New microfluidic device testseffects electric fields cancer cells

New microfluidic device that tests the effects of electric fields on cancer cells

10:53 AM, 6th July 2016
New microfluidic device that tests the effects of electric fields on cancer cells
A photo of three microfluidic devices filled with food colour dyes. The device, about the size of a credit card, is designed to help scientists narrow in on safe ranges of electric fields that might be used to noninvasively treat breast, lung, and other forms of cancer.

CAMBRIDGE, US: Researchers at MIT’s research center in Singapore have developed a new microfluidic device that tests the effects of electric fields on cancer cells. They observed that a range of low-intensity, middle-frequency electric fields effectively stopped breast and lung cancer cells from growing and spreading, while having no adverse effect on neighbouring healthy cells.

The device, about the size of a US dollar coin, is designed to help scientists narrow in on safe ranges of electric fields to noninvasively treat breast, lung, and other forms of cancer. The results are published online in the journal Scientific Reports.

The paper’s co-authors include Roger Kamm, professor of mechanical and biological engineering at MIT, as well as research scientists Andrea Pavesi and Giulia Adriani, postdoc Majid Ebrahimi Warkiani, and student Andy Tay of the Singapore-MIT Alliance for Research and Technology (SMART). Senior research officer Wei Hseun Yeap and associate professor Siew Cheng Wong of the Singapore Immunology Network also contributed to the report.

An electric recipe 

For the past decade, scientists have been experimenting with the use of electric fields to treat malignant cells, in an alternative cancer treatment called tumour treating field, or TTF. The therapy stems from the interaction between key cellular structures in tumours, and an external electric field.

In general, an electric field is a field of forces that act on objects that have an electric charge. An electric field can also influence the alignment of polar molecules in tumour cells, such as microtubules. Normally, these molecules are crucial for cell division, which, when it goes into overdrive, leads to tumour growth. When microtubules line up end to end to form a mitotic spindle, the cells genetic material attaches to the spindle fibers, pulling and splitting the cell into two cells.

In the past, scientists have observed that these charged molecules respond to a low-frequency electric field, between 100 and 300 kilohertz and with intensity as strong as the field strength of a mixer or toaster. Instead of forming mitotic spindles, the microtubule alignment is disrupted in such a way that it prevents cell division and tumour growth.

“Scientists have been trying to figure out a lot of different recipes to try to stimulate the cell with an electric field,” Pavesi said. “By tweaking the intensity and frequency, you can have an effect only on the cancer cells, leaving the other type of cells unaltered, without destroying them. That’s the key concept.”

A company, Novocure, has since been founded to develop TTF therapies for people with brain and lung cancer. Pavesi, who has been helping to design microfluidic devices with Kamm, came up with the idea for a device to test TTF after watching a TED talk by Novocure’s founder.

Gaining time

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 tumour masses. The researchers also injected healthy human endothelial cells. The hydrogels created a three-dimensional matrix to mimic the extracellular environment.

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.

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

“For personalized medicine, you can test if a recipe works for a specific person,” Adriani said. “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.

© MIT News



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