Abstract
The sparse cells that are shed from tumors into peripheral circulation are an increasingly promising resource for noninvasive monitoring of cancer progression, early diagnosis of disease, and serve as a tool for improving our understanding of cancer metastasis. However, the extremely sparse concentration of circulating tumor cells (CTCs) in blood (~1–100 CTC in 7.5 mL of blood) as well as their heterogeneous biomarker expression has limited their detection using conventional laboratory techniques. To overcome these challenges, we have developed a microfluidic chip-based micro-Hall detector (μHD), which can directly measure single, immunomagnetically tagged cells in whole blood. The μHD can detect individual cells even in the presence of vast numbers of blood cells and unbound reactants, and does not require any washing or purification steps. Furthermore, this cost-effective, single-cell analytical technique is well suited for miniaturization into a mobile platform for low-cost point-of-care use. In this chapter, we describe the methodology used to design, fabricate, and apply these chips to cancer diagnostics.
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References
Lang JM, Casavant BP, Beebe DJ (2012) Circulating tumor cells: getting more from less. Sci Transl Med 4:141ps13
Wang G-K, Zhu J-Q, Zhang J-T, Li Q, Li Y, He J, Qin Y-W, Jing Q (2010) Circulating microRNA: a novel potential biomarker for early diagnosis of acute myocardial infarction in humans. Eur Heart J 31:659–666
Alix-Panabieres C, Schwarzenbach H, Pantel K (2012) Circulating tumor cells and circulating tumor DNA. Annu Rev Med 63:199–215
Issadore D, Chung J, Shao H, Liong M, Ghazani AA, Castro CM, Weissleder R, Lee H (2012) Ultrasensitive clinical enumeration of rare cells ex vivo using a micro-hall detector. Sci Transl Med 4:141ra92
Nagrath S, Sequist LV, Maheswaran S, Bell DW, Irimia D, Ulkus L, Smith MR, Kwak EL, Digumarthy S, Muzikansky A, Ryan P, Balis UJ, Tompkins RG, Haber DA, Toner M (2007) Isolation of rare circulating tumour cells in cancer patients by microchip technology. Nature 450:1235
Mettlin C, Littrup PJ, Kane RA, Murphy GP, Lee F, Chesley A, Badalament R, Mostofi FK (1994) Relative sensitivity and specificity of serum prostate specific antigen (PSA) level compared with age-referenced PSA, PSA density, and PSA change. Cancer 74:1615–1620
de B, Johann S, Scher HI, Montgomery RB, Parker C, Miller MC, Tissing H, Doyle GV, Terstappen LWWM, Pienta KJ, Raghavan D (2008) Circulating tumor cells predict survival benefit from treatment in metastatic castration-resistant prostate cancer. Clin Cancer Res 14:6302–6309
Ozkumur E, Shah AM, Ciciliano JC, Emmink BL, Miyamoto DT, Brachtel E, Yu M, Chen P-I, Morgan B, Trautwein J et al (2013) Inertial focusing for tumor antigen – dependent and – independent sorting of rare circulating tumor cells. Sci Transl Med 5:179ra47
Gaster R, Hall D, Wang S (2011) nanoLAB: an ultraportable, handheld diagnostic laboratory for global health. Lab Chip 11:950–956
Issadore D, Westervelt RM (eds) (2013) Point of care diagnostics on a chip. Springer, Berlin, Heidelberg.
Ejsing L, Hansen MF, Menon AK, Ferreira HA, Graham DL, Freitas PP (2004) Planar Hall effect sensor for magnetic micro- and nanobead detection. Appl Phys Lett 84:4729–4731
Gaster RS, Hall DA, Nielsen CH, Osterfeld SJ, Yu H, Mach KE, Wilson RJ, Murmann B, Liao JC, Gambhir SS et al (2009) Matrix-insensitive protein assays push the limits of biosensors in medicine. Nat Med 15:1327–1332
Lee JH, Huh YM, Jun YW, Seo JW, Jang JT, Song HT, Kim S, Cho EJ, Yoon HG, Suh JS, Cheon J (2007) Artificially engineered magnetic nanoparticles for ultra-sensitive molecular imaging. Nat Med 13:95–99
Issadore D, Min C, Liong M, Chung J, Weissleder R, Lee H (2011) Miniature magnetic resonance system for point-of-care diagnostics. Lab Chip 11:2282–2287
Issadore D, Chung HJ, Chung J, Budin G, Weissleder R, Lee H (2013) μHall chip for sensitive detection of bacteria. Adv Healthc Mater 2(9):1224–1228. doi:10.1002/adhm.201200380
Weigl B, Domingo G, LaBarre P, Gerlach J (2008) Towards non-and minimally instrumented, microfluidics-based diagnostic devices. Lab Chip 8:1999–2014
Haun JB, Devaraj NK, Hilderbrand SA, Lee H, Weissleder R (2010) Bioorthogonal chemistry amplifies nanoparticle binding and enhances the sensitivity of cell detection. Nat Nanotechnol 5:660–665
Howell J, Peter B, Mott DR, Fertig S, Kaplan CR, Golden JP, Oran ES, Ligler FS (2005) A microfluidic mixer with grooves placed on the top and bottom of the channel. Lab Chip 5:524–530
Rhim AD, Mirek ET, Aiello NM, Maitra A, Bailey JM, McAllister F, Reichert M, Beatty GL, Rustgi AK, Vonderheide RH et al (2012) EMT and dissemination precede pancreatic tumor formation. Cell 148:349–361
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Issadore, D. (2015). Point-of-Care Rare Cell Cancer Diagnostics. In: Rasooly, A., Herold, K. (eds) Mobile Health Technologies. Methods in Molecular Biology, vol 1256. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2172-0_9
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DOI: https://doi.org/10.1007/978-1-4939-2172-0_9
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