低成本的材料與製程以及操作的簡易度將可決定實驗室晶片是否可以被大量使用於日常生活中的各種應用。目前發展中的平價實驗室晶片，一部分為紙基裝置應用的研究，另一部份則屬利用高分子材料，如：聚二甲基矽氧烷(polydimethylsiloxane, PDMS)製作之實驗室晶片。紙基裝置具有極低成本、可拋棄式及易於製造等特性。本研究發展紙基裝置應用於單一微藻細胞之分離：係利用隨處可得之碳粉印表機在一般濾紙上印出圖形，濾紙上有碳粉處流速低，而無碳粉處流速高，藉由濾紙上個別區域流速不同，將藻類細胞單一分離於特定位置， 製造分離及檢測效果。分離過程只需30秒，單一微藻分離效率平均可達37%。此紙基藻類細胞分離裝置為開放式設計，可用一般微量吸管將分離後之樣本吸取至其他裝置作後續應用分析。此紙基藻類細胞分離裝置也可作為培養藻類使用，經分離後的藻類生物樣本可直接於紙基裝置上培養。本研究並發展PDMS濾膜晶片應用於微藻及循環腫瘤細胞(Circulating Tumor Cells, CTCs)的分離及檢測。一直以來利用濾膜分離大小不同粒子的方法都面臨阻塞的缺點，而利用側流(cross-flow)過濾法是一種能有效降低阻塞的過濾方法。本研究發展一種同心圓離心式濾膜分離晶片。利用一般實驗室中常用之小型離心機作為動力，其所產生之離心力將會將粒子向圓周牽引，大小不同粒子會被不同孔徑之多層同心圓PDMS濾膜結構分離。利用改變離心機轉速，如瞬間停止或加速，製造流體與裝置的相對運動，將會使PDMS同心圓濾孔結構周圍產生側流，可有效將阻塞於濾孔附近的粒子及微藻沖散，減輕阻塞情形增加分離效率。結果顯示濾膜晶片所產生之側流可增加粒子分離效率達13.7%以上。此PDMS同心圓濾膜晶片也可應用於偵測稀少循環腫瘤細胞。利用抗體對於在細胞表面上的特殊抗原具專一性結合的特性，使接有特定腫瘤抗體之聚苯乙烯微球(PS beads)和CTCs結合，增加CTCs體積。利用離心力將體積較小且數量眾多之非癌細胞如白血球等分離至晶片的外層流道，與PS beads結合的CTCs由於體積較大而停留在同心圓濾膜結構中的中心內層流道內，由於同心圓內層流道的面積小而易於利用顯微鏡檢測CTCs。結果顯示此方法可於CTCs與白血球比例為 1:1,000,000的混和濃度下測得CTCs。

Material and fabrication at low-cost used for lab-on-a-chip (LOC) system and the ease of operation without expensive and complicated instruments are crucial for wide application in our daily life. The current low-cost LOC material could be categorized as two types: paper-based LOC and polymer like polydimethylsiloxane (PDMS) based device. Paper-based devices enable the advantages of easy fabrication, disposable nature and least cost. Using an office laser printer to create a carbon powder pattern on the filter paper, we created a microwell pattern area of which the uncovered carbon powder enables a flow rate greater than that where covered with carbon powder along the filter; the flow can carry and localize single microalgae into the microwell separately. The separation process only takes 30 seconds and the separation performance of isolating single microalgae could be over 37% in average. The open-structure design of the paper device makes it operable with a common laboratory micropipette for sample retrieval and transfer. The paper-device can also function as an incubator for microalgae growth on simply rinsing the paper with a growth medium. In this research, we developed PDMS based filter LOC devices to separate microalgae and detect circulating tumor cells (CTCs). Clogging always becomes a main issue on filter based separation; cross-flow system was proven to reduce this drawback. We develop a centrifugally driven, multilayer, concentric filter device, a small bench-top centrifuge, which is commonly available in biochemical laboratories, was employed as part of our centrifugal microfluidic separation system. The cross-flow in our separation system was simply generated on altering the rate of rotation, as revolutions per minute (RPM), instantly through the relative motion of the device and the fluid. This strong cross-flow can wash away the particle and microalgae clogs at the filter pores, so increasing the filtration performance over 13.7 % without complicated control and expensive equipment. The use of the PDMS filter device enabled variously sized microparticles and