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High School Students Built This Iphone App for the Visually Impaired

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We remain in a brand-new age of spaceflight: The nationwide area companies are no more the only video game in the area, as well as area is ending up being a lot more obtainable. Rockets constructed by industrial gamers like.
Blue Origin are currently bringingprivate citizens into orbit That stated, Blue Beginning, SpaceX, as well as Virgin Galactic are all backed by billionaires with huge sources, as well as they have actually all revealed purposes to market trips for thousands of thousands to numerous bucks. Copenhagen Suborbitals has an extremely various vision. Our team believe that spaceflight needs to be readily available to any individual that agrees to place in the moment as well as initiative.

Copenhagen Suborbitals was established in 2008 by a self-taught designer as well as an area designer that had formerly functioned for NASA From the get go, the goal was clear: crewed spaceflight. B oth owners left the company in 2014, yet already the job had regarding 50 volunteers as well as lots of energy.

The team took as its starting concept that the obstacles associated with developing a crewed spacecraft on the low-cost are all design troubles that can be fixed, one by one, by an attentive group of clever as well as devoted individuals. When individuals ask me why we’re doing this, I in some cases respond to, “Since we can.”.

Volunteers make use of a container of argon gas [left] to load a tube within which engine aspects are integrated with each other. The group just recently produced a gas container for the Spica rocket [right] in their workshop.

Our objective is to get to the Krmn line, which specifies the limit in between Planet’s environment as well as celestial spaces, 100 kilometers over water level. The astronaut that gets to that elevation will certainly have a number of mins of silence as well as weightlessness after the engines removed as well as will certainly delight in a spectacular sight. However it will not be a simple trip. Throughout the descent, the pill will certainly experience exterior temperature levels of 400 C as well as g– pressures of 3.5 as it speeds with the air at rates of approximately 3,500 kilometers per hr.

I signed up with the team in 2011, after the company had actually currently relocated from a manufacturer area inside a decommissioned ferryboat to a garage near the Copenhagen waterside. Previously that year, I had actually viewed Copenhagen Suborbital’s initial launch, in which the HEAT-1X rocket removed from a mobile launch system in the Baltic Seabut however crash-landed in the sea when the majority of its parachutes stopped working to release. I offered the company some standard understanding of sporting activities parachutes obtained throughout my years of sky diving, which I really hoped would certainly equate right into valuable abilities.

The group’s following turning point can be found in 2013, when we efficiently released the Sapphire rocket, our initial rocket to consist of assistance as well as navigating systems. Its navigating computer system utilized a 3-axis accelerometer as well as a 3-axis gyroscope to monitor its area, as well as its thrust-control system maintained the rocket on the proper trajectory by relocating 4 servo-mounted copper jet vanes that were put right into the exhaust setting up.

Our team believe that spaceflight needs to be readily available to any individual that agrees to place in the moment as well as initiative.

The HEAT-1X as well as the Sapphire rockets were sustained with a mix of strong polyurethane as well as fluid oxygen. We were eager to establish a bipropellant rocket engine that combined fluid ethanol as well as fluid oxygen, since such liquid-propellant engines are both effective as well as effective. The HEAT-2X rocket, arranged to release in late 2014, was indicated to show that modern technology. However, its engine increased in fires, essentially, in a fixed examination shooting some weeks prior to the arranged launch. That examination was intended to be a regulated 90-second melt; rather, due to a welding mistake, a lot of the ethanol spurted right into the burning chamber in simply a couple of secs, causing a substantial blaze. I was standing a couple of hundred meters away, as well as also from that range I really felt the warmth on my face.

The HEAT-2X rocket’s engine was provided unusable, as well as the goal was terminated. While it was a significant dissatisfaction, we discovered some useful lessons. Up until after that, we would certainly been basing our styles on our existing capabilitiesthe devices in our workshop as well as individuals on the job. The failing required us to take a go back as well as consider what brand-new innovations as well as abilities we would certainly require to understand to reach our objective. That reconsidering led us to develop the fairly tiny Nex I as well as Nex II rockets to show crucial innovations such as the parachute system, the bipropellant engine, as well as the stress policy setting up for the storage tanks.

For the Nex II launch in August 2018, our launch website was 30 k m eastern of Bornholm, Denmark’s easternmost island, in a component of the Baltic Sea utilized by the Danish navy for army workouts. W e left Bornholm’s Nex nurture at 1 a m to get to the marked spot of sea in time for a 9 a.m. launch, the moment authorized by Swedish air traffic control service. (While our watercrafts remained in worldwide waters, Sweden ha s oversight of the airspace over that component of the Baltic Sea.) Much of our team participants had invested the whole previous day evaluating the rocket’s numerous systems as well as obtained no rest prior to the launch We w ere operating on coffee

When the Nex II launched, dividing nicely from the launch tower, all of us supported. The rocket continued its trajectory, rejecting its nose cone when it reached its apogee of 6,500 meters, as well as sending out telemetry information back to our goal control ship all the while. As it started to come down, it initially released its ballute, a balloon-like parachute utilized to support spacecraft at high elevations, and afterwards released its major parachute, which brought it delicately to the sea waves.

