title: Microtube device for selectin-mediated capture of viable circulating tumor cells from blood.
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 cancer cells 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.
authors.affiliation: Department of Biomedical Engineering, Cornell University, Ithaca, NY, USA.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Hughes
authors.forename: Jeff
authors.initials: J
authors.lastname: Mattison
authors.forename: Laura T
authors.initials: LT
authors.lastname: Western
authors.forename: John D
authors.initials: JD
authors.lastname: Powderly
authors.forename: Bryan T
authors.initials: BT
authors.lastname: Greene
authors.forename: Michael R
authors.initials: MR
authors.lastname: King
mesh_terms: D000538:Aluminum Silicates; D000906:Antibodies; D000951:Antigens, Neoplasm / Q000276:immunology / Q000378:metabolism; D000954:Antigens, Surface / Q000276:immunology / Q000378:metabolism; D058621:Blood Buffy Coat / Q000473:pathology; D001943:Breast Neoplasms / Q000097:blood / Q000473:pathology; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000378:metabolism; D002452:Cell Count; D002469:Cell Separation / Q000295:instrumentation*; D000077215:Clay; D019040:E-Selectin; D000071858:Epithelial Cell Adhesion Molecule; D005260:Female; D043425:Glutamate Carboxypeptidase II / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007962:Leukocytes / Q000502:physiology; D008175:Lung Neoplasms / Q000097:blood / Q000473:pathology; D008297:Male; D043942:Nanotubes; D009362:Neoplasm Metastasis; D009360:Neoplastic Cells, Circulating / Q000378:metabolism / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000097:blood / Q000473:pathology; D011140:Polyurethanes; D011471:Prostatic Neoplasms / Q000097:blood / Q000473:pathology
chemical_list: D000538:Aluminum Silicates; D000906:Antibodies; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D015815:Cell Adhesion Molecules; D019040:E-Selectin; D000071858:Epithelial Cell Adhesion Molecule; D011140:Polyurethanes; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II; D000077215:Clay