environmentally collected microalgae samples to be readily separated in a few minutes. This device was also applied to detect CTCs. By using the anti–human EpCAM antibody coated polystyrene (PS) beads to capture CTCs which could enlarge the size of CTCs to create significant size different from normal cell like white blood cells (WBCs). With a concentric filter device and centrifugation, the unbound PS beads and WCBs would flow to the outer layer of the device; the targeted CTCs bound with PS beads would be retained in the inner filter layer. The inner filter layer is designed as a detection zone in which the bound cells are easily observed by microscope because of the small area of the inner channel and the enrichment effect. We successfully demonstrate that CTCs could be separated and detected in the concentration of one CTC per million of WBCs by this device and method.

[1] A. W. Martinez, S. T. Phillips, M. J. Butte, and G. M. Whitesides, "Patterned paper as a platform for inexpensive, low-volume, portable bioassays," Angew Chem Int Ed Engl, vol. 46, pp. 1318-20, 2007.
[2] D. A. Bruzewicz, M. Reches, and G. M. Whitesides, "Low-cost printing of poly(dimethylsiloxane) barriers to define microchannels in paper," Anal Chem, vol. 80, pp. 3387-92, May 1 2008.
[3] A. W. Martinez, S. T. Phillips, E. Carrilho, S. W. Thomas, 3rd, H. Sindi, and G. M. Whitesides, "Simple telemedicine for developing regions: camera phones and paper-based microfluidic devices for real-time, off-site diagnosis," Anal Chem, vol. 80, pp. 3699-707, May 15 2008.
[4] E. Carrilho, A. W. Martinez, and G. M. Whitesides, "Understanding wax printing: a simple micropatterning process for paper-based microfluidics," Anal Chem, vol. 81, pp. 7091-5, Aug 15 2009.
[5] Y. Lu, W. Shi, L. Jiang, J. Qin, and B. Lin, "Rapid prototyping of paper-based microfluidics with wax for low-cost, portable bioassay," Electrophoresis, vol. 30, pp. 1497-500, May 2009.
[6] J. Olkkonen, K. Lehtinen, and T. Erho, "Flexographically printed fluidic structures in paper," Anal Chem, vol. 82, pp. 10246-50, Dec 15 2010.
[7] W. Dungchai, O. Chailapakul, and C. S. Henry, "A low-cost, simple, and rapid fabrication method for paper-based microfluidics using wax screen-printing," Analyst, vol. 136, pp. 77-82, Jan 7 2011.
[8] G. Chitnis, Z. Ding, C. L. Chang, C. A. Savran, and B. Ziaie, "Laser-treated hydrophobic paper: an inexpensive microfluidic platform," Lab Chip, vol. 11, pp. 1161-5, Mar 21 2011.
[9] C. L. do Lago, H. D. da Silva, C. A. Neves, J. G. Brito-Neto, and J. A. da Silva, "A dry process for production of microfluidic devices based on the lamination of laser-printed polyester films," Anal Chem, vol. 75, pp. 3853-8, Aug 1 2003.
[10] K. M. Schilling, A. L. Lepore, J. A. Kurian, and A. W. Martinez, "Fully enclosed microfluidic paper-based analytical devices," Anal Chem, vol. 84, pp. 1579-85, Feb 7 2012.
[11] A. W. Martinez, S. T. Phillips, G. M. Whitesides, and E. Carrilho, "Diagnostics for the developing world: microfluidic paper-based analytical devices," Anal Chem, vol. 82, pp. 3-10, Jan 1 2010.
