New Microfluidic Device Offers Means for Studying Electric Field Cancer Therapy

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The researchers fabricated the device from PDMS, a widely used, gel-like polymer, and patterned small channels across the device. They then developed a conductive mixture made from micron-sized silver flakes and PDMS, which they cured, then injected into two channels in the device to form two tiny, separate electrodes. In the region between the electrodes, they injected hydrogels with breast or lung cancer cells as well as small tumor masses. The researchers also injected healthy human endothelial cells. The hydrogels created a three-dimensional matrix to mimic the extracellular environment.

The team subjected each cell type in the 3-D matrix to alternating electric fields at frequencies of 150 or 200 kilohertz, continuously, at an intensity of 1.1 volts per centimeter.

In the absence of an electric field, Pavesi says the cancer cells begin to proliferate and spread within two days. However, he and Adriani observed a significant slowdown in tumor progression after three days of continuous electric field stimulation: Proliferation was markedly reduced, while small masses of lung cancer cells did not disperse indicating an inhibition of their metastatic potential. What’s more, healthy endothelial cells in the same device were left unaffected. The researchers hypothesize that healthy cells may require different frequencies to be influenced by an electric field, as their size and electrical properties are far different from that of cancer cells.

Adriani hopes the microfluidic device can help scientists test a wide range of electric field intensities and frequencies on other cancer cell types. While TTF therapy has been approved by the Food and Drug Administration for treating brain tumors, that approval process took years to test electric fields, first in vitro, then in animals and in humans. Pavesi says a microfluidic device could speed up that process.

“Maybe by screening TTF to optimize frequency and intensity, you can at least reduce the time it takes for in vivo studies,” Pavesi says. “There may be thousands of variables, but you could first try them in this device. If you find 10 that work, you can go ahead and try those 10 in the animal model.”

Ultimately, the device may be used to identify the most effective electric field to treat cancer cells taken directly from a patient, says Chwee Teck Lim, a professor of biomedical engineering at the National University of Singapore, who did not participate in the study.

“One step forward that the group can take is to start testing on cancer patient-derived cells either obtained from tumor or liquid biopsy, such as circulating tumor cells, and to see if there are particular types of cancer cells that will succumb to or be more resistant to such TTF treatment,” Lim says.

“For personalized medicine, you can test if a recipe works for a specific person,” Adriani says. “In three days, you can have an answer. And for many cancer patients who are dying of metastasis, time is everything.”

This research was supported, in part, by the National Research Foundation of Singapore through the Singapore-MIT Alliance for Research and Technology BioSystems and Micromechanics interdisciplinary research group.