Cells’ electrical activity measured in 3-D model

Currently, researchers’ understanding of cell communication has been limited to two dimensions due to the fact that the electrical activity of cultured cells has only been done in a two-dimensional dish. However, one researcher at Carnegie Mellon has recently won a National Science Foundation (NSF) award for trying to kick things off the surface.

Tzahi Cohen-Karni, an assistant professor of biomedical engineering and materials science and engineering at Carnegie Mellon, is researching how cells communicate through electrical activity in three dimensions through the use of nanosensors. Cohen-Karni recently received an NSF CAREER Award entitled “3-D Nanosensors Array for Elucidating the Electrical Activity of Induced Pluripotent Stem Cells Derived Cardiomyocytes” for his research.

“We are not two-dimensional,” Cohen-Karni said in an interview with The Tartan. “Our excitable media is the brain: three-dimensions, essentially. So if we wanted to know how cells talk to each other, the most straightforward way is to look into three dimensions. There’s a bunch of professors around biomedical engineering that work on 3-D constructs, but now we’re trying to fuse sensors in with it.”

Instead of working with two-dimensional petri dishes, Cohen-Karni’s method works with microtissues. Specifically, he works with induced pluripotent cells, or stem cells which are capable of differentiating into many other types. These cells were derived from muscle cells from heart tissue (iPS-CM), with sensors to monitor electrophysiology.

“We are trying to create microtissues and then capture these inside three-dimensional assembly of sensors. The sensors themselves will be assembled in space in three dimensions,” Cohen-Karni said.

In order to surround the microtissue, the sensors are attached to a strip of polymer on a chip lined with thin strips of metal, which serve as leads and lift the polymer from the chip’s surface, where the sensors can then take measurements from all sides.

In the last 30–40 years, sensing units were usually laid onto a surface. For example, the Michigan probe, a needle-like probe that measures neural activity directly from the brain, has many points of detection, but still lies on a plane. “We’re trying to kick stuff off the surface,” Cohen-Karni said. “We’ll have an arrangement of sensing units in a barrel shape with x, y, z coordinates.”

All the materials used to create the microtissue and sensors are synthesized in Cohen-Karni’s lab at the Pittsburgh Technology Council. They synthesize nanowires and semiconductors that are silicon-based materials a thousand times smaller than a human hair and fabricate field effect transistors out of them. The lab also uses graphene, a single layer of hexagonally arranged carbon atoms, to make the sensors.

“We are not married to any of the materials we are using,” said Cohen-Karni.

After they synthesize materials, it is transported to the recently opened Scott Hall, where a majority of their experiments take place.

“It’s a multi-layer of complexity. Students in my lab are designing not just the sensing units, but are also working on the apparatus to measure these units.” Graduate students have the flexibility to change both the geometry of the devices themselves and of the microtissues the devices sense.

The NSF CAREER Award comes with a grant of $500,000 that will be used to further develop 3-D nanosensors array for elucidating the electrical activity of induced pluripotent stem cells, derived cardiomyocytes.

“It’s instrumental, I have to admit,” Cohen-Karni said. “It’s not about the finance itself. The biggest thing is that the NSF basically acknowledged that this is something important that researchers have to work on. And of course, the financial support is very important but I think the acknowledgement of the research and the outreach plan of the proposal got their attention more than anything. It’s recognition that we here at CMU do interesting stuff.”

In the future, Cohen-Karni hopes to expand this research to look at diseased brain and cardiac cells, where they can branch out to investigate different diseases and potentially do drug screenings based on the electrophysiology of the diseased cells.

“We are developing a platform,” Cohen-Karni said. “I’m not focused on single tissues. For now, let’s get the basic science, basic interfaces done and down the road we’ll start digging into disease related electrophysiology. Some of it can be really wild, even creating cyborgs.”

“Essentially, you take from each experience what you need to bring the grand idea to reality. Sometimes it’s not a linear combination, sometimes it’s synergetic.”