The latest version of a microfluidic device for capturing rare circulating tumor cells (CTCs) is the first designed specifically to capture clusters of two or more cells, rather than single cells. The new device, called the Cluster-Chip, was developed by the same Massachusetts General Hospital (MGH) research team that created previous microchip-based devices. Recent studies by MGH investigators and others have suggested that CTC clusters are significantly more likely to cause metastases than single circulating tumor cells.
The device is described in a Nature Methods paper that was published online May 18. Among the members of the research team is Fatih Sarioglu, now an assistant professor in the School of Electrical and Computer Engineering at Georgia Tech.
“Early theories of cancer metastasis were based on clumps of tumor cells traveling through the bloodstream, but given that CTC clusters are even rarer in the blood than single CTCs, they have attracted minimal attention for several decades,” explained Mehmet Toner, PhD, director of the BioMicroElectroMechanical Systems Resource Center in the MGH Center for Engineering in Medicine, the paper’s senior author. “The ability to isolate intact clusters will enable is to investigate carefully their role in the metastatic process, and understanding metastasis really is the ‘holy grail’ of cancer research.”
CTCs are living solid tumor cells found in the bloodstream at extremely low levels – about one in a billion cells. Starting in 2007, MGH researchers have developed three microchip-based devices that capture CTCs in ways that preserve molecular information that can help guide clinical treatment. The first two versions used antibodies directed at specific proteins on the surface of tumor cells, which limited the ability to capture cells that may have lost those marker proteins during the process of metastasis. The third version, developed in 2013, uses antigen-independent methods of isolating CTCs, which is also the case for the Cluster-Chip.
“Cancer is an extremely heterogeneous disease, and even within the same tumor you can find cells with different surface antigens,” said Sarioglu, co-lead author of the Nature Methods paper. “Since we are capturing clusters because of their physical properties, this chip is directly applicable to all types of cancer.”