[12] D. C. Duffy, J. C. McDonald, O. J. Schueller, and G. M. Whitesides, "Rapid Prototyping of Microfluidic Systems in Poly(dimethylsiloxane)," Anal Chem, vol. 70, pp. 4974-84, Dec 1 1998.
[13] G. M. Whitesides, E. Ostuni, S. Takayama, X. Jiang, and D. E. Ingber, "Soft lithography in biology and biochemistry," Annu Rev Biomed Eng, vol. 3, pp. 335-73, 2001.
[14] J. C. McDonald and G. M. Whitesides, "Poly(dimethylsiloxane) as a material for fabricating microfluidic devices," Acc Chem Res, vol. 35, pp. 491-9, Jul 2002.
[15] J. M. Ng, I. Gitlin, A. D. Stroock, and G. M. Whitesides, "Components for integrated poly(dimethylsiloxane) microfluidic systems," Electrophoresis, vol. 23, pp. 3461-73, Oct 2002.
[16] K. H. Cardozo, T. Guaratini, M. P. Barros, V. R. Falcao, A. P. Tonon, N. P. Lopes, et al., "Metabolites from algae with economical impact," Comp Biochem Physiol C Toxicol Pharmacol, vol. 146, pp. 60-78, Jul-Aug 2007.
[17] H. W. Yen, I. C. Hu, C. Y. Chen, S. H. Ho, D. J. Lee, and J. S. Chang, "Microalgae-based biorefinery - From biofuels to natural products," Bioresour Technol, Nov 1 2012.
[18] H. Guo, M. Daroch, L. Liu, G. Qiu, S. Geng, and G. Wang, "Biochemical features and bioethanol production of microalgae from coastal waters of Pearl River Delta," Bioresour Technol, vol. 127, pp. 422-8, Jan 2013.
[19] M. M. El Abed, B. Marzouk, M. N. Medhioub, A. N. Helal, and A. Medhioub, "Microalgae: a potential source of polyunsaturated fatty acids," Nutr Health, vol. 19, pp. 221-6, 2008.
[20] G. Zhao, X. Chen, L. Wang, S. Zhou, H. Feng, W. N. Chen, et al., "Ultrasound assisted extraction of carbohydrates from microalgae as feedstock for yeast fermentation," Bioresour Technol, vol. 128, pp. 337-44, Jan 2013.
[21] F. J. Zendejas, P. I. Benke, P. D. Lane, B. A. Simmons, and T. W. Lane, "Characterization of the acylglycerols and resulting biodiesel derived from vegetable oil and microalgae (Thalassiosira pseudonana and Phaeodactylum tricornutum)," Biotechnol Bioeng, vol. 109, pp. 1146-54, May 2012.
[22] A. C. Guedes, H. M. Amaro, and F. X. Malcata, "Microalgae as sources of high added-value compounds--a brief review of recent work," Biotechnol Prog, vol. 27, pp. 597-613, May-Jun 2011.
[23] S. Riethdorf, H. Wikman, and K. Pantel, "Review: Biological relevance of disseminated tumor cells in cancer patients," Int J Cancer, vol. 123, pp. 1991-2006, Nov 1 2008.
[24] J. M. Hou, M. Krebs, T. Ward, R. Sloane, L. Priest, A. Hughes, et al., "Circulating tumor cells as a window on metastasis biology in lung cancer," Am J Pathol, vol. 178, pp. 989-96, Mar 2011.
[25] G. T. Budd, M. Cristofanilli, M. J. Ellis, A. Stopeck, E. Borden, M. C. Miller, et al., "Circulating tumor cells versus imaging--predicting overall survival in metastatic breast cancer," Clin Cancer Res, vol. 12, pp. 6403-9, Nov 1 2006.
