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 we report a high throughput microfluidic technology, the OncoBean Chip, employing 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 was validated with cancer cell lines H1650 and MCF7, achieving a mean efficiency >80% at a throughput of 10 mL hr−1 in contrast to a flow rate of 1 mL hr−1 standardly reported with other microfluidic devices. Cells were recovered with a viability rate of 93% at these high speeds, increasing the ability to use captured CTCs for downstream analysis. Broad clinical application was demonstrated using comparable flow rates from blood specimens obtained from breast, pancreatic and lung cancer patients. Comparable CTC numbers were recovered in all the samples at the two flow rates demonstrating the ability of the technology to perform at high-throughputs.

The incorporation of microfluidics into circulating tumor cell isolation for clinical applications

“…This OncoBean Chip [19] also featured a redesigned functionalized micropost structure to minimize flow separation, increasing the area on the post utilized in capture.…”

Microfluidic techniques for high throughput single cell analysis

“…The accurate enumeration and characterization of CTCs from peripheral blood for prognostic, diagnostic, and individualized therapeutic applications therefore requires high throughput microfluidic characterization of CTCs at the single cell level. While affinity-based capture devices have been refined[25,26], recent work has provided high-throughput and label-free alternatives[27–29]. …”

A toolkit of thread-based microfluidics, sensors, and electronics for 3D tissue embedding for medical diagnostics

“…Microfluidic systems with integrated sensors have been widely used to perform molecular assays on blood samples 24 , capture circulating tumor cells 25 , and detect cancer-specific biomarkers 26 . However, these systems are mainly limited to planar structures and are able to transport liquid over small distances only.…”