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Lab-On-Chip Device Captures Circulating Tumor Cells

Tumor cell cluster in Cluster-Chip

Fluorescent tagged tumor cell cluster captured in a Cluster-Chip (Mehmet Toner, Massachusetts General Hospital)

19 May 2015. Engineers and medical researchers designed a microchip that detects clusters of circulating tumor cells that break away from tumors and can spread cancer throughout the body. The team from a joint Harvard-MIT health sciences technology program and Massachusetts General Hospital in Boston published its findings yesterday in the journal Nature Methods (paid subscription required).

Circulating tumor cells are individual cells that break off from original tumors or those formed from where cancer spreads, and flow through the blood stream. These cells make up a minute proportion of blood volume, but are implicated in the spread of cancer to other parts of the body. Because of their tiny amounts, circulating tumor cells are difficult to find, but when detected can offer an early warning about the spread of cancer in a patient.

The team from the lab of Harvard-MIT engineering professor Mehmet Toner designed a microfluidic device — a miniature chip with tiny channels through which blood or other fluid specimens can flow — that captures clusters of circulating tumor cells from whole blood. The chip is configured in rows of channels interspersed with triangle-shaped posts, and the top of the triangles in the following row pointed at the open space between posts in the row before it. Blood is forced through the channels, allowing individual cells to flow, but blocking circulating tumor cells in clusters.

Toner and colleagues tested the device, which they call Cluster-Chip, by attaching fluorescent tags to clusters of circulating tumor cells and found the rows of triangles in the device can trap clusters of up to 30 cells, and with as few as 2 cells. The authors report Cluster-Chip is able to trap nearly all (99%) of clusters with 4 or more cells, and a majority (70%) of 3-cell clusters, but only about 4 in 10 (41%) clusters of 2 tumor cells. Inspection of the clusters before and after flowing through the device show the integrity of the clusters remains largely intact.

Maintaining the integrity of the cell clusters likely adds to Cluster-Chip’s diagnostic potential. The researchers tested blood samples from 60 individuals with metastatic cancer, where the cancer spreads from the original tumor to other parts of the body. The results, confirmed through RNA sequencing, show the device captured circulating tumor cells in 41 percent of participants with breast cancer and 3 of 10 prostate (31%) and melanoma (30%) participants. Other analyses revealed additional properties of some captured tumor cell clusters, including a biomarker indicating a tendency for tumor cells to proliferate and, in a few cases, immune system cells not associated with the tumor.

Massachusetts General Hospital filed a patent for the Cluster-Chip technology, with Toner and first author Ali Fatih Sarioglu, now on the engineering faculty at Georgia Tech, as inventors. The research was funded by a Quantam grant from National Institute of Biomedical Imaging and Bioengineering, in National Institutes of Health, supporting research leading to technologies that make a profound impact on major diseases or public health problems.

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