In 2018, the Nex II rocket released efficiently [left] as well as returned securely to the Baltic Sea [right].

The launch brought us one action better to grasping the logistics of introducing as well as landing mixed-up. For this launch, we were additionally evaluating our capacity to anticipate the rocket’s course. I developed a design that approximated a splashdown 4.2 kilometres eastern of the launch system; it in fact landed 4.0 kilometres to the eastern. This regulated water landingour initially under a totally filled with air parachutewas a vital evidence of idea for us, considering that a soft touchdown is an outright important for any type of crewed goal.

A photo shows a metal engine nozzle with a jet of fire coming out of one end.
This previous April, the group checked its brand-new gas injectors in a fixed engine examination. Carsten Olsen

The Nex II’s engine, which we called the BPM5, was just one of minority parts we had not machined totally in our workshop; a Danish firm made one of the most difficult engine components. However when those components got here in our workshop soon prior to the launch day, we recognized that the exhaust nozzle was a little irregular. We really did not have time to buy a repair, so among our volunteers, Jacob Larsen, utilized a sledgehammer to batter it right into form. The engine really did not look prettywe nicknamed it the Franken-Enginebut it functioned. Given That the Nex II’s trip, we have actually test-fired that engine greater than 30 times, in some cases pressing it past its style limitations, yet we have not eliminated it yet.

The Spica astronaut’s 15-minute trip to the celebrities will certainly be the item of greater than twenty years of job.

That goal additionally showed our brand-new vibrant stress policy (DPR) system, which aided us regulate the circulation of gas right into the burning chamber. The Nex I had actually utilized a less complex system called stress blowdown, in which the gas storage tanks were one-third loaded with pressurized gas to drive the fluid gas right into the chamber. With DPR, the storage tanks are filled up to capability with gas as well as connected by a collection of control shutoffs to a different container of helium gas under high stress. That configuration allows us manage the quantity of helium gas streaming right into the storage tanks to press gas right into the burning chamber, allowing us to program in various quantities of drive at various factors throughout the rocket’s trip.

The 2018 Nex II goal confirmed that our style as well as modern technology were basically audio. It was time to begin dealing with the human-rated.
Spica rocket.

A computer rendering shows a rocket with the words Spica and Copenhagen Suborbitals on it flying above the clouds.
Copenhagen Suborbitals wants to send out an astronaut up in its Spica rocket in regarding a years. Caspar Stanley

With its team pill, the Spica rocket will certainly determine 13 meters high as well as will certainly have a gross liftoff weight of 4, 000 kilos, of which 2, 600 k g will certainly be gas It will certainly be, by a substantial margin, the biggest rocket ever before constructed by novices.

A computer rendering shows a metal rocket engine.
The Spica rocket will certainly make use of the BPM100 engine, which the group is presently making. Thomas Pedersen

Its engine, the 100-kN.
BPM100, makes use of innovations we grasped for the BPM5, with a couple of renovations. Like the previous style, it makes use of regenerative cooling in which a few of the propellant goes through networks around the burning chamber to restrict the engine’s temperature level. To press gas right into the chamber, it makes use of a mix of the basic stress blowdown technique in the initial stage of trip as well as the DPR system, which offers us better control over the rocket’s drive. The engine components will certainly be stainless-steel, as well as we intend to make the majority of them ourselves out of rolled sheet steel. The trickiest component, the double-curved “throat” area that attaches the burning chamber to the exhaust nozzle, needs computer-controlled machining devices that we do not have. The good news is, we have excellent market get in touches with that can assist.

One significant adjustment was the button from the Nex II’s showerhead-style gas injector to a coaxial-swirl gas injector. The showerhead injector had around 200 really tiny gas networks. It was difficult to produce, since if something failed when we were making one of those channelssay, the drill obtained stuckwe needed to toss the entire point away. In a coaxial-swirl injector, the fluid gas enter the chamber as 2 turning fluid sheets, and also as the sheets clash, they’re atomized to produce a propellant that ignites. Our swirl injector makes use of regarding 150 swirler aspects, which are set up right into one framework. This modular style needs to be simpler to produce as well as evaluate for quality control.

