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http://dx.doi.org/10.4218/etrij.15.0114.0572

Microdevice for Separation of Circulating Tumor Cells Using Embedded Magnetophoresis with V-shaped Ni-Co Nanowires and Immuno-nanomagnetic Beads  

Park, Jeong Won (IT Convergence Technology Research Laboratory, ETRI)
Lee, Nae-Rym (IT Convergence Technology Research Laboratory, ETRI)
Cho, Sung Mok (IT Convergence Technology Research Laboratory, ETRI)
Jung, Moon Youn (IT Convergence Technology Research Laboratory, ETRI)
Ihm, Chunhwa (Department of Clinical Dignostic, Eulji University)
Lee, Dae-Sik (IT Convergence Technology Research Laboratory, ETRI)
Publication Information
ETRI Journal / v.37, no.2, 2015 , pp. 233-240 More about this Journal
Abstract
The novelty of this study resides in a 6"-wafer-level microfabrication protocol for a microdevice with a fluidic control system for the separation of circulating tumor cells (CTCs) from human whole blood cells. The microdevice utilizes a lateral magnetophoresis method based on immunomagnetic nanobeads with anti-epithelial cell adhesive molecule antibodies that selectively bind to epithelial cancer cells. The device consists of a top polydimethylsiloxane substrate for microfluidic control and a bottom substrate for lateral magnetophoretic force generation with embedded v-shaped soft magnetic microwires. The microdevice can isolate about 93% of the spiked cancer cells (MCF-7, a breast cancer cell line) at a flow rate of 40/100 mL/min with respect to a whole human blood/buffer solution. For all isolation, it takes only 10 min to process 400 mL of whole human blood. The fabrication method is sufficiently simple and easy, allowing the microdevice to be a mass-producible clinical tool for cancer diagnosis, prognosis, and personalized medicine.
Keywords
Breast cancer; circulating tumor cells; Ni-Co electroplating; microfluidic; cancer diagnosis;
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Times Cited By KSCI : 2  (Citation Analysis)
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1 S.J. Cohen et al., "Relationship of Circulating Tumor Cells to Tumor Response, Progression-Free Survival, and Overall Survival in Patients with Metastatic Colorectal Cancer," J. Clinical Oncology, vol. 26, no. 19, July 2008, pp. 3213-3221.   DOI
2 W. He et al., "Quantitation of Circulating Tumor Cells in Blood Samples from Ovarian and Prostate Cancer Patients Using Tumor-Specific Fluorescent Ligands," Int. J. Cancer, vol. 123, no. 8, Oct. 2008, pp. 1968-1973.   DOI
3 M.C. Miller, G.V. Doyle, and L.W.M.M. Terstappen, "Significance of Circulating Tumor Cells Detected by the Cellsearch System in Patients with Metastatic Breast Colorectal and Prostate Cancer," J. Oncology, Jan. 2010, pp. 1-8.
4 M. Cristofanilli et al., "Circulating Tumor Cells, Disease Progression, and Survival in Metastatic Breast Cancer," New England J. Medicine, vol. 351, no. 8, Aug. 2004, pp. 781-791.   DOI
5 J.S. de Bono et al., "Circulating Tumor Cells Predict Survival Benefit from Treatment in Metastatic Castration-Resistant Prostate Cancer," Clinical Cancer Res., vol. 14, Oct. 2008, pp. 6302-6309.   DOI
6 C. Alix-Panabieres, S. Riethdorf, and K. Pantel, "Circulating Tumor Cells and Bone Marrow Micrometastasis," Clinical Cancer Res., vol. 14, no. 16, Aug. 2008, pp. 5013-5021.   DOI
7 B. Mostert et al., "Circulating Tumor Cells (Ctcs): Detection, Methods and their Clinical Relevance in Breast Cancer," Cancer Treatment Rev., vol. 35, no. 5, Aug. 2009, pp. 463-474.   DOI
8 S.K. Arya, B. Lim, and A.R.A. Rahman, "Enrichment, Detection and Clinical Significance of Circulating Tumor Cells," Lab Chip, vol. 13, Nov. 2013, pp. 1995-2027.   DOI
9 S. Riethdorf et al., "Detection of Circulating Tumor Cells in Peripheral Blood of Patients with Metastatic Breast Cancer : A Validation Study of the Cellsearch System," Clinical Cancer Res., vol. 13, no. 3, Feb. 2007, pp. 920-928.   DOI
10 K.A. Hyun and H.I. Jung, "Advances and Critical Concerns with the Microfluidic Enrichments of Circulating Tumor Cells," Lab Chip, vol. 14, Jan. 2014, pp. 45-56.   DOI
11 C. Alix-Panabieres and K. Pantel, "Technologies for Detection of Circulating Tumor Cells: Facts and Vision," Lab Chip, vol. 14, Jan. 2014, pp. 57-62.   DOI
12 S. Nagrath et al., "Isolation of Rare Circulating Tumor Cells in Cancer Patients by Microchip Technology," Nature, vol. 450, Dec. 2007, pp. 1235-1239.   DOI
13 J.D. Adams, U. Kim, and H.T. Soh, "Multitarget Magnetic Activated Cell Sorter," PNAS, vol. 105, no. 47, Nov. 2008, pp. 18165-18170.   DOI
14 A. Salmanzadeh and R.V. Davalos, "Isolation of Rare Cells through their Dielectrophoretic Signature," J. Membra. Sci. Technol., vol. 3, Jan. 2013, pp. 1-4.