[26] M. Cristofanilli, G. T. Budd, M. J. Ellis, A. Stopeck, J. Matera, M. C. Miller, et al., "Circulating tumor cells, disease progression, and survival in metastatic breast cancer," N Engl J Med, vol. 351, pp. 781-91, Aug 19 2004.
[27] H. I. Scher, X. Jia, J. S. de Bono, M. Fleisher, K. J. Pienta, D. Raghavan, et al., "Circulating tumour cells as prognostic markers in progressive, castration-resistant prostate cancer: a reanalysis of IMMC38 trial data," Lancet Oncol, vol. 10, pp. 233-9, Mar 2009.
[28] S. J. Cohen, C. J. Punt, N. Iannotti, B. H. Saidman, K. D. Sabbath, N. Y. Gabrail, et al., "Prognostic significance of circulating tumor cells in patients with metastatic colorectal cancer," Ann Oncol, vol. 20, pp. 1223-9, Jul 2009.
[29] P. Gazzaniga, A. Gradilone, E. de Berardinis, G. M. Busetto, C. Raimondi, O. Gandini, et al., "Prognostic value of circulating tumor cells in nonmuscle invasive bladder cancer: a CellSearch analysis," Ann Oncol, vol. 23, pp. 2352-6, Sep 2012.
[30] D. Olmos, H. T. Arkenau, J. E. Ang, I. Ledaki, G. Attard, C. P. Carden, et al., "Circulating tumour cell (CTC) counts as intermediate end points in castration-resistant prostate cancer (CRPC): a single-centre experience," Ann Oncol, vol. 20, pp. 27-33, Jan 2009.
[31] J. Y. Pierga, D. Hajage, T. Bachelot, S. Delaloge, E. Brain, M. Campone, et al., "High independent prognostic and predictive value of circulating tumor cells compared with serum tumor markers in a large prospective trial in first-line chemotherapy for metastatic breast cancer patients," Ann Oncol, vol. 23, pp. 618-24, Mar 2012.
[32] E. A. Punnoose, S. Atwal, W. Liu, R. Raja, B. M. Fine, B. G. Hughes, et al., "Evaluation of circulating tumor cells and circulating tumor DNA in non-small cell lung cancer: association with clinical endpoints in a phase II clinical trial of pertuzumab and erlotinib," Clin Cancer Res, vol. 18, pp. 2391-401, Apr 15 2012.
[33] M. J. Serrano, P. Sanchez-Rovira, M. Delgado-Rodriguez, and J. J. Gaforio, "Detection of circulating tumor cells in the context of treatment: prognostic value in breast cancer," Cancer Biol Ther, vol. 8, pp. 671-5, Apr 2009.
[34] A. A. Bhagat, S. S. Kuntaegowdanahalli, and I. Papautsky, "Continuous particle separation in spiral microchannels using Dean flows and differential migration," Lab Chip, vol. 8, pp. 1906-14, Nov 2008.
[35] S. C. Hur, N. K. Henderson-MacLennan, E. R. McCabe, and D. Di Carlo, "Deformability-based cell classification and enrichment using inertial microfluidics," Lab Chip, vol. 11, pp. 912-20, Mar 7 2011.
[36] J. Zhou, P. V. Giridhar, S. Kasper, and I. Papautsky, "Modulation of aspect ratio for complete separation in an inertial microfluidic channel," Lab Chip, vol. 13, pp. 1919-29, May 21 2013.
[37] J. Zhou and I. Papautsky, "Fundamentals of inertial focusing in microchannels," Lab Chip, vol. 13, pp. 1121-32, Mar 21 2013.
[38] G. Guan, L. Wu, A. A. Bhagat, Z. Li, P. C. Chen, S. Chao, et al., "Spiral microchannel with rectangular and trapezoidal cross-sections for size based particle separation," Sci Rep, vol. 3, p. 1475, 2013.