A photo shows two metallic circles. The one on the left is made of brass and has 19 large holes on its front. The one on the right is made of steel and has dozens of tiny holes on its front.
The BPM100 engine will certainly change an old showerhead-style gas injector [right] with a coaxial-swirl injector [left], which will certainly be simpler to produce. Thomas Pedersen

In April of this year, we ran fixed examinations of a number of kinds of injectors. We initially did a test with a well-understood showerhead injector to develop a standard, after that checked brass swirl injectors made by typical device milling in addition to steel swirl injectors made by 3D printing. We were completely satisfied total with the efficiency of both swirl injectors, as well as we’re still evaluating the information to identify which worked far better. Nevertheless, we did see some.
combustion instability specifically, some oscillation in the fires in between the injector as well as the engine’s throat, a possibly harmful sensation. We have an excellent suggestion of the reason for these oscillations, as well as we’re certain that a couple of style tweaks can address the trouble.

A man seated at a table holds a circular brass object toward the camera. The brass object has 19 large holes and has black char marks across its front.
Volunteer Jacob Larsen holds a brass gas injector that did well in a 2021 engine examination. Carsten Olsen

We’ll quickly begin developing a major BPM100 engine, which will inevitably include a brand-new assistance system for the rocket. Our previous rockets, within their engines’ exhaust nozzles, had steel vanes that we would certainly transfer to alter the angle of drive. However those vanes created drag within the exhaust stream as well as minimized reliable propelled by around 10 percent. The brand-new style has.
gimbals that pivot the whole engine backward and forward to regulate the drive vector. As more assistance for our idea that challenging design troubles can be fixed by clever as well as devoted individuals, our gimbal system was developed as well as checked by a 21-year-old undergraduate trainee from the Netherlands called Jop Nijenhuis, that utilized the gimbal style as his thesis job (for which he obtained the greatest feasible quality).

We’re making use of the exact same assistance, navigating, as well as control (GNC) computer systems that we utilized in the Nex rockets. One brand-new difficulty is the team pill; as soon as the pill divides from the rocket, we’ll need to regulate each component by itself to bring them both pull back to Planet in the wanted positioning. When splitting up happens, the GNC computer systems for both parts will certainly require to recognize that the criteria for optimum trip have actually transformed. However from a software application perspective, that’s a small trouble contrasted to those we have actually fixed currently.

A woman is seated in front of a computer and a table that has a large drone on it.
Bianca Diana works with a drone she’s making use of to evaluate a brand-new assistance system for the Spica rocket. Carsten Olsen

My specialized is parachute style. I have actually dealt with the ballute, which will certainly blow up at an elevation of 70 kilometres to slow down the crewed pill throughout its high-speed preliminary descent, as well as the major parachutes, which will certainly blow up when the pill is 4 kilometres over the sea. We have actually checked both kinds by having skydivers leap out of aircrafts with the parachutes, most just recently in a.
2019 test of the ballute. The pandemic forced us to stop our parachute screening, yet we need to return to quickly.

A photo shows a camera descending; itu2019s attached to a parachute made of many thin orange ribbons.
For the parachute that will certainly release from the Spica’s booster rocket, the group checked a little model of a bow parachute. Mads Stenfatt

For the drogue parachute that will certainly release from the booster rocket, my initial model was based upon a style called Supersonic X, which is a parachute that looks rather like a flying onion as well as is really simple to make. Nevertheless, I hesitantly switched over to ribbon parachutes, which have actually been better checked in high-stress scenarios as well as located to be a lot more secure as well as durable. I state “hesitantly” since I recognized just how much job it would certainly be to put together such a gadget. I initially made a 1.24-meter-diameter parachute that had 27 bows crossing 12 panels, each connected in 3 locations. So on that particular tiny model, I needed to stitch 972 links. A major variation will certainly have 7,920 link factors. I’m attempting to maintain an open mind regarding this difficulty, yet I additionally would not object if more screening reveals the Supersonic X style to be adequate for our functions.

We have actually checked 2 team pills in previous objectives: the Tycho Brahe in 2011 as well as the Tycho Deep Space in 2012. The next-generation Spica crew capsule will not be roomy, yet it will certainly be large sufficient to hold a solitary astronaut, that will certainly continue to be seated for the 15 min s of trip (as well as for 2 hrs of preflight checks) The initial spacecraft we’re developing is a hefty steelboilerplate” pill, a standard model that we’re making use of to come to an useful design as well as style. We’ll additionally utilize this version to evaluate hatch style, total resistance to stress as well as vacuum cleaner, as well as the aerodynamics as well as hydrodynamics of the form, as we desire the pill to crash right into the sea with marginal shock to the astronaut inside. When we enjoy with the boilerplate style, we’ll make the light-weight trip variation.

