 452(7187):548–552

    Article  CAS  PubMed  Google Scholar 

  • Seal SH (1959) Silicone flotation: a simple quantitative method for the isolation of free-floating cancer cells from the blood. Cancer 12(3):590–595

    Article  CAS  PubMed  Google Scholar 

  • Seal SH (1964) A sieve for the isolation of cancer cells and other large cells from the blood. Cancer 17(5):637–642

    Article  CAS  PubMed  Google Scholar 

  • Segré G (1961) Radial particle displacements in Poiseuille flow of suspensions. Nature 189:209–210

    Article  Google Scholar 

  • Segré G, Silberberg A (1962) Behaviour of macroscopic rigid spheres in Poiseuille flow Part 2. Experimental results and interpretation. J Fluid Mech 14(1):136–157

    Article  Google Scholar 

  • Shaffer DR, Leversha MA, Danila DC et al (2007) Circulating tumor cell analysis in patients with progressive castration-resistant prostate cancer. Clin Cancer Res 13(7):2023–2029

    Article  CAS  PubMed  Google Scholar 

  • Shen Q, Xu L, Zhao L et al (2013) Specific capture and release of circulating tumor cells using aptamer-modified nanosubstrates. Adv Mater 25(16):2368–2373

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sheng W, Chen T, Kamath R et al (2012) Aptamer-enabled efficient isolation of cancer cells from whole blood using a microfluidic device. Anal Chem 84(9):4199–4206

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sheng W, Chen T, Tan W et al (2013) Multivalent DNA nanospheres for enhanced capture of cancer cells in microfluidic devices. ACS Nano 7(8):7067–7076

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Smirnov DA, Zweitzig DR, Foulk BW et al (2005) Global gene expression profiling of circulating tumor cells. Cancer Res 65(12):4993–4997

    Article  CAS  PubMed  Google Scholar 

  • Sollier E, Go DE, Che J et al (2014) Size-selective collection of circulating tumor cells using Vortex technology. Lab Chip 14(1):63–77

    Article  CAS  PubMed  Google Scholar 

  • Song KM, Lee S, Ban C (2012) Aptamers and their biological applications. Sensors 12(1):612–631

    PubMed  Google Scholar 

  • Song Y, Tian T, Shi Y et al (2017) Enrichment and single-cell analysis of circulating tumor cells. Chem Sci 8(3):1736–1751

    Article  CAS  PubMed  Google Scholar 

  • Stone HA, Kim S (2001) Microfluidics: basic issues, applications, and challenges. AIChE J 47(6):1250–1254

    Article  CAS  Google Scholar 

  • Stott SL, Hsu CH, Tsukrov DI et al (2010) Isolation of circulating tumor cells using a microvortex-generating herringbone-chip. Proc Natl Acad Sci U S A 107(43):18392–18397

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stroock AD, Dertinger SKW, Ajdari A et al (2002) Chaotic mixer for microchannels. Science 295(5555):647–651

    Article  CAS  PubMed  Google Scholar 

  • Sun H, Zhu X, Lu PY et al (2014) Oligonucleotide aptamers: new tools for targeted cancer therapy. Mol Ther Nucleic Acids 3:e182

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tachibana M (1973) On the behaviour of a sphere in the laminar tube flows. Rheol Acta 12(1):58–69

    Article  Google Scholar 

  • Talasaz AH, Powell AA, Huber DE et al (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  PubMed  PubMed Central  Google Scholar 

  • Tan SJ, Yobas L, Lee GY et al (2009) Microdevice for the isolation and enumeration of cancer cells from blood. Biomed Microdevices 11(4):883–892

    Article  PubMed  Google Scholar 

  • Tuerk C, Gold L (1990) Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. Science 249(4968):505–510

    Article  CAS  PubMed  Google Scholar 

  • van de Stolpe A, Pantel K, Sleijfer S et al (2011) Circulating tumor cell isolation and diagnostics: toward routine clinical use. Cancer Res 71(18):5955–5960

    Article  PubMed  CAS  Google Scholar 

  • Viraka Nellore BP, Kanchanapally R, Pramanik A et al (2015) Aptamer-conjugated graphene oxide membranes for highly efficient capture and accurate identification of multiple types of circulating tumor cells. Bioconjug Chem 26(2):235–242

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vona G, Sabile A, Louha M et al (2000) Isolation by size of epithelial tumor cells: a new method for the immunomorphological and molecular characterization of circulating tumor cells. Am J Pathol 156(1):57–63

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wan Y, Liu Y, Allen PB et al (2012) Capture, isolation and release of cancer cells with aptamer-functionalized glass bead array. Lab Chip 12(22):4693–4701

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang L, Zheng Q, Zhang QA et al (2012) Detection of single tumor cell resistance with aptamer biochip. Oncol Lett 4(5):935–940

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang S, Liu K, Liu J et al (2011) Highly efficient capture of circulating tumor cells by using nanostructured silicon substrates with integrated chaotic micromixers. Angew Chem Int Ed 50(13):3084–3088