[39] D. Di Carlo, D. Irimia, R. G. Tompkins, and M. Toner, "Continuous inertial focusing, ordering, and separation of particles in microchannels," Proc Natl Acad Sci U S A, vol. 104, pp. 18892-7, Nov 27 2007.
[40] M. Yamada, M. Nakashima, and M. Seki, "Pinched flow fractionation: continuous size separation of particles utilizing a laminar flow profile in a pinched microchannel," Anal Chem, vol. 76, pp. 5465-71, Sep 15 2004.
[41] M. Yamada, K. Kano, Y. Tsuda, J. Kobayashi, M. Yamato, M. Seki, et al., "Microfluidic devices for size-dependent separation of liver cells," Biomed Microdevices, vol. 9, pp. 637-45, Oct 2007.
[42] D. W. Inglis, J. A. Davis, R. H. Austin, and J. C. Sturm, "Critical particle size for fractionation by deterministic lateral displacement," Lab Chip, vol. 6, pp. 655-8, May 2006.
[43] S. Choi, J. M. Karp, and R. Karnik, "Cell sorting by deterministic cell rolling," Lab Chip, vol. 12, pp. 1427-30, Apr 21 2012.
[44] C. H. Hsu, D. Di Carlo, C. Chen, D. Irimia, and M. Toner, "Microvortex for focusing, guiding and sorting of particles," Lab Chip, vol. 8, pp. 2128-34, Dec 2008.
[45] D. Di Carlo and L. P. Lee, "Dynamic single-cell analysis for quantitative biology," Anal Chem, vol. 78, pp. 7918-25, Dec 1 2006.
[46] D. Di Carlo, L. Y. Wu, and L. P. Lee, "Dynamic single cell culture array," Lab Chip, vol. 6, pp. 1445-9, Nov 2006.
[47] S. Lindstrom and H. Andersson-Svahn, "Miniaturization of biological assays -- overview on microwell devices for single-cell analyses," Biochim Biophys Acta, vol. 1810, pp. 308-16, Mar 2011.
[48] H. M. Ji, V. Samper, Y. Chen, C. K. Heng, T. M. Lim, and L. Yobas, "Silicon-based microfilters for whole blood cell separation," Biomed Microdevices, vol. 10, pp. 251-7, Apr 2008.
[49] V. VanDelinder and A. Groisman, "Separation of plasma from whole human blood in a continuous cross-flow in a molded microfluidic device," Anal Chem, vol. 78, pp. 3765-71, Jun 1 2006.
[50] H. Mohamed, J. N. Turner, and M. Caggana, "Biochip for separating fetal cells from maternal circulation," J Chromatogr A, vol. 1162, pp. 187-92, Aug 31 2007.
[51] P. Sethu, A. Sin, and M. Toner, "Microfluidic diffusive filter for apheresis (leukapheresis)," Lab Chip, vol. 6, pp. 83-9, Jan 2006.
[52] S. Nagrath, L. V. Sequist, S. Maheswaran, D. W. Bell, D. Irimia, L. Ulkus, et al., "Isolation of rare circulating tumour cells in cancer patients by microchip technology," Nature, vol. 450, pp. 1235-9, Dec 20 2007.
[53] J. P. Gleghorn, E. D. Pratt, D. Denning, H. Liu, N. H. Bander, S. T. Tagawa, et al., "Capture of circulating tumor cells from whole blood of prostate cancer patients using geometrically enhanced differential immunocapture (GEDI) and a prostate-specific antibody," Lab Chip, vol. 10, pp. 27-9, Jan 7 2010.
[54] M. S. Kim, T. S. Sim, Y. J. Kim, S. S. Kim, H. Jeong, J. M. Park, et al., "SSA-MOA: a novel CTC isolation platform using selective size amplification (SSA) and a multi-obstacle architecture (MOA) filter," Lab Chip, vol. 12, pp. 2874-80, Aug 21 2012.
