Skip to main content

Point-of-Care Rare Cell Cancer Diagnostics

  • Protocol
  • First Online:
Mobile Health Technologies

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1256))

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.

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

Access this chapter

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 99.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 129.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
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

  1. Lang JM, Casavant BP, Beebe DJ (2012) Circulating tumor cells: getting more from less. Sci Transl Med 4:141ps13

    Article  Google Scholar 

  2. 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

    Article  Google Scholar 

  3. Alix-Panabieres C, Schwarzenbach H, Pantel K (2012) Circulating tumor cells and circulating tumor DNA. Annu Rev Med 63:199–215

    Article  CAS  Google Scholar 

  4. 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

    Article  Google Scholar 

  5. 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

    Article  CAS  Google Scholar 

  6. 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

    Article  CAS  Google Scholar 

  7. 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

    Article  Google Scholar 

  8. 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

    Article  Google Scholar 

  9. Gaster R, Hall D, Wang S (2011) nanoLAB: an ultraportable, handheld diagnostic laboratory for global health. Lab Chip 11:950–956

    Article  CAS  Google Scholar 

  10. Issadore D, Westervelt RM (eds) (2013) Point of care diagnostics on a chip. Springer, Berlin, Heidelberg.

    Google Scholar 

  11. 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

    Article  CAS  Google Scholar 

  12. 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

    Article  CAS  Google Scholar 

  13. 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

    Article  CAS  Google Scholar 

  14. 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

    Article  CAS  Google Scholar 

  15. 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

    Article  CAS  Google Scholar 

  16. Weigl B, Domingo G, LaBarre P, Gerlach J (2008) Towards non-and minimally instrumented, microfluidics-based diagnostic devices. Lab Chip 8:1999–2014

    Article  CAS  Google Scholar 

  17. 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

    Article  CAS  Google Scholar 

  18. 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

    Article  CAS  Google Scholar 

  19. 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

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to David Issadore .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer Science+Business Media New York

About this protocol

Cite this protocol

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

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-2172-0_9

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-2171-3

  • Online ISBN: 978-1-4939-2172-0

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics