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It took a global pandemic to accomplish one of the most significant advances in the history of vaccinology: widespread, commercial deployment of vaccines derived from nucleic acids. As of this writing, hundreds of millions of people have been vaccinated against SARS-CoV-2, the virus that causes COVID-19. And most of those shots have been the Pfizer-BioNTech and Moderna offerings, which are both of a type known as an mRNA (messenger RNA) vaccine.
Conceived decades ago but released to the public for the first time during the pandemic, mRNA vaccines so far are living up to their promise. Both the Pfizer and Moderna vaccines have proven to be about 95 percent effective against the novel coronavirus. In addition, this kind of vaccine can be tweaked with relative ease to target new variants of a virus, and its production does not rely on items that can be difficult to produce quickly in enormous quantities. And yet, a couple of drawbacks of mRNA vaccines have also been widely noted over the past six months: They depend on deep-freeze supply chains and storage, and they can produce significant side effects such as fever, chills, and muscle aches.
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 effects—and, 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.
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 vaccines—enabled by a new delivery technology—could 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 humans—or 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.
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.
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 dose—a 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 scale—although 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 yet—first 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 OncoSec—are 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.
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 feet—or 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 (JPEO–CBRND). “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."
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 corner—man, 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."
Emily Waltz is a contributing editor at Spectrum covering the intersection of technology and the human body. Her favorite topics include electrical stimulation of the nervous system, wearable sensors, and tiny medical robots that dive deep into the human body. She has been writing for Spectrum since 2012, and for the Nature journals since 2005. Emily has a master's degree from Columbia University Graduate School of Journalism and an undergraduate degree from Vanderbilt University. She aims to say something true and useful in every story she writes. Contact her via @EmWaltz on Twitter or through her website.
But beware a hardware glitch in the Pi’s RP2040 chip
Matthias Rosezky has a bachelor's degree in technical physics and is currently studying for a master's degree in physical energy and measurement Engineering at the Vienna University of Technology.
Radioactive minerals can be identified in a surprising number of places, including old ceramic glazes.
The global semiconductor shortage has made life tough for anyone using microcontrollers, with lead times now sometimes quoted in years. But there has been one bright spot: the US $4 Pi Pico, a microcontroller based on the new RP2040 chip. Not only does the RP2040 have lots of compute power, it hasn’t suffered the kind of shortages afflicting other chips. So when I decided to build a cheap DIY scintillating gamma spectrometer, it was the natural choice—although I didn’t realize I’d find myself navigating around teething problems of the sort that often affect a first-generation integrated circuit.
My interest in gamma-ray spectroscopy came from my physics studies. I find it fascinating that you can get so much information out of a single device. A gamma-ray spectrometer can be used like a Geiger counter with much better sensitivity, but unlike a Geiger counter, you can identify the exact composition of any gamma-emitting radioisotopes down to the picogram (or less). I started thinking about creating my own gamma-ray spectrometer when I saw the high price of even the cheapest commercially made devices. I wanted to see if I could make it easy and affordable to build a spectrometer.
The first step was to choose the scintillator at the heart of the spectrometer. In a nutshell, a scintillator measures both the energy and intensity of a flux of gamma rays, thanks to a transparent crystal. A gamma ray produces a free electron in the crystal, and this electron’s energy is proportional to the gamma ray’s. As the electron moves through the crystal, it excites atoms. The atoms, in turn, emit visible photons, with the total number of photons emitted proportional to the energy of the exciting electron. Thus, by counting the number of photons, you can gauge the energy of the original gamma ray. Counting how many gamma rays you detect over time gives you the radiation’s intensity, and looking at the energies of the gamma rays gives you a spectral fingerprint of a radioisotope.
The photon signal must be amplified to be detectable. Historically, this was done using a photomultiplier vacuum tube, but silicon photomultipliers (SiPMs) have become more common, and for my project they have a number of advantages, particularly in eliminating the need for a high-voltage power supply. You can buy various used scintillator crystals on eBay fairly cheaply: I purchased a small sodium iodide crystal, 18 millimeters in diameter and 30 mm long, for about US $40. It came with a photomultiplier tube, which I removed and replaced with my SiPM, wrapping the assembly in black tape to prevent external light from leaking in and triggering the sensor.
A Raspberry Pi Pico [left] provides both compute power and the gamma-ray spectrometer’s analog-to-digital converter. A carrier board [middle] provides power and an interface with the silicon photomultiplier [top right] and scintillating crystal [bottom right] that react to gamma rays.James Provost
The scintillator and SiPM plug into a carrier board, which has a DC/DC boost converter to convert 5 volts into the 29.3 V the SiPM needs. The carrier board also hosts the Pico microcontroller along with some other supporting circuitry, including an amplifier that increases the output voltage of the SiPM to a level that the Pico’s built-in analog-to-digital converter (ADC) can detect.
On paper, the Pi Pico’s ADC looks very good. But there’s a flaw lurking in it.
The ADC in the Pico’s RP2040 chip is a critical component, and on paper it looks very good. It has 12-bit resolution and can take measurements between 0 and 3.3 V at a rate of 500 kilosamples per second. But there’s a flaw lurking in the RP2040’s ADC.
I didn’t realize it existed until I started taking test spectra, writing software for the Pi that breaks up the ADC’s readings into 4,096 channels and counts the number of events in each channel over time. I noticed one channel kept reporting very high count values, creating a thin spike in my spectra. Puzzled, I took a four-hour background radiation measurement and discovered there were four problematic channels where the signal spiked unrealistically.
I started searching for what could be causing this and discovered I was not the first to run into problems with the ADC. A great website by Mark Omo—an EE who took it upon himself to investigate the problem—provides a detailed analysis, but in summary the issue is this: Ideally, an ADC chops the voltage range it can measure into an identically sized sequence of steps, producing a linear relationship between the input voltage and the numeric measurements it outputs. Of course, no ADC has a perfectly linear response across its measurement range, but the RP2040 has four spots where input voltages produce a wildly nonlinear response. This was the source of the mystery spikes in my spectra.
Radioactive minerals are more common than many people think: some sample spectra captured with the DIY detector and the isotopes responsible for their signatures. The boxes beneath each spectrum show the raw, uncalibrated data.James Provost
Until the RP2040 is revised to fix this glitch, there’s not much you can do about it directly. Fortunately, with 4,096 channels, I could afford to employ the simplest software fix—just throwing away the measurements in the affected channels—without affecting the quality of the overall spectrum significantly. Controlling and getting data from the spectrometer can be done via a USB interface (which also provides the power needed to operate it). I wrote software that can accept serial commands to, for example, put the spectrometer into Geiger counter or energy-measurement modes, or upload a histogram of all the measurements taken since the last power-up. You can write your own code to communicate with the spectrometer, or use a Web app I created that also plots spectra. (A link to the Web app, along with full build details and PCB files, is available on GitHub.)
For the future, I hope to make the spectrometer hardware capable of using a wider range of SiPMs and scintillators, so that people can use whatever detectors they can find. I hope you join me in this fascinating hobby!
This article appears in the July 2022 print issue as “DIY Gamma-Ray Spectroscopy.”
The new device boosts signals 1,000 times and promises applications in telecom and lidar
Charles Q. Choi is a science reporter who contributes regularly to IEEE Spectrum. He has written for Scientific American, The New York Times, Wired, and Science, among others.
An erbium-doped waveguide amplifier on a 1-by-1-square-centimeter photonic integrated chip, with a green emission from optically excited erbium ions.
Photonics has long held the promise of microchips that operate faster and consume less energy than their electronic counterparts. However, developing such circuitry has proven challenging over the years. One of the primary difficulties involves providing enough output power to yield a strong enough signal. However, researchers have now developed a chip-scale power booster for light with performance roughly as good as those already seen in commercial telecommunications.
