• A new device could simplify the delivery of vaccines.
  • It was inspired by lighters and microneedles.
  • It requires no batteries and could be mass produced a low cost.

Inspired by barbecue lighters and microneedles, researchers have developed and tested an innovative method that may simplify delivery of vaccines through a handheld device called an electroporator.

While electroporation is commonly used in the research lab using short electric pulses to drive molecules into cells, the technique currently requires large, complex, and costly equipment, severely limiting its use for vaccine delivery.

The new approach does the job using a new pen-size device that requires no batteries and can be mass produced at low cost.

'Aha moment'

The inspiration for the breakthrough came from an everyday device that people use to start a grill: the electronic barbecue lighter.

“My lab figured out that you could use something all of us are familiar with on the Fourth of July when we do a barbecue—a barbecue lighter,” says Saad Bhamla, assistant professor in the School of Chemical and Biomolecular Engineering at the Georgia Institute of Technology, explaining that every time one clicks the lighter, it generates a brief pulse of electricity to ignite the flame.

His team took the innards of a lighter and reengineered them into a tiny spring-latch mechanism. The device creates the same electric field in the skin as the large bulky electroporation machines already in use, but using widely available, low-cost components that require no battery to operate.

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“Our aha moment was the fact that it doesn’t have a battery or plug into the wall, unlike conventional electroporation equipment,” he says. “And these lighter components cost just pennies, while currently available electroporators cost thousands of dollars each.”

Pairing the reimagined lighter device with microneedle technology has resulted in a new ultra-low-cost electroporation system, or “ePatch.”

Handheld pen-sized epatch

Besides the lighter, a key innovation involved tightly spacing the electrodes and using extremely short microneedles. While commonly used in cosmetics to rejuvenate skin and for potential medical applications, microneedles are not generally used as electrodes. Coupling the tiny electroporation pulser with microneedle electrodes made an effective electrical interface with the skin and further reduced the ePatch’s cost and complexity.

The microneedle-based system uses voltages similar to conventional electroporation but with pulses that are 10,000 times shorter and using electrodes that penetrate just .01 inch into the skin surface, says Mark Prausnitz, professor of chemical and biomolecular engineering.

“The close spacing of the microneedles allows us to use microsecond pulses rather than the millisecond pulses applied in conventional electroporation. This shorter pulse, plus the shallow location of the microneedle electrodes, minimizes nerve and muscle stimulation, which can avoid pain and twitching, both common side effects of conventional electroporation,” he says.

“Our goal was to design a method for COVID-19 vaccination that uses a device that is simple, low-cost, and manufacturable,” says Dengning Xia, associate professor at Sun Yat-sen University in China, who was the lead author of the study in the Proceedings of the National Academy of Sciences.

“The ePatch is a handheld device the size of a pen, weighing less than two ounces, and requiring no battery or power sources. It operates by simply pushing a button, which makes it very simple to use,” he says.

mRNA vaccination

But could their system be used with a vaccine to generate an immune response?

To find out, the researchers teamed with Chinglai Yang, associate professor in the microbiology and immunology department at Emory University School of Medicine, to test the delivery system first using a fluorescent protein to ensure it worked, and to deliver an actual COVID-19 vaccine. They selected an experimental DNA vaccine for COVID-19 as their model.

“In the beginning, I wasn’t sure that it would be successful when Georgia Tech asked me to collaborate on this project,” Yang says. “Surprisingly, even in the first try, it went far beyond my expectations.

“Using this method with the same amount of vaccine, the ePatch induced an almost tenfold improved immune response over intramuscular immunization or intradermal injection without electroporation. It also showed no lasting effects to the mice’s skin. What this means is that it is easier to achieve protection,” he says.

The researchers say the ePatch should also work for mRNA vaccination, which they are currently studying.

But devising a simpler, cost-effective electroporator that works with the DNA vaccine could dramatically reduce the cost and complexity of vaccinations since it doesn’t require deep-freeze storage of mRNA vaccines, which need frigid temperatures because they contain lipid nanoparticles.

“We think the key to making DNA vaccination work is to make electroporation simple, low-cost, and scalable,” Prausnitz says.

The ePatch is generating excitement among health experts, including Nadine Rouphael, professor of medicine and executive director of the Hope Clinic at the Emory Vaccine Center. She notes that today’s genetic vaccines, whether mRNA or DNA, remain expensive as a global solution because they either require a complicated cold chain and costly manufacturing due to the formulation of lipid nanoparticles for mRNA delivery or they need a sophisticated electroporation device for DNA vaccine delivery.

Vaccine delivery revolution

The “portable and affordable electroporation ePatch can overcome these limitations and can be a potential game changer in the vaccine delivery arena,” Rouphael predicts.

The researchers are already looking at ways to refine their system, examining how to optimize the immune response on the skin site and integrating the device into one unit. “That would revolutionize the vaccination process,” Yang says.

The team must meet multiple milestones before human trials. Prausnitz anticipates it will be more than five years before their invention could complete clinical study and be ready for widespread use. He envisions the ePatch following a more traditional device approval process than the accelerated vaccine approvals that happened during the pandemic.

All four researchers echo Rouphael’s enthusiasm for the potential of their ePatch to democratize access to vaccinations. Bhamla explains that vaccines work for those who can afford them and have access to health care resources, but that is not feasible for large segments of the developing world.

“We know that COVID-19 won’t be the last pandemic,” Bhamla says. “We need to think from a cost as well as design perspective about how to simplify and scale up our hardware so these modern interventions can be more equitably dispersed—to reach more underserved and more under-resourced areas of the world.”

Additional coauthors are from Georgia Tech and Emory University.

Mark Prausnitz is an inventor of patents licensed to companies, is a paid advisor to companies, and is a founder/shareholder of companies developing microneedle-based products. This potential conflict of interest has been disclosed and is managed by Georgia Tech.