Presence of circulating tumor cells (CTCs) in blood is an important intermediate step in cancer metastasis, a mortal consequence of cancer. However, CTCs are extremely rare in blood with highly heterogeneous morphologies and molecular signatures, thus making their isolation technically very challenging. In the past decade, a flurry of new microfluidic-based technologies has emerged to address this compelling problem. This chapter highlights the current state of the art in microfluidic systems developed for CTCs separation and isolation. The techniques presented are broadly classified as physical- or affinity-based isolation depending on the separation principle. The performance of these techniques is evaluated based on accepted separation metrics including sensitivity, purity and processing/analysis time. Finally, further insights associated with realizing an integrated microfluidic CTC lab-on-chip system as an onco-diagnostic tool will be discussed.
Circulate Tumor Cell Microfluidic System Hematologic Cell Microfluidic Approach Inertial Lift Force
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Hayes DF 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):4218–4224PubMedCrossRefGoogle Scholar
Morgan TM, Lange PH, Vessella RL (2007) Detection and characterization of circulating and disseminated prostate cancer cells. Front Biosci 12:3000–3009PubMedCrossRefGoogle Scholar
Zheng S et al (2007) Membrane microfilter device for selective capture, electrolysis and genomic analysis of human circulating tumor cells. J Chromatogr A 1162(2):154–161PubMedCrossRefGoogle Scholar
Miller MC, Doyle GV, Terstappen L (2010) Significance of circulating tumor cells detected by the Cell Search system in patients with metastatic breast colorectal and prostate cancer. J Oncol 2010:617421PubMedGoogle Scholar
Vona G 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):57–63PubMedCrossRefGoogle Scholar
Hosokawa M et al (2010) Size-selective microcavity array for rapid and efficient detection of circulating tumor cells. Anal Chem 82(15):6629–6635PubMedCrossRefGoogle Scholar
Zabaglo L et al (2003) Cell filtration-laser scanning cytometry for the characterisation of circulating breast cancer cells. Cytometry Part A 55A(2):102–108CrossRefGoogle Scholar
Tan SJ et al (2009) Microdevice for the isolation and enumeration of cancer cells from blood. Biomed Microdevices 11(4):883–892PubMedCrossRefGoogle Scholar
Marrinucci D et al (2007) Case study of the morphologic variation of circulating tumor cells. Hum Pathol 38(3):514–519PubMedCrossRefGoogle Scholar
Tan SJ et al (2010) Versatile label free biochip for the detection of circulating tumor cells from peripheral blood in cancer patients. Biosensors and Bioelectronics 26(4):1701–1705PubMedCrossRefGoogle Scholar
Bhagat AAS et al (2011) Pinched flow coupled shear-modulated inertial microfluidics for high-throughput rare blood cell separation. Lab on a Chip 11(11):1870–1878PubMedCrossRefGoogle Scholar
Sim TS et al (2011) Multistage-multiorifice flow fractionation (MS-MOFF): continuous size-based separation of microspheres using multiple series of contraction/expansion microchannels. Lab on a Chip 11(1):93–99PubMedCrossRefGoogle Scholar
Kuntaegowdanahalli SS et al (2009) Inertial microfluidics for continuous particle separation in spiral microchannels. Lab on a Chip 9(20):2973–2980PubMedCrossRefGoogle Scholar
Bhagat AAS, Kuntaegowdanahalli SS, Papautsky I (2008) Enhanced particle filtration in straight microchannels using shear-modulated inertial migration. Phys Fluids 20:101702CrossRefGoogle Scholar
Nagrath S et al (2007) Isolation of rare circulating tumour cells in cancer patients by microchip technology. Nature 450(7173):1235–1239PubMedCrossRefGoogle Scholar
Stott SL et al (2010) Isolation of circulating tumor cells using a microvortex-generating herringbone-chip. Proc Natl Acad Sci 107(43):18392PubMedCrossRefGoogle Scholar
Gleghorn JP et al (2010) Capture of circulating tumor cells from whole blood of prostate cancer patients using geometrically enhanced differential immunocapture (GEDI) and a prostate-specific antibody. Lab on a Chip 10(1):27–29PubMedCrossRefGoogle Scholar
Saliba AE et al (2010) Microfluidic sorting and multimodal typing of cancer cells in self-assembled magnetic arrays. Proc Natl Acad Sci 107(33):14524PubMedCrossRefGoogle Scholar
Sieuwerts AM et al (2009) Anti-epithelial cell adhesion molecule antibodies and the detection of circulating normal-like breast tumor cells. J Natl Cancer Inst 101(1):61–66PubMedGoogle Scholar
Xu Y et al (2009) Aptamer-based microfluidic device for enrichment, sorting, and detection of multiple cancer cells. Anal Chem 81(17):7436–7442PubMedCrossRefGoogle Scholar