[55] J. Doyen, C. Alix-Panabieres, P. Hofman, S. K. Parks, E. Chamorey, H. Naman, et al., "Circulating tumor cells in prostate cancer: a potential surrogate marker of survival," Crit Rev Oncol Hematol, vol. 81, pp. 241-56, Mar 2012.
[56] T. B. Jones, Electromechanics of particles. Cambridge ; New York: Cambridge University Press, 1995.
[57] S. Park and A. Beskok, "Alternating current electrokinetic motion of colloidal particles on interdigitated microelectrodes," Anal Chem, vol. 80, pp. 2832-41, Apr 15 2008.
[58] B. H. Lapizco-Encinas, B. A. Simmons, E. B. Cummings, and Y. Fintschenko, "Dielectrophoretic concentration and separation of live and dead bacteria in an array of insulators," Anal Chem, vol. 76, pp. 1571-9, Mar 15 2004.
[59] A. Lenshof, C. Magnusson, and T. Laurell, "Acoustofluidics 8: applications of acoustophoresis in continuous flow microsystems," Lab Chip, vol. 12, pp. 1210-23, Apr 7 2012.
[60] T. Laurell, F. Petersson, and A. Nilsson, "Chip integrated strategies for acoustic separation and manipulation of cells and particles," Chem Soc Rev, vol. 36, pp. 492-506, Mar 2007.
[61] L. Johansson, F. Nikolajeff, S. Johansson, and S. Thorslund, "On-chip fluorescence-activated cell sorting by an integrated miniaturized ultrasonic transducer," Anal Chem, vol. 81, pp. 5188-96, Jul 1 2009.
[62] X. Ding, P. Li, S. C. Lin, Z. S. Stratton, N. Nama, F. Guo, et al., "Surface acoustic wave microfluidics," Lab Chip, vol. 13, pp. 3626-49, Sep 21 2013.
[63] S. H. Cho, C. H. Chen, F. S. Tsai, J. M. Godin, and Y. H. Lo, "Human mammalian cell sorting using a highly integrated micro-fabricated fluorescence-activated cell sorter (microFACS)," Lab Chip, vol. 10, pp. 1567-73, Jun 21 2010.
[64] O. Jakobsson, C. Grenvall, M. Nordin, M. Evander, and T. Laurell, "Acoustic actuated fluorescence activated sorting of microparticles," Lab Chip, vol. 14, pp. 1943-50, Jun 7 2014.
[65] P. Spolaore, C. Joannis-Cassan, E. Duran, and A. Isambert, "Commercial applications of microalgae," J Biosci Bioeng, vol. 101, pp. 87-96, Feb 2006.
[66] S. H. Ho, S. W. Huang, C. Y. Chen, T. Hasunuma, A. Kondo, and J. S. Chang, "Bioethanol production using carbohydrate-rich microalgae biomass as feedstock," Bioresour Technol, Oct 16 2012.
[67] W. Liu, N. Dechev, I. G. Foulds, R. Burke, A. Parameswaran, and E. J. Park, "A novel permalloy based magnetic single cell micro array," Lab Chip, vol. 9, pp. 2381-90, Aug 21 2009.
[68] K. Ramser and D. Hanstorp, "Optical manipulation for single-cell studies," J Biophotonics, vol. 3, pp. 187-206, Apr 2010.
[69] B. M. Taff and J. Voldman, "A scalable addressable positive-dielectrophoretic cell-sorting array," Anal Chem, vol. 77, pp. 7976-83, Dec 15 2005.
[70] A. Yusof, H. Keegan, C. D. Spillane, O. M. Sheils, C. M. Martin, J. J. O'Leary, et al., "Inkjet-like printing of single-cells," Lab Chip, vol. 11, pp. 2447-54, Jul 21 2011.