15 S. Kim et al., "Circulating Tumor Cell Microseparator Based on Lateral Magnetophoresis and Immuno-Magnetic Nanobeads," Anal. Chem., vol. 85, no. 5, Feb. 2013, pp. 2779-2786.   DOI
16 K.-A. Hyun et al., "Microfluidic Flow Fractionation Device for Label-Free Isolation of Circulating Tumor Cells (CTCs) from Breast Cancer Patients," Biosen. Bioelectron., vol. 40, no. 1, Feb. 2013, pp. 206-212.   DOI
17 T. Huang et al., "Highly Sensitive Enumeration of Circulating Tumor Cells in Lung Cancer Patients Using a Size-Based Filtration Microfluidic Chip," Biosen. Bioelectron., vol. 51, Jan. 2014, pp. 213-218.   DOI
18 E. Sollier et al., "Size-Selective Collection of Circulating Tumor Cells Using Vortex Technology," Lab. Chip, vol. 40, Jan. 2014, pp. 63-77.
19 M. Duch et al., "Development and Characterization of Co-Ni Alloys for Microsystems Applications," J. Electrochem. Soc., vol. 149, no. 4, Feb. 2002, pp. C201-C208.   DOI
20 W.P. Taylor et al., "Electroplated Soft Magnetic Materials for Microsensors and Microactuators," Proc. Int. Conf. Solid-State Sensors Actuators, Chicago, IL, USA, vol. 2, June 16-19, 1997, pp. 1445-1448.
21 B. Lochel and A. Maciossek, "Electrodeposited Magnetic Alloys for Surfac Micromachining," J. Electrochem. Soc., vol. 143, Oct. 1996, pp. 3343-3348.   DOI
22 D.-S. Lee et al., "Construction of Membrane Sieves Using Stoichiometric and Stress-Reduced $Si_3N_4/Sio_2/Si_3N_4$ Multilayer Films and their Applications in Blood Plasma Separation," ETRI J., vol. 34, no. 2, Apr. 2012, pp. 226-234.   DOI
23 Z. Zhang, P. Zhao, and G. Xiao, "The Fabrication of Polymer Microfluidic Devices Using a Solid-to-Solid Interfacial Polyaddition," Polymer, vol. 50, no. 23, Nov. 3, 2009, pp. 5358-5361.   DOI
24 S.E. Moon et al., "Semiconductor-Type MEMS Gas Sensor for Real-Time Environmental Monitoring Applications," ETRI J., vol. 35, no. 4, Aug. 2013, pp. 617-624.   DOI
25 M.S. Kim et al., "SSA-MOA: A Novel CTC Isolation Platform Using Selective Size Amplification (SSA) and a Multi-obstacle Architecture (MOA) Filter," Lab Chip, vo1. 12, no. 16, Aug. 2012, pp. 2874-2880.   DOI
26 D.-S. Lee et al., "Fabrication of Microdevices for Separation of Circulating Tumor Cell Using Lateral Magnetophoresis and Immunomagnetic Nanobeads," Proc. IEEE Sens., Baltimore, MD, USA, Nov. 3-6, 2013, pp. 1299-1302.
27 J.M.K. Ng et al., "Components for Integrated Poly (Dimethylsiloxane) Microfluidic Systems," Electrophoresis, vol. 23, no. 20, Oct. 2002, pp. 3461-3473.   DOI
28 S. Talaei et al., "Hybrid Microfluidic Cartridge Formed by Irreversible Bonding of SU-8 and PDMS for Multi-layer Flow Applications," Procedia Chem., vol. 1, no. 1, Sept. 2009, pp. 381-384.   DOI
29 D.W. Inglis et al., "Continuous Microfluidic Immunomagnetic Cell Separation," Appl. Phys. Lett., vol. 85, Nov. 2004, pp. 5093-5095.   DOI
30 S.L. Stott et al., "Isolaton of Circulating Tumor Cells Using a Microvortex-Generating Herringbone-Chip," PNAS, vol. 107, no. 43, Oct. 2010, pp. 18392-18397.   DOI
31 A.S.W. Ng et al., "Electrokinetic Generation of Microvortex Patterns in a Microchannel Liquid Flow," J. Micromechanics Microeng., vol. 14, no. 2, Nov. 2004, pp. 247-253.   DOI
32 D.R. Parkinson et al., "Considerations in the Development of Circulating Tumor Cell Technology for Clinical Use," J. Transl. Medicine, vol. 10, no. 138, Oct. 2012, pp. 1-20.   DOI
33 G.T.A. Kovacs, "Micromachined Transducers Sourcebook," Boston, MA, USA: McGraw-Hill, 1999, pp. 779-883.
34 P. Chen et al., "Multiscale Immunomagnetic Enrichment of Circulating Tumor Cells: From Tubes to Microchips," Lab Chip, vol. 14, Feb. 2014, pp. 446-458.   DOI
35 B. Hong and Y. Zu, "Detecting Circulating Tumor Cells: Current Challenges and New Trends," Theranostics, vol. 3, no. 6, Apr. 2013, pp. 377-394.   DOI