    Article  CAS  Google Scholar 

  • Wang S, Wang H, Jiao J et al (2009) Three-dimensional nanostructured substrates toward efficient capture of circulating tumor cells. Angew Chem Int Ed 48(47):8970–8973

    Article  CAS  Google Scholar 

  • Warkiani ME, Khoo BL, Wu L et al (2016) Ultra-fast, label-free isolation of circulating tumor cells from blood using spiral microfluidics. Nat Protoc 11(1):134–148

    Article  CAS  PubMed  Google Scholar 

  • Watanabe S (1954) The metastasizability of tumor cells. Cancer 7(2):215–223

    Article  CAS  PubMed  Google Scholar 

  • Went PT, Lugli A, Meier S et al (2004) Frequent EpCam protein expression in human carcinomas. Hum Pathol 35(1):122–128

    Article  CAS  PubMed  Google Scholar 

  • Wunsch BH, Smith JT, Gifford SM et al (2016) Nanoscale lateral displacement arrays for the separation of exosomes and colloids down to 20 nm. Nat Nanotechnol 11:936–940

    Article  CAS  PubMed  Google Scholar 

  • Xu Y, Phillips JA, Yan J et al (2009) Aptamer-based microfluidic device for enrichment, sorting, and detection of multiple cancer cells. Anal Chem 81(17):7436–7442

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang L, Lang JC, Balasubramanian P et al (2009) Optimization of an enrichment process for circulating tumor cells from the blood of head and neck cancer patients through depletion of normal cells. Biotechnol Bioeng 102(2):521–534

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yoo CE, Moon HS, Kim YJ et al (2016) Highly dense, optically inactive silica microbeads for the isolation and identification of circulating tumor cells. Biomaterials 75:271–278

    Article  CAS  PubMed  Google Scholar 

  • Yoon Y, Kim S, Lee J et al (2016) Clogging-free microfluidics for continuous size-based separation of microparticles. Sci Rep 6:26531

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yu M, Bardia A, Aceto N et al (2014) Ex vivo culture of circulating breast tumor cells for individualized testing of drug susceptibility. Science 345(6193):216–220

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yu M, Stott S, Toner M et al (2011) Circulating tumor cells: approaches to isolation and characterization. J Cell Biol 192(3):373–382

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zamay GS, Kolovskaya OS, Zamay TN et al (2015) Aptamers selected to postoperative lung adenocarcinoma detect circulating tumor cells in human blood. Mol Ther 23(9):1486–1496

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhao L, Tang C, Xu L et al (2016) Enhanced and differential capture of circulating tumor cells from lung cancer patients by microfluidic assays using aptamer cocktail. Small 12(8):1072–1081

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhao W, Ali MM, Brook MA et al (2008) Rolling circle amplification: applications in nanotechnology and biodetection with functional nucleic acids. Angew Chem Int Ed 47(34):6330–6337

    Article  CAS  Google Scholar 

  • Zhao W, Cui CH, Bose S et al (2012) Bioinspired multivalent DNA network for capture and release of cells. Proc Natl Acad Sci U S A 109(48):19626–19631

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhao Y, Xu D, Tan W (2017) Aptamer-functionalized nano/micro-materials for clinical diagnosis: isolation, release and bioanalysis of circulating tumor cells. Integr Biol 9(3):188–205

    Article  Google Scholar 

  • Zheng S, Lin H, Liu JQ et al (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  PubMed  Google Scholar 

  • Zhou J, Rossi JJ (2014) Cell-type-specific, aptamer-functionalized agents for targeted disease therapy. Mol Ther Nucleic Acids 3(6):e169

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhou MD, Hao S, Williams AJ et al (2014) Separable bilayer microfiltration device for viable label-free enrichment of circulating tumour cells. Sci Rep 4:7392

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Georgia Institute of Technology, Atlanta, USA

    Mert Boya, Chia-Heng Chu, Ruxiu Liu, Tevhide Ozkaya-Ahmadov & Ali Fatih Sarioglu

Authors
  1. Mert Boya
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chia-Heng Chu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ruxiu Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tevhide Ozkaya-Ahmadov
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ali Fatih Sarioglu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ali Fatih Sarioglu .

Editor information

Editors and Affiliations

  1. Cancéropôle Est , Strasbourg, France

    Florence Schaffner

  2. Institut de Cancérologie de Lorraine, CNRS UMR7039 CRAN, Université de Lorraine, Vandoeuvre-lès-Nancy, France

    Jean-Louis Merlin

  3. Department of Hematology and Oncology, Medical Center, University of Schleswig-Holstein, Lübeck, Germany

    Nikolas von Bubnoff

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Boya, M., Chu, CH., Liu, R., Ozkaya-Ahmadov, T., Sarioglu, A.F. (2020). Circulating Tumor Cell Enrichment Technologies. In: Schaffner, F., Merlin, JL., von Bubnoff, N. (eds) Tumor Liquid Biopsies. Recent Results in Cancer Research, vol 215. Springer, Cham. https://doi.org/10.1007/978-3-030-26439-0_2

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-26439-0_2

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-26438-3

  • Online ISBN: 978-3-030-26439-0

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation