Plasma Promise

Growing up, Keidar was fascinated by space. As an undergraduate at Kharkov Aviation Institute in Ukraine, he studied new electric propulsion systems for spacecraft. Scientists had long used chemical propulsion to send rockets into space — when a fuel burns, its chemical bonds break, releasing a powerful burst of energy. But chemical propulsion relies on a weighty fuel supply and provides diminishing returns: A heavier craft requires more fuel to move, which in turn adds to its weight. 

Electric propulsion, on the other hand, uses solar panels or nuclear reactors to generate an electric charge that can propel a rocket with lighter components and less waste.

“These electric rockets were incredibly efficient and were really the forefront of research in rocketry at the time,” says Keidar. 

As he began his graduate studies at Tel Aviv University in Israel, plasma — the charged gas generated by many electric propulsion systems — captured Keidar’s interests.

When a typical gas is heated to thousands of degrees, its atoms are ripped apart into positively and negatively charged particles. Both visible light and heat are often emitted. This plasma — different enough from typical gas that it is considered a fourth state of matter — makes up most of the universe, including the center of our sun. On Earth, you can see plasma within flames, flashes of lightning and the auroras. 

“What’s so fascinating about plasma is that it’s very abundant in the universe but very rare here on Earth,” says Keidar. “We can’t experience it and learn how to manipulate it unless we recreate it in the lab. I really wanted to understand it better.”

When plasma is created within an electric field — positive at one end and negative at the other — its charged ions are ejected out of the system at incredible speed because of the repulsion of the charges. This forceful burst of gas propels whatever is attached to the thruster, in the same way an untied balloon buzzes around a room as air shoots out. 

When he launched his research career, first at Cornell University and then at the University of Michigan, Keidar saw incredible promise in using plasma to maneuver small satellites around in space. Tiny shoebox-sized satellites are increasingly used for communication, to track weather patterns and to carry out reconnaissance. But controlling the motion of such satellites, which can’t support large fuel tanks or bulky solar panels, has been tricky. Keidar helped solve the problem, becoming a leader in the design of small plasma thrusters that use powerful magnetic and electric fields to turn gas into plasma. 

Over the years, he has filed more than a dozen patents related to plasma propulsion and seen multiple versions of his devices launched into space to guide satellites designed by the United States Naval Academy and NASA. 

But, Keidar didn’t stop at rocket science.

When Keidar moved his lab to GW in 2007, he saw an opportunity to collaborate with biologists and biomedical engineers to study the impact of charged plasma on living tissue. First, he needed to create a device that could generate plasma at a safe temperature and still be small and nimble enough for a person to wield, whether in the lab or the hospital. 

While the plasma thrusters Keidar developed for steering satellites aimed to convert 99 percent of the atoms within a gas into charged ions, his new cold plasma device for medicine aimed to convert just one charged particle in every 100,000 atoms into such charged ions — essentially, a weakly ionized gas. 

“What we do is use a very high electric field for a very, very short period of time,” Keidar explains. “Because it’s such a short interaction, you don’t heat up the material. You can touch this stream of plasma with your finger, and you won’t feel anything at all.”

Once he had a toothbrush-sized device that could eject a stream of cold plasma, Keidar approached Mary Ann Stepp, a professor of anatomy and cell biology at GW’s School of Medicine and Health Sciences who studies the cellular basis of wound healing. Some researchers had proposed using plasma to improve and speed wound healing.  

“They were physicists and really didn’t know anything about culturing cells and carrying out these studies,” says Stepp. “I didn’t know anything about plasma but felt like I could cross these bridges between physics and biology and really help them advance their research a lot.”

In their first tests of applying cold plasma to living cells, Keidar and Stepp’s research groups aimed cold plasma at cells in a Petri dish for 30 seconds at a time. The rush of charged particles ejected from Keidar’s cold plasma device had little effect on most cells but subtly slowed the movement of some. The researchers began to wonder whether, in addition to wound healing — a situation when you want cells to stay still — cold plasma could keep cancer cells from spreading around the body. So they tested the impact of cold plasma on isolated cancer cells. 

“I still have those first images,” says Keidar. “It was unbelievable, really a shock. We thought we might see a small effect but it was dramatic. The plasma was incredibly selective in killing cancer cells.”

In 2010 and 2011, a few chance encounters further shaped the direction of this work. While on a treadmill at the gym, Keidar struck up a conversation with Johns Hopkins University researcher Barry Trink, who studied head and neck cancer. The scientists began collaborating and, together, tested whether cold plasma could kill the cells making up these tumors. 

