A radial flow microfluidic device for ultra-high-throughput affinity-based isolation of circulating tumor cells.

Abstract

Circulating tumor cells (CTCs) are believed to play an important role in metastasis, a process responsible for the majority of cancer-related deaths. But their rarity in the bloodstream makes microfluidic isolation complex and time-consuming. Additionally the low processing speeds can be a hindrance to obtaining higher yields of CTCs, limiting their potential use as biomarkers for early diagnosis. Here, a high throughput microfluidic technology, the OncoBean Chip, is reported. It employs radial flow that introduces a varying shear profile across the device, enabling efficient cell capture by affinity at high flow rates. The recovery from whole blood is validated with cancer cell lines H1650 and MCF7, achieving a mean efficiency >80% at a throughput of 10 mL h(-1) in contrast to a flow rate of 1 mL h(-1) standardly reported with other microfluidic devices. Cells are recovered with a viability rate of 93% at these high speeds, increasing the ability to use captured CTCs for downstream analysis. Broad clinical application is demonstrated using comparable flow rates from blood specimens obtained from breast, pancreatic, and lung cancer patients. Comparable CTC numbers are recovered in all the samples at the two flow rates, demonstrating the ability of the technology to perform at high throughputs.

• Authors: Vasudha Murlidhar, Mina Zeinali, Svetlana Grabauskiene, Mostafa Ghannad-Rezaie, Max S Wicha, Diane M Simeone, Nithya Ramnath, Rishindra M Reddy, Sunitha Nagrath
• Journal: Small (Weinheim an der Bergstrasse, Germany) (Small) Vol. 10 Issue 23 Pg. 4895-904 (Dec 10 2014) ISSN: 1613-6829 [Electronic] Germany
• PMID: 25074448 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• Dimethylpolysiloxanes
• baysilon

Topics

• Breast Neoplasms (blood)
• Cell Count
• Cell Line, Tumor
• Cell Separation (instrumentation)
• Cell Survival
• Dimethylpolysiloxanes (chemistry)
• Female
• Finite Element Analysis
• Humans
• Lung Neoplasms (blood)
• MCF-7 Cells
• Microfluidic Analytical Techniques
• Microfluidics (instrumentation, methods)
• Neoplastic Cells, Circulating
• Pancreatic Neoplasms (blood)
• Shear Strength
• Stress, Mechanical