Building Tumor Balls for Better Drug Discovery
Over the past few years, researchers have found that small, spherical conglomerations of tumor cells are superior to individual cells for predicting the response of malignant cells to a variety of anticancer treatments. Now, researchers at the University of California, Berkeley, have developed a microfluidics device that can form tumor spheroids in a large-scale, reproducible manner amenable to high-throughput drug screening protocols. This work is reported in the journal Biomedical Microdevices.
To trap a reproducible number of cells in an environment that causes the cells to adhere to one another in discrete structures (the tumor spheroid), Luke Lee, Ph.D., and colleagues designed a microfluidics device that uses the properties of fluid flow at the nanoscale to capture cells within a U-shaped structure. Once trapped, the cells continue receiving nutrients and oxygen—or added drug molecules—as the fluid passes through a tiny perfusion channel sounding the larger U-shaped structure, in much the same way that small tumors receive nutrients as they leak from surrounding blood vessels.
The researchers are able to create as many as 7,500 traps per square centimeter, each of which can hold between 9 and 11 cells. Research by other investigators has shown that tumor spheroids of this size, though difficult to make, have higher resistance to drug than do monolayers of cells. Once trapped, the cells begin to adhere to one another, forming what resembles a small mass of cells, rather than a collection of discrete cells. These small masses may accurately represent tumors early in their development. The researchers note that they can alter the size of the U-shaped traps to produce larger spheroids.
This work is detailed in the paper "Microfluidic self-assembly of tumor spheroids for anticancer drug discovery." An abstract of this paper is available through PubMed.View abstract