Microchip Technology Capturing CTC Clusters

Funded by the National Institute of Biomedical Imaging and Bioengineering (NIBIB), part of the National Institutes of Health, researchers have developed a microfluidic chip that can capture rare clusters of circulating tumor cells, a game-changing discovery that could result to new important insights into how cancer spreads.

What are circulating tumor cells? Circulating tumor cells (CTCs) are cells that break away from a tumor and advances to the cancer patient’s bloodstream. Some cells can reside in a patient’s distant organs, which researchers believe is one of the ways by which cancer spreads. These cells are called Single CTCs, exceptionally rare CTCs, typically fewer than 1 in 1 billion cells.

While single CTCs are rare, small groups of CTCs called clusters,  are even less common than single CTCs. CTC clusters’ pervasiveness in the blood and their role in metastasis hasn’t been further researched due to its elusiveness despite its existence for more than 50 years. Nonetheless, recent advancements in the biomedical technologies that allow researchers to capture since CTCs have revived the interests in CTC clusters, which are occasionally captured along with single CTCs.

Researchers led by Mehmet Toner, Ph.D., report the development of a novel microfluidic chip that is specifically designed for the efficient and effective capture of CTC clusters from whole unprocessed blood.

Not much is known about CTC clusters, particularly of what their role is in the progress of cancer. Advancements in this area could result in a major breakthrough concerning cancer research.

With support from a Quantum Grant from IBIB, a new technology called Cluster-Chip was developed which funds which funds transformative technological innovation designed to solve major medical problems with a substantial disease burden, such as preventing cancer metastasis or precisely tailoring therapeutics to an individual’s cancer cell biology.

Recently, the Cluster Chip was used by Dr. Toner to trap and examine CTC clusters in a group of patients with metastatic breast, prostate, and skin cancers.The researchers found CTC clusters — ranging from two to 19 cells — in 30-40 percent of the patients.

Further analysis of the patients’ CTC clusters provided new understanding of the biology of CTC clusters. On May 18, 2015, the researchers published their results which was featured in the advance online issue of Nature Methods.

The chip is designed to slowly push blood through many rows of microscopic triangle-shaped posts. The posts are sequenced in such a way that every two posts funnels cells towards the tip of a third post. At the tip, single cells — including single CTCs and blood cells– easily slide to either side of the post and continue through the chip until reaching the next tip. 

Researchers introduced fluorescently tagged cell clusters, ranging from 2-30 cells, into the chip and counted the number of clusters that were captured and the number that flowed through undetected in order to determine the efficiency of the Cluster-Chip. It was found that the chip had no negative effects on the integrity of the clusters as a whole upon comparing clusters under a microscope before and after capture.

Efficiency of their novel chip to two currently-used methods that have had some success capturing CTC clusters was what researched compared next. The results highlight the importance of the technology’s specialized technique, which is grounded on the structural properties of CTC clusters rather than their size or the presence of surface proteins.

Researchers went on to test the Cluster-Chip in a trial of patients with metastatic cancer. The study suggests a possibly greater role for clusters in the metastatic cascade after finding the large number of clusters found in the patient samples.