Andrew D. Hughes1,
Jeff Mattison1,
Laura T. Western1,
John D. Powderly2,3,
Bryan T. Greene2,3 and
Michael R. King1,*
+ Author Affiliations
1Department of Biomedical Engineering, Cornell University, Ithaca, NY;
2Bio-Cytics, Inc., Huntersville, NC;
3Carolina BioOncology Institute, PLLC, Huntersville, NC.
↵* Address correspondence to this author at: E-mail mike.king@cornell.edu.
Abstract
BACKGROUND: Circulating tumor cells (CTCs) can be used clinically to treat cancer. As a diagnostic tool, the CTC count can be used to follow disease progression, and as a treatment tool, CTCs can be used to rapidly develop personalized therapeutic strategies. To be effectively used, however, CTCs must be isolated at high purity without inflicting cellular damage.
METHODS: We designed a microscale flow device with a functionalized surface of E-selectin and antibody molecules against epithelial markers. The device was additionally enhanced with a >> halloysite nanotube << coating. We created model samples in which a known number of labeled CTCs were suspended in healthy whole blood to determine device capture efficiency. We then isolated and cultured primary CTCs from buffy coat samples of patients diagnosed with metastatic cancer.
RESULTS: Approximately 50% of CTCs were captured from model samples. Samples from 12 metastatic cancer patients and 8 healthy participants were processed in nanotube-coated or smooth devices to isolate CTCs. We isolated 20–704 viable CTCs per 3.75-mL sample, achieving purities of 18%–80% CTCs. The nanotube-coated surface significantly improved capture purities (P = 0.0004). Experiments suggested that this increase in purity was due to suppression of leukocyte spreading.
CONCLUSIONS: The device successfully isolates viable CTCs from both blood and buffy coat samples. The approximately 50% capture rate with purities >50% with the nanotube coating demonstrates the functionality of this device in a clinical setting and opens the door for personalized cancer therapies.
Received for publication October 7, 2011.
Accepted for publication January 9, 2012.
© 2012 The American Association for Clinical Chemistry
Associate Professor, Biomedical Engineering, Cornell-Ithaca
607 255 9803
Michael King is an Associate Professor of Biomedical Engineering at Cornell University. King is an expert on the receptor-mediated adhesion of circulating cells, and has developed new computational and in vitro models to study the function of leukocytes, platelets, stem and cancer cells under flow. He is a former Whitaker Investigator, a James D. Watson Investigator of New York State, and an NSF CAREER Award recipient. King received the 2008 ICNMM Outstanding Researcher Award from the American Society of Mechanical Engineers, was the 2007-2008 Professor of the Year in Engineering at the University of Rochester, and received the 2009 Outstanding Contribution for a Publication in the International Journal Clinical Chemistry. He is the co-author of several books and over 50 journal articles. He is the leader of Project 3.NaturalNano Announces Dr. King's Scientific Paper Published on Capture of Circulating Tumor Cells From Blood Using Halloysite Nanotubes
(GLOBE NEWSWIRE) -- NaturalNano, Inc. (OTCBB:NNAN.OB ) (www.naturalnano.com) announced today that Dr. Michael King of Cornell University published his new technique for the isolation of circulating tumor cells (CTC) using NaturalNano's halloysite nanotubes. Dr. King's report explains his lab's recent work showing how thin coatings of naturally-forming halloysite nanotubes can greatly improve the efficiency of CTC capture from patient blood samples under flow.
James Wemett, NaturalNano CEO, said, "We are pleased to have Dr. King's work with our HNT materials published. Wemett continued,"Dr. King's work with HNT continues to build on our understanding of the potential role that HNT may play in life science applications."
The abstract can be viewed at the following link: http://www.clinchem.org/content/early/2012/02/16/clinchem.2011.176669.abstract or contact Dr. King for further details.