Then neurosurgeon Jonathan Sherman joined the faculty at GW and was mistakenly referred to Keidar while searching for a radiation system he wanted to use to treat brain cancer. Keidar didn’t have the system but told Sherman about his results with cold plasma. Sherman was intrigued and suggested they study whether Keidar’s device might help treat glioblastoma, one of the most aggressive types of cancer. 

“Brain tumors are incredibly complex, making them difficult to study, and we have very few good treatment options,” says Sherman, now director of surgical neuro-oncology at West Virginia University Berkeley Medical Center. “Many of these therapies show promise in the lab yet don’t work once you test them in patients, so I was very cautiously optimistic.”

Keidar’s results with both Trink and Sherman were promising: In test after test, cold plasma had no impact on healthy cells but killed cancer cells — from an ever-expanding list of tumors types, including not only head and neck cancer and glioblastoma but also breast, ovarian, prostate, colorectal and lung cancers. 

Yet one question remained: Why?

Under the microscope, GW graduate student Vikas Soni watches a glioblastoma cell, fluorescently stained blue so he can see its internal structures. He has just exposed it to one minute of cold plasma. 

“First, you see the nucleus being fragmented into pieces. In biology that means the cell has DNA damage,” he narrates. “That cell is not going to survive.” Indeed, within 30 minutes of incubation, the cell shrivels up, its contents spilling into the surrounding culture dish. Ultimately, it dies. 

Keidar, Stepp and their colleagues knew that some of the charged atoms contained in cold plasma were oxygen and nitrogen. In biology, these are called reactive oxygen species (ROS) and reactive nitrogen species (RNS); they carry out more chemical reactions within cells than the usual oxygen and nitrogen in the air we breathe. In general, higher levels of these reactive molecules are bad for cells. Cancer cells typically have higher-than-usual levels, thought to be both a cause and consequence of their faster-than-usual growth. 

In a series of experiments, Soni and other members of the Keidar lab showed that when tumor cells are barraged with cold plasma, ROS and RNS seep through their outer membranes and overwhelm the cells, causing death. When otherwise healthy cells, however, are exposed to cold plasma, they end up with only moderate levels of the reactive species. 

Part of that difference is attributed to the initial amounts of reactive species in the cells — cancer cells start out with higher levels so are in greater danger of becoming overloaded. But some of the differences also have to do with mutations, the membranes of cancer cells, and pores within those membranes, which allow more reactive species through. Other dysfunctional molecules within cancer cells also make it harder for the cells to combat the reactive species once they are inside. 

“Healthy cells can proofread themselves and get those reactive species back down to a normal level pretty easily and attain homeostasis [stability],” says Soni. “But cancer cells can’t do that.”

After incredibly positive data on the ability of cold plasma to shrink tumors on the sides of mice, even with skin acting as a barrier, Soni wondered whether the technology might work on brain tumors not only during surgery but from the outside. To mimic the protective shield made by the skull, he cut slices of thick human leg bone and placed them on top of lab dishes containing glioblastoma cells. After Soni aimed the plasma wand at the setup, the cancer cells died. He then tested this in mice with brain tumors—the first time a non-invasive treatment for glioblastoma using cold plasma had ever made it to animal models. Once again, the tumors shrank. 

“We thought maybe we did something wrong,” Soni laughs. “But we repeated the experiment a few times and kept getting similar results.”

The results did not make sense at first; ROS and RNS molecules cannot penetrate bone. But cold plasma releases something more than charged atoms — a unique spectrum of electromagnetic waves. Those waves, students in Keidar’s lab group discovered, traveled through skin and bone and coaxed cells to increase their own production of reactive species, having the same impact as the direct physical effects of ROS and RNS. Keidar, Soni and Sherman reported this finding in a 2021 article in the journal Cancers.

In 2013, a biomedical device company, US Medical Innovations (USMI), licensed Keidar's patented cold plasma technology. USMI carried out their own experiments with cold plasma using the device and began to plan clinical trials. The Food and Drug Administration’s “compassionate use” program allows new treatments to be used on seriously ill patients who have no other treatment options — this allowed several tests of the device, including the 2015 surgery that Keidar watched in Louisiana. 

More recently, USMI led a larger Phase I trial at Rush University Medical Center in Chicago and Sheba Medical Center in Israel. The trial tested the cold plasma device on 20 patients undergoing surgery for a variety of advanced stage 4 cancers. While many patients ultimately succumbed to their cancer, the trial helped establish the safety of the technology and showed that few patients had any tumor regrowth in the areas treated with cold plasma.

“What’s amazing about this technology is that there’s no damage to the normal tissue, so if it hits a nerve, an artery or a normal brain cell it has no effect,” said USMI CEO Jerome Canady in a 2023 interview. “It’s truly a lifesaver.”