[71] L. Lin, Y. S. Chu, J. P. Thiery, C. T. Lim, and I. Rodriguez, "Microfluidic cell trap array for controlled positioning of single cells on adhesive micropatterns," Lab Chip, vol. 13, pp. 714-21, Feb 21 2013.
[72] A. K. Yetisen, M. S. Akram, and C. R. Lowe, "Paper-based microfluidic point-of-care diagnostic devices," Lab Chip, vol. 13, pp. 2210-51, Jun 21 2013.
[73] X. Li, D. R. Ballerini, and W. Shen, "A perspective on paper-based microfluidics: Current status and future trends," Biomicrofluidics, vol. 6, pp. 11301-1130113, Mar 2012.
[74] H. Wang, W. Zhang, L. Chen, J. Wang, and T. Liu, "The contamination and control of biological pollutants in mass cultivation of microalgae," Bioresour Technol, vol. 128, pp. 745-50, Jan 2013.
[75] R. Devendra and G. Drazer, "Gravity driven deterministic lateral displacement for particle separation in microfluidic devices," Anal Chem, vol. 84, pp. 10621-7, Dec 18 2012.
[76] S. S. Kuntaegowdanahalli, A. A. Bhagat, G. Kumar, and I. Papautsky, "Inertial microfluidics for continuous particle separation in spiral microchannels," Lab Chip, vol. 9, pp. 2973-80, Oct 21 2009.
[77] K. B. Andersen, S. Levinsen, W. E. Svendsen, and F. Okkels, "A generalized theoretical model for "continuous particle separation in a microchannel having asymmetrically arranged multiple branches"," Lab Chip, vol. 9, pp. 1638-9, Jun 7 2009.
[78] D. Huh, J. H. Bahng, Y. Ling, H. H. Wei, O. D. Kripfgans, J. B. Fowlkes, et al., "Gravity-driven microfluidic particle sorting device with hydrodynamic separation amplification," Anal Chem, vol. 79, pp. 1369-76, Feb 15 2007.
[79] J. Takagi, M. Yamada, M. Yasuda, and M. Seki, "Continuous particle separation in a microchannel having asymmetrically arranged multiple branches," Lab Chip, vol. 5, pp. 778-84, Jul 2005.
[80] B. Cetin and D. Li, "Lab-on-a-chip device for continuous particle and cell separation based on electrical properties via alternating current dielectrophoresis," Electrophoresis, vol. 31, pp. 3035-43, Sep 2010.
[81] M. D. Vahey and J. Voldman, "High-throughput cell and particle characterization using isodielectric separation," Anal Chem, vol. 81, pp. 2446-55, Apr 1 2009.
[82] L. C. Jellema, T. Mey, S. Koster, and E. Verpoorte, "Charge-based particle separation in microfluidic devices using combined hydrodynamic and electrokinetic effects," Lab Chip, vol. 9, pp. 1914-25, Jul 7 2009.
[83] T. Kawamata, M. Yamada, M. Yasuda, and M. Seki, "Continuous and precise particle separation by electroosmotic flow control in microfluidic devices," Electrophoresis, vol. 29, pp. 1423-30, Apr 2008.
[84] J. Shi, H. Huang, Z. Stratton, Y. Huang, and T. J. Huang, "Continuous particle separation in a microfluidic channel via standing surface acoustic waves (SSAW)," Lab Chip, vol. 9, pp. 3354-9, Dec 7 2009.
[85] S. Roath, T. E. Thomas, J. H. Watson, P. M. Lansdorp, R. J. Smith, and A. J. Richards, "Specific capture of targeted hematopoietic cells by high gradient magnetic separation by the use of ordered wire array filters and tetrameric antibody complexes linked to a dextran iron particle," Prog Clin Biol Res, vol. 389, pp. 155-63, 1994.
[86] C. L. Chen, K. C. Chen, Y. C. Pan, T. P. Lee, L. C. Hsiung, C. M. Lin, et al., "Separation and detection of rare cells in a microfluidic disk via negative selection," Lab Chip, vol. 11, pp. 474-83, Feb 7 2011.
