Capturing, creating, and characterizing circulating tumor cells and clusters

Tumors can shed circulating tumor cells (CTCs) into the bloodstream. These cells are extremely rare: there are often less than one hundred CTCs in one milliliter of whole blood. In contrast, the same blood volume contains ten million white blood cells and five billion red blood cells.

Compared to individual CTCs, clusters of CTCs are thought to be more resistant to the harsh vascular environment and have a higher potential to successfully metastasize onto a secondary site. They are also associated with worse clinical outcomes and higher metastatic potential.

Macaraniag et al. highlighted microfluidic techniques for isolating, forming, and characterizing CTC clusters. Other work has focused on modeling solid tumors and their microenvironment with miniature tissue constructs, but little research has examined these clusters specifically.

“Microfluidic isolation of CTCs and clusters has progressed in efficiency and throughput, paving the way for liquid biopsy as a relatively easy and minimally invasive way to obtain primary cells for disease monitoring,” said author Ian Papautsky. “Microfluidics can also be used for development of in vitro models of CTC clusters due to superior spatial control needed to mimic the cellular microenvironment.”

Downstream analysis techniques at the single-cell level remain a challenge because they require a significant number of CTCs per test.

The team hopes an improved understanding of microfluidics and its role in characterizing CTC clusters can lead to increased sophistication and application of microfluidic devices, possibly resulting in platforms that integrate multiple procedures. They also see opportunities for in vitro models that fully encompass the intricacies of the metastatic cascade.

Source: “Microfluidic techniques for isolation, formation, and characterization of circulating tumor cells and clusters,” by Celine Macaraniag, Qiyue Luan, Jian Zhou, and Ian Papautsky, APL Bioengineering (2022). The article can be accessed at https://doi.org/10.1063/5.0093806 .