Two men stand on either side of a seated woman wearing an orange flight suit. The man on the left holds an orange flight helmet.
Copenhagen Suborbitals presently has 3 astronaut prospects for its initial trip: from left, Mads Stenfatt, Anna Olsen, as well as Carsten Olsen. Mads Stenfatt

3 participants of the Copenhagen Suborbitals group are presently prospects to be the astronaut in our initial crewed missionme, Carsten Olsen, as well as his child, Anna Olsen. Most of us recognize as well as approve the dangers associated with flying right into area on a homemade rocket. In our everyday procedures, we astronaut prospects do not obtain any type of unique therapy or training. Our one additional obligation so far has actually been being in the team pill’s seat to examine its measurements. Because our initial crewed trip is still a years away, the prospect listing might well alter. When it comes to me, I assume there’s significant delight in simply belonging to the goal as well as assisting to develop the rocket that will certainly bring the initial amateur astronaut right into area. Whether I wind up being that astronaut, I’ll for life boast of our success.

A computer rendering shows a cutaway of a small crew capsule for a spacecraft. Inside the capsule is a person seated in a chair.
The astronaut will certainly most likely to area inside a little team pill on the Spica rocket. The astronaut will certainly continue to be seated for the 15-minute trip (as well as for the 2-hour trip check prior to). Carsten Brandt

Individuals might question exactly how we manage on a small spending plan of regarding $100,000 a yearparticularly when they find out that fifty percent of our revenue mosts likely to paying lease on our workshop. We maintain prices down by getting conventional off-the-shelf components as long as feasible, as well as when we require custom-made styles, we’re fortunate to deal with business that provide us charitable discount rates to sustain our job. We release from worldwide waters, so we do not need to pay a launch center. When we take a trip to Bornholm for our launches, each volunteer pays his/her very own means, as well as we remain in a sporting activities club near the harbor, resting on floor coverings on the flooring as well as bathing in the altering spaces. I in some cases joke that our spending plan has to do with one-tenth what NASA invests in coffee. Yet it might well suffice to do the work.

We had actually meant to release Spica for the very first time in the summer season of 2021, yet our routine was postponed by the COVID-19 pandemic, which shut our workshop for numerous months. Currently we’re wishing for an examination launch in the summer season of 2022, when problems on the Baltic Sea will certainly be fairly tame. For this initial examination of Spica, we’ll load the gas storage tanks just partway as well as will certainly intend to send out the rocket to an elevation of around 30 to 50 kilometres.

If that trip is a success, in the following examination, Spica will certainly lug a lot more gas as well as rise greater. If the 2022 trip stops working, we’ll determine what failed, repair the troubles, as well as attempt once more. It’s impressive to assume that the Spica astronaut’s ultimate 15-minute trip to the celebrities will certainly be the item of greater than twenty years of job. However we understand our.
supporters are counting down till the historical day when an amateur astronaut will certainly climb up aboard a homemade rocket as well as wave farewell to Planet, all set to take a huge jump for DIY-kind.

This short article shows up in the December 2021 print concern as “The First Crowdfunded Astronaut.”

A Skydiver That Stitches

A man attached to  a parachute in the sky.

HENRIK JORDAHN

Mads Stenfatt initially gotten in touch with Copenhagen Suborbitals with some useful objection. In 2011, while checking out images of the do it yourself rocketeers’ most recent rocket launch, he had actually observed a cam placed near to the parachute device. Stenfatt sent out an e-mail describing his concernnamely, that a parachute’s lines can quickly obtain entangled around the cam. “The response I obtained was basically, ‘If you can do far better, come join us as well as do it on your own,'” he keeps in mind. That’s exactly how he came to be a volunteer with the globe’s only crowdfunded crewed spaceflight program.

As an amateur skydiver, Stenfatt recognized the standard technicians of parachute packaging as well as release. He began assisting Copenhagen Suborbitals style as well as pack parachutes, as well as a couple of years later on he took control of the work of stitching the chutes also. He had actually never ever utilized a stitching device prior to, yet he discovered promptly over evenings as well as weekend breaks at his dining-room table.

Among his preferred tasks was the style of a high-altitude parachute for the Nex II rocket, released in 2018. While dealing with a model as well as confusing over the style of the air consumption, he located himself on a Danish stitching web site checking out brassiere parts. He made a decision to make use of bra underwires to tense the air consumption as well as maintain them open, which functioned rather well. Though he ultimately entered a various style instructions, the episode is a traditional instance of the Copenhagen Suborbitals values: Collect ideas as well as sources from any place you locate them to do the job.

Today, Stenfatt functions as lead parachute developer, regular agent, as well as astronaut prospect. He additionally remains to skydive in his extra time, with thousands of dives to his name. Having adequate experience zooming down with the skies, he’s intently interested regarding what it would certainly seem like to go the various other instructions.

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ASSISTIVE TECH

Assistive Tech And Video Games

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Assistive innovations have a rather large visibility right here on Hackaday, as well as this hack is absolutely nothing except intriguing. [kerchoo_22] is servicing a hands-free video game controller as a final project for her engineering class as well as we assume it deserves sharing.