[87] H. Mohamed, L. D. McCurdy, D. H. Szarowski, S. Duva, J. N. Turner, and M. Caggana, "Development of a rare cell fractionation device: application for cancer detection," IEEE Trans Nanobioscience, vol. 3, pp. 251-6, Dec 2004.
[88] K. D. Jensen, S. K. Williams, and J. C. Giddings, "High-speed particle separation and steric inversion in thin flow field-flow fractionation channels," J Chromatogr A, vol. 746, pp. 137-45, Oct 4 1996.
[89] J. Murkes and C.-G. Carlsson, Crossflow filtration : theory and practice. Chichester England ; New York: Wiley, 1988.
[90] U. Frenander and A. S. Jonsson, "Cell harvesting by cross-flow microfiltration using a shear-enhanced module," Biotechnol Bioeng, vol. 52, pp. 397-403, Nov 5 1996.
[91] R. Gorkin, J. Park, J. Siegrist, M. Amasia, B. S. Lee, J. M. Park, et al., "Centrifugal microfluidics for biomedical applications," Lab Chip, vol. 10, pp. 1758-73, Jul 21 2010.
[92] M. G. Krebs, R. Sloane, L. Priest, L. Lancashire, J. M. Hou, A. Greystoke, et al., "Evaluation and prognostic significance of circulating tumor cells in patients with non-small-cell lung cancer," J Clin Oncol, vol. 29, pp. 1556-63, Apr 20 2011.
[93] T. Okegawa, K. Nutahara, and E. Higashihara, "Immunomagnetic quantification of circulating tumor cells as a prognostic factor of androgen deprivation responsiveness in patients with hormone naive metastatic prostate cancer," J Urol, vol. 180, pp. 1342-7, Oct 2008.
[94] S. C. Williams, "Circulating tumor cells," Proc Natl Acad Sci U S A, vol. 110, p. 4861, Mar 26 2013.
[95] A. Ring, I. E. Smith, and M. Dowsett, "Circulating tumour cells in breast cancer," Lancet Oncol, vol. 5, pp. 79-88, Feb 2004.
[96] I. Cruz, J. Ciudad, J. J. Cruz, M. Ramos, A. Gomez-Alonso, J. C. Adansa, et al., "Evaluation of multiparameter flow cytometry for the detection of breast cancer tumor cells in blood samples," Am J Clin Pathol, vol. 123, pp. 66-74, Jan 2005.
[97] S. J. Tan, L. Yobas, G. Y. Lee, C. N. Ong, and C. T. Lim, "Microdevice for the isolation and enumeration of cancer cells from blood," Biomed Microdevices, vol. 11, pp. 883-92, Aug 2009.
[98] M. Hosokawa, T. Hayata, Y. Fukuda, A. Arakaki, T. Yoshino, T. Tanaka, et al., "Size-selective microcavity array for rapid and efficient detection of circulating tumor cells," Anal Chem, vol. 82, pp. 6629-35, Aug 1 2010.
[99] S. Zheng, H. K. Lin, B. Lu, A. Williams, R. Datar, R. J. Cote, et al., "3D microfilter device for viable circulating tumor cell (CTC) enrichment from blood," Biomed Microdevices, vol. 13, pp. 203-13, Feb 2011.
[100] T. Xu, B. Lu, Y. C. Tai, and A. Goldkorn, "A cancer detection platform which measures telomerase activity from live circulating tumor cells captured on a microfilter," Cancer Res, vol. 70, pp. 6420-6, Aug 15 2010.
[101] J. S. Kuo, Y. Zhao, P. G. Schiro, L. Ng, D. S. Lim, J. P. Shelby, et al., "Deformability considerations in filtration of biological cells," Lab Chip, vol. 10, pp. 837-42, Apr 7 2010.