Novel microfluidic device detects CTCs expressing cancer stem cell marker in HCC

A new Labyrinth microfluidic device, coupled with three clinically validated markers, isolates and quantifies circulating tumour cells (CTCs) from blood samples of patients with hepatocellular carcinoma (HCC), reports a study.

“Our methodology markedly improved the capability to isolate heterogeneous HCC CTCs with high recovery rate and purity among all label-free technologies,” the researchers said.

“The device was able to detect CTCs in the majority of patients with HCC, and the positivity rate of HCC CTCs was significantly correlated with HCC disease stages, demonstrating the clinical potential for early detection, treatment selection and monitoring response to targeted therapies,” they added.

The novel Labyrinth microfluidic device was developed and optimized to efficiently isolate CTCs from peripheral blood of patients with HCC. It successfully identified CTCs in 88.1 percent of patients over different tumour stages. The CTC positivity rate was significantly higher in those with more advanced HCC stages. [Sci Rep 2019;9:18575]

Of the HCC patients, 71.4 percent exhibited CTCs positive for the cancer stem cell marker CD44, which indicated that the major population of CTCs could possess stemness properties to facilitate tumour cell survival and dissemination. In addition, more than half (55 percent) had the presence of circulating tumour microemboli (CTM), which also correlated with advanced HCC stage. This suggested the association of CTM with tumour progression.

CTM or CTC clusters that were observed in all HCC stages could provide additional survival signal and metastasis potential, the researchers said. [Phys Biol 2012;9:016001; Cancer Res 2017;77:5194-5206]

“Importantly, the detection of CTCs with stemness markers and CTM provides unique insights into the biology of CTCs and their mechanisms influencing metastasis, recurrence and therapeutic resistance,” they added.

Label-free, size-based microfluidic devices are useful in improving HCC CTC detection rate, identifying different HCC CTCs and allowing future downstream analysis capacity. Size-based CTC isolation devices consist of filtration and inertial methods, the researchers noted. [Clin Cancer Res 2015;21:4786-4800]

However, filtration approaches struggle with pore clogging and high-pressure drop, potentially causing cell damage and encountering CTC loss from forcing the cells to squeeze through the pores, which limits throughput and the amount of blood being processed, they said.

Alternatively, other approaches apply inertial forces to isolate CTCs with high-throughput capacity using sinusoidal or spiral channel geometries.

“Our high-throughput label-free Labyrinth device has demonstrated successful enrichment of CTCs from patients with breast cancer and pancreatic cancer,” the researchers said. “The Labyrinth offers unique features over previous inertial devices by incorporating 56 sharp corners that allows focusing of smaller cells which was difficult to achieve using previous technology.” [Cell Syst 2017;5:295-304]

One of the most lethal cancers, HCC has a high mortality and recurrence rate. CTC detection offers various opportunities to advance early detection as well as HCC tumour monitoring, which is key to improving patient outcome, according to the researchers.