The standard facility of the circuit is rather basic. She do it yourself had actually a couple of get in touch with buttons making use of conductive plates constructed from cardboard, air duct tape, as well as light weight aluminum foil. The outcome of the button reads by analog input pins on an Arduino Leonardo. When the buttons are off, the analog input pins are drawn HIGH making use of 1 MegaOhm resistors. Yet when the customer strikes their directly among the 4 conductive pads, the button is involved, as well as the analog input pins are shorted to ground.

The Arduino Leonardo, having an indigenous USB port, has the ability to straight mimic a key-board. Each conductive pad is mapped to a various essential press representing various features within the video game. Left, right, shoot, and so on. As well as there you have it, gameplay without making use of hands or a controller!

Currently, it appears as if [kerchoo_22] placed a proper quantity of pillow on the head pads, so there possibly isn’t much threat of a blast. In either case, you can never ever be also cautious.

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Assistive technologies

Help Build the Future of Assistive Technology

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So hopes remain high for another kind of nucleic-acid vaccine, one that makes use of DNA rather than mRNA. DNA-based vaccines have most of the advantages of mRNA vaccines, yet they produce no significant side effectsand, crucially, they don’t need to be refrigerated. These attributes could make these vaccines a boon to rural and low-resource regions. If we really have to vaccinate 7 billion people, we might just need every possible technology,” says Margaret Liu, chairman of the board of the International Society for Vaccines.

Image of Kate Broderick, Inoviou2019s senior vice president of R&D.
Inovio’s device uses a technique called electroporation to sneak a DNA vaccine into cells. Kate Broderick, Inovio’s senior vice president of R&D, has been working on this technique for years, but the pandemic provided both motivation and funding to accelerate development.
Spencer Lowell

DNA vaccines come with a major challenge, however. When administered with an ordinary hypodermic needle, they’ve conferred only weak immunity, at best, in many human studies. But if a small, ambitious Pennsylvania company backed by the U.S. Department of Defense succeeds in its clinical trials, DNA vaccinesenabled by a new delivery technologycould soon join the fight against COVID-19, and a host of other viral illnesses.

The company, Inovio Pharmaceuticals, is using a technique known as electroporation, in which an electrical pulse applied to the skin briefly opens channels in cells to allow the vaccine to enter. After a standard vaccine injection, Inovio’s electroporation device, which looks like an electric toothbrush, is held against the skin. At the press of a button, a weak electric field pulses into the arm, opening channels into the cells. The tool gives DNA vaccines the boost they need to work in humansor so the company says. It’s an engineering solution to a biological problem.

With its overseas warfighters in mind, the U.S. Department of Defense (DOD) has backed Inovio’s approach with a US $71 million contract to scale up the manufacturing of its electroporation device, and an undisclosed sum to cover phase 2 and 3 studies of the company’s COVID-19 vaccine. And the Bill and Melinda Gates Foundation gave the company $5 million as part of an effort to increase equitable access to COVID-19 vaccines.

Inovio is now finishing phase 2 studies that are testing the vaccine’s safety and efficacy on relatively small groups in the United States and China, and those results are imminent. In the meantime, the company has ramped up manufacturing with a plan to supply hundreds of millions of COVID-19 vaccine doses to the global population, should the vaccine prove successful.

But here’s the rub: The electroporation tool is essential to Inovio’s vaccine, but it also adds a layer of complication. It’s both an enabler and a handicap. Inovio must manufacture not only the vaccine but also the device and its disposable tips. Any vaccination site planning to administer Inovio’s vaccine will need not only the device but also people who know how to use it. The public will have to develop trust in a new apparatus. And all of this will have to happen during a pandemic and a frenzied vaccine rollout characterized by rampant misinformation and, in some quarters, an unwillingness to be vaccinated.

Given that backdrop, the idea of complicating mass vaccinations with an electric device has drawn skepticism. This is not standard methodology for giving vaccines,” notes John Moore, an immunologist at Weill Cornell Medicine, in New York City. The technique might work, but how practical it is is another question entirely,” he says.

Neither the skeptics nor tough questions from regulators have deterred Inovio. Nor has the fact that, despite more than a decade of research and development in other disease areas, the company has yet to bring a DNA vaccine to market. These are hardly normal times. The coronavirus has propelled many other novel technologies, medicines, and vaccines into the mainstream, and in the process has created massive business success stories. Inovio is betting that its technology will make it into that elite group of pandemic-era winners.

Nucleic-acid-based vaccines have captivated scientists for decades because they can be quickly designed and easily manufactured. These vaccines are typically made with either DNA, the double-stranded molecule that carries the genetic code for living organisms, or messenger RNA (mRNA), a single-stranded molecule that is complementary to DNA and carries instructions from DNA for synthesizing proteins. DNA and mRNA vaccines can be thought of as blueprints that instruct a cell to produce a specific protein from the virus that will trigger an immune response.