At the same time USMI was moving forward with Keidar’s initial device — which projected a physical stream of cold plasma, full of reactive molecules — Keidar’s group was developing a second type of device, based on the finding that the electromagnetic waves alone could have a biological impact. The new device keeps the plasma contained within a tube that simply has to be held in the vicinity of tumor cells. Keidar won a National Science Foundation Innovation Corps (I-Corps) grant to help commercialize the technology and began talking to surgeons and oncologists about how they might use it. 

Keidar (right) and Johns Hopkins University researcher Barry Trink (left) demonstrated that cold plasma could kill head and neck cancer cells while leaving healthy cells unharmed. Jerome Canady (center), a surgical oncologist and CEO of US Medical Innovations (USMI), has conducted Phase 1 clinical trials to test the safety and effectiveness of the cold plasma device on patients with advanced cancers.  

“We talked to hundreds of doctors and hospitals, and everyone was, in general, intrigued. Most surgeons, though, said, ‘It’s interesting but I have lots of other tools and don’t know exactly how this works,’” remembers Keidar. “But there was one group of people who were really excited: neurosurgeons.”

When removing a brain tumor, neurosurgeons must walk a fine line between ensuring they get all of a tumor out and protecting healthy brain cells. While a surgeon removing a breast tumor may be able to err on the side of removing extra healthy tissue, inside the skull this can cost patients their brain function. Moreover, few drugs are effective in treating glioblastoma after safely removing as much tumor as possible. Using cold plasma to kill the remaining cancer cells around where a brain tumor was removed, without harming other cells, could help save a patient’s ability to walk or talk. Shrinking a tumor from the outside before surgery could similarly mean a smaller area of the brain affected by surgery. 

With collaborators at Duke University — which has one of the largest banks of brain tumors in the world — Keidar and Sherman are now moving their new, contained cold plasma device toward clinical trials for glioblastoma. 

“It’s incredibly exciting to think about the potential this has, but we’re also trying to be cautious,” says Sherman. “We want to go to clinical trials with a high confidence of success. So over the years, I’ve really pushed to wait for trials until we have enough data to determine how best to deliver treatment with the device. We’re trying to be patient right now, however, we are very close to moving into the trial phase of our research.”

Since discovering the effect of cold plasma on cancer cells, Keidar’s lab has also continued studying rocket propulsion; some of their most impactful work on satellites has come in the last few years. He keeps both lines of research active and engaged, splitting his students and staff between projects. 

“I think my students enjoy being a part of this lab because they end up having really versatile skills, getting a very broad education and being able to go into different fields,” says Keidar. “I have several students who did their PhDs on propulsion but then ended up working for biomedical companies.”

Graduate student Anmol Taploo agrees. His research, funded by the Defense Advanced Research Projects Agency (DARPA), focuses on developing plasma thrusters that convert air from Earth’s upper atmosphere into plasma to guide very low-Earth orbit satellites. But he collaborates regularly with Soni, helping with plasma diagnostics.

“There’s definitely a bridge between propulsion and medicine,” says Taploo. “We both have to be able to do plasma diagnostics — measuring the properties of plasma. And so there’s knowledge that can be shared there.” 

Keidar also doesn’t shy away from taking his work in new directions. 

During the COVID-19 pandemic, members of Keidar’s lab wondered whether the same plasma devices they were using to kill cancer cells could also be used to inactivate the COVID-19 virus. Initial results suggested that they could, and Keidar won an NSF RAPID grant to develop a “plasma brush” that could decontaminate personal protective equipment like masks. 

Since then, Keidar’s student Soni has tested the experimental brush on other pathogens, including the flu virus, Escherichia coli (E. coli) and methicillin-resistant Staphylococcus aureus (MRSA) bacteria. In all cases, the plasma brush killed the germs — something potentially useful in decontaminating surfaces at hospitals or other places prone to spreading infections. Now, armed with a GW Technology Maturation Award, Soni is moving the technology toward commercialization.

Keidar’s broad research portfolio is reflected in the diversity of funders who’ve supported his work over the years, including NSF, the Department of Defense and DARPA, the Department of Energy, NASA, the National Institutes of Health and even industry partners through corporate research agreements. 

Yet, after all his successes in translating his research to both outer space and medicine, Keidar remains grounded in basic questions about plasma. He says what he most wants to know right now is how to better control low-temperature plasmas in very subtle ways. That could not only improve medical devices and thrusters but also the use of extremely precise jets of plasma to etch patterns onto computer microchips — a third area plasma research has the potential to impact. It’s a topic he’s only recently begun to explore but is already making strides in. 

“He is really a genius outside-the-box thinker,” says Sherman when talking about Keidar. “He’s an easy-going guy who is an innovator and an entrepreneur at heart and wants to take his ideas and have success with them.”

For Keidar, the sky’s no limit.

Photography: William Atkins