The ultrabroadband fiber-optic networks that now connect the globe depend on erbium-doped fiber amplifiers that enable ultrafast data rates worldwide. Optical signals must be amplified many times when transmitted over great distances due to signal losses from the optical fibers and other network components. First developed in the 1980s, erbium-doped fiber amplifiers help boost optical signals without the extra step of converting them into electrical signals beforehand. (Specifically, these devices can amplify light in the 1.55-micrometer or 1,550-nanometer wavelength region, where optical fibers experience the fewest transmission losses.)
“The most exciting part of this work is how well the amplifiers work and that they are on par with commercial amplifiers, despite just being a few hundred microns across in each dimension.” —Tobias Kippenberg, Swiss Federal Institute of Technology Lausanne
For decades, scientists have sought to invent similar amplifiers that can work onboard photonic microchips. However, attempts to develop such chip-scale amplifiers resulted in devices whose output power was typically less than a milliwatt—too weak for many practical applications—due mostly to losses from the waveguides used to route light inside the chips. These amplifiers typically also had large footprints, and their fabrication was not compatible with contemporary photonic integrated circuit manufacturing techniques.
Now researchers have developed a chip-scale version of an erbium-doped fiber amplifier. The new device has a record-high output power of more than 145 milliwatts given just 2.61 mW of input power with more than 30 decibels of small-signal gain. This resulted in a more than a thousandfold amplification in the telecommunication band in continuous operation, a performance already comparable to that of commercial high-end erbium-doped fiber amplifiers.
“The most exciting part of this work is how well the amplifiers work and that they are on par with commercial amplifiers, despite just being a few hundred microns across in each dimension,” says study senior author Tobias Kippenberg, an optical engineer at the Swiss Federal Institute of Technology Lausanne. “That it would be possible to realize such amplifiers seemed impossible just a few years ago.”
Moreover, the researchers packed this device’s erbium-doped waveguide of up to a half-meter long into a spiral whose footprint measured just 1.2 millimeters by 3.6 mm across. The device also operates with a high power-conversion efficiency of roughly 60 percent.
The key to this new device is an ultralow-loss chip-scale photonic waveguide based on silicon nitride, a material that has already widely used in the semiconductor industry. Recently, Kippenberg and his colleagues fabricated ultralow-loss silicon nitride waveguides up to meters long. This led them to investigate whether implanting erbium into such waveguides might result in optical amplifiers.
“Erbium ions can provide amplification of light but only very faintly,” Kippenberg says. “It is only when they are embedded into very-low-loss optical fibers, and when they interact with light for very long distances, typically meters in length, that one can achieve gain.”
In experiments, the researchers showed they could boost the output power of devices known as soliton microcombs by 100 times. Soliton microcombs, can be used in spectroscopy, metrology, and other applications, but their output power is limited to only tens to hundreds of microwatts, requiring amplification in almost every application.
The scientists also revealed their device could directly amplify more than 20 wavelength-division multiplexing channels for data transmission over a 1-kilometer-long optical fiber link. This suggests it could be used in chip-scale amplification for telecommunication networks.
The researchers noted their optical amplifier still needs a pump laser that dwells off the microchip. Therefore, the entire unit is still not integrated together yet. “This is a key deficiency we need to address in the future via hybrid integration,” Kippenberg says.
Ultimately, the scientists hope their optical amplifiers may help enable chip-scale, mode-locked lasers delivering bursts just quadrillionths of a second (a.k.a. femtoseconds) long. Such devices may have a wide variety of uses, such as lidar, says study lead author Yang Liu, an optical engineer at the Swiss Federal Institute of Technology Lausanne.
“The femtosecond mode-locked laser is clearly a holy grail, and what we now are setting our sights on,” Kippenberg says.
The scientists detailed their findings 16 June in the journal Science.
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