Image of a scientist working with DNA being amplified.

Image of a scientists working with DNA being purified.
Inovio’s vaccine contains a snippet of DNA that codes for the production of a coronavirus protein. If the body is exposed to a real virus later, the immune system will recognize that protein and mount a defense. The DNA is first amplified in bacterial cells (top) and then purified (bottom).
Spencer Lowell

In making a nucleic-acid vaccine, scientists first sequence the virus’s genome. Next, they figure out which of its proteins is the most important and most recognizable by the human immune system. Then they manufacture either DNA or mRNA that codes for the production of that protein and formulate it into a vaccine. That genetic material gets injected into the body, where nearby cells take it in and start following their new instructions for making a viral protein. To the immune system, this looks like a viral infection, and it mounts a response. Now, should the real virus ever appear, the immune system is primed and ready to attack.

Altering the design of a nucleic-acid vaccine is as easy as plugging in a new code. That’s incredibly important when facing a virus that mutates frequently. Indeed, several highly contagious variants of SARS-CoV-2, the virus that causes COVID-19, have already emerged globally, and scientists have warned that the currently available vaccines may be less effective against some of them.

Despite the allure of nucleic-acid vaccines, none had been approved for commercial use in humans by medical regulators prior to the pandemic. In fact, most nucleic-acid-based vaccines hadn’t made it past midstage clinical trials. The problem: Human cells don’t readily take in foreign DNA or mRNA. After injection, much of the vaccine would remain inert in the body and eventually break down, without prompting much of an immune response.

Developers of mRNA vaccines recently resolved the issue by packaging the vaccine with chemicals. In one approach, researchers encapsulate mRNA within fat droplets called lipid nanoparticles, which fuse with the cell membrane and help the vaccine get inside.

Companies such as BioNTech, Moderna, and CureVac were in the midst of testing various mRNA vaccines against other viruses when the COVID-19 pandemic hit. Market pressure and billions of dollars from governments helped companies finish the job, and quickly. The mRNA vaccine from BioNTech, through a collaboration with Pfizer, was first to market in the United States and Europe, followed swiftly by the one from Moderna.

But the delivery strategies used for mRNA vaccines haven’t worked out for DNA vaccines. That challenge has led to an outpouring of creative development and the eventual adoption of an electrical engineering approach.

The first human studies of DNA vaccines, which began in the mid-1990s, were a complete flop,” says Kate Broderick, senior vice president of R&D at Inovio. The vaccine just didn’t prompt much of an immune response. It was a big surprise and disappointment,” adds Jeffrey Ulmer, who was head of preclinical R&D at the pharma giant GSK until last year and is now an industry consultant. Despite very good data in a wide variety of animal models for a wide variety of different disease targets, it just did not seem to translate into humans,” he says.

The problem was getting the DNA, which is a big molecule, to penetrate not only through the cell’s outer layers but also through the cell’s nuclear membrane into the nucleus. Unlike an mRNA vaccine, which can function in parts of the cell outside the nucleus, a DNA vaccine can function only inside the nucleus. Some researchers reasoned that DNA vaccines worked well in small animals because the injection needle created pressure that damaged many surrounding cells, allowing DNA molecules to enter. But in the larger bodies of humans, the needle generates relatively little pressure, and fewer cells take in the vaccine.

So scientists began experimenting with more physical ways to deliver vaccines and increase cellular uptake. It’s common sense: Instead of saying ‘Please, open a little window and let me get in,’ you have a violent approach where you break the door,” says Shan Lu, an immunologist at the University of Massachusetts Medical School.

To that end, researchers engineered all sorts of creative methods to physically force vaccines into the body. They tried sonoporation, which uses sound waves to permeate a cell’s outer layer, and pressurized injections, whereby a piston pushed by a sudden release of energy delivers a narrow, high-pressure stream of liquid. They experimented with micro shock waves, in which a spark generated by electrodes causes a microexplosion, sending a wave of energy that forces a vaccine through the skin without a needle. They tried gene guns that propel DNA-coated gold particles into cells and microneedles that were laced with vaccine and engineered into skin patches.

Image of a person working on the Cellectra 3PSP.

Image of a person working on the Cellectra 3PSP.

Image of workers working on the Cellectra 3PSP.
The newest Inovio device, the Cellectra 3PSP, is currently manufactured at Inovio’s facility in San Diego. The handheld Cellectra delivers about a hundred doses on a single battery charge. Its electrodes administer a series of electrical pulses that cause nearby cells to open channels through which the vaccine can enter.
Spencer Lowell

Among all these contenders, electroporation stood out as particularly promising. Electroporation was arguably the technology that allowed DNA vaccines to really reemerge as a technology that could be deployed,” says Amy Jenkins, a biological technologies program manager at the U.S. military’s research arm, DARPA, which has invested in both mRNA- and DNA-based vaccines.

