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.

Links

Publisher Full Text

Authors

Hughes AD, Mattison J, Western LT, Powderly JD, Greene BT, King MR

Institution

Department of Biomedical Engineering, Cornell University, Ithaca, NY, USA.

Source

Clinical chemistry 58:5 2012 May pg 846-53

MeSH

Aluminum Silicates
Antibodies
Antigens, Neoplasm
Antigens, Surface
Blood Buffy Coat
Breast Neoplasms
Cell Adhesion
Cell Adhesion Molecules
Cell Count
Cell Separation
E-Selectin
Female
Glutamate Carboxypeptidase II
Humans
Leukocytes
Lung Neoplasms
Male
Nanotubes
Neoplasm Metastasis
Neoplastic Cells, Circulating
Ovarian Neoplasms
Polyurethanes
Prostatic Neoplasms

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Validation Studies

Language

eng

PubMed ID

22344286