Researchers have used electroporation routinely for decades to transfer genetic material into cells in the lab. Doctors have also used a high-voltage version of electroporation to break up cancerous masses in humans as part of a surgical technique. So adapting it to vaccines wasn’t a radical step.

Inovio’s newest electroporation device, the Cellectra 3PSP, is handheld and battery operated. It can deliver about a hundred doses on a single charge and has a life-span of about 5,000 uses, due to battery limitations. Each use requires a disposable tip. As with more conventional vaccines, the injection site is the upper arm. Vaccination starts with an intradermal injection of the vaccine dosea shot that’s only skin deep. Then, the tip of the Cellectra device is pressed against the skin, directly over the location of the shot. Electrodes about 3 millimeters in length administer a series of four square-wave electrical pulses that last 42 milliseconds each, at 0.2 amperes.

The recipient feels a brief twinge, similar to the level of pain people experience from a flu shot, according to a clinical study by Inovio. Recipients rated it at an average of about 2.5 on a 0-to-10 pain scalealthough the feeling is said to be like a buzzing sensation, rather than the prick and pressure of a shot.

The pulses cause nearby cells to temporarily open channels through which the vaccine can enter. As soon as the electrical pulses finish, those channels close. Now this DNA molecule is trapped inside the cells,” says Inovio’s Broderick. The DNA then acts like a code, so your cells become a factory for producing the vaccine,” she explains. Electroporation is generally 10 to 100 times as efficient at provoking an immune response as the same DNA vaccine given by a conventional needle injection alone, says Lu of the University of Massachusetts.

Over the last decade, Inovio’s DNA vaccines have been tested against HIV, Ebola, MERS, Lassa fever, and human papillomavirus (HPV), each delivered with some form of electroporation. In total, more than 3,000 people have received one of Inovio’s electroporated medicines, largely through phase 1 and 2 studies, Broderick says.

In a phase 1 study involving 40 volunteers, Inovio’s COVID-19 vaccine, which is given in two doses, proved safe and generated an immune response. The results don’t tell us much about how well the vaccine will protect against COVID-19 in real life. That will be clearer following the completion of a phase 2 study of 400 volunteers in the United States, which is currently underway. The company is also conducting a phase 2 study of 640 volunteers in China, where it has partnered with biotech company Advaccine Biopharmaceuticals Suzhou Co. to commercialize the vaccine.

During the pandemic, some vaccine developers have been linking the different phases of their clinical trials in an effort to speed up the process. But Inovio can’t start on a phase 3 trial in the United States yetfirst it has to answer questions from the U.S. Food and Drug Administration about the Cellectra 3PSP device. In September, the FDA notified Inovio of a partial clinical hold” on trials, a tactic the agency uses when its reviewers find issues with safety or product quality that have not been addressed by the drug developer. Inovio’s vaccine comes with a separate novel device, so that requires additional, independent oversight by the FDA’s device reviewers, says Dennis Klinman, a former senior reviewer of vaccines at the FDA, and now a consultant. The additional device oversight is likely the reason for the clinical hold, he says.

Inovio says it plans to answer the FDA’s questions using data from the phase 2 study, but it would not disclose the specifics of the agency’s queries. It was nothing about the safety or the use of the device in the clinic,” Broderick says. It’s more logistical areas for us to clarify.”

In addition to Inovio, at least three other companies Genexine, Takis, and OncoSecare conducting human studies of an electroporated DNA vaccine against COVID-19. Other companies, such as Ichor Medical Systems and IGEA Clinical Biophysics, have developed electroporation devices that they license to pharma companies for DNA vaccine delivery against other diseases. Not everyone thinks electroporation is the solution for DNA vaccines, however. Some groups continue to work on alternative delivery methods, hoping the surge of interest from the pandemic will push their strategies over the finish line too.

Image of the vaccine and the Cellectra 3PSP device.
In Inovio’s two-step process, the DNA vaccine is first administered via a syringe. Then the Cellectra device is pressed against the skin for electroporation of the cells.
Spencer Lowell

Introducing a new, unfamiliar device to the vaccination process, particularly during a pandemic, undoubtedly brings logistical challenges. The devices must be mass produced and delivered, which will add to the cost of the vaccine. Medical personnel must be trained to operate the Cellectra. The extra step (the zap after the shot) adds time to each vaccination. Considering that people have been lining up by the thousands in miles-long car lines to get their COVID-19 vaccines, these inconveniences are not trivial.

I don’t know that [Inovio’s vaccine] is going to get used” during this pandemic, says Moore, the immunologist at Weill Cornell. It’s not among the most potent, and it’s among the most inconvenient to deliver, so in the end people will vote with their feetor their arms, as it may be,” he says. Liu of the International Society for Vaccines adds: We don’t even have enough people trained in the U.S. to give enough syringe injections.” Complicating things with a new device and new administration method is going to be hard to do,” she says.

And then there’s the issue of consumer acceptance of an unfamiliar device that zaps the skin. I think the device presents a much larger problem, not from a logistical perspective but from a marketing perspective,” says Bruce Goodwin, who currently leads research on enabling biotechnologies at the U.S. DOD’s Joint Program Executive Office for Chemical, Biological, Radiological, and Nuclear Defense (JPEOCBRND). A device that [looks] basically [like] a mix between a sonicator and a stun gun isn’t necessarily the kind of PR people are looking to put out there unless there’s no other choice.”

Image of the vaccine device from the side and front.
Spencer Lowell

On the other hand, the COVID-19 vaccines available right now can’t reach large swaths of the world. Pfizer’s and Moderna’s vaccines initially had to be transported and stored in freezers at about 80 C and 25 C, respectively. (In February, Pfizer revised its storage guidelines to allow for storage at
25 C for up to two weeks.) The COVID-19 vaccines developed by Johnson & Johnson, AstraZeneca, and Novavax as well as those deployed in China and Russia don’t need ultracold freezers, but they all need refrigeration.

In many poor and remote parts of the world, this complicated supply chain of refrigerators or freezers simply doesn’t exist. Even in more developed and urbanized countries, stories of mishaps abound. Poor temperature control spoiled 12,000 doses en route to Michigan. An unplugged freezer killed 2,000 doses at a hospital in Massachusetts. Widespread power outages in Texas halted deliveries and left officials scrambling to administer thousands of doses before they went bad.

A vaccine that can be stored at room temperature would avoid these pitfalls and greatly facilitate distribution of the vaccine globally,” says Ulmer, the former GSK researcher. It’s a big advantage.” Inovio’s vaccine is stable for a year at room temperatures of about 19 C to 25 C, and for at least a month in hot climates, according to the company.

Pfizer’s and Moderna’s mRNA vaccines also tend to trigger flulike side effects, such as fever, chills, headache, muscle pain, nausea, and fatigue. Some of those reactions have been incredibly strong, says Barbara Felber, a senior investigator in the vaccine branch of the National Cancer Institute. For example, within hours of getting an mRNA COVID-19 vaccine, Felber’s 25- year-old son was trembling and shivering head to toe while wearing all the blankets in his apartment. He had such a bad reaction that we were on the phone with him all night,” Felber says. Of course, most people don’t have this kind of reaction, she adds, and the side effects are transient. It is better to have [side effects] than to get infected by SARS-CoV-2,” she stresses.

The United States’ Centers for Disease Control and Prevention (CDC) tracks adverse events of COVID-19 vaccines via a smartphone-based tool called
V-safe, which recipients can use to self-report their symptoms. About 25 percent of people who have participated have reported fevers, and 42 percent have reported headaches after taking the second dose of the Pfizer vaccine. I have not heard of anybody who got a DNA injection with electroporation who had any of these types of side effects,” Felber says.

For Inovio’s DNA vaccine, the only side effect is that momentary buzzing twinge at the injection site, says Broderick, the company’s R&D head.

The upsides of DNA vaccines, plus the ease of manufacturing and its low cost per dose, were enough to convince the DOD to invest heavily in Inovio early in the pandemic. In June 2020 the agency awarded $71 million to scale up the manufacturing of the Cellectra device for COVID-19 vaccines. The DOD will also pay for phase 2 and 3 studies of Inovio’s clinical trials, says Nicole Dorsey, director of technology selection and evaluation at the DOD’s JPEO-CBRND, which oversees the funding. The electroporation device is probably the less appealing part of a DNA vaccine,” but deploying it is a lot easier than maintaining cold-chain transportation overseas, she says.

The logistics of a new device seem quite manageable for the military. Trying to roll out these [Cellectra] 3PSP devices for 300 million people at every Walgreens on every cornerman, it’s a logistical problem that probably just isn’t soluble,” says Chris Earnhart, chief technology officer of the enabling biotechnologies program at JPEO-CBRND. In the DOD’s case, it’s easily soluble, because we have a very specific population and the numbers are just lower.”

Even if Inovio’s technology and vaccines don’t get adopted in the civilian world during this pandemic, they may prove useful in the long run. The investments we’re making now are related to the COVID response, but in a lot of ways, we’re also preparing for the next event,” says Earnhart. That could be a biowarfare event, or it could be another endemic outbreak.”

And perhaps it’s time for a tech upgrade. Inovio’s Broderick notes that people first began administering medicine via syringe around 1650, when goose quills were used for needles. It’s actually a really antiquated modality,” she says. At a time when we carry more computing power around in our pockets than what went to the moon, we should be open to newer technologies for vaccine delivery.”

This article appears in the June 2021 print issue as Vaccines Go Electric.”

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